Drugs Used in the Treatment of Cancer
Cancer is a disease characterized by a shift in the control mechanisms that govern cell survival, proliferation, and differentiation.
Uncontrolled multiplication of cells leads to the formation of tumors that may be benign or malignant. Benign tumors do not spread to other tissues, while malignant tumors do.
Types of Cancer
- Carcinoma: Affects the skin and cells in the tissue lining internal organs.
- Sarcoma: Affects muscles, bones, and fibrous tissues.
- Leukemia: Affects white blood cells.
- Lymphoma: Affects the lymph glands.
Drugs used in the treatment of cancer either kill cancer cells or modify their growth.
Table 1: Classification of Anticancer Drugs
Bleomycin
Available Preparations:
- Powder for Injection: 15 units/vial
Available Brands: Blenoxane®
Pharmacokinetics: IM administration results in lower serum levels than those occurring after equivalent IV doses. It distributes widely into total body water, mainly in the skin, lungs, kidneys, peritoneum, and lymphatic tissue. It undergoes extensive tissue inactivation in the liver and kidney; bleomycin and its metabolites are excreted primarily in urine.
Indications:
- Squamous cell carcinoma (head, neck, penis, cervix)
- Testicular carcinoma
- Non-Hodgkin’s lymphoma
- Lymphosarcoma
Contraindications:
- Pregnancy
- Breastfeeding
- Previous allergic reaction
Dosage:
- A test dose of 1-2 units given 2-4 hours prior to therapy is recommended.
- 0.25-0.5 unit/kg body weight or 10-20 units/m² body surface area given IV, IM, or SC once or twice weekly.
Side Effects:
- Skin rash
- Striae
- Redness of the skin
- Fever
- Acute anaphylactoid reaction
- Anorexia
- Urticaria
- Pruritus
- Hyperpigmentation
- Stomatitis
- Hyperkeratosis
- Weight loss
- Progressive pulmonary fibrosis
- Mucositis
- Pneumonitis
- Phlebitis
- Vomiting
Drug Interactions:
- Cisplatin may decrease bleomycin clearance and increase the risk of bleomycin toxicity.
- Concomitant use may decrease serum levels of phenytoin and digoxin.
Key Issues to Note:
- Increased pigmentation, particularly affecting the flexures and subcutaneous sclerotic plaques, may occur.
- A test dose should be administered before starting therapy to check for hypersensitivity reactions.
- Monitor pulmonary function tests during treatment.
Doxorubicin
Available Preparations:
- Powder for Injection: 10 mg/vial, 50 mg/vial
Available Brands: Doxorubin®
Pharmacokinetics: It distributes widely into body tissues, with the highest concentrations found in the liver, heart, kidneys, skin, and muscles; it does not cross the blood-brain barrier. It is metabolized both in the liver and plasma; excreted largely in feces, with small amounts in urine.
Indications:
- Acute leukemia
- Lymphomas
- Breast carcinoma
- Thyroid carcinoma
- Non-Hodgkin’s lymphoma
- Ovarian carcinoma
- Bone and soft tissue sarcomas
- Hodgkin’s disease
- Kaposi’s sarcoma in patients with AIDS
- Transitional cell bladder carcinoma
Contraindications:
- Hepatic dysfunction
- Cardiomyopathy
- Pregnancy and lactation
- Persistent myelosuppression
- Severe cardiac failure
- Recent myocardial infarction
Dosage:
- 60-74 mg/m² or 1.2-2.4 mg/kg once every 3 weeks as a single intravenous injection of a solution in sodium chloride 0.9% or glucose 5% over 3 minutes or more.
- Children: 35-75 mg/m² as a single intravenous injection, once every 3 weeks.
Side Effects:
- Bone marrow depression
- Anorexia
- Hyperpigmentation of nail beds
- Diarrhea
- Irreversible CHF
- Reversible alopecia
- Nausea and vomiting
- Stomatitis
- Fever and chills
- Urticaria
- Conjunctivitis
- Lacrimation
Drug Interactions:
- Cholestasis induced by mercaptopurine may be potentiated by the concurrent administration of doxorubicin.
- Concomitant use of daunorubicin or cyclophosphamide may potentiate the cardiotoxicity of doxorubicin through additive effects on the heart.
- Serum digoxin, carbamazepine, and phenytoin levels may be decreased if used concomitantly with doxorubicin.
- Phenobarbitone increases the elimination of doxorubicin.
Key Issues to Note:
- Notify the patient that the urine may turn red for the first 1-2 days.
- Doxorubicin may induce hyperuricemia; therefore, monitor the patient’s blood uric acid levels.
