Trimetrexate in the treatment of recurrent or advanced leiomyosarcoma of the uterus: a phase II study of the Gynecologic Oncology Group.

OBJECTIVE

This study was conducted to determine the objective response of trimetrexate in patients with advanced or recurrent leiomyosarcoma of the uterus.

METHODS

Eligibility was restricted to patients with measurable disease who had received no more than one prior chemotherapy regimen, who had adequate bone marrow, renal, and hepatic function, and who had recovered from previous therapy. Trimetrexate was begun at 5 mg/m2/day orally for 5 days every other week, with dose modifications specified by study design.

RESULTS

Of 28 patients entered into the study, 27 were evaluable for toxicity and 23 for response. Prior therapy included radiation (7 patients) and/or chemotherapy (10 patients). Measurable disease was extrapelvic in 20 cases and confined to the pelvis in 3. The overall response rate was 4.3%; there were no complete responses and 1 partial response. Toxicities were mild to moderate with no treatment-related deaths. Hematological toxicity was most common, consisting of leukopenia (grade 1 to 2, 8 patients; grade 3 or 4, 2 patients), thrombocytopenia (grade 1 to 2, 10 patients; grade 3 or 4, 1 patient), and anemia (grade 1 to 2, 6 patients; grade 3 or 4, 4 patients. Severe (grade 3 or 4) nonhematologic toxicity was uncommon: nausea/vomiting/gastrointestinal (3 patients) and neurological (1 patient). Progression-free and overall survival, in months, was 2.2 (range: 0.9-13.4) and 7.2+ (range: 1.0-13.4+), respectively.

CONCLUSIONS

Although toxicity is acceptable, trimetrexate at this dose and schedule is ineffective therapy for patients with recurrent leiomyosarcoma. Further development of this specific regimen for this indication is unwarranted.