Agronomy

The management of uterine sarcomas continues to present many difficulties. Primary surgery is the optimal treatment but the role of post-operative radiation remains uncertain. In the mid-1980s, the European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study proposed a trial to evaluate adjuvant radiotherapy, as previous non-randomised studies had suggested a survival advantage and improved local control when post-operative radiation was administered. The study opened in 1987 taking 13 years to accrue 224 patients. All uterine sarcoma subtypes were permitted. Patients were required to have undergone as a minimum, TAH and BSO and wahsings (166 patients) but nodal sampling was optional. There were 103 leiomyosarcomas (LMS), 91 carcinosarcomas (CS) and 28 endometrial stromal sarcomas (ESS). Patients were randomised to either observation or pelvic radiation, 51 Gy in 28 fractions over 5 weeks. Hundred and twelve were recruited to each arm. The initial analysis has shown a reduction in local relapse (14 versus 24, p = 0.004) but no effect on either OS or PFS. No unexpected toxicity was seen in the radiation arm. No difference in either overall or disease-free survival was demonstrated but there is an increased local control for the CS patients receiving radiation but without any benefit for LMS. Prognostic factor analysis shows that stage, age and histological subtype were important predictors of behaviour which may explain differences between CS and LMS. CS appears to show more kinship to poorly differentiated endometrial carcinomas in behaviour. LMS did not show the same benefit from radiation. These results will help shape future management and clinical trials in uterine sarcomas.

BACKGROUNDThe objective of this study was to evaluate the activity and toxicity of temozolomide given as an extended schedule in patients with advanced sarcoma.The objective of this study was to evaluate the activity and toxicity of temozolomide given as an extended schedule in patients with advanced sarcoma.METHODSForty-nine patients with pretreated soft tissue sarcoma (the STS arm) and 18 patients with previously untreated gastrointestinal stromal tumor (the GIST arm) were enrolled onto a 2-arm, multicenter, Phase II study between November 1999 and July 2001. Temozolomide was administered on a 6-week, continuous, oral schedule at a dose of 75 mg/m2 per day in 41 patients and, after an amendment, at a dose of 100 mg/m2 per day in 22 patients.Forty-nine patients with pretreated soft tissue sarcoma (the STS arm) and 18 patients with previously untreated gastrointestinal stromal tumor (the GIST arm) were enrolled onto a 2-arm, multicenter, Phase II study between November 1999 and July 2001. Temozolomide was administered on a 6-week, continuous, oral schedule at a dose of 75 mg/m2 per day in 41 patients and, after an amendment, at a dose of 100 mg/m2 per day in 22 patients.RESULTSAmong 45 eligible patients in the STS arm, there were 7 partial responses, for an overall response rate of 15.5% (95% confidence interval [95% CI], 5–26%). Responses were seen in 5 of 11 patients who had gynecologic leiomyosarcoma. The median response duration was 12.5 months (range, 3.9–58.0 mos). In 4 patients, response lasted > 1 year, and 2 of those patients remained progression free for > 3 years. The median time to progression was 2.2 months (95% CI, 1.8–2.5 mos), and the median overall survival was 8.1 months (95% CI, 5.6–10.6 mos). Progression-free survival rates at 3 months and 6 months were 39.5% and 26%, respectively. In the GIST arm, no responses were noted. Grade 3–4 granulocytopenia, thrombocytopenia, and anemia were observed in 6 patients, 5 patients, and 7 patients, respectively. The most common nonhematologic toxicities were emesis and fatigue.Among 45 eligible patients in the STS arm, there were 7 partial responses, for an overall response rate of 15.5% (95% confidence interval [95% CI], 5–26%). Responses were seen in 5 of 11 patients who had gynecologic leiomyosarcoma. The median response duration was 12.5 months (range, 3.9–58.0 mos). In 4 patients, response lasted > 1 year, and 2 of those patients remained progression free for > 3 years. The median time to progression was 2.2 months (95% CI, 1.8–2.5 mos), and the median overall survival was 8.1 months (95% CI, 5.6–10.6 mos). Progression-free survival rates at 3 months and 6 months were 39.5% and 26%, respectively. In the GIST arm, no responses were noted. Grade 3–4 granulocytopenia, thrombocytopenia, and anemia were observed in 6 patients, 5 patients, and 7 patients, respectively. The most common nonhematologic toxicities were emesis and fatigue.CONCLUSIONSTemozolomide at the extended schedule was tolerated well and had activity in patients with pretreated soft tissue sarcomas, and especially among patients with gynecologic leiomyosarcoma. Cancer 2005. © 2005 American Cancer Society.Temozolomide at the extended schedule was tolerated well and had activity in patients with pretreated soft tissue sarcomas, and especially among patients with gynecologic leiomyosarcoma. Cancer 2005. © 2005 American Cancer Society.