Can carboplatin or etoposide replace actinomycin-D for second-line treatment of methotrexate resistant low-risk gestational trophoblastic neoplasia?

Objective. To evaluate the impact of periodic shortage of actinomycin-D (Act-D) in the treatment of Brazilian patients with low-risk gestational trophoblastic neoplasia (GTN) after methotrexate and folinic acid rescue (MTX/FA) resistance, treated alternately with carboplatin or etoposide as a second-line regimen. Methods. Retrospective cohort that included patients with failure of first-line MTX/FA regimen for low-risk GTN treated at Rio de Janeiro Federal University, Universidade Federal de Sao Paulo and Irmandade da Santa Casa de Misericordia de Porto Alegre, from January/2010- December/2017. Results. From 356 patients with low-risk GTN treated with MTX/FA, 75 (21.1%) developed resistance, of which 40 (53.3%) received Act-D, 23 (30.7%) carboplatin and 7 (9.3%) etoposide. Although patients treated with single-agent chemotherapy as a second-line regimen had comparable clinical and primary treatment characteristics, those treated with Act-D (80%, p = 0.033) or etoposide (71.4%, p = 0.025) had higher remission rates when compared with carboplatin (47.8%). Only 29% of patients treated with carboplatin received the chemotherapy cycles without delay compared to Act-D (98%, p < 0.001) or etoposide (85%, p = 0.009). Patients treated with carboplatin had significantly more hematological toxicity, notably anemia (30.4%, p = 0.008), lymphopenia (47.7%, p < 0.001) and thrombocytopenia (43.4%, p < 0.001), as well as a higher occurrence of febrile neutropenia (14.4%, p = 0.044) and vomiting (60%, p < 0.001) than those receiving Act-o (5%, none, 2.5%, none, 10%, respectively). Conclusion. Carboplatin did not have a satisfactory clinical response rate, likely due to severe hematological toxicity, which postponed chemotherapy. Our results reinforce the preference for Act-o as a second-line agent in patients with low-risk GTN after MTX/FA resistance. (C) 2019 Elsevier Inc. All rights reserved.