Which of the following medications is essential for ameliorating the toxicity of pemetrexed?

Toxicity amelioration: High doses and intensive regimens are being employed aiming at cure of the malignancy. The associated toxicity may be ameliorated to some extent by- 1. Toxicity blocking drugs: Folinic acid rescue has permitted administration of > 100 fold dose of Mtx . It is professed that normal cells are rescued more than the cancer cells-therapeutic index is increased. * Cystitis caused by cyclophosphamide and ifosphamide can be blocked by systemically administered mesna and by irrigating the bladder with acetylcysteine. Both these are -SH containing compounds that combine with and detoxify the toxic metabolites in the bladder. Generous fluid intake and frequent bladder voiding also helps. * For controlling cytotoxic drug induced vomiting, ondansetron, a 5-HT3 antagonist, has surpassed the efficacy of metoclopramide, which neveheless is still used (see Ch. 47). Addition of dexamethasone and/ or lorazepam fuher enhances the protection against vomiting. 2. Hyperuricaemia occurring as a consequence of rapid destruction of bulky tumour masses and degradation of large amount of purines can be reduced by allopurinol, alkalinization of urine and plenty of fluids. Coicosteroids also reduce hyperuricemia. 3. Hypercalcaemia occurring as a complication of ceain malignancies like myeloma, cancer breast/prostate, etc. may be aggravated by chemotherapy. lt is treated by vigorous hydration and i.v. bisphosphonates 3. Hypercalcaemia occurring as a complication of ceain malignancies like myeloma, cancer breast/prostate, etc. may be aggravated by chemotherapy. lt is treated by vigorous hydration and i.v. bisphosphonates (see Ch. 24). 4. Drugs given in pulses with 2-3 week intervals for normal cells to recover improve the efficacy of therapy: malignant cells recovering more slowly. 5. Selective exposure of tumour to the drug by intraaerial infusion into a limb or head and neck; intrapleural/ intraperitoneal injectionespecially for rapidly accumulating pleural effusion or ascitis; topical application on the lesion-<m skin, buccal mucosa, vagina, etc. may reduce systemic toxicity. 6. Platelet and/ or granulocyte transfusion after treatment-to prevent bleeding or infection. 7. Use of biological response modifiers like recombinant GM-CSF /G-CSF hastens recovery from cytotoxic drug induced myelosuppression. Pemetrexed is a novel multitargeted antifolate that inhibits > or = 3 enzymes involved in folate metabolism and purine and pyrimidine synthesis. These enzymes are thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. This agent has broad antitumor activity in phase II trials in a wide variety of solid tumors, and is approved in combination with cisplatin for the therapy of malignant mesothelioma. In a recent phase III trial, pemetrexed demonstrated equivalent efficacy to docetaxel, but with significantly less toxicity, in second-line treatment of non-small-cell lung cancer. The most common and serious toxicities of pemetrexed--myelosuppression and mucositis--have been significantly ameliorated by folic acid and vitamin B12 supplementation. More impoant, vitamin supplementation has not been shown to adversely affect efficacy in some tumor types. Tumors with codeletion of the methylthioadenosine phosphorylase gene, as a consequence of p16 deletions, may be paicularly sensitive to pemetrexed REFERENCE:1)ESSENTIALS OF MEDICAL PHARMACOLOGY K.D.TRIPATHI SIXTH EDITION PAGE NO:833 2)www.ncbi.nlm.nih.gov