By Funom Makama
The aim of therapy is to reduce the tumor mass within the shortest possible time and to destroy the remaining cells and prevent them from multiplying and disseminating. This ideal is possibly achieved only in the case of very few cancers but in the majority of cases this is not possible due to:
1. late diagnosis
2. presence of secondaries early in the disease
3. surgical risk, and
4. toxic effects of radiation and chemotherapeutic agents.
Surgery and radiotherapy are most effective to reduce the initial tumor load. These are the prime modalities of treatment in solid tumors. In the case of disseminated neoplasms like leukemia and myeloma and in the case of some rapidly growing tumors like trophoblastic tumors, chemotherapy has to be employed as the first line of treatment.
Radiotherapy
Tumor cells are more radiosensitive as they proliferate faster than normal cells. Radio-therapy may be given as the only modality of treatment or combined with surgery and chemotherapy. With the advent of highly sophisticated equipment such as the linear accelerator, large doses (5000-6000 rads) may be focused on deep seated tumors with only minimal injury to adjacent tissues. Therapeutic efficacy of radiation is enhanced by exposure to hyperbaric oxygen and radiosensitizing drugs such as metronidazole.
Chemotherapy
Chemotherapy is the sheet anchor of therapy in leukemia, advanced lymphomas, chorio-carcinoma and other widely disseminated malignancies. It is combined with surgery in embronal tumors and used as the primary treatment in advanced cancers not amenable to surgery or radiation. The effectiveness of cytotoxic drugs is directly proportional to the inversely proportional to the number of cancer cells. Prior reduction of tumor mass by veness of chemotherapy. Cytotoxic drugs are nonselective and affect all cells which are in certain phases of their proliferative activity.
Commonly used anticancer drugs
alkylating agents
They form electrophilic ions making covalent bonds (alkylation) with guanine residues leading to cross-linking of DNA strands and interference in DNA replication.
1. cycclophosphamide, Endoxan, cytoxan: 10-150 mg oral daily or 1g/m2 every 3 weeks. Most important side effects are cystitis and marrow suppression.
2. Nitrogen mustard, mustargen: 6 mg/m2 infusion/intravenous. S.E could be Local inflammation.
3. Phenylalanine mustard, Alkeran Melphalan: 6 mg/m2/d oral for 5-10 days, every 4-6 weeks intravenous or oral.
4. Chlorambucil Leukeran: 0.1 mg/Kg/day.
5. Busulfan Myeleran: 4-12 mg/day oral. Most important side effect is primary fibrosis.
Antifolates
They inhibit dihydrofolate reductase; tetrahydrofolate is not produced; one carbon unit is not available for DNA synthesis. An example of such drugs is Amethopterin Methotrexate. Dosage is 5 mg/day oral or 30 mg/ m2 intravenous twice weekly. S.E could be Marrow suppression; hepatic and renal toxicity.
antipyrimidines
Inhibit thymidylate synthetase and thus DNA synthesis. Example of such is 5-fluorouracil. Dose is 15-20 mg/Kg/ week intravenous; maximum dose is 1g. Important S.E are gastro intestinal disturbance and marrow suppression.
Also inhibit deoxycytidine and DNA synthesis and a good example is Cytosine arabinoside and Cytosar Ara-C cytarabine. Normal does is 100 mg/day intravenously.
Antipurines
Interfere with purine biosynthesis and interconversions.
1. 6-Mercaptopurine Purinethol (Hypoxanthine analogue). Dosage is 2.5 mg/Kg/day Oral. Most important S.E is Hepatoxicity and marrow suppression.
2. 6-Thioguanine (Guanine analogue): 2 mg/Kg/day/oral.
Vinca alkaloids
Derived from periwinkle (Vinca rosea) plant. Interfere with microtubule assembly in mitotic spindle formation.
1. Vinblastine Velban: 5-15 mg/m2 every 1-2 weeks intravenous. Side effects are mental depression, Local inflammation and marrow suppression.
2. Vincristine Oncovin: 0.5-2 mg/m2 every 1-2 weeks intravenous. Side effects are Peripheral and autonomic neuropathy; alopecia and local inflammation.
Antibiotics
Inhibiting DNA directed RNA synthesis.
1. Actinomycin Dactinomycin Cosmegan: 12-15 g/Kg/day for 5 days for 2-4 weeks intravenously. Side effects are Marrow suppression and local inflammation.
2. Bleomycin: 1-5 mg/day intravenous or intramuscular maximum 300 mg/m2. Side effects are: Pulmonary fibrosis with minimal myelo-suppression.
Also can inhibit DNA synthesis. Examples are as follow:
1. Daunomycin, Daunorubicin, Rubidomycin and Adriamycin: 60 mg/m2 intravenous 3-4 weeks. Main side effect is Cardiotoxicity.
