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


METHODS
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.


RESULTS
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.


CONCLUSIONS
This combination results in a substantial response rate in previously treated patients but with significant toxicity. Responses are, however, relatively short.
Whelan
Jeremy S
JS
The London Bone and Soft Tissue Tumour Service, The Middlesex Hospital, University College London Hospitals NHS Trust, United Kingdom. jeremy.whelan@uclh.org
McTiernan
Anne
A
Kakouri
Eleni
E
Kilby
Anne
A
D000293:Adolescent; D000328:Adult; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D015331:Cohort Studies; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D012512:Sarcoma, Ewing / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology*; D015996:Survival Rate
D016190:Carboplatin