What is the best protocol of single-agent methotrexate chemotherapy in nonmetastatic or low-risk metastatic gestational trophoblastic tumors? A review of the evidence.

OBJECTIVE: Gestational trophoblastic diseases (GTD), a group of rare placenta disorders, have a varying potential for invasion, either local, or remote under the form of metastases, and are definitely cured by chemotherapy in 85 to 99% of cases. Single-agent methotrexate is the usual primary treatment for women with low-risk trophoblastic tumors (TT), yet various regimens are currently used worldwide. We reviewed these regimens and the available evidence for evaluating their respective efficacy and tolerance.

METHODS: We performed an exhaustive literature search and applied the French agency for evaluation in healthcare (HAS) methodology for critical appraisal and level of evidence. We summarised the protocols used in the selected studies and their respective results regarding efficacy and toxicity.

RESULTS: We selected 18 original studies on the efficacy and tolerance of methotrexate used alone or in association with folinic acid for the treatment of nonmetastatic or low-risk metastatic trophoblastic tumors. Among these 18 studies, 15 were retrospective series, 3 were prospective series without any control group, and none were controlled clinical trial. We identified four main chemotherapy regimens and two very different strategies for repeating the treatment courses. It was not possible to perform a meta-analysis due to the lack of controlled clinical trials. Because all studies were observational with no control group and methods were heterogeneous for scoring women, setting criteria for starting therapy, defining remission, and collecting information on adverse events, we found no objective element allowing recommending one protocol rather than another.

CONCLUSION: Objective comparison should be addressed in the scope of comparative trials organised at the national or even international level. However their feasibility is highly problematic for rare diseases such as GTD. International collaborative works should be encouraged to reduce practice variations and allow a better comparability between strategies.