- Encourage the patient to take adequate fluid intake to increase urine output and facilitate excretion of uric acid.
- Advise the patient to call if fever, bleeding, and sore throat occur.
- Avoid exposure to sunlight to prevent sunburns.
- Warn the patient that alopecia will occur. Explain that hair growth should resume 2-5 months after the drug is stopped.
- Tell the patient not to receive any immunization during therapy and for several weeks after.
- Advise the patient to avoid exposure to people with infections.
Methotrexate
Available Preparations:
- Tablets: 2.5 mg
- Injection: 25 mg/ml
Available Brands: Texol®
Indications:
- Treatment and palliation of solid tumors
- Burkitt’s lymphoma
- Leukemia
- Psoriasis
Contraindications:
- Known hypersensitivity to methotrexate
- Pregnancy and lactation
- Severe hepatic and renal impairment
- Bone marrow suppression
- Anemia
- Immunodeficiency syndromes
- Active infection
Dosage:
- Leukemia: 15-30 mg/m² orally, intramuscularly, or intravenously; once a week.
Side Effects:
- Nausea and vomiting
- Stomatitis
- Diarrhea
- Anorexia
- Malaise
- Headache
- Skin rash
- Dermatitis
- Pruritus
- Dizziness
- Blurred vision
Drug Interactions:
- Concomitant use with probenecid and salicylates increases the therapeutic and toxic effects of methotrexate by inhibiting its renal clearance.
- Alcohol enhances the hepatotoxicity caused by methotrexate.
- Phenytoin, co-trimoxazole may give additive antifolate activity and increase the risk of methotrexate toxicity.
Key Issues to Note:
- Full blood count, urea, and liver function tests should be carried out prior to and during treatment.
- Folinic acid is required for rescue procedures.
- Patients with hyperuricemia should maintain adequate fluid intake and alkalinization of urine.
Vincristine
Available Preparations:
- Solution for Injection: 1 mg/ml, 0.1 mg/ml
Available Brands: Cristol®
Indications:
- Leukemias
- Lymphomas
- Some solid tumors
Contraindications:
- Demyelinating form of Charcot-Marie-Tooth syndrome
- Pregnancy
- Breastfeeding mothers
- Current radiotherapy to the liver
- Known hypersensitivity to vincristine
Dosage:
- Adult: IV 1.4 mg/m² up to a max weekly dose of 2 mg/m².
- Children: IV 2 mg/m² once a week.
- Children < 10 kg: 0.05 mg/kg once a week.
Side Effects:
- Hair loss
- Stomatitis
- Constipation
- Abdominal cramps
- Diarrhea
- Skin rash
- Headache
- Jaw pain
- Hoarseness
- Diplopia
- Nausea and vomiting
- Abdominal distention
- Urinary tract disturbance
- Peripheral neuropathy
Drug Interactions:
- Vincristine may decrease digoxin plasma levels and renal excretion.
- Vincristine may reduce phenytoin plasma levels.
Key Issues to Note:
- Allopurinol may be given to prevent uric acid nephropathy.
- Stool softeners should be used for constipation prophylaxis.
- Vincristine is a tissue irritant; care should be taken to avoid extravasation.
Tamoxifen
Available Preparations:
- Tablets: 10 mg, 20 mg
Available Brands: Nolvadex®
Pharmacokinetics: Tamoxifen is well absorbed after oral administration, distributed widely into total body water, metabolized extensively in the liver, and excreted primarily in feces.
Indications:
- Breast cancer
- Female infertility (induction of ovulation)
Contraindications:
- Known hypersensitivity to tamoxifen
- History of deep vein thrombosis or pulmonary embolism in high-risk women
- Pregnancy
Dosage:
- Breast cancer: 20 mg daily.
- Induction of ovulation (infertility): 20 mg daily on days 2, 3, 4, and 5 of the cycle; if necessary, the daily dose may be increased to 40 mg then 80 mg for subsequent courses.
Side Effects:
- Hot flushes
- Nausea
- Vomiting
- Lightheadedness
- Bone pain
- Confusion
- Vaginal bleeding
- Vaginal discharge
- Headache
- Decreased libido
- Weakness
Drug Interactions:
- Estrogen may decrease the effect of tamoxifen.
- The anticoagulant effect of oral anticoagulants may be increased by tamoxifen.
- Bromocriptine may elevate serum levels of tamoxifen.
Key Issues to Note:
- Adverse effects may be controlled by dosage reduction.
- Use cautiously in pre-existing leukopenia and thrombocytopenia.
- Advise women not to become pregnant during therapy with tamoxifen.