OBJECTIVE: Our purpose was to evaluate the efficacy and toxicity of single-agent methotrexate chemotherapy and to identify factors associated with chemotherapy resistance in patients with nonmetastatic gestational trophoblastic tumors.

STUDY DESIGN: A total of 337 patients with nonmetastatic gestational trophoblastic tumors (choriocarcinoma and invasive model) received treatment at the Brewer Trophoblastic Disease Center of Northwestern University Medical School form 1962 through 1990. Of the 337 patients, 253 (75.0%) were treated initially with single-agent methotrexate .4 mg/kg intravenously daily for 5 days per treatment course repeated every 14 days.

RESULTS: All 337 patients with nonmetastatic gestational trophoblastic tumors were cured. Of the 253 patients initially treated with methotrexate, resistance developed in 27 (10.7%), 22 (8.7%) required a second agent (actinomycin D), 3 (1.2%) required multiagent chemotherapy, and 2 (0.8%) had a hysterectomy to achieve complete remission. Factors associated with the development of resistance were pretreatment human chorionic gonadotropin level ≥50,000 mlU/ml (36%, p < 0.001), nonmolar antecedent pregnancy (26%, p < 0.02), and clinicopathologic diagnosis of choriocarcinoma (20.5%, p = 0.02). Significant methotrexate toxicity requiring a change to a second agent occurred in only 12 patients (4.7%), the most common side effect being severe stomatitis.

CONCLUSIONS: In a large series of patients with nonmetastatic gestational trophoblastic disease, single-agent methotrexate chemotherapy proved to be an extremely well-tolerated and effective treatment.