Topotecan/carboplatin regimen for refractory/recurrent rhabdomyosarcoma in children: Report from the AIEOP Soft Tissue Sarcoma Committee.

Introduction: From 2002 to 2011, the Italian Soft Tissue Sarcoma Committee explored a combination of topotecan and carboplatin as a second-line strategy for children with resistant or relapsing rhabdomyosarcoma.

Methods: Patients received two blocks of topotecan 2 mg/m on days 1, 2, and 3, and carboplatin 250 mg/m on days 4 and 5, followed by alternating blocks of topotecan-cyclophosphamide and carboplatin-etoposide for a total of six courses with 3-week intervals. Tumor response was assessed after two cycles, and local control was implemented when feasible.

Results: A total of 38 patients were included in this study: 18/38 had alveolar rhabdomyosarcoma (RMS), 10/38 had metastatic disease at diagnosis, 8/38 had tumor progression during first-line chemotherapy, 21/38 had locoregional relapses, and 9/38 had distant relapses. Thirty-two patients could be assessed for tumor response to topotecan-carboplatin, and 9 (28%) showed a complete or partial response. Twenty-four patients experienced grade IV hematologic toxicity, while transient grade 1 tubulopathy, grade 3 mucositis, transient grade 2 nephrotoxicity, and a grade 2 decline in cardiac function occurred in one patient each. The 5-year overall and progression-free survival rates were 17% and 14%, respectively.

Conclusion: the prognosis for children with resistant or relapsing RMS remains unsatisfactory. The topotecan-carboplatin regimen was well-tolerated. Though in case of late relapse the response rate was similar to those reported for other regimes, the result achieved remains unsatisfactory. New approaches, possibly including target agents, seem more attractive for future studies.