A phase II study of gefitinib for patients with advanced HER-1 expressing synovial sarcoma refractory to doxorubicin-containing regimens

Rationale. Advanced synovial sarcomas (SyS) refractory to doxorubicin and ifosfamide are highly resistant to the currently available cytotoxic agents. Based on a report showing a specific overexpression of HER-1 in SyS, we investigated an HER-1 inhibitor, gefitinib, in refractory SyS. Subjects and Methods. To establish the efficacy and safety of gefitinib in HER-1 -positive SyS refractory to one or two lines of doxorubicin- and ifosfamide-based chemotherapy, a phase II study was conducted from December 2002 to October 2005 by 12 centers of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Gefitinib was given at a 500-mg/day oral dose until progression or intolerance. Results. Forty-eight patients were included (46 eligible). All patients had previously received chemotherapy for metastatic disease, with a median number of two lines (range, 1-4). The most frequent metastatic sites were the lungs (n = 44, 92%), lymph nodes (n = 11, 23%), and soft tissues (n = 10, 21%). The median duration of treatment was 43 days (range, 13-315). Treatment was interrupted in five patients (10%). Treatment was halted for progression in 45 (94%) patients. The best response was stable disease in 10 patients (21%). Disease progression occurred in 32 patients (70%), with a median time to disease progression of 6 weeks. Progression-free survival at 4 and 6 months was 21% and 6%, respectively. Conclusion. The results show that gefitinib monotherapy in advanced SyS refractory to conventional chemotherapy did not demonstrate sufficient activity to warrant further investigation in this setting. This may suggest that HER-1 is not a critical protein in tumor progression in this disease.

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