A phase II trial of temozolomide as a 6-week, continuous, oral schedule in patients with advanced soft tissue sarcoma: a study by the Spanish Group for Research on Sarcomas.
BACKGROUND
The objective of this study was to evaluate the activity and toxicity of temozolomide given as an extended schedule in patients with advanced sarcoma.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Garcia del Muro
Xavier
X
Department of Medical Oncology, Institut Catala d'Oncologia, Institut d'Investigacio Bellvitge (IDIBELL), Barcelona, Spain. garciadelmuro@iconcologia.net
Lopez-Pousa
Antonio
A
Martin
Javier
J
Buesa
Jose M
JM
Martinez-Trufero
Javier
J
Casado
Antonio
A
Poveda
Andres
A
Cruz
Josefina
J
Bover
Isabel
I
Maurel
Joan
J
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011379:Prognosis; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D000077204:Temozolomide; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide