Antineoplastic Agents

ANTINEOPLASTIC AGENTS One branch of chemotherapy involves drugs developed to act on and kill or alter human cells – the antineoplastic drugs, which are designed to fight neoplasms, or cancers. When chemotherapy is mentioned, most people think of cancer treatment. Antineoplastic drugs alter human cells in a variety of ways, and they are intended to have a greater impact on the abnormal cells that make up the neoplasm or cancer than on normal cells. This area of pharmacology which has grown tremendously in recent years now includes many drugs that act on or are part of the immune system; these substances fight the cancerous cells using components of the immune system instead of destroying cells directly. This chapter discusses the classic antineoplastic approach and those drugs that are used in cancer chemotherapy.  Neoplasms All cancers start with a single cell that is generally different from the other cells in the surrounding tissue. This cell divides, passing along its abnormalities to daughter cells, eventually producing a tumor or neoplasm that has characteristics quite different from the original tissue. The cancerous cells exhibit anaplasia, a loss of cellular differentiation and organization, which leads to a loss of their ability to function normally. They also exhibit autonomy, growing without the usual homeostatic restrictions that regulate cell growth and control, which allows the cells to form a tumor. Over time, these neoplastic cells grow uncontrollably, invading and damaging healthy tissue in the surrounding area and even undergoing metastasis, or traveling from the place of origin to develop new tumors in other areas of the body where conditions are favorable for cell growth. The abnormal cells release enzymes that generate blood vessels (angiogenesis) in the area to supply both oxygen and nutrients to the cells, thus contributing to their growth. Overall, the cancerous cells rob the host cells of energy and nutrients and block normal lymph and vascular vessels as the result of pressure and intrusion on normal cells, leading to a loss of normal cellular function.  Causes of Cancer What causes the cells to mutate and become genetically different is not clearly understood. In some cases, a genetic predisposition to such mutation can be found. Breast cancer, for example, seems to have a definite genetic link. In other cases, constant irritation and cell turnover, and even stress have been blamed for the ensuring cancer. Stress reactions suppress the activities of the immune system, so if a cell is mutating while a person is under prolonged stress, research indicates that the cell has a better chance of growing into a neoplasm than when a person’s immune system is fully active. Pipe smokers are at increased risk for development of tongue and mouth cancers because the heat and chemicals in the pipe are constantly destroying normal cells, which must be increased rapidly, increasing the chances for development of a mutant cell. People living in areas with carcinogenic or cancer-causing chemicals in the air, water, or even the ground are at increased risk of developing mutant cells as a reaction to those toxic chemicals. Cancer clusters are often identified in such high-risk areas. Most likely, a

mosaic of factors coming together in one person would eventually lead to the development of the neoplasm.  Cell-Cycle Nonspecific and Specific Drugs Anticancer drugs cause cancer death by interfering with cell replication. Cellcycle nonspecific (CCNS) drugs act during any phase of the cell cycle, and cell-cycle specific (CCS) drugs exert their influence during a specific phase of the cell cycle. CCNS drugs (also called cell-cycle independent) kill cells during the M and G0 phases. CCS drugs (also called cell-cycle dependent) are most effective against rapidly growing cancer cells. In general CCNS drugs include the alkylating drugs, antitumor antibiotics, and hormones. The CCS drugs include the antimetabolites and the mitotic inhibitors. Growth fraction and doubling time are two factors that play a major role in the response of cancer cells to anticancer drugs. Anticancer drugs are more effective against neoplastic cells that have a high growth fraction. Leukemias and some lymphomas have high growth fractions and thus respond well to anticancer drug therapy. Small and early forming cancer cells and fast-growing tumors respond well to chemotherapy and have va higher cure rate than slow-growing tumors in the advanced stages.

ALKYLATING AGENTS One of the largest groups of anticancer drugs is the alkylating compounds. Alkylating agents cause cross-linking of DNA strands, abnormal base pairing, or DNA strand breaks, thus preventing the cell from dividing. Drugs in this group belong to the CCNS category and kill cells in various and multiple phases of the cell cycle. However, they are most effective against cells in the G0 phase. They are effective against many types of cancer, including acute and chronic leukemias, lymphomas, multiple myeloma, and solid tumors. I. BUSULFAN (Busulfex, Myleran) 

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ACTION: Changes essential cellular ions to covalent bonding with resulting alkylation; this interferes with normal biologic function of DNA; activity is not phase specific; action is due to myelosuppresion. Used for treatment of chronic myelocytic leukemia (CML) INDICATIONS AND DOSAGES: Adults: PO (Induction) – 1.8 mg/m2/day or 60mcg (0.06 mg)/kg/day until WBCs <15,000/mm3. Usual dose is 4-8 mg/day (range 1-12 mg/ Day). PO (Maintenance) – 1-3 mg/day Adults: IV – 0.8 mg/kg q6hr (dose based on IBW or actual weight, whichever is less; in obese patients, dosage should be based on adjusted IBW) for 4 days (total of 16 doses); given in combination with cyclophosphamide.

 Children: PO – 0.06-0.12 mg/kg/day or 1.8-4.6 mg/m2/day initially. Titrate dose to Maintain WBC of approximately 20,000/mm3. ADVERSE REACTIONS: PO Route  CV: Hypotension, thrombosis, chest pain, tachycardia, atrial fibrillation, heart block, pericardial effusion, cardiac tamponade (high dose with cyclophosphamide)  GI: Anorexia, constipation, diarrhea, dry mouth, nausea, vomiting  RESP: Alveolar hemorrhage, atelectasis, cough, hemoptysis, hypoxia, pleural effusion, pneumonia, sinusitis, pulmonary fibrosis IV Route  CNS: Cerebral Hemorrhage, coma, seizures, anxiety, depression, dizziness, headache, encephalopathy, weakness, mental changes  EENT: Pharyngitis, epistaxis, cataracts  GI: Nausea, vomiting, diarrhea, weight loss  GU: Impotence, sterility, amenorrhea, gynecomastia, renal toxicity, hypreuremia, adrenal insufficiency-like syndrome  HEMA: Thrombocytopenia, leukopenia, pancytopenia, severe bone marrow depression  INTEG: Dermatitis, hyperpigmentation, alopecia  OTHER: Chromosomal aberrations  RESP: Irreversible pulmonary fibrosis, pneumonitis INTERACTION:  Concurrent or previous (within 72 hours) use of acetaminophen may ↓ elimination and ↑ toxicity. Concurrent use with high-dose cyclophosphamide in patients with thassalemia may result in cardiac tamponade. Concurrent use with itraconazole or phenytoin ↓ blood levels effectiveness. Long-term continuous therapy with thioguanine may ↑ risk of hepatic toxicity. ↑ Bone marrow suppression with other antineoplastics or radiation therapy. May ↓ the antibody response to and ↑ risk of adverse reactions from live-virus vaccines. CONTRAINDICATIONS AND CAUTIONS:  Contraindications: Hypersensitivity. Pregnancy or lactation (pregnancy D 3rd trimester). Failure to respond to previous courses (radiation and chemotherapy).  Precautions: Active infections; decreased bone marrow reserve; obese patients (base dose on IBW); other chronic debilitating diseases (leukopenia, thrombocytopenia); patients with childbearing potential. NURSING CONSIDERATIONS:  Assessment: • High Alert: Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures. Apply pressure to venipuncture sites for at least 10min. Assess for signs infection (fever, chills, sore throat, etc.) during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension. Notify physician if these symptoms occur.

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Monitor I/O ratios and daily weights. Report significant changes in totals. Assess for pulmonary fibrosis (fever, cough, SOB) periodically during and after therapy. D/C therapy at the 1st sign of fibrosis. Usually occur at 8mo-10yrs (average 4yrs) after initiation of therapy. • IV: Premedicate patient with phenytoin before IV administration to minimize the risk of seizures. • Lab-test Considerations: Monitor CBC with differential and platelet count before and weekly during therapy. The nadir of leukopenia occurs within 10-15 days and the nadir of WBC at 11-30 days. Recovery usually occurs within 12-20wks. Notify physician if WBC is <15,000/mm3 or if a precipitous drop occurs. Institute thrombocytopenia precautions if platelet count is <150,000/mm3. Bone marrow depression may be severe and progressive, with recovery taking 1mo-2yrs after continuation of therapy. • Monitor serum ALT, bilirubin, alkaline phosphatase, and uric acid before and periodically during therapy. May cause ↑ uric acid levels.  Patient/Family Teaching: • Instruct patient to take medication exactly as directed, at the same time each day, even if nausea and vomiting are a problem. Consult health care professional if vomiting occurs shortly after dose is taken. If a dose is missed, do not take at all; do not have double doses. • Advise patient to notify health care professional if fever; sore throat; signs of infection; lower back or side pain; difficult or painful urination; sores in the mouth or on the lips; chills; dyspnea; persistent cough; bleeding gums; bruising; petechiae; or blood in urine, stool, or emesis occurs. Instruct patient to use soft toothbrush and electric razor. Caution patient not to drink alcoholic beverages or to take products containing aspirin or NSAIDs. • Caution patient to avoid crowds and persons with known infections. Health care professional should be informed immediately if symptoms of infection occur. • Discuss with patient the possibility of hair loss. Explore methods of coping. • Review with patient the need for contraception during therapy. Women need to use contraception even if amenorrhea occurs. • Instruct patient not to receive any vaccinations without advice of health care professional. • Inform patient of increased risk of a second malignancy with busulfan. II. CARBOPLATIN (Paraplatin, Paraplatin-AQ) ACTION:  Inhibits DNA synthesis by producing cross-linking of parent DNA strands (cell-cycle phase–nonspecific).  Used for treatment of advanced ovarian carcinoma (with other agents) and palliative treatment of ovarian carcinoma unresponsive to other modalities. INDICATIONS AND DOSAGES:  Adults: IV – (Initial treatment) 300 mg/m2 with cyclophosphamide at 4-wk intervals.

