Phase II study of weekly gemcitabine and vinorelbine for children with recurrent or refractory Hodgkin's disease: A children's Oncology group report

Purpose The Children's Oncology Group conducted this phase II study to assess the efficacy and toxicity of gemcitabine and vinorelbine (GV) in pediatric patients with heavily pretreated relapsed/refractory Hodgkin's disease. Both agents have significant single-agent response rates in this setting. Methods GV was given on days 1 and 8 of each 21-day treatment cycle: vinorelbine 25 mg/m²/dose administered via intravenous (IV) push before gemcitabine 1,000 mg/m²/dose IV over 100 minutes. Any patients who demonstrated a measurable response (complete response [CR], very good partial response [VGPR], or partial response [PR]) were considered to have experienced a response to GV. Response was evaluated after every two cycles. A two-stage minimax rule was used to test the null hypothesis that the response rate is ≤ 40% against an alternative hypothesis of a response rate more than 65%. Results Thirty eligible patients with a median age of 17.7 years (range, 10.7 to 29.4 years) were enrolled. All patients had received at least two prior chemotherapy regimens, and 17 patients had undergone prior autologous stem-cell transplantation. Hematologic toxicity was predominant in all treatment cycles. Nonhematologic grade 3 to 4 toxicity, including elevated hepatic enzymes and hyperbilirubinemia, was less common. Pericardial and pleural effusions developed in one patient after cycles 4 and 5 of GV, consistent with gemcitabine-induced radiation recall. There were no toxic deaths. Measurable responses were seen in 19 (76%) of 25 assessable patients (95% exact binomial CI, 55% to 91%), including six CRs, 11 VGPRs, and two PRs. Conclusion GV is an effective and well-tolerated reinduction regimen for children with relapsed or refractory Hodgkin's disease.