A phase II trial of temozolomide in patients with unresectable or metastatic soft tissue sarcoma.
BACKGROUND
The objective of this study was to assess the efficacy and toxicity of the imidazotetrazine derivative temozolomide for patients with unresectable or metastatic soft tissue sarcoma.


METHODS
Twenty-five of 26 patients were eligible and assessable for toxicity and response. Temozolomide was administered twice daily on a 12-hour schedule for 5 days as an oral bolus dose of 200 mg/m(2) followed by 9 doses of 90 mg/m(2) every 4 weeks.


RESULTS
There were 2 partial responses, 2 mixed responses, and 3 patients with stable disease that lasted > 6 months, for an overall objective response rate of 8%. At a median follow-up of 13.2 months, the median progression-free survival and the median overall survival were 2.0 months (95% confidence interval [95% CI], 1.7-2.3) and 13.2 months (95% CI, 4.7-31.1), respectively. All responding patients had leiomyosarcoma of uterine or nonuterine origin; and, in a subset analysis of these patients, the objective response rate was 18% (2 of 11 patients), with disease stabilization occurring in 3 of 11 patients (27%). For this subgroup, at a median follow-up of 24.4 months, the median progression-free survival and the median overall survival were 3.9 months (95% CI, 1.9-21.9) and 30.8 months (lower-bound 95% CI, 7.8), respectively. There were no treatment-related deaths or National Cancer Institute Grade 4 toxicities. Grade 3 toxicities included nausea, anemia, fatigue, elevated alkaline phosphatase levels and nonneutropenic fever (1 patient each).


CONCLUSIONS
Temozolomide at the dose schedule employed in the current study was tolerated well and had modest activity against previously treated unresectable or metastatic leiomyosarcoma of both uterine and nonuterine origin.
Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
Susan M
SM
Talbot
Mary Louise
ML
Keohan
Mary
M
Hesdorffer
Russell
R
Orrico
Emilia
E
Bagiella
Andrea B
AB
Troxel
Robert N
RN
Taub
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007890:Leiomyosarcoma / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012509:Sarcoma / Q000188:drug therapy* / Q000556:secondary; D000077204:Temozolomide; D016896:Treatment Outcome; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000556:secondary
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide