Phase II trial of pulse dactinomycin as salvage therapy for failed low-risk gestational trophoblastic neoplasia - A Gynecologic Oncology Group study

BACKGROUND. The purpose of the study was to determine the activity and toxicity of pulse dactinomycin as salvage treatment of patients with low-risk gestational trophoblastic neoplasia (GTN) who failed methotrexate therapy. METHODS. Eligible patients had persistent/recurrent low-risk GTN defined by changes in serum human chorionic gonadotropin (hCG) levels (< 10% fall over 3 consecutive weekly titers, > 20% rise over the previous value, or a rise after attaining institutional normal [> 5 mu/mL]); World Health Organization (WHO) score 26; Gynecologic Oncology Group (GOG) performance status 0-1; and previous treatment restricted to methotrexate. Dactinomycin administration was 1.25 mg/m(2) intravenous (i.v.) every 2 weeks until documented complete response (CR) or treatment failure. CR was defined as an institutional normal serum hCG level sustained for >= 4 consecutive weeks; treatment failure was a < 10% fall (3 assays over 4 weeks) or > 20% rise (over previous value) in hCG serum level. Levels were monitored biweekly x 8 weeks beyond the first normal value, then monthly x 10. RESULTS. Five of 44 enrolled patients were ineligible due to choriocarcinoma and normal pretreatment serum hCG level (2 each), no history of methotrexate (1), and 1 patient with documented phantom hCG syndrome was unevaluable. In all, 28 of 38 (74%) evaluable patients attained CR. The median number of cycles was 4 (range, 2-10). Severe toxicity was minimal, causing no patient to discontinue therapy. All treatment failures achieved a CR after receiving subsequent chemotherapy; 3 patients also underwent hysterectomy. CONCLUSIONS. Pulse dactinomycin is an active regimen for patients with low-risk GTN who fail previous methotrexate therapy.