Malnourished Malawian patients presenting with large Wilms tumours have a decreased vincristine clearance rate

Introduction: In developing countries, patients with a Wilms' tumour often present late with a high degree of malnutrition and large tumours. We investigated whether this affects vincristine pharmacokinetics. Methods: Patients newly diagnosed with Wilms' tumour in Malawi and the UK were included. We documented anthropometric parameters, nutritional status and tumour size. Vincristine (1.50 mg/m2) was administered as part of the standard chemotherapy regimen. Vincristine plasma concentrations were measured at several time points by liquid chromatography-mass spectrometry. Vincristine pharmacokinetic parameters (clearance and area under the curve) were calculated by non-compartmental analysis. Results: Eleven Malawian and 8 UK patients were included. Mean Z-score of (corrected) weight for height was significantly lower in the Malawian patients than in the UK patients (-2.3 versus 0.42, p < 0.0001). Mean tumour weight at diagnosis was significantly larger in Malawian patients (2.8 kg versus 0.7 kg, p = 0.007). Mean vincristine log Clearance was lower in Malawian as compared to UK patients (2.2 versus 2.6 ml/min, p = 0.001). Mean log AUC values were higher in Malawian than in UK patients (3.8 versus 3.5 μg/ml min, p = 0.003). This difference is reflected in the, on average, 1.98-fold larger vincristine AUC values for Malawian patients. The difference in AUC values was statistically significantly explained by nutritional status (p = 0.043). Conclusion: Malnourished patients in Malawi exhibited lower vincristine clearance rates and thus higher AUC values than a comparable patient population with a better nutritional status in the UK. In malnourished patients, dose reductions may need to be considered to prevent an increased incidence and severity of toxicity. © 2010 Elsevier Ltd. All rights reserved.