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(Refractory tumors) 360 mg/m2 as a single dose; may be repeated at 4-wk intervals, depending on response. Renal Impairment: IV – CCr 41-59 ml/min–initial dose 250 mg/m2 CCr 16-40 ml/min–initial dose 200 mg/m2 ADVERSE REACTIONS: CNS: Seizures, central neurotoxicity, peripheral neuropathy, dizziness, confusion CV: Cardiac abnormalities EENT: Tinnitus, hearing loss, vestibular toxicity, visual changes GI: Severe nausea, vomiting, diarrhea, weight loss, mucositis, anorexia, constipation, taste change HEMA: Thrombocytopenia, leukopenia, pancytopenia, neutropenia, anemia, bleeding INTEG: Dermatitis, rash, alopecia, erythema, pruritus, urticaria META: Hypomagnasemia, hypocalcemia, hypokalemia, hyponatremia, hyperuremia SYST: Anaphylaxis INTERACTION: ↑ nephrotoxicity and ototoxocity with other nephritic and ototoxic drugs (aminoglycosides, loop diuretics). ↑ Bone marrow depression with other bone marrow-depressing drugs or radiation therapy. May ↓ antibody response to livevirus vaccines and ↑ risk of adverse reactions. CONTRAINDICATIONS AND CAUTIONS: Contraindications: Hypersensitivity to carboplatin, cisplatin, or mannitol. Pregnancy or lactation (pregnancy D). Precautions: Hearing loss; active infections; electrolyte abnormalities; diminished bone marrow reserve (dose reduction recommended); renal impairment (dose reduction recommended if creatinine <60ml/min); other chronic debilitating diseases (leukopenia, thrombocytopenia); patients with childbearing potential. NURSING CONSIDERATIONS: Assessment: • Assess patient for Paraplatin-AQ for neurotoxocity (paresthesias in a stocking– glove distribution, areflexia, loss of proprioception and vibratory sensations). D/C when symptoms are first observed. • Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures. Apply pressure to venipuncture sites for at least 10min. Assess for signs infection (fever, chills, sore throat, etc.) during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension. Notify physician if these symptoms occur. • Monitor for signs of anaphylaxis. D/C medication immediately and notify physician if these occur. Epinephrine and resuscitation equipment should be readily available. • Audiometry is recommended before intiation of therapy and subsequent doses. Ototoxicity manifests as tinnitus and unilateral or bilateral hearing loss in high frequencies and becomes more frequent and severe with repeated doses.

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Lab-test Considerations: Monitor CBC with differential and platelet count before and weekly during therapy. For Palaplatin: the nadir of thrombocytopenia and leukopenia occur after 21 days and recover by 30 days after a dose. Nadir of granulocyte counts usually occurs after 21-28 days and recovers by day 35. Withhold subsequent doses until neutrophil count is >2000/mm3 and platelet count is >100,000/mm3. For Paraplatin-AQ: the nadirs of thrombocytopenia and leukopenia occur between days 18 and 23 and recover by day 39. Anemia also occurs with the same frequency and timing as thrombocytopenia and leukopenia. • Monitor renal function and serum electrolytes before initiation of therapy and before each course of carboplatin. Nephrotoxocity with Paraplatin-AQ is cumulative and is potentiated with aminoglycoside antibiotics. Monitor serum creatinine, BUN, CCr, and Mg+, Na+, K+, and Ca+ levels prior to initiating therapy and before each subsequent dose. May cause ↑ BUN and serum creatinine concentrations and ↓ CCr. May cause ↓ serum K+, Mg+, and Na+ concentrations. Renal function must return to normal before each dose of Paraplatin-AQ is given. • Paraplatin-AQ may cause hyperuricemia, usually occurring 3-5 days after therapy. Allopurinol may be used to ↓ uric acid levels. • Paraplatin-AQ may cause ↑ serum amylase levels.  Patient/Family Teaching: • Advise patient to notify health care professional if fever; sore throat; signs of infection; lower back or side pain; difficult or painful urination; chills; dyspnea; persistent cough; bleeding gums; bruising; petechiae; or blood in urine, stool, or emesis; increased fatigue, dyspnea, or orthostatic hypotension occurs. • Caution patient to avoid crowds and persons with known infections. Health care professional should be informed immediately if symptoms of infection occur. Instruct patient to use soft toothbrush and electric razor. Caution patient not to drink alcoholic beverages or to take products containing aspirin or NSAIDs because they may precipitate gastric bleeding. • Instruct patient to promptly report any numbness or tingling in the extremities or face, decreased coordination, difficulty with hearing or ringing in the ears, unusual swelling, or weight gain to health care professional. • Discuss with patient the possibility of hair loss. Explore methods of coping. • Review with patient the need for contraception during therapy (if patient is not infertile as a result of surgical or radiation therapy). • Instruct patient not to receive any vaccinations without advice of health care professional and to avoid contact with persons who have received OPV w/in the past several months. • Emphasize the need for periodic lab tests to monitor for side effects. III. CARMUSTINE (BCNU, BiCNU, Gliadel) ACTION:  Alkylates DNA, RNA; is able to inhibit enzymes that allow synthesis of amino acids in proteins (cell-cycle phase–nonspecific).  Used alone or with other treatments in the management of: Brain tumors, Multiple

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myeloma, Hodgkin’s disease, other lymphomas. INDICATIONS AND DOSAGES: Adults and Children: IV – 150-200 mg/m2 single dose every 6-8wks or 75-100mg/ m2/day for 2 days q6wk or 40 mg/m2/day for 5 days q6wk. Adults: Intracavity – Up to 61.1 mg (8 implants) placed in cavity created during Surgical resection of brain tumor. ADVERSE REACTIONS: GI: Nausea, vomiting, anorexia, stomatitis, hepatotoxicity GU: Azothemia, renal failure HEMA: Thrombocytopenia, leukopenia, severe bone marrow depression, anemia INTEG: Pain, burning, hyperpigmentation at the injection site RESP: Fibrosis, pulmonary infiltrate INTERACTION: ↑ Bone marrow depression with other bone marrow-depressing drugs or radiation therapy. Smoking ↑ risk of pulmonary toxicity. May ↓ antibody response to livevirus vaccines and ↑ risk of adverse reactions. Myelosupression may be ↑ by cimetidine. CONTRAINDICATIONS AND CAUTIONS: Contraindications: Hypersensitivity. Pregnancy or lactation (pregnancy D 3rd trimester). Precautions: Active infections; decreased bone marrow reserve; obese patients (base dose on IBW); other chronic debilitating diseases (leukopenia, thrombocytopenia); patients with childbearing potential. NURSING CONSIDERATIONS: Assessment: • Monitor V/S before and frequently during therapy. • Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures. Apply pressure to venipuncture sites for at least 10min. Assess for signs infection (fever, chills, sore throat, etc.) during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension. Notify physician if these symptoms occur. • Monitor I/O ratios and daily weights. Report significant changes in totals. • Assess for pulmonary fibrosis (fever, cough, SOB) periodically during and after therapy. D/C therapy at the 1st sign of fibrosis. Usually occur at 8mo-10yrs (average 4yrs) after initiation of therapy. • IV: Premedicate patient with phenytoin before IV administration to minimize the risk of seizures. • Lab-test Considerations: Monitor CBC with differential and platelet count before and weekly during therapy. The nadir of thrombocytopenia occurs in 4-5 wks; the nadir of leukopenia in 5-6 wks. Recovery usually occurs within 6-7wks but may take 10-12 wks after therapy. Notify physician if WBC is <4,000/mm 3 or if a precipitous drop occurs. Institute thrombocytopenia precautions if platelet count is

