The efficacy and toxicity of SIOP preoperative chemotherapy in Malawian children with a Wilms tumour

BACKGROUND: In Malawi, preoperative chemotherapy for Wilms tumour is a logical strategy, but detailed information on toxicity and efficacy in such a resource limited setting has been unavailable. PROCEDURE: Patients diagnosed with a unilateral Wilms tumour received preoperative chemotherapy-a two-drug 4-week regimen for localized disease and 6 weeks of a three-drug regimen for metastatic disease. Estimated maximum tumour diameter, decrease in tumour size, resectability, stage distribution and haematological toxicity during therapy were documented. RESULTS: At diagnosis, 28% of 72 patients had an estimated maximum tumour diameter of more than 25 cm; 29% of patients had metastases. Eight children (11%) died during preoperative chemotherapy. More than half (59%) of the patients developed moderate neutropenia (neutrophils <1.0 × 10(9) /L; CTC grade 3) and 27% severe neutropenia (CTC grade 4 neutrophils <0.5 × 10.9/L). Grade 4 neutropenia occurred significantly more frequently in children receiving the three-drug regimen compared to the two-drug regimen; 50% (10/20) versus 15% (6/40) (P = 0.004). Fifty-seven percent of all patients had CTC grade 4 anaemia (Hb < 6.5 g/dL) during treatment. Most tumours (92%, 56/61) showed a response to chemotherapy but 14% (8/58) remained unresectable. CONCLUSION: Preoperative chemotherapy for Wilms tumour causes considerable haematological toxicity and treatment-related mortality in malnourished Malawian children. A significant number of children have unresectable disease despite preoperative chemotherapy. To reduce treatment related mortality, consideration should be given to starting treatment with reduced doses in acutely malnourished patients.