Any significant change in the pharmacokinetics of an anticancer drug would have a bearing on its therapeutic efficacy and toxicity. Nutritional deficiencies have been shown to affect the pharmacokinetics of a drug. Since malnutrition and undernutrition are widely prevalent in India, the effect of initial nutritional status on the overall kinetics of methotrexate (MTX) administered to cancer patients appeared to be of practical importance. A study of 6 Indian children with malignancies was made to examine the pharmacokinetics of low dose MTX and its relationship to the nutritional status. The results indicate that the relative weight correlates well with the anthropometric parameters, nutritional parameters and dietary intake and may be used as a marker of nutritional status.

Since anticancer drugs have a low therapeutic index, any significant change in the pharmacokinetics of a drug would have a bearing on therapeutic efficacy and drug toxicity. Nutritional deficiencies have been shown to affect the four processes of pharmacokinetics, ie, absorption, distribution, biotransformation, and excretion. Malnutrition and undernutrition are widely prevalent in India and thus it was thought to be of practical importance to study the effect of initial nutritional status on the overall kinetics of methotrexate, a widely used anticancer drug. The results of the study reveal that relative weight correlates well with the anthropometric parameters, nutritional parameters, and dietary intake and may be used as a marker of nutritional status. When grouped on the basis of relative weights, the undernourished patients revealed a significant (P less than 0.01) prolongation of biological half-life and a significant (P less than 0.001) reduction in clearance. Based on these results, relative weight has been proposed as a basis for drug dosage determinations in place of the existing practice of administering antineoplastic drugs on the basis of body surface area or body weight alone.

Vincristine and prednisolone are important drugs for induction therapy in acute lymphoblastic leukemia. In our experience quite a number of patients relapse during maintenance therapy after induction. At this stage some of the patients are resistant to vincristine and prednisolone. In the present study we attempted to explore whether vincristine could be used together with cytosine arabinoside. Vincristine being a phase-specific agent is known to synchronize the leukemic cells in vitro and a drug like cytosine arabinoside added after vincristine at the appropriate time is expected to have added cell kill. In vitro studies with leukemic cells confirmed the expected increase in cell kill with the addition of cytosine arabinoside 6 h after vincristine treatment. Simultaneously, the same approach was explored in the clinic. Acute lymphoblastic leukemia patients who were resistant to vincristine and prednisolone for reinduction, remitted with this strategy, i.e. with the addition of cytosine arabinoside 6h after the vincristine treatment.