<100,000/mm3. Anemia is usually mild. • Monitor serum ALT, AST, bilirubin, and LDH before and periodically during therapy. May cause mild, reversible ↑ in AST, alkaline phosphatase, and bilirubin. • Monitor BUN, serum creatinine, and uric acid before and periodically during therapy. Notify physician is BUN is elevated.  Patient/Family Teaching: • Advise patient to notify health care professional if fever; sore throat; signs of infection; lower back or side pain; difficult or painful urination; sores in the mouth or on the lips; chills; dyspnea; persistent cough; bleeding gums; bruising; petechiae; or blood in urine, stool, or emesis occurs. • Caution patient to avoid crowds and persons with known infections. Health care professional should be informed immediately if symptoms of infection occur. Instruct patient to use soft toothbrush and electric razor. Caution patient not to drink alcoholic beverages or to take products containing aspirin or NSAIDs. • Instruct patient to notify health care professional if shortness of breath or increased cough occurs. Enc ourage patient not to smoke, because smokers are at greater risk for pulmonary toxicity. • Discuss with patient the possibility of hair loss. Explore methods of coping. • Review with patient the need for contraception during therapy. • Instruct patient not to receive any vaccinations without advice of health care professional. • Emphasize need for periodical lab tests to monitor for side effects. IV. CHLORAMBUCIL (Leukeran)  

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ACTION: Alkylates DNA, RNA; is able to inhibit enzymes that allow synthesis of amino acids in proteins (cell-cycle phase–nonspecific). Used for treatment: lymphocytic leukemia, other lymphomas, nephrotic syndrome, non-Hodgkin’s/Hodgkin’s disease, choriocarcinomas. INDICATIONS AND DOSAGES: Adults: PO – 0.1-0.2 mg/kg/day for 3-6 wks(initial), then 4-10 mg/day(maintenance) Children: PO – 0.1-0.2 mg/kg/day (4.5 mg/m2/day) in divided doses. ADVERSE REACTIONS: CNS: Seizures, tremors, confusion, agitation, ataxia GI: Nausea, vomiting, diarrhea, weight loss, weight loss, hepatotoxicity, jaundice GU: Hyperuremia HEMA: Thrombocytopenia, leukopenia, pancytopenia, permanent bone marrow depression INTEG: Dermatitis, rash, alopecia RESP: Irreversible pulmonary fibrosis, pneumonitis INTERACTION: ↑ Bone marrow depression with other bone marrow-depressing drugs or radiation therapy. Smoking ↑ risk of pulmonary toxicity. May ↓ antibody response to live-

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virus vaccines and ↑ risk of adverse reactions. CONTRAINDICATIONS AND CAUTIONS: Contraindications: Hypersensitivity. Pregnancy or lactation (pregnancy D). Precautions: Active infections; decreased bone marrow reserve and other chronic debilitating diseases (leukopenia, thrombocytopenia) NURSING CONSIDERATIONS: Assessment: • Monitor V/S before and frequently during therapy. • Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures. Apply pressure to venipuncture sites for at least 10min. Assess for signs infection (fever, chills, sore throat, etc.) during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension. Notify physician if these symptoms occur. • Monitor I/O ratios and daily weights. Report significant changes in totals. • Assess for pulmonary fibrosis (fever, cough, SOB) periodically during and after therapy. • Lab-test Considerations: Monitor CBC with differential and platelet count before and weekly during therapy. Notify physician if WBC is <2000/mm3 or if granulocyte count is <1000/mm2. • Monitor serum ALT, AST, bilirubin, and LDH before and periodically during therapy. • Monitor BUN, serum creatinine, and uric acid before and periodically during therapy. Notify physician is BUN is elevated. Patient/Family Teaching: • Advise patient to notify health care professional if fever; sore throat; signs of infection; lower back or side pain; difficult or painful urination; sores in the mouth or on the lips; chills; dyspnea; persistent cough; bleeding gums; bruising; petechiae; or blood in urine, stool, or emesis occurs. • Caution patient to avoid crowds and persons with known infections. Health care professional should be informed immediately if symptoms of infection occur. Instruct patient to use soft toothbrush and electric razor. Caution patient not to drink alcoholic beverages or to take products containing aspirin or NSAIDs. • Instruct patient to notify health care professional if shortness of breath or increased cough occurs. Enc ourage patient not to smoke, because smokers are at greater risk for pulmonary toxicity. • Discuss with patient the possibility of hair loss. Explore methods of coping. • Review with patient the need for contraception during therapy. • Instruct patient not to receive any vaccinations without advice of health care professional. • Emphasize need for periodical lab tests to monitor for side effects.

V. CISPLATIN (Platinol, Platinol-AQ)

ACTION:  Inhibits DNA synthesis by producing cross-linking of parent DNA strands (cell-cycle phase–nonspecific).  Used for treatment of metastatic testicular and ovarian carcinoma. Advanced bladder cancer. Head and neck cancer. Cervical cancer. Other tumors.

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INDICATIONS AND DOSAGES: Adults: IV – Metastatic testicular tumors–20 mg/m2 daily for 5 days repeated q3 to q4 wks. Metastatic ovarian cancer–75-100 mg/m2, repeated q4wks in combination cyclophosphamide or 100 mg/m2 q3wks is used as a single agent. Advanced bladder cancer–50-70 mg/m2 q3-4wks (single agent). ADVERSE REACTIONS: CNS: Seizures, peripheral neuropathy CV: Cardiac abnormalities EENT: Tinnitus, hearing loss, vestibular toxicity, visual changes GI: Severe nausea, vomiting, diarrhea, weight loss HEMA: Thrombocytopenia, leukopenia, pancytopenia INTEG: Dermatitis, rash, alopecia, erythema, pruritus, urticaria META: Hypomagnasemia, hypocalcemia, hypokalemia, hyponatremia, hyperuremia RESP: Fibrosis SYST: Anaphylaxis INTERACTION: ↑ nephrotoxicity and ototoxocity with other nephritic and ototoxic drugs (aminoglycosides, loop diuretics). ↑ Bone marrow depression with other bone marrow-depressing drugs or radiation therapy. May ↓ antibody response to livevirus vaccines and ↑ risk of adverse reactions. CONTRAINDICATIONS AND CAUTIONS: Contraindications: Hypersensitivity to carboplatin, cisplatin, or mannitol. Pregnancy or lactation (pregnancy D). Precautions: Hearing loss; active infections; electrolyte abnormalities; diminished bone marrow reserve (dose reduction recommended); renal impairment (dose reduction recommended if creatinine <60ml/min); other chronic debilitating diseases (leukopenia, thrombocytopenia); patients with childbearing potential. NURSING CONSIDERATIONS: Assessment: • Monitor V/S before and frequently during therapy. Report significant changes. • Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures. Apply pressure to venipuncture sites for at least 10min. Assess for signs infection (fever, chills, sore throat, etc.) during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension. Notify physician if these symptoms occur. • Monitor for signs of anaphylaxis. D/C medication immediately and notify physician if these occur. Epinephrine and resuscitation equipment should be

readily available. Audiometry is recommended before intiation of therapy and subsequent doses. Ototoxicity manifests as tinnitus and unilateral or bilateral hearing loss in high frequencies and becomes more frequent and severe with repeated doses. • Lab-test Considerations: Monitor CBC with differential and platelet count before and weekly during therapy. The nadir of thrombocytopenia, leukopenia, and anemia occur within 18-23 days and recover by 39 days after a dose. Withhold subsequent doses until WBC is >4000/mm3 and platelet count is >100,000/mm3. • Monitor renal function and serum electrolytes before initiation of therapy and before each course of carboplatin. Nephrotoxocity with Paraplatin-AQ is cumulative and is potentiated with aminoglycoside antibiotics. Monitor serum creatinine, BUN, CCr, and Mg+, Na+, K+, and Ca+ levels prior to initiating therapy and before each subsequent dose. May cause ↑ BUN and serum creatinine concentrations and ↓ CCr. May cause ↓ serum K+, Mg+, and Na+ concentrations. Renal function must return to normal before another dose is given. • May cause transiently ↑ serum bilirubin and AST concentrations.  Patient/Family Teaching: • Advise patient to notify health care professional if fever; sore throat; signs of infection; lower back or side pain; difficult or painful urination; chills; dyspnea; persistent cough; bleeding gums; bruising; petechiae; or blood in urine, stool, or emesis; increased fatigue, dyspnea, or orthostatic hypotension occurs. • Caution patient to avoid crowds and persons with known infections. Health care professional should be informed immediately if symptoms of infection occur. Instruct patient to use soft toothbrush and electric razor. Caution patient not to drink alcoholic beverages or to take products containing aspirin or NSAIDs because they may precipitate gastric bleeding. • Instruct patient to promptly report any numbness or tingling in the extremities or face, decreased coordination, difficulty with hearing or ringing in the ears, unusual swelling, or weight gain to health care professional. • Discuss with patient the possibility of hair loss. Explore methods of coping. • Review with patient the need for contraception during therapy (if patient is not infertile as a result of surgical or radiation therapy). • Instruct patient not to receive any vaccinations without advice of health care professional and to avoid contact with persons who have received OPV w/in the past several months. • Emphasize the need for periodic lab tests to monitor for side effects. •