2. Mitomycin-C and Mutamycin: 20 mg/m2 intravenous every 4-6 weeks. Local inflammation and marrow suppression are common side effects.
Enzymes
L-asparaginase depletes asparagine availability; inhibits protein synthesis. A good example of a drug under this category is the L-asparaginase. Dosage is 1000 IU/Kg/day intravenous. Common side effect is Allergy-coagulation defects.
Nitrosoureas
Inhibit nucleic acid sythesis. A good example is the Cyclohexyl Chloroethyl nitrosourea (CCNU). Dosage is 100 mg/m2 oral every 4-6 weeks. Delayed marrow suppression is the major side effect. Also, Bis chloroethyl nitrosourea (BCNU): 200 mg/m2/intravenous every 4-6 weeks.
Hydrazine derivatives
Damages DNA through peroxide formation. A good example is Procarbazine methylhydrazine. Dosage is 50-100 mg/m2 daily. Orally for 10-14 days. Side effects are Myelosuppression and CNS depression.
Imidazole derivatives
Mechanism uncertain probably alkylation. Dimethyl triazenoimidazole carbodamide (DTIC) and Dacarpazine. Dosage is 150-250 mg/m2 intravenous for 5 days. Myelosuppression.
Platinum complexes
Inhibit DNA synthesis via crosslinking. Good examples are Cis-diamino dichloroplatinum. Cis-platinum. Dosage is 100 mg intravenous. Once in 3-4 weeks. Side effects are Rnal toxicity and ototoxicity.
Hormones
1. Androgens e.g, Testosterone: 300 mg weekly and intramuscular. Major side effect is virilization.
2. Estrogen e.g, Diethyl stibesterol: 5-15 mg Oral daily. Its side effect is Feminisation.
3. Progestogens e.g, Medroxy progesterone acetate (Provera): 300 mg daily orally. Its side effect is mainly withdrawal bleeding.
4. Anti-estrogens e.g, Tamoxifen (Nolvadex): 20-30 mg daily, Orally.
5. Adrenocorticoids e.g, Prednisone: 40-60 mg/m2 orally per day. Side effect is Cushingoid features.
6. Thyroxine e.g, Eltroxin: 0.1-0.3 mg daily, orally. Major side effect is Hyperthyroidism.
The aim of therapy is to reduce the tumor mass within the shortest possible time and to destroy the remaining cells and prevent them from multiplying and disseminating. This ideal is possibly achieved only in the case of very few cancers but in the majority of cases this is not possible due to:
1. late diagnosis
2. presence of secondaries early in the disease
3. surgical risk, and
4. toxic effects of radiation and chemotherapeutic agents.
Surgery and radiotherapy are most effective to reduce the initial tumor load. These are the prime modalities of treatment in solid tumors. In the case of disseminated neoplasms like leukemia and myeloma and in the case of some rapidly growing tumors like trophoblastic tumors, chemotherapy has to be employed as the first line of treatment.
Radiotherapy
Tumor cells are more radiosensitive as they proliferate faster than normal cells. Radio-therapy may be given as the only modality of treatment or combined with surgery and chemotherapy. With the advent of highly sophisticated equipment such as the linear accelerator, large doses (5000-6000 rads) may be focused on deep seated tumors with only minimal injury to adjacent tissues. Therapeutic efficacy of radiation is enhanced by exposure to hyperbaric oxygen and radiosensitizing drugs such as metronidazole.
Chemotherapy
Chemotherapy is the sheet anchor of therapy in leukemia, advanced lymphomas, chorio-carcinoma and other widely disseminated malignancies. It is combined with surgery in embronal tumors and used as the primary treatment in advanced cancers not amenable to surgery or radiation. The effectiveness of cytotoxic drugs is directly proportional to the inversely proportional to the number of cancer cells. Prior reduction of tumor mass by veness of chemotherapy. Cytotoxic drugs are nonselective and affect all cells which are in certain phases of their proliferative activity.
Commonly used anticancer drugs
alkylating agents
They form electrophilic ions making covalent bonds (alkylation) with guanine residues leading to cross-linking of DNA strands and interference in DNA replication.
1. cycclophosphamide, Endoxan, cytoxan: 10-150 mg oral daily or 1g/m2 every 3 weeks. Most important side effects are cystitis and marrow suppression.
