Phase II study of gemcitabine combined with oxaliplatin in relapsed or refractory paediatric solid malignancies: An innovative therapy for children with Cancer European Consortium Study

Eur J Cancer. 2011 Jan;47(2):230-8. doi: 10.1016/j.ejca.2010.09.015. Epub 2010 Oct 11.

Abstract

Aim: To assess objective response rates after 4 cycles of gemcitabine in combination with oxaliplatin in children and adolescents with relapsed or refractory solid tumours.

Methods: This multicentre, non-randomised Phase II study included five strata: neuroblastoma, osteosarcoma, medulloblastoma and other CNS tumours strata with two-stage Simon designs and a miscellaneous, extra-cranial solid tumour stratum with descriptive design. Eligibility criteria included: age 6 months to 21 years; measurable, relapsed or refractory solid malignancy; no more than one previous salvage therapy. Gemcitabine was administered intravenously at 1000 mg/m(2) over 100 min followed by oxaliplatin at 100mg/m(2) over 120 min on Day 1 of a 14-d cycle. Tumour response was assessed every 4 cycles according to WHO criteria.

Results: Ninety-three out of 95 patients enrolled in 25 centres received treatment: 12 neuroblastoma; 12 osteosarcoma; 14 medulloblastoma; 13 other CNS tumours and 42 miscellaneous non-CNS solid tumours. Median age was 11.7 years (range, 1.3-20.8 years). Tumour control (CR+PR+SD) at 4 cycles was obtained in 30/93 evaluable patients (32.3%; 95% confidence interval (CI), 22.9-42.7%), including four PR: 1/12 patients with osteosarcoma, 1/12 with medulloblastoma, 1/12 with rhabdomyosarcoma and 1/4 with other sarcoma. Five out of 12 eligible patients with neuroblastoma experienced stable disease. During a total of 481 treatment cycles (median 4, range 1-24 per patient), the most common treatment-related toxicities were haematologic (leukopenia, neutropenia, thrombocytopenia) and neurological (dysesthesia, paresthesia).

Concluding statement: The gemcitabine-oxaliplatin combination administered in a bi-weekly schedule has acceptable safety profile with limited activity in children with relapsed or refractory solid tumours.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Child
  • Child, Preschool
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Drug Administration Schedule
  • Female
  • Gemcitabine
  • Humans
  • Infant
  • Male
  • Maximum Tolerated Dose
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasms / drug therapy*
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Oxaliplatin
  • Treatment Outcome
  • Young Adult

Substances

  • Organoplatinum Compounds
  • Oxaliplatin
  • Deoxycytidine
  • Gemcitabine