CYCLOPHOSPHAMIDE Cycloblastin, Cytoxan, Cytoxan Lyophilized, Endoxan, Neosar, Proxytox INDICATIONS and DOSAGES Breast and ovarian cancer, Hodgkin’s disease, chronic lymphocytic leukemia, chronic myelocytic leukemia, acute lymphoblastic leukemia, acute myelocytic and monocytic

leukemia, neuroblastoma, retinoblastoma, malignant lymphoma, multiple myeloma, mycosis fungoides, sarcoma. Adults: Initially for induction, 40 to 50 mg/kg I.V. in divided doses over 2 to 5 days. Or, 10 to 15 mg/kg I.V. q 7 to 10 days, 3 to 5 mg/kg I.V. twice weekly, or 1 to 5 mg/kg P.O. daily, based on patient tolerance Children: Initially for induction, 2 to 8 mg/kg or 60 to 250 mg/m² P.O. or I.V daily. Maintenance dose is 2 to 5 mg/kg P.O. or 50 to 150 mg/m² P.O. twice weekly. Adjust subsequent doses according to evidence of antitumor activity or leukopenia. INCOMPATIBILITIES Amphotecerin B cholesteryl sulfate complex ACTION Cross-links strands of cellular DNA and interferes with RNA transcription, causing an imbalance of growth that leads to cell death. Not specific to cell cycle. ADVERSE REACTIONS CV: cardiotoxicity with very high doses and with doxorubicin, flushing. GI: anorexia, nausea and vomiting, abdominal pain, stomatitis, mucositis. GU: hemorrhagic cystitis, impaired fertility. Hematologic: leukopenia, thrombocytopenia, anemia Hepatic: hepatotoxicity Metabolic: hyperuricemia, SIADH Respiratory: pulmonary fibrosis with high doses. Skin: reversible alopecia, rash, pigmentation, nail changes, itching. Other: secondary malignant disease, anaphylaxis, hypersensitivity reactions. INTERACTIONS (Drug-drug,) Allopurinol, myelosuppressives: May increase myelosuppresions. Monitor patient for toxicity. Anticoagulants: May increase anticoagulant effect. Monitor patient for bleeding. Aspirin, NSAIDs: May increase risk of bleeding. Avoid using together. Barbiturates: May enhance cyclophosphamide toxicity. Monitor patient closely. Cardiotoxic drugs: May increase adverse cardiac effects. Monitor patient for toxicity. Chloramphenicol, corticosteroids: May reduce activity of cyclophosphamide. Use together cautiously. Ciprofloxacin: May decrease antimicrobial effect. Monitor patient for effect. Digoxin: May decrease digoxin level. Monitor level closely. Succinycholine: May prolong neuromuscular blockage. Avoid using together.

CONTRAINDICATIONS and CAUTIONS 1. Contraindicated to patients with hypersensitivity to drug and in those with severe bone marrow suppression. 2. Use cautiously in patients with leukopenia, thrombocytopenia, malignant cell infiltration of bone marrow, or hepatic or renal disease and in those who have recently undergone radiation therapy or chemotherapy. NURSING CONSIDERATIONS 1. Don’t give drug at bed time; infrequent urination during the night may increase possibility of cystitis. If cystitis occurs, stop drug and notify prescriber. Cystitis can occur months after therapy ends. Mesna may be given to reduce frequent and severity of bladder toxicity. Test urine for blood. 2. Adequately hydrate patients before and after dose to decrease cystitis. 3. Use caution to ensure correct dose to decrease risk of cardiac toxicity. 4. Monitor CBC and renal and liver function test results. 5. Monitor patient closely for leukopenia (nadir between days 8 and 15, recovery in 17 to 28 days). 6. Monitor uric acid level. To prevent hyperuricemia with resulting uric acid nephropathy, allopurinol may be used with adequate hydration. 7. Alert: If patient’s corticosteroid therapy is stopped, monitor patient for toxicity. 8. To prevent bleeding, avoid all I.M. injections when platelet count is less than 50,000/ cubic mm. 9. Anticipate blood transfusions because of cumulative anemia. Patients may receive injections of RBC colony-stimulating factor to promote RBC production and decrease need for blood transfusions. 10. Therapeutic effects are often accompanied by toxicity. 11. In boys, using drug for nephrotic syndrome for more than 60 days increases the incidence of oligospermiaand azoospermia. Use for more than 90 days increases the risk of sterility. 12. Drug may be used to treat non-ocologic disorders, such as lupus, nephritis, and rheumatoid arthritis. PATIENT TEACHING 1. 2. 3. 4.

Warn patient that their hair loss is likely to occur but is reversible. Advise patient to watch for signs and symptoms of infection and bleeding. Instruct patient to avoid OTC products that contain aspirin. To minimize risk of hemorrhagic cystitis, encourage patient to urinate every 1 to 2 hours while awake and to drink at least 3L of fluid daily. 5. If patient is taking tablets, tell him not to take it at bed time because infrequent urination increases risk of cystitis.

IFOSFAMIDE Haloxan, Ifex

INDICATIONS and DOSAGES •

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Testicular cancer Adults: 1.2 g/ square m daily I.V. for 5 consecutive days. Repeat treatment q 3 weeks or after patient recovers from hematologic toxicity. Don’t repeat doses until WBC count exceeds 4,000/cubic mm and platelet exceeds 100,000/cubic mm. Sarcomas, small-cell lung cancer, cervical cancer, ovarian cancer, uterine cancer. Adults: 1.2 to 2.5 g/square m I.V. daily for 3 to 5 days. Repeat cycle prn, based on patient response.

INCOMPATIBILITIES Cefepime, mesna with epiribucin, methotrexate sodium. ACTION Cross-links strands of cellular DNA and interferes with RNA transcription, causing an imbalance of growth that leads to cell death. Not specific to cell cycle. ADVERSE REACTION CNS: somnolence, confusion, coma, seizures, ataxia, hallucinations, depressive psychosis, dizziness, disorientation, cranial nerve dysfunction. GI: nausea, vomiting, diarrhea. GU: hemorrhagic cystitis, hematuria, nephrotoxicity, Fanconi’s syndrome. Hematologic: Leukopenia, thrombocytopenia, myelosuppression. Hepatic: hepatotoxicity. Matabolic: metabolic acidosis. Skin: alopecia. Other: infection, phlebitis. INTERACTIONS (Drug-drug) Anticoagulants, aspirin, NSAIDs: May increase risk of bleeding. Avoid using together. Barbiturates, chloral hydrate, fosphenytoin, phenytoin: May increase infosfamide toxicity. Monitor patient closely. Corticosteroids: May inhibit hepatic enzymes, reducing ifosfamide’s effect. Monitor patient for increased ifosfamide toxicity if corticosteroid dosage is suddnely reduced or stopped. Cyclophosphamide: May increase risk of cardiac temponade in patients with thalasemia. Monitor patient closely. Myelosuppresives: May enhance hematologic toxicity. Dosage adjustment may be needed CONTRAINDICATIONS and CAUTIONS 1. Contraindicated in patients hypersensitivity to drug and in those with severe bone marrow suppresion.

2. Use cautiously in patients with renal impairment or compromised bone marrow reserve as indicated by leukopenia, granulocytopenia, extensive bone marrow mestastase, previous radiation therapy, or previous therapy with cytotoxic drugs. NURSING CONSIDERATIONS 1. Give antiemetic before drug, to reduce nausea. 2. Ensure the patient is adequately hydrated during therapy. 3. Don’t give drug at bed time; infrequent urination during the night may increase possibility of cystitis. If cystitis occurs, stop drug and notify prescriber. 4. Bladder irrigation with normal saline solution may be done to treat cystitis. 5. Monitor CBC and renal and liver function test results. 6. To prevent bleeding, avoid all I.M. injections when platelet count is less than 50,000/ cubic mm. 7. Anticipate blood transfusions because of cumulative anemia. Patients may receive injections of RBC colony-stimulating factor to promote RBC production and decrease need for blood transfusions. 8. Assess patient for mental status changes; dosage may have to be decreased. 9. Look alike-sound alike: Don’t confuse ifosfamide with cyclophosphamide. PATIENT TEACHING 1. Remind patient to urinate frequently to minimize contact of drug and its metabolites with the lining of the bladder. 2. Advise patient to watch for signs and symptoms of infection and bleeding. 3. Instruct patient to avoid OTC products that contain aspirin. 4. Caution woman of childbearing age to avoid becoming pregnant during therapy.

LOMUSTINE (CCNU) CeeNU INDICATIONS and DOSAGES •

Brain Tumor, Hodgkin’s disease Adults and children: 100 to 130mg/square m P.O. as single dose q 6 weeks. Repeat doses shouldn’t be given until WBC count exceeds 4,000/cubicmm and platelet count is greater than 100,000/cubic mm. Adjust-a-dose: Reduce dosage according to degree of bone marrow suppression or when used with other myelosuppresive drugs.

