Original Article

Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 2, pp 399-404

First online:

Phase II study of cisplatin and oral VP16 in patients with refractory or relapsed Ewing sarcoma

  • Cormac OwensAffiliated withDepartment of Paediatric Oncology, Institut Gustave Roussy Email author 
  • , Valerie LaurenceAffiliated withDepartment of Medical Oncology, Institut Curie
  • , Lofti BenboubkerAffiliated withDepartment of Medical Oncology, Centre hospitalo-universitaire Bretonneau
  • , Anne-Sophie DefachellesAffiliated withDepartment of General Oncology, Centre Oscar Lambret
  • , Didier CupissolAffiliated withDepartment of Medical Oncology, Centre Val d’Aurelle Paul Lamarque
  • , Hervé RubieAffiliated withDepartment of Paediatric Oncology, Centre hospitalo-universitaire Purpan
  • , Hervé BrisseAffiliated withDepartment of Radiology, Institut Curie
  • , Annie ReyAffiliated withDepartment of Biostatistics, Institut Gustave Roussy
  • , Liliane OllivierAffiliated withDepartment of Radiology, Institut Curie
    • , Dominique CouanetAffiliated withDepartment of Radiology, Institut Gustave Roussy
    • , Christiane BauninAffiliated withDepartment of Radiology, Centre hospitalo-universitaire Purpan
    • , Céline Mahier Aït-OukhatarAffiliated withFédération Nationale des Centres Lutte Contre le Cancer
    • , Odile OberlinAffiliated withDepartment of Paediatric Oncology, Institut Gustave Roussy

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access



Phase II trials demonstrate the activity of cisplatin in patients with refractory Ewing sarcoma family tumours (ESFT) and also the feasibility of giving cisplatin with oral VP16 in a variety of different cancers. This trial was conducted to evaluate the activity and toxicity profile of this combination delivered as outpatient therapy in patients with refractory/relapsed ESFT.


Cisplatin was administered on days 1, 8 and 15 and days 29, 36 and 43 (70 mg/m2/dose for patients <21 years of age and 50 mg/m2/dose ≥21 years). VP16 was administered at a dose of 50 mg/m2 on days 1–15 and days 29–43 inclusive. A three-stage Fleming statistical design was used for analysis.


Between January 2003 and October 2006, 45 patients aged between 5 and 46 years (median 19) were enrolled. Thirty-eight were evaluable for response. Patients had previously received one to three lines of chemotherapy (median = one). Seventy-three per cent of the patients had grade 3/4 neutropenia, 20 % developed fever, 40 % had grade 3/4 anaemia, 68 % grade 3/4 thrombocytopenia and 16 % grade 2/3 ototoxicity. Measured response after 2 cycles: 0 CR, 7 PR (18 %), 13 SD (34 %), 18 PD (48 %). There was excellent concordance between unidimensional and bidimensional criteria in 31 of 33 responses (94 %). PFS at 1 year was 39 %, with a median PFS of 6 months. Overall survival at 1 year was 44 %; median survival was 11 months.


Cisplatin combined with oral VP16 is well tolerated and has acceptable side effects, but limited clinical activity in refractory/relapsed ESFT.


Ewing sarcoma Relapse Paediatric Phase II trial Cisplatin VP-16