Vinorelbine and low dose cyclophosphamide in pediatric sarcoma. A pilot study for the future European rhabdomyosarcoma protocol

Abstract

8540 Background: Following our previous report (Casanova et al. Cancer 2002; 94: 3263) on the activity of vinorelbine (VNB) in rhabdomyosarcoma (RMS), we report the results of a pilot study aimed to define the dose of VNB in combination with low dose continuous oral cyclophosphamide (CTX) in patients with refractory or recurrent sarcomas. The study was performed in the view of utilizing this treatment as maintenance therapy in the future European protocol for high risk RMS patients. Methods: The dose of CTX was fixed at 25 mg/m2/day for 28 days. VNB given i.v. on days 1, 8, and 15 was escalated from a starting dose of 15 mg/m2 by 5-mg/m2 increments in subsequent cohorts of at least 3 patients until the maximum tolerated dose was reached. Results: Between April 2003 and November 2003, 18 patients (10 M, 8 F) aged 2–23 years (median 12) received 88 cycles (9 had RMS). There was a median of 2 prior regimens (range 1–4); 5 patients previously received high dose chemotherapy with PBSC rescue and 12 prior radiotherapy. Three patients were treated at dose level 1, 4 at dose level 2, and 3 at dose level 3. Among 5 patients treated at dose level 4 (VNB 30 mg/m2) 2 dose limiting toxicities (grade 4 neutropenia) were observed in the first 2 cycles therefore a decision was made to enter 3 more patients at dose level 3. In the 39 cycles administered at dose level 3, neutropenia grade ≥ 3 was observed in 14 (36%) with no other major toxicity. The interval between courses 1 and 2 was as scheduled (28 days) in 12 patients, 5 had a delay ≤ 3 days. One patient, with parameningeal RMS who underwent RT a few weeks before study entry, had a delay of 2 weeks due to prolonged grade 2 mucositis. A median of 5 cycles (range 1–10) were administered per patient. Four patients were still on treatment after 5–10 cycles. Partial responses were observed in 7/17 assessable patients: 3/8 RMS (2 embryonal, 1 alveolar), 1/1 clear cell sarcoma, 1/2 synovial sarcoma, 1/2 desmoplastic small round cell tumor, 1/1 osteosarcoma. Conclusions: This combination appears to be feasible and active in relapsed sarcoma. Recommended doses for the new study will be CTX 25 mg/m2/day for 28 days and VNB 25 mg/m2 on days 1,8, and 15. No significant financial relationships to disclose.