ACTION Cross-links strands of cellular DNA and interferes with RNA transcription, causing an imbalance of growth that leads to cell death. Not specific to cell cycle. ADVERSE REACTIONS

CNS: disorienattion, lethargy, ataxia. GI: nausea, vomiting, stomatitis. GU: Nephrotoxicity, progressive azotemia, renal failure, amenorrhea, azoospermia. Hematologic: anemia, leukopenia, thrombocytopenia, bone marrow suppression. Hepatic: hepatotoxicity Respiratory: pulmonary fibrosis. Skin: alopecia. Other: Secondary malignant disease. INTERACTIONS (Drug-drug) Anticoagulants, aspirin, NSAIDs: May increase risk of bleeding. Avoid using together. Myelosuppresives: May increase myelosuppression. Monitor patient. CONTRAINDICATIONS and CAUTIONS 1. Contraindicated in patients with hypersensitivity to drug. 2. Use cautiously in patients with decreased platelet, WBC, or RBC counts and in those receiving other myelosuppressives. NURSING CONSIDERATIONS 1. Give antiemetic before drug, to reduce nausea. 2. Give 2 to 4 hours after meals; drug will be more completely absorbed if taken when stomach is empty. 3. To prevent bleeding, avoid all I.M. injections when platelet count is less than 50,000/ cubic mm. 4. Anticipate blood transfusions because of cumulative anemia. Patients may receive injections of RBC colony-stimulating factor to promote RBC production and decrease need for blood transfusions. 5. Therapeutic effects are often accompanied by toxicity. PATIENT TEACHING 1. Advise patient to take capsules on an empty stomach, if possible. 2. Advise patient to watch for signs and symptoms of infection and bleeding. Tell patient to take temperature daily. 3. Instruct patient to avoid OTC products that contain aspirin. 4. Advise women to stop breast-feeding during therapy because possible risk of toxicity to infant. 5. Caution woman of childbearing age to avoid becoming pregnant during therapy.

MECHLORETHAMINE HYDROCHLORIDE (Nitrogen mustard) Mustargen

INDICATIONS and DOSAGES Dosage is based on patient response and degree of toxicity. • Hodgkin’s disease Adults and children: 6mg/square m daily on days 1 and 8 of 28-day cycle in combination with other antineoplastics, such as mechlorethamine-vincristineprocarbazine-prednisone (MOPP) regimen. Repeat dosage for six cycle. • Polycythemia vera, chronic lymphocytic leukemia, chronic myelocytic leukemia, bronchogenic cancer Adults and children: 0.4 mg/kg as single dose or 0.1 to 0.2 mg/kg divided in two or four successive daily doses during each course of therapy. • Malignant effusions (pericardial, peritoneal, pleural) Adults: 0.4mg/kg intracavitarily, although 0.2 mg/kg (10 to 20mg) has been used intrapericardially. INCOMPATIBILITIES Allopurinol, cefepime, D5W, methohexital, normal saline solution. ACTION Cross-links strands of cellular DNA and interferes with RNA transcription, causing an imbalance of growth that leads to cell death. Not specific to cell cycle. ADVERSE REACTIONS CNS: weakness, vertigo, neurotoxicity. CV: thrombophlebitis. EENT: tinnitus, deafness with high doses. GI: nausea, vomiting, anorexia, diarrhea, metallic taste. GU: menstrual irregularities, impaired spermatogenesis. Hematologic: thrombocytopenia, lymphocytopenia, agranulocytosis, mild anemia beginning in 2 to 3 weeks. Hepatic: jaundice. Metabolic: hyperuricemia. Skin: alopecia, rash, sloughing, severe skin irritation with extravasation or contact Other: precipitation of herpes zoster, anaphylaxis, secondary malignant disease. INTERACTIONS (Drug-drug) Anticoagulants, aspirin, NSAIDs: May increase risk of bleeding. Avoid using together. Myelosuppressives: May increase myelosuppression. Monitor patient. CONTRAINDICATIONS and CAUTIONS 1. Contraindicated in patients with hypersensitivity to drug and in those with infectious diseases.

2. Use cautiously in patients with severe anemia or depressed neutrophil or platelet count and in those who have recently undergone radiation therapy or chemotherapy. NURSING INTERVENTIONS 1. When given intracavitarily for sclerosing effect, dilute using up to 100ml of normal saline solution for injection. Turn patient from side to side every 5 to 10 minutes for 1 hour to distribute drug. 2. Monitor uric acid level. To prevent hyperuricemia with resulting uric acid or nephropathy, make sure patient is adequately hydrated. Alkalinizing the urine and allopurinol may also be useful. 3. Therapeutic effects are commonly accompanied by toxicity. 4. Neurotoxicity increases with dosage and patient age. 5. To prevent bleeding, avoid all I.M. injections when platelet count is less than 50,000/ cubic mm. 6. Anticipate blood transfusions because of cumulative anemia. Patients may receive injections of RBC colony-stimulating factor to promote RBC production and decrease need for blood transfusions. 7. Monitor patient closely for bone marrow suppression. PATIENT TEACHING 1. Advise the patient to report any pain or burning at site of injection during or after administration. 2. Advise patient to watch for signs and symptoms of infection and bleeding. Tell patient to take temperature daily. 3. Instruct patient to avoid OTC products that contain aspirin. 4. Advise women to stop breast-feeding during therapy because possible risk of toxicity to infant. 5. Caution woman of childbearing age to avoid becoming pregnant during therapy. 6. Tell patient that severe nausea and vomiting can occur. 7. Tell patient about the risk of sterility.

MELPHALAN (L-phenylalanine mustard, L-sarcolysin) Alkeran

MELPHALAN HYDROCHLORIDE Alkeran

INDICATIONS and DOSAGES •

•

Multiple myeloma Adults: Initially, 6mg P.O. daily for 2 to 3 weeks; then stop drug for up to 4 weeks or until WBC and platelet counts stop dropping and begin to rise again; maintenace dose is 2mg daily. Or, o.15mg/kg P.O. daily for 7 days, or 0.25mg/kg for 4 days; repeat q 4 to 6 weeks. Or, give I.V. to patients who can’t tolerate oral therapy, 16mh/square m given by perfusion over 15 to 20 minutes at 2-week intervals for four doses. After patient has recovered from toxicity, give drug at 4-week intervals. Adjust-a-dose: For patients with renal insufficiency, reduce dosage by up to 50%. Nonresectable advanced ovarian cancer Adults: 0.2mg/kg P.O. daily for 5 days. Repeat q 4 to 6 weeks, depending on bone marrow recovery.

INCOMPATIBILITIES Amphoterecin B, chlorpromazine, D5W, lactated Ringer’s injection. Compatibility with normal saline injection depends on the concentration; don’t prepare solutions with a concentration exceeding 0.45mg/ml. ACTION Cross-links strands of cellular DNA and interferes with RNA transcription, causing an imbalance of growth that leads to cell death. Not specific to cell cycle. ADVERSE REACTIONS CV: hypotension, tachycardia, edema. GI: nausea, vomiting, diarrhea, oral ulceration, stomatitis. Hematologic: thrombocytopenia, leukopenia, bone marrow suppression, hemolytic anemia. Hepatic: hepatotoxicity. Metabolic: hyperuricemia. Respiratory: pneumonitis, pulmonary fibrosis, dyspnea, bronchospasm. Skin: pruritus, alopecia, urticaria, ulceration at injection site. Other: anaphylaxis, hypersensitivity reactions. INTERACTIONS (Drug-drug for IV melphalan only) Anticoagulants, aspirin, NSAIDs: May increase risk of bleeding. Avoid using together. Carmustine: May decrease threshold for pulmonary toxicity. Use together cautiously. Cimetidine: May decrease melphalan level. Monitor patient closely. Cisplatin: May increase renal impairment, decreasing melphalan clearance. Monitor patient closely. Cyclosporine: May cause severe renal impairment. Monitor renal function closely. Interferon alfa: May increase melphalan elimination. Monitor patient closely.

Myelosuppressives: May increase myelosuppression. Monitor patient. Vaccines: May decrease effectiveness of killed virus vaccines and increase risk of toxicity from live virus vaccines. Postpone routine immunization for at least 3 months after last dose of melphalan. Drug-food. Any food: May decrease oral drug absorption. Advise patient to take drug on empty stomach. CONTRAINDICATIONS and CAUTIONS 1. Contraindicated in patients hypersensitive to drug and in those with disease resistant to drug. Patients hypersensitive to chlorambucil may have cross-sensitivity to this drug. 2. Contraindicated in patients with severe leukopenia, thrombocytopenia, or anemia and in those with chronic lymphocytic anemia. 3. Use cautiously in patients receiving radiation and chemotherapy. 4. Safe use in children hasn’t been established. NURSING CONSIDERATIONS 1. 2. 3. 4. 5.

