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

Autor: Mora PAR; Rio de Janeiro Trophoblastic Disease Center, Maternity School of Rio de Janeiro Federal University, Antonio Pedro University Hospital, Fluminense Federal University, Rio de Janeiro, RJ, Brazil; Postgraduate Program in Medical Sciences, Fluminense Federal University, Niterói, RJ, Brazil; Brazilian National Cancer, Hospital do Câncer 2, Rio de Janeiro, RJ, Brazil., Sun SY; São Paulo Hospital Trophoblastic Disease Center, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil., Velarde GC; Postgraduate Program in Medical Sciences, Fluminense Federal University, Niterói, RJ, Brazil., Filho JR; Rio de Janeiro Trophoblastic Disease Center, Maternity School of Rio de Janeiro Federal University, Antonio Pedro University Hospital, Fluminense Federal University, Rio de Janeiro, RJ, Brazil; Postgraduate Program in Perinatal Health, Faculty of Medicine, Maternity School of Rio de Janeiro Federal University, Rio de Janeiro, RJ, Brazil., Uberti EH; Porto Alegre Trophoblastic Disease Center, Mario Totta Maternity Ward, Irmandade da Santa Casa de Misericórdia Hospital, Porto Alegre, RS, Brazil., Dos Santos Esteves APV; Rio de Janeiro Trophoblastic Disease Center, Maternity School of Rio de Janeiro Federal University, Antonio Pedro University Hospital, Fluminense Federal University, Rio de Janeiro, RJ, Brazil; Postgraduate Program in Perinatal Health, Faculty of Medicine, Maternity School of Rio de Janeiro Federal University, Rio de Janeiro, RJ, Brazil., Elias KM; New England Trophoblastic Disease Center, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Horowitz NS; New England Trophoblastic Disease Center, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Braga A; Rio de Janeiro Trophoblastic Disease Center, Maternity School of Rio de Janeiro Federal University, Antonio Pedro University Hospital, Fluminense Federal University, Rio de Janeiro, RJ, Brazil; Postgraduate Program in Medical Sciences, Fluminense Federal University, Niterói, RJ, Brazil; Postgraduate Program in Perinatal Health, Faculty of Medicine, Maternity School of Rio de Janeiro Federal University, Rio de Janeiro, RJ, Brazil. Electronic address: antonio.braga@ufrj.br., Berkowitz RS; New England Trophoblastic Disease Center, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Jazyk: angličtina
Zdroj: Gynecologic oncology [Gynecol Oncol] 2019 May; Vol. 153 (2), pp. 277-285. Date of Electronic Publication: 2019 Mar 08.
DOI: 10.1016/j.ygyno.2019.03.005
Abstrakt: 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 São Paulo and Irmandade da Santa Casa de Misericórdia 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-d (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-d as a second-line agent in patients with low-risk GTN after MTX/FA resistance.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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