Differences in Administration of Methotrexate and Impact on Outcome in Low-Risk Gestational Trophoblastic Neoplasia.

Abstract

Simple SummaryLow-risk gestational trophoblastic neoplasia is a rare but highly curable malignancy. The most common first line treatment is methotrexate, which can be administered in different forms. In order to investigate the impact of route of administration on methotrexate resistance, toxicity demanding treatment switch, complete remission and relapse, we performed an observational study including women with low-risk gestational trophoblastic neoplasia in a population-based setting in Sweden and Denmark. We found that oral compared to intra-muscular administration of methotrexate gives a higher rate of drug resistance, but does not affect rates of complete remission, recurrence or overall survival. Intra-muscular treatment was associated with more toxicity leading to switch of treatment. We conclude that, although a larger proportion of women develop drug resistance, oral methotrexate, which is easy to administer and highly tolerable, could be an option for well-informed and motivated women.Methotrexate (MTX) is frequently used as first-line treatment for low-risk gestational trophoblastic neoplasia (GTN). Intravenous and intramuscular (im) routes of administration are the most common methods, although oral administration is used by some Scandinavian centers. The primary aim of this study was to assess the impact of form of administration (im/oral) on resistance to methotrexate (MTX-R) treatment in low-risk GTN. Secondary aims were time to hCG normalization, rates of toxicity-induced treatment switch, and rates of complete remission and recurrence. In total, 170 women treated at Karolinska University Hospital in Sweden and Aarhus University Hospital in Denmark between 1994 and 2018 were included, of whom 107 were given im and 63 oral MTX. MTX-R developed in 35% and 54% in the im and oral groups, respectively (p = 0.01). There was no difference in days to hCG normalization (42 vs. 41 days, p = 0.50) for MTX-sensitive women. Toxicity-induced treatment switch was only seen in the im group. Complete remission was obtained in 99.1% and 100% (p = 0.44), and recurrence rate within one year was 2.8% and 1.6% (p = 0.29). The form of administration of MTX had a significant impact on development of MTX-R and treatment-associated toxicity, but does not affect rates of complete remission, recurrence or survival.