Dosage may need to be reduced in patients with renal impairment. Melphalan is drug of choice with prednisone in patients with multiple myeloma. Give oral form on empty stomach because food decreases drug absorption. Monitor uric acid level and CBC. To prevent bleeding, avoid all I.M. injections when platelet count is less than 50,000/ cubic mm. 6. Anticipate blood transfusions because of cumulative anemia. Patients may receive injections of RBC colony-stimulating factor to promote RBC production and decrease need for blood transfusions. 7. Anaphylaxis may occur. Keep antihistamines and steroids readily available to give if needed. 8. Look alike-sound alike: Don’t confuse melphalan with mephyton. PATIENT TEACHING 1. Advise patient to take tablets on empty stomach. 2. Advise patient to report pain or redness at I.V. site. 3. Advise patient to watch for signs and symptoms of infection and bleeding. Tell patient to take temperature daily. 4. Instruct patient to avoid OTC products that contain aspirin. 5. Advise women to stop breast-feeding during therapy because possible risk of toxicity to infant. 6. Caution woman of childbearing age to avoid becoming pregnant during therapy.

OXIPLATIN Eloxatin

INDICATIONS and DOSAGES •

•

First-line treatment of advanced colorectal cancer with 5-fluorouracil and leucovorin(5-FU/LV) Adults: On day 1, give 85mg/square m oxaliplatin I.V. in 250 to 500 ml D5W and leucovorin 200mg/square m I.V. in D5W simultaneously over 120 minutes, in separate bags using a Y-line, followed by 5-FU 400 mg/square m I.V. bolus over 2 to 4 minutes, followed by 600mg/square m 5-FU I.V. infusion in 500ml D5W over 22 hours. On day 2, give 200 mg/square m leucovorin I.V. infusion over 120 minutes, followed by 400mg/square m 5-FU I.V. bolus over 2 to 4 minutes, followed by 600mg/square m 5-FU I.V. infusion in 500ml d5w over 22 hours. Repeat cycle q 2 weeks. With 5-FU/LV for the adjuvant treatment of stage III colon cancer in patients who have had complete resection of the primary tumor Adults: On day 1, give oxaliplatin, 85mg/square m I.V. in 250 to 500ml D5W and 200mg/square m leucovorin I.V. infusion in D5W, both over 120 minutes at the same time, in separate bags, using a Y line. Follow with 5-FU 400mg/square m I.V. bolus over 2 to 4 minutes, then 600mg/square m 5-FU in 500 ml D5W as a 22-hour continuous infusion.

INCOMPATIBILITIES Alkaline solutions or drugs such as 5-FU. Flush infusion line with D5W before giving any other drugs simultaneously. ACTION Probably inhibits cell replication and transcription by forming platinum complexes that cross-link with DNA molecules. Not specific to cell cycle. ADVERSE REACTIONS CNS: pain, peripheral neuropathy, fatigue, headache, dizziness, insomia, fever. CV: chest pain, thromboembolism, edema, flushing, peripheral edema. EENT: rhinitis, pharyngitis, epistaxis, abnormal lacrimation. GI: nausea, vomiting, diarrhea, stomatitis, abdominal pain, anorexia, constipation, dyspepsia, taste perversion, gastroesophageal reflux, flatulence, mucositis. GU: dysuria, hematuria. Hematologic: febrile neutropenia, anemia, leukopenia, thrombocytopenia. Metabolic: hypokalemia, dehydration. Musculoskeletal: back pain, arthralgia. Respiratory: dyspnea, cough, upper respiratory tract infection, hiccups, pulmonary toxicity. Skin: injection site reaction, rash, alopecia. Other: anaphylaxis, hand-foot syndrome, allergic reaction, rigors. INTERACTIONS (Drug-drug)

Nephrotic drugs: May decrease elimination of nephrotoxic drugs and increase gentamicin levels. Monitor patients for signs and symptoms of toxicity. CONTRAINDICATIONS and CAUTIONS 1. Contraindicated in patients allergic to drug or other platinum-containing compounds and in pregnant or breast-feeding patients. 2. Use cautiously in patients with renal impairment or peripheral sensory neuropathy. NURSING CONSIDERATIONS: 1. Drug doesn’t require patient prehydration. 2. Give antiemetic with or without dexamethasone before drug to reduce nausea. 3. Drug clearance is reduced in patients with renal impairment. Dosage adjustment for parents with renal impairment hasn’t been established. 4. Monitor CBC, platelet count, and liver and kidney function before each chemotherapy cycle. 5. Monitor patient for hypersensitivity reactions, which may occur within minutes of administration. 6. Monitor patient for injection site reaction; extravasation may occur. 7. Monitor patient for neuropathy and pulmonary toxicity. 8. Avoid ice and cold exposure during infusion of drug because cold temperatures can worsen acute neurologic symptoms. Cover patient with blanket during infusion 9. Diarrhea, dehydration, hypokalemia, and fatigue may occur more frequently in elderly patients. PATIENT TEACHING 1. Inform patient of potential adverse reactions. 2. Tell patient to avoid exposure to cold or cold objects, which can bring on or worsen acute symptoms of peripheral neuropathy. 3. Tell patient to contact prescriber immediately if he has trouble breathing or experiences signs and symptoms of an allergic reactions, such as rash, hives, swelling of lips or tongue, or sudden cough. 4. Tell patient to contact prescriber if fever, signs and symptoms of an infection, persistent vomiting, diarrhea, or signs and symptoms of dehydration (thirst, dry mouth, light-headedness, and decreased urination) occur.

THIOTEPA (TESPA, triethylenethiophosphoramide, TSPA) Thioplex

INDICATIONS and DOSAGES • • •

Breast and ovarian cancers, lymphoma, Hodgkin’s disease Adults and children older than age 12: 0.3 to 0.4mg/kg I.V. q 1 to 4 weeks or 0.2mg/kg for 4 to 5 days at intervals of 2 to 4 weeks. Bladder tumor Adults and children older than age 12: 30 to 60 mg in 30 to 60 ml of normal saline solution instilled in bladder for 2 hours once weekly for 4 weeks. Neoplastic effusions: Adults and children older than age 12: 0.6 to 0.8mg/kg intracavitarily q 1 to 4 weeks.

INCOMPATIBILITIES Cisplatin, filgrastim, minocycline, vinorelbine. ACTION Cross-links strands of cellular DNA and interferes with RNA transcription, causing an imbalance of growth that leads to cell death. Not specific to cell cycle. ADVERSE REACTIONS CNS: headache, dizziness, fatigue, weakness, fever. EENT: blurred vision, conjunctivitis, GI: nausea, vomiting, abdominal pain, anorexia, stomatitis. GU: amenorrhea, decreased spermatogenesis, dysuria, increased urine levels of uric acid, urine retention, hemorrhagic cystitis (with intravesical administration) Hematologic: leukopenia, thrombocytopenia, neutropenia, anemia. Metabolic: hyperuricemia. Skin: dermatitis, alopecia, pain at injection site. Other: hypersensitivity reactions (including, anaphylaxis, laryngeal edema, urticaria, rash). INTERACTIONS (Drug-drug) Anticoagulants, aspirin, NSAIDs: May increase risk of bleeding. Avoid using together. Myelosuppressives: May increase myelosuppression. Monitor patient. Neuromuscular blockers: May prolong muscular paralysis. Monitor patient. Other alkylating drugs, irradiation therapy: May intensify toxicity rather than enhance therapeutic response. Avoid using together. Pancuronium, succinylcholine: May increase apnea. Avoid using together.

CONTRAINDICATIONS and CAUTIONS 1. Contraindicated in patients hypersensitive to drug, in breast-feeding patients, and in those with severe bone marrow, hepatic, or renal dysfunction.

2. Use in pregnant women only when benefits to mother outweigh risk of teratogenicity. 3. Use cautiously in patients with mild bone marrow suppression and renal or hepatic dysfunction. NURSING CONSIDERATIONS 1. For bladder instillation, dehydrate patient 8 to 10 hours before therapy. Instill drug into bladder by catheter; ask patient to retain solution for 2 hours. If discomfort is too great with 60 ml, reduce volume to 30 ml. Reposition patient every 15 minutes for maximum area contact. 2. Monitor CBC weekly for at least 3 weeks after last dose. 3. If patient’s WBC count drops below 3,000/cubic mm or if platelet count falls below 150,000/ cubic mm, stop drug and notify prescriber. If WBC count falls below 2,000/ cubic mm or granulocyte count falls below 1,000/ cubic mm, follow institutional policy for infection control in immunocompromisedpatients. 4. Monitor uric acid level. To prevent hyperuricemia with resulting uric acid nephropathy, give allopurinol along with adequate hydration. 5. Therapeutic effects are commonly accompanied by toxicity. 6. To prevent bleeding, avoid all I.M. injections when platelet count is below 50,000/ cubic mm. 7. Give blood transfusions for cumulative anemia. Inject RBC colony-stimulating factor to promote RBC production and decreased need for transfusions. PATIENT TEACHING 1. Advise patient to watch for signs and symptoms of infection and bleeding. Tell patient to take temperature daily. 2. Instruct patient to avoid OTC products that contain aspirin. 3. Advise women to stop breast-feeding during therapy because possible risk of toxicity to infant. 4. Caution woman of childbearing age to avoid becoming pregnant during therapy. Antimetabolites Antimetabolites resemble natural metabolites. Thus they disrupt the metabolic process, and some of the agents inhibit enzyme synthesis. They are classified as CSS and affect the S phase (DNA synthesis and metabolism) of the cell cycle. Fluororunacil (5FU) and floxuridine (FUDR) can be classified as CCNS as well as CCS. This group is classified according to the substances with which they interfere and include folic acid (folate) antagonists (e.g. methotrexate [MTX]), pyrimidine antagonists (e.g., 5-FU), purine antagonists (e.g., 6-mercaptopurine [Purinethol]), and adenosine inhibitors (e.g. fludarabine [Fludaral]). Antimetabolites are used to treat acute leukemia, breast cancer, head and neck cancer, lung cancer, osteosarcoma, and non-Hodgkin’s lymphoma.

