9563 Objectives: The current first line standard chemotherapy for advanced soft-tissue sarcomas is the combination of doxorubicine and ifosfamide. Liposomal encapsulation is a strategy pursued to reduce toxicity and improve tumor uptake. There are so far only limited systematic data regarding the efficacy of liposomal anthracyclines in advanced soft-tissue sarcomas. We have previously reported on a phase II study with liposomal daunorubicine (L-Dauno) with ifosfamide, named IDx1. Here we report on an additional cohort of the phase II study using liposomal doxorubicine (L-Doxo). Methods: In a single-arm two cohort phase II study 55 patients with advanced soft-tissue sarcoma had received first line a maximum of 6 cycles (median 2 cycles) of ifosphamide (5 g/m2) and in cohort 1 L-Dauno (100 mg/m2, 40 patients) or in cohort 2 the approximate equivalent of L-Doxo (75 mg/m2, 15 patients). Cycles were repeated every 4 weeks in absence of disease progression. Primary study endpoint was response rate. Results: The overall response rate was 25% (n = 14). In the L-Dauno group the results were as follows: CR 3% (n = 1), PR 29% (n = 10), SD 17% (n = 6), PD 37% (n = 13), NED or intermittent death 14% (n = 5), and in the L-Doxo group: PR 20% (n =3), SD 26% (n =4) and PD 53% (n = 8). Interestingly, all three liposarcoma patients (two in the L-Dauno group, one in the L-Doxo group) responded, whereas liposarcoma usually carries a poor response rate. For both combinations toxicity was similarly tolerable with short episodes of hematotoxicity (leucocyte nadir on day 9, platelet nadir on day 11), 11 febrile episodes, no grade 3 or 4 mucositis, no cardiac toxicity and 5 episodes of grade 2 acute ifosfamide-related CNS-toxicity. Based on the hematotoxicity kinetics, three weekly regimens appear feasible. Conclusion: The combination of liposomal anthracyclines and ifosfamide is a safe and effective first line regimen in the treatment for advanced soft tissue sarcoma. Further evaluation in a randomized trial will be pursued. The unexpected high responsiveness of liposarcoma warrants further phase II investigation. 1Siehl JM et al. Cancer 2005. No significant financial relationships to disclose.
Significant clinical benefit of first-line palliative chemotherapy in advanced soft-tissue sarcoma
