Treatment of nonmetastatic and metastatic low-risk gestational trophoblastic neoplasia: Factors associated with resistance to single-agent methotrexate chemotherapy

Objective: To determine factors associated with resistance to methotrexate treatment of low-risk gestational trophoblastic neoplasia (GTN). Methods: We reviewed the records of 358 patients with low-risk GTN (FIGO stage I and stages II-III, score < 7) treated initially with methotrexate 0.4 mg/kg (max 25 mg) IV push daily × 5 days every 14 days between 1979 and 2009. Actinomycin D 0.5 mg IV push daily × 5 days every 14 days was used in 64 patients who developed resistance or toxicity to initial methotrexate chemotherapy, and combination drug regimens were used in 20 patients who failed single-agent chemotherapy. Adjuvant surgery was used in 34 selected patients. Clinical response and survival as well as factors affecting outcomes were analyzed retrospectively. Results: The complete response rate to initial methotrexate chemotherapy was 81% (290/358) and the complete response rate to actinomycin D as secondary therapy was 75% (48/64), for an overall complete response rate to sequential single-agent chemotherapy of 94% (338/358). The remaining 20 patients (6%) were all placed into permanent remission with the use of multiagent chemotherapy with or without surgery. Resistance to initial methotrexate chemotherapy was associated with increasing FIGO score (p <.0001), clinicopathologic diagnosis of choriocarcinoma (p =.028), higher pretreatment hCG (p = 0.001) and presence of metastatic, disease (p =.018). Conclusions: Sequential single-agent chemotherapy with methotrexate (0.4 mg/kg-max 25 mg) followed by actinomycin D (0.5 mg) each given IV push for 5 consecutive days every other week for treatment of low-risk GTN resulted in only 6% of patients requiring multiagent chemotherapy and a 100% survival rate.