2. Nitrogen mustard, mustargen: 6 mg/m2 infusion/intravenous. S.E could be Local inflammation.
3. Phenylalanine mustard, Alkeran Melphalan: 6 mg/m2/d oral for 5-10 days, every 4-6 weeks intravenous or oral.
4. Chlorambucil Leukeran: 0.1 mg/Kg/day.
5. Busulfan Myeleran: 4-12 mg/day oral. Most important side effect is primary fibrosis.
Antifolates
They inhibit dihydrofolate reductase; tetrahydrofolate is not produced; one carbon unit is not available for DNA synthesis. An example of such drugs is Amethopterin Methotrexate. Dosage is 5 mg/day oral or 30 mg/ m2 intravenous twice weekly. S.E could be Marrow suppression; hepatic and renal toxicity.
antipyrimidines
Inhibit thymidylate synthetase and thus DNA synthesis. Example of such is 5-fluorouracil. Dose is 15-20 mg/Kg/ week intravenous; maximum dose is 1g. Important S.E are gastro intestinal disturbance and marrow suppression.
Also inhibit deoxycytidine and DNA synthesis and a good example is Cytosine arabinoside and Cytosar Ara-C cytarabine. Normal does is 100 mg/day intravenously.
Antipurines
Interfere with purine biosynthesis and interconversions.
1. 6-Mercaptopurine Purinethol (Hypoxanthine analogue). Dosage is 2.5 mg/Kg/day Oral. Most important S.E is Hepatoxicity and marrow suppression.
2. 6-Thioguanine (Guanine analogue): 2 mg/Kg/day/oral.
Vinca alkaloids
Derived from periwinkle (Vinca rosea) plant. Interfere with microtubule assembly in mitotic spindle formation.
1. Vinblastine Velban: 5-15 mg/m2 every 1-2 weeks intravenous. Side effects are mental depression, Local inflammation and marrow suppression.
2. Vincristine Oncovin: 0.5-2 mg/m2 every 1-2 weeks intravenous. Side effects are Peripheral and autonomic neuropathy; alopecia and local inflammation.
Antibiotics
Inhibiting DNA directed RNA synthesis.
1. Actinomycin Dactinomycin Cosmegan: 12-15 g/Kg/day for 5 days for 2-4 weeks intravenously. Side effects are Marrow suppression and local inflammation.
2. Bleomycin: 1-5 mg/day intravenous or intramuscular maximum 300 mg/m2. Side effects are: Pulmonary fibrosis with minimal myelo-suppression.
Also can inhibit DNA synthesis. Examples are as follow:
1. Daunomycin, Daunorubicin, Rubidomycin and Adriamycin: 60 mg/m2 intravenous 3-4 weeks. Main side effect is Cardiotoxicity.
2. Mitomycin-C and Mutamycin: 20 mg/m2 intravenous every 4-6 weeks. Local inflammation and marrow suppression are common side effects.
Enzymes
L-asparaginase depletes asparagine availability; inhibits protein synthesis. A good example of a drug under this category is the L-asparaginase. Dosage is 1000 IU/Kg/day intravenous. Common side effect is Allergy-coagulation defects.
Nitrosoureas
Inhibit nucleic acid sythesis. A good example is the Cyclohexyl Chloroethyl nitrosourea (CCNU). Dosage is 100 mg/m2 oral every 4-6 weeks. Delayed marrow suppression is the major side effect. Also, Bis chloroethyl nitrosourea (BCNU): 200 mg/m2/intravenous every 4-6 weeks.
Hydrazine derivatives
Damages DNA through peroxide formation. A good example is Procarbazine methylhydrazine. Dosage is 50-100 mg/m2 daily. Orally for 10-14 days. Side effects are Myelosuppression and CNS depression.
Imidazole derivatives
Mechanism uncertain probably alkylation. Dimethyl triazenoimidazole carbodamide (DTIC) and Dacarpazine. Dosage is 150-250 mg/m2 intravenous for 5 days. Myelosuppression.
Platinum complexes
Inhibit DNA synthesis via crosslinking. Good examples are Cis-diamino dichloroplatinum. Cis-platinum. Dosage is 100 mg intravenous. Once in 3-4 weeks. Side effects are Rnal toxicity and ototoxicity.
Hormones
1. Androgens e.g, Testosterone: 300 mg weekly and intramuscular. Major side effect is virilization.
2. Estrogen e.g, Diethyl stibesterol: 5-15 mg Oral daily. Its side effect is Feminisation.
3. Progestogens e.g, Medroxy progesterone acetate (Provera): 300 mg daily orally. Its side effect is mainly withdrawal bleeding.
4. Anti-estrogens e.g, Tamoxifen (Nolvadex): 20-30 mg daily, Orally.
5. Adrenocorticoids e.g, Prednisone: 40-60 mg/m2 orally per day. Side effect is Cushingoid features.
6. Thyroxine e.g, Eltroxin: 0.1-0.3 mg daily, orally. Major side effect is Hyperthyroidism.
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