Actinomycin D for methotrexate-failed low-risk gestational trophoblastic neoplasia

OBJECTIVE: To determine outcomes and factors associated with failure of 5-day actinomycin D for treatment of methotrexate-failed low-risk gestational trophoblastic neoplasia (GTN). STUDY DESIGN: We reviewed the records of 358 patients treated with methotrexate 0.4 mg/kg (max 25 mg) IV push q.d. × 5 d every 14 d for FIGO-defined, lowrisk GTN between 1979 and 2009. Actinomycin D 0.5 mg IV push q.d. × 5 d every 14 d was given to 64 of 68 patients (18%) who failed methotrexate: 48 (75%) for resistance and 16 (25%) for toxicity. Adjuvant surgery was used in selected patients. Clinical response and survival as well as factors affecting outcomes were analyzed retrospectively. RESULTS: The complete response rate to secondary chemotherapy with actinomycin D for failed methotrexate treatment of low-risk GTN was 75% (48/64), including 71% (34/48) for methotrexate resistance and 88% (14/16) for methotrexate toxicity. All 20 patients (6%) who failed sequential single-agent chemotherapy with methotrexate and actinomycin D were placed into permanent remission with the use of multiagent chemotherapy with or without surgery. The only factor significantly associated with resistance to secondary actinomycin D chemotherapy was clinicopathologic diagnosis of choriocarcinoma versus postmolar GTN (56% versus 20%, p=0.025). CONCLUSION: Actinomycin D 0.5 mg IV q.d. × 5 d every 14 d used as secondary therapy in methotrexatefailed low-risk GTN resulted in a 75% complete response rate and eventual 100% cure with subsequent multiagent chemotherapy with or without surgery. Resistance to sequential methotrexate and actinomycin D chemotherapy was significantly associated with original FIGO score ≥ 3 and clinicopathologic diagnosis of choriocarcinoma.