Methotrexate (MTX), a folic acid antagonist, was discovered in 1948 and is used for the treatment of both cancerous and noncancerous (e.g. rheumatoid arthritis) conditions. MTX acts as a substitute for folic acid, which is needed for the synthesis of proteins and DNA. Cancer clients receiving high doses of MTX must be given leucovorin calcium to “rescue” (leucovorin rescue) normal cells from the adverse effects of the drug. Pharmacokinetics MTX is metabolized in the liver and excreted in the urine. Eighty to ninety percent is excreted unchanged in the urine within 24 hours. Pharmacodynamics MTX is absorbed from the GI tract and peaks in 1 hour, with peak concentration in 3 to 12 hours. It is one of the anticancer drugs that can be administered orally, IV, or by injection. Numerous drug interactions may occur with MTX. Protein-bound drugs (e.g., aspirin, phenytoin) increase the toxicity of MTX. Non-steroidal anti-inflammatory drugs (NSAIDs) increase and prolong MTX levels. Cotrimoxazole and pyrimethanine increase MTX levels. Clients who are taking penicillins, cyclo-oxygenase 2 (COX-2) inhibitors, and OTC drugs should share this information with their physician because product interact with MTX as well. Fluoruracil Pharmacokinetics Fluoruracil (5-FU) is administered IV for solid tumors and topically for superficial basal cell carcinoma. Less than 10% bound to protein, and the half-life for the IV route is 10 to 20 minutes. A small amount of the drug is excreted in the urine, and up to 80% is excreted by the lungs as carbon dioxide. Pharmacodynamics Floururacil, a CSS drug, blocks the enzyme action necessary for DNA and ribonucleic acid (RNA) synthesis. The drug has a low therapeutic index and is used alone or in combination with other anticancer drugs. Flurouracil can cross the blood-brain barrier. Its duration of the action is 30 days. Side Effects and Adverse Reactions The side effects of 5-FU are similar to other anticancer drugs. These include anorexia, nausea, vomiting, diarrhea, stomatitis, alopecia, photosensitivity, increased pigmentation, rash, and erythema. Stomatitis is an early sign for toxicity and should be

reported to the physician. Bone marrow depression may occur 4 to 8 days after the beginning of drug therapy. The general side effects for antimetabolite drugs include bone marrow suppression (leucopenia, thrombocytopenia), stomatitis (inflammation of the oral mucosa), and alopecia. Nursing Process Antimetabolites: Fluoruracil (5-FU) Assessment • • • •

Assess complete blood count (CBC), differential, and platelet count weekly. Chemotherapy may be held if red cell, white cell, and platelet counts drop below predetermined levels. Conduct thorough physical assessment and document findings Assess renal function studies before and during drug therapy. Assess temperature; fever may be an early sign of infection

Nursing Diagnoses • • • • •

Risk for infection (secondary to bone marrow depression) Risk for altered nutrition; less than body requirements (secondary to GI side effects for chemotherapy) Risk for pain (mucositis/stomatitis) (secondary to diarrhea caused by chemotherapy) Risk for impaired perianal integrity (secondary to diarrhea aused by chemotherapy) Knowledge deficit (client/ family: related to chemotherapeutic control)

Planning • • • • •

Client will have blood counts in the desired range Client will maintain nutritional status Client will experience adequate pain control Client will limit exposure to sunlight Client will demonstrate understanding of chemotherapeutic control

Nursing Interventions • •

Monitor blood counts and laboratory values Handle drug with care during preparation; avoid direct skin contact with anticancer drugs. Follow protocols

• • • • • • • • •

Monitor IV site frequently. Extravasation produces severe pain. If this occurs, apply ice pack and notify health care provider Administer antiemetic 30 to 60 minutes before drug to prevent vomiting Assess for hyperpigmentation along the vein in which 5-FU was administered Offer client food and fluids that may decrease nausea, such as cola, crackers, or ginger ale Plan small, frequent meals Maintain strict medical asepsis Support good oral hygiene; brush teeth with soft toothbrush and use waxed dental floss Encourage mouth rinses every two hours with normal saline Monitor fluid intake and output and nutritional intake, GI effects are common on the fourth day of treatment

Client Teaching General • • • • • • • • •

Emphasize protective precautions as necessary Teach client to examine mouth daily and report signs of stomatitis, oral hygiene several times a day is essential; if stomatits occurs, rinse mouth with baking soda or normal saline; use a soft toothbrush Instruct client to take pain medication as prescribed to relieve mouth pain related to mucositis/ stomatitis Advise client to take year-round photosensitivity precautions, use sunscreen when outdoors Advise client not to visit anyone who has a respiratory infection. A decreased white blood cell count puts the client at risk for acquiring an infection Teach importance of using birth control measures Teach client that pregnancy should be avoided for 3 to 4 months Emphasize protective isolation precautions Instruct client to promptly report signs of infection

Side Effects • • • •

Instruct client about good oral hygiene with a soft tootbrush Remind premenopausal females that they may experience amenorrhea, menstrual irregularities or sterility Advise client of possible hair loss Assess for use of alternative/ complementary therapy that may interact with chemotherapy agent

Diet • • •

Encourage small frequent meals Encourage the use of cool bland foods Offer ice chips or ice pops to help relieve mouth pain

Evaluation • • • • •

Client is free of infection Oral mucosa is free of pain, erythema, and swelling Pain is controlled Skin integrity is intact Client and family education needs have been met

Hormonal Agents Although hormones are not considered true chemotherapeutic agents, several classes of hormonal agents are used in the treatment of cancer. These include corticosteroids, sex hormones, antiestrogens, aromatase inhibitors, gonadotropinreleasing hormone analogues, and antiandrogens. Corticosteroids Corticosteroids (glucocorticoids) are anti inflammatory agents that suppress the inflammatory process that occurs as a result of tumor growth. Although the exact mechanism of the action is unknown, these agents may block steroid-specific receptors on the surface of the cells. This blocking action slows the growth fraction of the tumor, thus retarding its growth. Prednisone, dexamesthasone, and hydrocortisone can help decrease cerebral edema caused by a malignant brain tumor. Cortisone drugs give a client a sense of well being and varying degrees of euphoria. Cortisone derivatives that are taken internally produce many side effects, such as fluid retention, potassium loss, increased risk of infection, increase in blood sugar, increase in fat distribution, muscle weakness, increased bleeding tendency, and euphoria. Sex Hormones The sex hormones (estrogen, androgen) or hormone-like agents are used to slow the growth of hormone dependent tumors (e.g. prostate cancer, breast cancer). Estrogen therapy is a palliative treatment used to decrease the progression of prostatic cancer in men and to slow the growth of hormone- dependent breast cancer in women. Estrogen preparations suppress tumor growth, and the drug promotes remission of the cancer for up to a year. Examples of this group are diethylstilbestrol, (DES, stilbestrol), ethinyl estradiol (Estnyl), Chlorotrianisene (TACE), and conjugated estrogens (Premarin).

Progestins may be prescribed to treat breast cancer, endometrial carcinoma, and renal cancer. These drugs (e.g. hydroxyprogesterone caproate [Duralutin]), medroxyprogesterone acetate [Depo-Provera], and megestrol acetate [megace]) act by shrinking the cancer tissues. Adverse reactions include fluid retention and thrombotic (clot) disorders. Androgens are given to treat advanced breast cancer in pre menopausal women. This male hormone promotes regression of the tumor. If androgen therapy is used for a long time, masculine secondary sexual characteristics, such as body hair growth, lowering of the voice, and muscle growth will occur. Antiestrogens (e.g. tamoxifen [nolvadex] are used to treat breast cancer tumors that are estrogen receptor positive. A newer drug, raloxifene (evista) is a selective estrogen receptor modulator (SERM) that acts like an antiestrogen to slow growth tumor, but it has fewer side effects than tamoxifen. Both tamoxifen and raloxifene have been found to decrease the risk of breast cancer in postmenopausal women. Gonadotropin Releasing Hormone Analogues Luteinizing hormone-releasing hormone (LH-RH) agonists (e.g., leuprolide [lupron], gserelin [zoladex] suppress the secretion of follicle-stimulating hormone and leutinizing hormone from the pituitary gland. Initially, an increase in testosterone levels is seen. However, with continued use, the pituitary becomes insensitive to this situation which leads to a reduction in the production of androgens and estrogens. Antiandrogens Antiandrogens (e.g., flutramide [eulexin], nilutamide [nilandron], bicalutamide [casodex]) are useful in treating men with hormone- responsive prostate cancer that has metastasized. These agents work by binding to androgen receptors and blocking the effects of dihydrotestosterone on the prostate cancer cells. Aromatase Inhibitors In postmenopausal females, the ovaries no longer produce estrogen, but androgen is converted to estrogen in this group of women. The aromatse inhibitors block the peripheral conversion of androgens to estrogens, thus suppressing the postmenopausal synthesis of estrogen and slowing tumor growth. Aromatase inhibitors are used in treatment of hormonally sensitive breast cancer in postmenopausal women or premenopausal woman who had their ovaries removed. Anastrozole (arimidex), letrozole (femara), and exemestane (aromasin) are examples of aromatase inhibitors currently in use. Increasingly, these agents are being used before taxomifen in postmenopausal women with hormonally responsive metastatic breast cancer.

