Carboplatin-based chemotherapy for refractory and recurrent Ewing's tumours

Failure of first line therapy for the Ewing's family of tumours (EFT) is associated with a very poor outlook. Studies of second line chemotherapy are therefore necessary to identify active agents and drug combinations. Cisplatin-based therapy is frequently used in these circumstances but there are few studies to clearly define activity and toxicity. This report details outcome in a cohort of patients with poor risk EFT treated with a carboplatin-based combination.

Between 1990 and 1998, 23 males and 16 females aged between 6 and 48 years (median 23) with relapsed or refractory EFT were treated with carboplatin-based chemotherapy. Previous chemotherapy had included ifosfamide and doxorubicin in all but two patients. Twenty patients were treated at the time of recurrence, and 19 after a poor response to initial chemotherapy. Treatment comprised of carboplatin to give an area under the plasma carboplatin concentration versus time curve of (AUC) 6 mg/ml, etoposide 120 mg/m2 for 3 days, and cyclophosphamide 500-750 mg/m2 for 2 days, repeated every 21 days.

A total of 105 cycles were given, median 2 per patient (range 1-5). Overall response was 26%, with one complete response and nine partial responses. Median time to progression was 10 weeks (range 2-54). Haematological toxicity was severe requiring dose reductions in 53% of patients. Six patients proceeded to high dose consolidation treatment with bone marrow or peripheral stem cell rescue.

This combination results in a substantial response rate in previously treated patients but with significant toxicity. Responses are, however, relatively short.