Rapid escalation of weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease: a Gynecologic Oncology Group study.

Patients with postmolar nonmetastatic gestational trophoblastic disease were entered into this Gynecologic Oncology Group study to determine the relationship of efficacy and toxicity to a rapidly escalating dose of weekly intramuscular methotrexate. The treatment was initiated at 40 mg/m2 weekly of intramuscular methotrexate. If no major toxicity was encountered, the weekly dose was escalated 5 mg/m2 at 2-week intervals until a maximum dose of 50 mg/m2 per week was achieved. Complete response was defined as three normal beta-hCG values measured on consecutive weeks. Forty-six of sixty-two (74%) evaluable patients had a complete response to this regimen. Duration of therapy ranged from 3 to 16 weeks with a median of 7 weeks. No major toxicity occurred. Eight patients experienced leukopenia at a median of 3200/microliters (range 2100-3900). Two patients had platelet nadirs of 128,500 and 131,000. Only 50% (8/16) of the nonresponders subsequently responded to second-line 5-day methotrexate every 2 weeks. Fifteen of the sixteen weekly intramuscular methotrexate failures ultimately had complete responses after treatment with subsequent chemotherapy. In this study, second-line therapy results support administration of another agent such as dactinomycin rather than 5-day methotrexate. This higher dose (1.36 relative dose intensity to median complete response) of weekly intramuscular methotrexate therapy (40 mg/m2) is no more effective and of similar toxicity to a lower-dose regimen (30 mg/m2) reported earlier.