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 2-6; Gynecologic Oncology Group (GOG) performance status 0-1; and previous treatment restricted to methotrexate. Dactinomycin administration was 1.25 mg/m2 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 >or=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.

CONCLUSION: Pulse dactinomycin is an active regimen for patients with low-risk GTN who fail previous methotrexate therapy.