Section 9/ Chemotherapy 378 ogy is discussed in chapter ‘Oral Contraceptives.’ MEGESTROL ACETATE It belongs to group of progesterone which are mainly used as second or third line therapy in breast and endometrial cancer Adverse effects include nausea, acne, fluid retention, GI disturbances and weight changes TAMOXIFEN It exerts its action by binding to estrogen receptors Tumours with estrogen receptors respond It is given orally, the drug has biphasic half life and is primarily excreted in bile Adverse effects include nausea, vomiting, hot flushes, vaginal bleeding, pruritus vulvae and menstrual irregularities It is used as palliative treatment of estrogen receptor positive advanced or metastatic carcinoma of breast MISCELLANEOUS AGENTS HYDROXYUREA The primary action is inhibition of enzyme ribonucleoside diphosphate reductase The drug is specific for S phase of the cell cycle and causes cell to arrest at the G1-S interface After oral administration it is readily absorbed from GI tract Hydroxyurea readily crosses blood brain barrier It is indicated in treatment of chronic granulocytic leukaemia, polycythemia vera, essential thrombocytosis, melanoma, metastatic or inoperable carcinoma of ovary In combination with radiotherapy in carcinoma of cervix, head, neck and lung Adverse effects include nausea, vomiting, rash Bone marrow depression is the major toxic effect Alopecia, stomatitis, dysuria; inflammation and increased pigmentation may occur in areas exposed to radiation Rarely neurological disturbances occur PROCARBAZINE After metabolic activation, it depolymerizes DNA and causes chromosomal damage and also nucleic acid synthesis inhibition It is found to be effective in Hodgkin’s disease and carcinoma of lungs Adverse effects include drowsiness, restlessness, anaemia, leucopenia, thrombocytopenia, bone marrow toxicity and disulfiram like reaction with alcohol L-ASPARAGINASE It destroys essential amino acid (asparagine) hence leukaemic cells are deprived of amino acid and leads to cell death It is given by parenteral route Adverse effects include nausea, vomiting, headache, fever, abdominal pain, hyperglycemia leading to coma, hypersensitivity, renal damage, coagulation defects, thrombosis, CNS depression or hyperexcitability and acute haemorrhagic pancreatitis It is used in the treatment of malignant lymphoma and acute leukaemia Chemotherapy of Malignancy CISPLATIN It acts by cross-linking of DNA It also has radiomimetic property It is bound to plasma proteins and is excreted slowly unchanged in urine It is effective in metastatic testicular and ovarian carcinoma, advanced bladder carcinoma and refractory squamous cell head and neck carcinoma Adverse effects include nausea, vomiting, fever, anaphylactic reactions, hypokalemia, hypomagnesaemia, haemolysis, renal damage, sterility, teratogenesis, ototoxicity, peripheral neuropathy, Raynaud’s disease and bone marrow depression INTERFERON ALFA It is highly purified protein containing 165 amino acids and is manufactured by recombinant DNA technology Mechanism of action is not clearly understood but direct antiproliferative action against tumour cells and modulation of the host immune response may play important roles It exhibits half life of 3.7-8.5 hours Alpha interferons are filtered through the glomeruli and undergo rapid proteolytic degradation during tubular reabsorption It is indicated in hairy cell leukemia, AIDS related Kaposi’s sarcoma (the detailed pharmacology and its use as antiviral agent is discussed in chapter ‘Antiviral agents’) Adverse effects include GI haemorrhage, leukopenia and elevation in liver enzyme levels Recently introduced interferon a-2b is used in chronic myeloid leukaemia, chronic hepatitis B and C 379 IMMUNOSUPPRESSANTS The drugs like azathioprine and cyclosporine A are used chiefly to prevent transplant rejection and in the treatment of autoimmune diseases They are used to prevent graft rejection after kidney, liver, lung, pancreas transplant or bone marrow transplantation AZATHIOPRINE It is a purine antimetabolite which has marked effect on T-lymphocytes, suppresses cell mediated immunity (CMI) It selectively affects differentiation and functions of T cells and inhibits cytolytic lymphocytes It is used primarily as immunosuppressant in organ transplantation, progressive rheumatoid arthritis and some other autoimmune diseases CYCLOSPORINE It is a cyclic polypeptide with 11 amino acids It selectively inhibits T-lymphocytes proliferation, IL-2 and other cytokine production It is the most effective drug for prevention and treatment of graft rejection reaction It is used in cardiac, hepatic, renal, bone marrow transplantation and as second line drug in rheumatoid arthritis, inflammatory bowel disease, dermatomyositis, bronchial asthma and certain other autoimmune diseases Mycophenolate mofetil, a semisynthetic derivative of mycophenolic acid, isolated from the mould Penicillium glaucum is used in kidney and liver transplant patient Another newer compound mizoribine is used in kidney transplantation This page intentionally left blank Section 10 Vitamins and Trace Elements This page intentionally left blank ... reabsorption It is indicated in hairy cell leukemia, AIDS related Kaposi’s sarcoma (the detailed pharmacology and its use as antiviral agent is discussed in chapter ‘Antiviral agents’) Adverse... Recently introduced interferon a-2b is used in chronic myeloid leukaemia, chronic hepatitis B and C 379 IMMUNOSUPPRESSANTS The drugs like azathioprine and cyclosporine A are used chiefly to prevent... inhibits T-lymphocytes proliferation, IL-2 and other cytokine production It is the most effective drug for prevention and treatment of graft rejection reaction It is used in cardiac, hepatic, renal,