GONADOTROPIN-RELEASING HORMONE ANALOGUES GnRH/ LH-RH and its analouges (GnRH-a) are used extensively for the treatment of prostate cancer and other hormone-dependent diseases via the desensitization of pituitary gonadotropes, which consequently leads to the inhibition of gonadotropins, gonadal steroids and tumor growth. This suppresses the secretion of follicle-stimulating hormone and luteinizing hormone from the pituitary gland. Initially, an increase in testosterone levels is seen. The actions of GnRH-a are mediated by the GnRH receptor (GnRHR) that is expressed in both the pituitary and extrapituitary sites, including normal tissues and tumors. Several studies have provided evidence that besides its pituitary effects, GnRH-a may exert direct anti-proliferative and apoptotic effects in tumor cells. These effects are mediated by the GnRHRs via signal transduction mechanisms that are distinct from the classical pituitary mechanisms. Interestingly, androgen ablation by GnRH-a is the main treatment for hormone-dependent prostate cancer. However, most of these tumors become eventually hormone-refractory, and are no longer sensitive to the GnRH-a-mediated reduction in androgen levels. Hence, the ability of GnRH-a to induce direct effects such as apoptosis may have large implications regarding the clinical use of GnRH-a. Therefore, an understanding of the cellular mechanisms involved in GnRH-a action may lead to better therapeutic modalities for the treatment of advanced prostate cancer and other malignancies. ANTIANDROGENS Antiandrogens competitively inhibit ligand binding to the androgen receptor (AR) and blocking the effects of dihydrotestosterone, and are used therapeutically in prostate cancer patients. The AR functions as a ligand dependent transcription factor that transduces androgen binding into increased transcription of androgen dependent genes. AR blockade induces programmed cell death in the vast majority of malignant and benign prostate cancer cells that have not previously been exposed to androgen ablation. The antiandrogens are divided structurally into the steroidal and non steroidal agents. The biological effects of the steroidal versus nonsteroidal agents are distinguished by differences in their effects on serum testosterone levels, and by their activity at receptors other than the androgen receptor. There is extensive clinical experience in the palliative and curative therapy of prostate cancer using antiandrogens as monotherapy or antiandrogens in combination with luteinizing hormone agonists or surgical castration. Prolonged therapy with antiandrogens selects for mutations in the AR that change the AR ligand specificity and permits stimulation by ligands that are usually inhibitory. These mutations give insight into one of the means by which prostate cancer progresses despite antiandrogen therapy, and also helps to explain the antiandrogen withdrawal syndrome. Areas of active research that may affect the future use of antiandrogens include the ongoing evaluation of antiandrogens in combination with 5 alpha reductase inhibitors to achieve AR blockade without inducing castrate testosterone levels. There is also interest in developing selective androgen receptor modulators (SARM) that can achieve AR blockade without causing the increased testosterone levels produced by the nonsteroidal antiandrogens currently in use.

AROMATASE INHIBITORS In postmenopausal females, the ovaries no longer produce estrogen, but androgen is converted to estrogen in this group of women. The aromatase inhibitors block the peripheral conversion of androgens to estrogens, thus suppressing the postmenopausal synthesis of estrogen and slowing tumor growth. Aromatase inhibitors are used in the treatment hormonally sensitive breast cancer in postmenopausal women or premenopausal woman who have had their ovaries removed. Increasingly, these agents are being used before tamoxifen in postmenopausal women with hormonally responsive metastatic breast cancer. ANTINEOPLASTICS: ENZYMES Androgens testolactone (Teslac)

HORMONES,

progesterone (Gesterol 50) Hormonal Antagonists aminoglutethimide (Cytadren)

anastrozole (Arimidex) bicalutamide (Casodex) exemestane (Aromasin) flutamide (Eulexin) fulvestrant (Faslodex) goserelin acetate (Zoladex)

letrozole (Femara)

leuprolide (Lupron)

HORMONE

ANTAGONISTS

AND

Palliative treatment of breast carcinoma in postmenopausal women. Serum calcium levels should periodically be checked. Voice may deepen and facial hair may increase. Pregnance Catergory: D; PB: UK; t ½: UK Palliative treatment of endometrial and breast carcinomas. Pregnancy Category: X; PB: UK; t ½: 5 min Adrenal carcinoma, ectopic ACTH-producing tumors. Drug suppresses adrenal activity. May be used in breast cancer therapy. Treatment usually used for 3 months. Pregnancy Category: D; PB: 20-25%; t ½: 7-15 h Advanced breast cancer in postmenopausal women. Diarrhea, headache, hot flashes, pain, HPN, and dyspnea might occur. Pregnancy Category: D; PB: 40%; t ½: 50 h Advanced metastatic prostatic carcinoma. Pregnancy Category: D; PB: UK; t ½: 5.8 d Advanced breast cancer in postmenopausal women. Prostatic cancer. Pregnancy Category: D; PB: UK; t ½: 24 h Metatstatic prostatic carcinoma, usually in combination with other anticancer drugs. Pregnancy Category: D; PB: 95%; t ½: 5-10 h Treatment of hormone-receptor positive metatstatic breast cancer in postmenopausal women whose disease has progressed after antiestrogen therapy. Pregnance Category: D; PB: 99%; t ½: 40 d Metastatic prostatic carcinoma. It is a synthetic luteinizing hormone-releasing analogue. May also be used in breast cancer and endometriosis. Gynecomastia, breast swelling and hot flashes may occur. Pregnancy Category: X; PB: UK; t ½: 4-6 h Advanced breast cancer in postmenopausal women.

megestrol acetate (Megace) mitotane (Lysodren)

nilutamide (Nilandron) polyestradiol PO4 (Estradurin)

tamoxifen citrate (Nolvadex) raloxifene (Evista)

toremifene citrate (Fareston) Miscellaneous Enzymes L-asparaginase (Elspar)

pegaspargase (Oncaspar)

Decreases estrogen biosynthesis. May be more effective than megestrol acetate and aminoglutethimide. Pregnancy Category: UK; PB: UK; t ½: 2 d Used to slow the growth of prostate cancer. Can be given daily (Lupron) or at 3- to 4-month intervals (Lupron Depot). May be used to treat endometriosis. Hypersensitivity reactions may occur in people with allergy to benzyl alcohol. Pregnant women should not take this drug (high risk of fetal damage). Pregnancy Category: X; PB: 49%; t ½: 3 h Palliative treatment of advanced carcinoma of the breast and endometrium. May promote weight gain by increasing appetite. Pregnancy Category: X; PB: UK; t ½: 15-20 h Palliative treatment of inoperable adrenal cortical carcinoma. Adverse reactions include hemorrhagic cystitis, hypouricemia, and hypercholesterolemia. Monitor vitals signs. Pregnancy Catefory: C; PB: UK; t ½: 20-160 d Prostatic carcinoma. Loss of libido and sexual potency may occur. Monitor liver function. Pregnancy Category: C; PB: UK; t ½: 24-72 h Palliative treatment of inoperable prostatic carcinoma. Estrogen derivative. Side effects may include fluid retention, nausea, vomiting, HPN, weight change and thromboembolic disorders. Pregnancy Category: X; PB: UK; t ½: UK Palliative treatment of advanced breast carcinoma with positive lymph nodes in postmenopausal women. Pregnancy Category: X; PB: UK; t ½: 7 d A selective estrogen receptor modulator (SERM) originally approved to fight osteoporosis in postmenopausal women. Reduces risk of breast cancer with fewer side effects than tamoxifen. Pregnancy Category: X; PB: 95%; t ½: 27 h Advanced breast cancer in postmenopausal women. An antiestrogen drug. Pregnancy Category: D; PB: >99%; t ½: 5 d Acute lymphocytic leukemia. Used in combination with another anticancer drug. Common side effects include nausea, vomiting, anorexia, leukopenia, and impaired pancreatic function. Pregnancy Category: C; PB: 30%; t ½: 8-30 h (IV) Acute lymphocytic leukemia. A CCS agent affecting G1 phase of the cell cycle. It interferes with DNA, RNA, and protein synthesis. Pregnancy Category: C; PB: UK; t ½: 1.4 to 5.2 d