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

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.