Vinblastine dosage

Loehrer PJ, Elson P, Dreicer R, et al. Escalated dosages of methotrexate, vinblastine, doxorubicin, and cisplatin plus recombinant human granulocyte colony-stimulating factor in advanced urothelial carcinoma an Eastern Cooperative Oncology Group trial. J Clin Oncol 1994 12 483-488. 

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). 

Vinblastine is used in combination with other cytotoxic agents for the treatment of disseminated Hodgkin s disease stages III and IV, non-Hodgkin s lymphoma, histiocytic lymphoma, and advanced carcinoma of the testis. It has also been used for the treatment of bladder cancer, melanoma, and renal cell cancer. The usual adult dosage is 3-6 mg/m intravenously for the treatment of testicular germ cell tumors and Hodgkin s disease (1,2). 

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. 

The combination of vinblastine and mitomycin C has caused shortness of breath and bronchospasm. Vinblastine reduces the level and, hence, the effectiveness of phenytoin, requiring increased dosage. Vinblastine produces nausea and vomiting and marrow depression as well as alopecia (see Figure 15). 

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. 

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... 

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