Vincristine dosage

These studies confirm that caution should be taken when vincristine and azoles are coadministered. Moreover, the reduction in vincristine dosage has uncertain effects in cancer chemotherapy. Alternatives to azoles for prophylaxis of fungal infections in this population are urgently needed. 

R. T. Sane, V. G. Nayak, V. B. Malkar, and M. L. Kubal, High-performance liquid chromatographic determination of vinblastine sulfate and vincristine sulfate in pharmaceutical dosage forms, Indian Drugs, 22 89 (1984). 

Vincristine is part of many chemotherapeutic regimens, based on its lack of myelosuppressive toxicity. It is used, for example, in the treatment of acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), lymphomas, neuroblastoma, brain tumors, and Wilms tumor. The generally recommended dose in adults is 1.4 mg/m /week intravenously (5). Some clinicians have recommended an absolute upper limit of 2 mg, but this limitation is still a matter of debate (6). The usual pediatric dosage is 1.5-2 mg/m, but for children weighing 10 kg or less or who have a body surface area less than 1 m, the manufacturers recommend that treatment should be begun at 0.05 mg/kg once a week (5). 

Despite only a minor difference in the chemical structures of vinblastine and vincristine, the clinical effects differ considerably. Surprisingly there is no clinical evidence of cross resistance between them, or with radiation and other presently known oncolytic agents. The rise and fall of the blood activity level of vincristine is steeper than that of vinblastine.The dosage requirements of both alkaloids differ markedly the weekly intravenous dose of vinblastine for humans is 0.1—0.2 mg per kg, that of vincristine, however, is approximately one tenth of this. Concerning the side-effects, vincristine shows more neurotoxic effects and vinblastine is considered to have more potency in bone-marrow depression. This is not without consequences on human therapy therapy is limited by bone-marrow depression with vinblastine and neuromuscular effects, with vincristine. Early symptoms of side-effects are vomiting, fever, and exanthemes. Late symptoms are C.N.S. disturbances, alopecia, and leukopenia. C.N.S. disturbances are manifested by various symptoms such as paresthesias, neuritis, paresis, and muscular atrophy, accompanied by quenched reflexes. Even behaviour may be affected after a long period of treatment. But why do all these side-effects happen, when Vinca alkaloids are unable to pass the blood-brain barrier The only explanation we have at hand is that they are possibly caused by metabolites or breakdown products of the normal biochemical pathways, which are disturbed by the alkaloids. 

Items 80-81. A patient with metastatic choriocarcinoma was ti eated first with methotrexate plus dactinomycin and subsequently with a combination of cisplatin and vincristine. In both regimens, drug dosage was maximized to a toxicity limit of a 2-log decrease in blood platelets. The effects of chemotherapy were monitored by urinary chorionic gonadotropin (UCG, U/24 h), as shown in the data below. 

Vinorelbine tartrate (Fig. 42.35) is used alone or in combination with cispiatin for first-line treatment of nonsmall cell lung cancer. This semisynthetic alkaloid is unique in having oral bioavailability (85), but it currently is available only for IV injection. The initial phase elimination half-life is on par with that observed for vincristine and vinblastine, and the terminal phase half-life is between 28 and 44 hours. Although dose-limiting granulocytopenia is the major adverse effect, potentially fatal interstitial pulmonary changes have been noted, and patients with symptoms of respiratory distress should be promptly evaluated. As with all vinca alkaloids, elimination is primarily hepatobiliary, and dosage reduction should be considered in patients with liver dysfunction. 

Etretinate. A man with T-cell lymphoma who had recently been given chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisolone) was anticoagulated with warfarin after developing a pulmonary embolism. About three weeks later, he started etretinate 40 mg daily and it was found necessary to increase his warfarin dosage from 7 to 10 mg daily. His liver function tests were normal. This patient had also recently started taking co-proxamol , (p.436), tolbutamide , (p.380) and cimeti-dine , (p.412) , but all of these have been reported to only rarely increase the effect of warfarin. 

The UK manufacturer of aprepitant recommends caution when it is used with antineoplastics that are metabolised by CYP3A4, particularly irinotecan, because of the possibility of increased toxicity with this drug. They also mention that etoposide, vinoreibine, docetaxel, paclitaxel, ifosfamide, imatinib, vinblastine and vincristine, were given without dosage adjustment for potential interactions, but as this was not a formal interaction study they recommend caution. However, with intravenous docetaxel, it appears that no important changes in pharmacokinetics occur, and therefore dosage adjustments are unlikely to be needed for this drug,... 

The yield of the dimeric alkaloids from Catharanthus plants is 0.0005 %. The dosage required per adult per injection is 1.4 mg/m body surface. Currently, a single kilogram of vincristine costs around US 20 million, making it one of the costliest dmgs around [23]. Vinblastine, another anticancer drug from the same... 

As part of the diet of rats, chicory inulin inhibited tumor formation (colon, mammary, and lung) and potentiated the cytotoxic effects of various common anticancer drugs at subtherapeutic dosages (cyclophosphamide, cytarabine, doxorubicine, 5-fluoroura-cil, methotrexate, and vincristine). ... 

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