Etoposide, ifosfamide, and cisplatin therapy for refractory childhood solid tumors. Response and toxicity

Etoposide, ifosfamide, and cisplatin (VIP) are each active in treating pediatric solid tumors, and this combination has been shown to be effective in treating adult germ cell tumors. Etoposide, ifosfamide, and cisplatin therapy was used to treat 11 patients, with ages ranging from 14 months to 22 years, with relapsed sarcoma, Wilm's tumor, and hepatoblastoma.

Etoposide, ifosfamide, and cisplatin therapy was administered daily for 3 days in doses of cisplatin 20 mg/m2 with mannitol 10 g/m2 for 1 hour, etoposide 100 mg/m2, and ifosfamide 1.5 g/m2 with MESNA 360 mg/m2 x 3 doses. A total of 65 courses (range, 3-10/patient) were administered, with 86% of the courses administered at full dose. Hematopoietic growth factors were not used.

All 10 evaluable patients responded. Six patients had a complete response (CR) by computed tomographic or magnetic resonance imaging scan after one to three courses. The remaining four patients had a partial response (PR) (> 50% decrease in disease). One PR was converted to a CR by resection of the residual lesions. The major toxicity was myelosuppression. The median nadirs after full doses were as follows: leukocyte count of 900/mm3, absolute neutrophil count (ANC) of 156/mm3, platelet count of 61,000/mm3, and hemoglobin count of 8.6 g/dl; 75% of full dose courses led to an ANC of less than 500. Fever and neutropenia were observed after 8/55 (15%) full dose courses. Two episodes of bacteremia were noted, one with Staphylococcus epidermidis after full recovery of counts. The median time to hematologic recovery was 21 days (range, 14-29 days). No patient developed a decreased creatinine clearance level during therapy. Significant renal solute losses were observed in two patients, both of whom had been pretreated heavily with ifosfamide and had losses before VIP therapy.

Etoposide, ifosfamide, and cisplatin appear to be active in treating childhood solid tumors. This therapy has predictable and tolerable myelotoxicity, and nephrotoxicity does not appear to be more severe than that observed after treatment with ifosfamide alone.