Phase II Study of Ifosfamide+Doxorubicin in Patients With Advanced Synovial Sarcomas (E1793): A Trial of the Eastern Cooperative Oncology Group

Purpose Because we had observed in the synovial sarcoma subgroup of a broad phase III advanced soft tissue sarcoma study a significantly greater objective regression rate from ifosfamide+doxorubicin (88%) than from doxorubicin alone (20%) (P = 0.02), the Eastern Cooperative Oncology Group (ECOG) decided to further assess this two drug combination in a subsequent Phase II study

Phase II study of IfosfamideþDoxorubicin in patients with advanced synovial sarcomas (E1793): a trial of the Eastern Cooperative Oncology Group

Abstract Purpose Because we had observed in the synovial sarcoma subgroup of a broad phase III advanced soft tissue sarcoma study a significantly greater objective regression rate from ifosfamideþdoxorubicin (88%) than from doxorubicin alone (20%) ( P ¼ 0.02), the Eastern Cooperative Oncology Group (ECOG) decided to further assess this two drug combination in a subsequent Phase II study. Patients Between 1994 and 1999, twelve adult patients with advanced synovial sarcomas were enrolled to receive, as their initial chemotherapy, ifosfamide 7.5 gm/m 2 plus doxorubicin 60 mg/m 2 , given intravenously over two consecutive days every 3 weeks. Methods Each day for 2 days doxorubicin 30 mg/m 2 was infused over 5 min through a running i.v., followed by ifosfamide 3750 mg/m 2 over 4 h. Continuous i.v. fluid was infused at 300 mL /h for 3 h on day 1, before chemotherapy was begun; then the infusion was continued at 100 mL /h for a total of 3 days. Mesna 750 mg/m 2 was given 15 min before ifosfamide and at 4 and 8 h after ifosfamide on days 1 and 2 of each treatment cycle. Filgrastim (G-CSF) 5 mg/kg was given subcutaneously each day for 14 days beginning on day 3 of each treatment cycle to limit the severity of neutropenia. Results Five of our 12 patients (42%) experienced partial regression of their advanced synovial sarcomas; however, this first stage result was borderline for proceeding to the second planned stage of accrual and our case accrual was quite poor. Thus, the study was closed after stage one accrual. Our patients received a median of four cycles of chemotherapy (range: 1 to 6). All patients experienced at least grade 3 neutropenia (grade 4 in nine of them), and one patient died of treatment-related sepsis following the initial cycle of chemotherapy. Median survival was 11 months

Phase II Study of Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Patients with Squamous Cell Carcinoma of the Upper Respiratory or Alimentary Passages of the Head and Neck.

BACKGROUND: The chemotherapy drugs methotrexate, vinblastine, doxorubicin, and cisplatin have shown activity in patients with recurrent or metastatic squamous cell carcinoma arising from the upper respiratory or alimentary passages of the head and neck. This study was undertaken to assess the antitumor activity and toxicity profile of the drug combination methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in this patient population. METHODS: Patients with histologically confirmed unresectable, recurrent, or metastatic squamous cell carcinoma arising from the upper respiratory or alimentary passages of the head and neck were treated with MVAC over a 4-week cycle. The doses were as follows: 30 mg/m2 of methotrexate on Days 1, 15, and 22; 3 mg/m2 of vinblastine on Days 2, 15, and 22; 30 mg/m2 of doxorubicin on Day 2; and 70 mg/m2 of cisplatin on Day 2. The total cumulative dose of doxorubicin was not to exceed 450 mg/m2. Treatment was discontinued after four cycles for those whose disease remained stable. Patients were evaluated for chemotherapy response, progression free survival, and survival. RESULTS: Thirty-six patients were accrued onto this study between April 1993 and February 1996. One patient (3%) with a history of cardiac heart failure was declared ineligible. Severe leukopenia (leukocyte count \u3c 2000 cells/m3) was observed in 55% of the patients during the first cycle of treatment and in 81% of the patients during the entire course of their treatment. The overall objective response rate over the first 4 cycles of treatment was 46% (90% confidence interval [CI], 33-60%). Two of the 18 patients who responded had a complete response. The median time to progression was 19 weeks, and 1-year progression free survival rate was 17% (95% CI, 8-36%). The median survival was 49 weeks, and the 1-year survival rate was 43% (95% CI, 29-63%). Among the 22 patients with unresected residual or recurrent disease, the median time to progression was 11 weeks, and 1-year progression free survival rate was 14% (95% CI, 5-39%), and median survival was 24 weeks, and the 1-year survival rate was 36% (95% CI, 21-63%). Among the 13 patients with metastatic disease, the median time to progression was 26 weeks, and the 1-year progression free survival rate was 23% (95% CI, 9-62%), the median survival was 54 weeks, and the 1-year survival rate was 54% (95% CI, 33-89%). CONCLUSIONS: Methotrexate, vinblastine, doxorubicin, and cisplatin is an active chemotherapy regimen in patients with recurrent or metastatic squamous cell cancer arising from the upper respiratory or alimentary passages of the head and neck