Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 2, pp 399–404 | Cite as

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

  • Cormac Owens
  • Valerie Laurence
  • Lofti Benboubker
  • Anne-Sophie Defachelles
  • Didier Cupissol
  • Hervé Rubie
  • Hervé Brisse
  • Annie Rey
  • Liliane Ollivier
  • Dominique Couanet
  • Christiane Baunin
  • Céline Mahier Aït-Oukhatar
  • Odile Oberlin
Original Article

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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

Keywords

Ewing sarcoma Relapse Paediatric Phase II trial Cisplatin VP-16 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Cormac Owens
    • 1
  • Valerie Laurence
    • 5
  • Lofti Benboubker
    • 6
  • Anne-Sophie Defachelles
    • 7
  • Didier Cupissol
    • 8
  • Hervé Rubie
    • 10
  • Hervé Brisse
    • 4
  • Annie Rey
    • 2
  • Liliane Ollivier
    • 4
  • Dominique Couanet
    • 3
  • Christiane Baunin
    • 9
  • Céline Mahier Aït-Oukhatar
    • 11
  • Odile Oberlin
    • 1
  1. 1.Department of Paediatric OncologyInstitut Gustave RoussyVillejuifFrance
  2. 2.Department of BiostatisticsInstitut Gustave RoussyVillejuifFrance
  3. 3.Department of RadiologyInstitut Gustave RoussyVillejuifFrance
  4. 4.Department of RadiologyInstitut CurieParisFrance
  5. 5.Department of Medical OncologyInstitut CurieParisFrance
  6. 6.Department of Medical OncologyCentre hospitalo-universitaire BretonneauToursFrance
  7. 7.Department of General OncologyCentre Oscar LambretLilleFrance
  8. 8.Department of Medical OncologyCentre Val d’Aurelle Paul LamarqueMontpellierFrance
  9. 9.Department of RadiologyCentre hospitalo-universitaire PurpanToulouseFrance
  10. 10.Department of Paediatric OncologyCentre hospitalo-universitaire PurpanToulouseFrance
  11. 11.Fédération Nationale des Centres Lutte Contre le CancerParisFrance

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