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http://dx.doi.org/10.3802/jgo.2018.29.e89

Treatment results of the second-line chemotherapy regimen for patients with low-risk gestational trophoblastic neoplasia treated with 5-day methotrexate and 5-day etoposide  

Kanno, Toshiyuki (Department of Obstetrics and Gynecology, Tokyo Women's Medical University)
Matsui, Hideo (Department of Obstetrics and Gynecology, Tokyo Women's Medical University)
Akizawa, Yoshika (Department of Obstetrics and Gynecology, Tokyo Women's Medical University)
Usui, Hirokazu (Department of Reproductive Medicine, Chiba University Graduate School of Medicine)
Shozu, Makio (Department of Reproductive Medicine, Chiba University Graduate School of Medicine)
Publication Information
Journal of Gynecologic Oncology / v.29, no.6, 2018 , pp. 89.1-89.8 More about this Journal
Abstract
Objective: Highly effective chemotherapy for patients with low-risk gestational trophoblastic neoplasia (GTN) is associated with almost a 100% cure rate. However, 20%-30% of patients treated with chemotherapy need to change their regimens due to severe adverse events (SAEs) or drug resistance. We examined the treatment outcomes of second-line chemotherapy for patients with low-risk GTN. Methods: Between 1980 and 2015, 281 patients with low-risk GTN were treated. Of these 281 patients, 178 patients were primarily treated with 5-day intramuscular methotrexate (MTX; n=114) or 5-day drip infusion etoposide (ETP; n=64). We examined the remission rates, the drug change rates, and the outcomes of second-line chemotherapy. Results: The primary remission rates and drug resistant rates of 5-day ETP were significantly higher (p<0.001) and significantly lower (p=0.002) than those of 5-day MTX, respectively. Forty-seven patients (26.4%) required a change in their chemotherapy regimen due to the SAEs (n=16) and drug resistance (n=31), respectively. Of these 47 patients failed the first-line regimen, 39 patients (39/47, 82.9%) were re-treated with single-agent chemotherapy, and 35 patients (35/39, 89.7%) achieved remission. Four patients failed second-line, single-agent chemotherapy and eight patients (17.0%) who failed first-line regimens were treated with combined or multi-agent chemotherapy and achieved remission. Conclusions: Patients with low-risk GTN were usually treated with single-agent chemotherapy, while 20%-30% patients had to change their chemotherapy regimen due to SAEs or drug resistance. The second-line regimens of single-agent chemotherapy were effective; however, there were several patients who needed multiple agents and combined chemotherapy to achieve remission.
Keywords
Low-risk Gestational Trophoblastic Neoplasm; Drug Resistance; Chemotherapy;
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1 Matsui H, Seki K, Sekiya S, Takamizawa H. Reproductive status in GTD treated with etoposide. J Reprod Med 1997;42:104-10.
2 Kizaki S, Hashimoto K, Matsui H, Usui H, Shozu M. Comparison of 5-day MTX and 5-day ETP treatment results and early predictors of drug resistance to 5-day MTX in patients with post-molar low-risk gestational trophoblastic neoplasia. Gynecol Oncol 2015;139:429-32.   DOI
3 National Cancer Institute (US). Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [Internet]. Rockville, MD: National Cancer Institute; [2018 Jul 1]. Available from: http://ctep.cancer.gov/protocolDevelopment/electric_applications/ctc.htm#ctc_40.
4 Matsui H, Suzuka K, Iitsuka Y, Seki K, Sekiya S. Combination chemotherapy with methotrexate, etoposide, and actinomycin D for high-risk gestational trophoblastic tumors. Gynecol Oncol 2000;78:28-31.   DOI
5 Seckl MJ, Sebire NJ, Berkowitz RS. Gestational trophoblastic disease. Lancet 2010;376:717-29.   DOI
6 Aghajanian C. Treatment of low-risk gestational trophoblastic neoplasia. J Clin Oncol 2011;29:786-8.   DOI
7 Foulmann K, Guastalla JP, Caminet N, Trillet-Lenoir V, Raudrant D, Golfier F, et al. What is the best protocol of single-agent methotrexate chemotherapy in nonmetastatic or low-risk metastatic gestational trophoblastic tumors? A review of the evidence. Gynecol Oncol 2006;102:103-10.   DOI
8 Soper JT, Clarke-Pearson DL, Berchuck A, Rodriguez G, Hammond CB. 5-day methotrexate for women with metastatic gestational trophoblastic disease. Gynecol Oncol 1994;54:76-9.   DOI
9 McGrath S, Short D, Harvey R, Schmid P, Savage PM, Seckl MJ. The management and outcome of women with post-hydatidiform mole 'low-risk' gestational trophoblastic neoplasia, but hCG levels in excess of 100 000 IU l-1. Br J Cancer 2010;102:810-4.   DOI
10 McNeish IA, Strickland S, Holden L, Rustin GJ, Foskett M, Seckl MJ, et al. Low-risk persistent gestational trophoblastic disease: outcome after initial treatment with low-dose methotrexate and folinic acid from 1992 to 2000. J Clin Oncol 2002;20:1838-44.   DOI
11 Osborne RJ, Filiaci V, Schink JC, Mannel RS, Alvarez Secord A, Kelley JL, et al. Phase III trial of weekly methotrexate or pulsed dactinomycin for low-risk gestational trophoblastic neoplasia: a gynecologic oncology group study. J Clin Oncol 2011;29:825-31.   DOI
12 Chapman-Davis E, Hoekstra AV, Rademaker AW, Schink JC, Lurain JR. Treatment of nonmetastatic and metastatic low-risk gestational trophoblastic neoplasia: factors associated with resistance to single-agent methotrexate chemotherapy. Gynecol Oncol 2012;125:572-5.   DOI
13 Matsui H, Iitsuka Y, Seki K, Sekiya S. Comparison of chemotherapies with methotrexate, VP-16 and actinomycin-D in low-risk gestational trophoblastic disease. Remission rates and drug toxicities. Gynecol Obstet Invest 1998;46:5-8.   DOI
14 Maesta I, Growdon WB, Goldstein DP, Bernstein MR, Horowitz NS, Rudge MV, et al. Prognostic factors associated with time to hCG remission in patients with low-risk postmolar gestational trophoblastic neoplasia. Gynecol Oncol 2013;130:312-6.   DOI
15 Savage P, Cooke R, O'Nions J, Krell J, Kwan A, Camarata M, et al. Effects of single-agent and combination chemotherapy for gestational trophoblastic tumors on risks of second malignancy and early menopause. J Clin Oncol 2015;33:472-8.
16 Newlands ES, Bagshawe KD. Anti-tumour activity of the epipodophyllin derivative VP16-213 (etoposide: NSC-141540) in gestational choriocarcinoma. Eur J Cancer 1980;16:401-5.   DOI
17 Rustin GJ, Newlands ES, Lutz JM, Holden L, Bagshawe KD, Hiscox JG, et al. Combination but not single-agent methotrexate chemotherapy for gestational trophoblastic tumors increases the incidence of second tumors. J Clin Oncol 1996;14:2769-73.   DOI
18 Pedersen-Bjergaard J, Daugaard G, Hansen SW, Philip P, Larsen SO, Rorth M. Increased risk of myelodysplasia and leukaemia after etoposide, cisplatin, and bleomycin for germ-cell tumours. Lancet 1991;338:359-63.   DOI