Chemo-resistant gestational trophoblastic neoplasia: a review of cases at a tertiary cancer centre
Keywords:Chemoresistance, Chemotherapy, Gestational trophoblastic neoplasia
Background: Gestational trophoblastic neoplasia (GTN) was earlier a dreaded malignancy with high mortality rates. GTN is now considered to be one of the most curable solid tumours in women with cure rates greater than 90% even in the presence of metastases. Despite the high chemo sensitivity, treatment failure or drug resistance has been described in both groups.
Methods: In this study, available records of GTN cases over 6 years were reviewed with emphasis on those who were resistant to the first line of chemotherapy. Of these, 37(34.58%) were resistant to the first line of chemotherapy. These cases were studied with respect to age, parity, antecedent pregnancy, interval from antecedent pregnancy, pretreatment β hCG, risk score and presence of metastases. The data was analyzed in order to find any risk factors associated with chemo-resistance.
Results: Total number of cases of GTN was 107. Out of these 107 cases, 63 (58.88%) were low risk and 44 (41.12%) were high risk according to FIGO scoring system. Complete response was achieved with first line chemotherapy in 70 (65.42%) patients. The remaining 37 (34.57%) were resistant to first line chemotherapy. In the low risk group, 30 (47.62%) cases, and in the high-risk group, 7(15.91%) were resistant to first line of chemotherapy.
Conclusions: Despite the high chemo sensitivity of GTN, resistance to first line chemotherapy may be encountered in up to 40% of cases. It is important to identify the patients who are at risk to develop resistance, early identification of resistance and change of chemotherapy so as to minimize the exposure of these patients to ineffective chemotherapy.
LiM C, Hertz R, Spencer DB .Effect of methotrexate therapy upon choriocarcinoma and chorioadenoma. Proc Soc Exp Biol Med. 1956;93(2):361-6.
Schink JC, Lurain III JR. Gestational trophoblastic disease: molar pregnancy and gestational trophoblastic Neoplasia. InPrinciples and Practice of Gynecologic Oncology: Sixth Edition 2013. Wolters Kluwer Health pp. 886-908.
Alazzam M1, Tidy J, Osborne R, Coleman R, Hancock BW, Lawrie TA, Chemotherapy for resistant or recurrent gestational trophoblastic neoplasia. Cochrane Database Syst Rev. 2012;12:CD008891.
Hemida RA, Toson E, Shalaby H, Refaie E, Eldin DS. Chemo-resistant gestational trophoblastic neoplasia, 5-years’ experience of Mansoura University Hospital, Egypt. Open J Obstet Gynecol. 2011;1(03):153.
Kuyumcuoglu U, Guzel AI, Erdemoglu M, Celik Y. Risk factors for persistent gestational trophoblastic neoplasia. J Experiment Therapeut Oncol. 2011;9(1):81-4.
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 Clinic Oncol. 2011;29(7):825-31.
Mousavi AS, Zamani A, Khorasanizadeh F, Gilani MM, Zendehdel K. Resistance to single‐agent chemotherapy and its risk factors in low‐risk gestational trophoblastic neoplasms. J Obstet Gynaecol Res. 2015;41(5):776-83.
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 Brit J Cancer 2010;102(5):810-4.
El-Helw LM, Coleman RE, Everard JE, Tidy JA, Horsman JM, Elkhenini HF, et al. Impact of the revised FIGO/WHO system on the management of patients with gestational trophoblastic neoplasia. Gynecol Oncol 2009;113(3):306-11.
Lurain JR, Elfstrand EP. Single-agent methotrexate chemotherapy for the treatment of nonmetastatic gestational trophoblastic tumors. Am J Obstet Gynecol. 1995;172(2):574-9.
Matsui H, Suzuka K, Yamazawa K, Tanaka N, Mitsuhashi A, Seki K, et al. Relapse rate of patients with low-risk gestational trophoblastic tumor initially treated with single-agent chemotherapy. Gynecol Oncol. 2005;96(3):616-20.
Seckl MJ, Sebire NJ, Berkowitz RS. Gestational trophoblastic disease. The Lancet. 2010;376(9742):717-29.
Seckl MJ, Sebire NJ, Fisher RA, Golfier F, Massuger L, Sessa C, ESMO Guidelines Working Group. Gestational trophoblastic disease: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals Oncol. 2013;24(6):vi39-50.
McNeish IA, Strickland S, Holden L, Rustin GJ, Foskett M, Seckl MJ, Newlands ES. Low-risk persistent gestational trophoblastic disease: outcome after initial treatment with low-dose methotrexate and folinic acid from 1992 to 2000. J Clinic Oncol. 2002;20(7):1838-44.
Goldstein DP, Berkowitz RS. Current management of gestational trophoblastic neoplasia. Hematol Oncol Clinic North America 2012;26(1):111-31.
Siew-FeiNgu, Karen K. L. ChanManagement of Chemoresistant and Quiescent Gestational Trophoblastic Disease. Curr Obstet Gynecol Rep. 2014;3(1):84-90.
Newlands ES, Mulholand PJ, Holden L, et al. Etoposide and cisplatin/etoposide, methotrexate, and actinomycin D (EMA) chemotherapy for patients with high-risk gestational trophoblastic tumors refractory to EMA/cyclophosphamide and vincristine chemotherapy and patients presenting with metastatic placental site trophoblastic tumors. J Clin Oncol. 2000;18(4):854-859.
Wang J, Short D, Sebire NJ, Lindsay I, Newlands ES, Schmid P et al. Salvage chemotherapy of relapsed or high-risk gestational trophoblastic neoplasia (GTN) with paclitaxel/cisplatin alternating with paclitaxel/etoposide (TP/TE). Ann Oncol.2008;19(9):1578-83.
Lurain JR, Schink JC. Importance of salvage therapy in the management of high-risk gestational trophoblastic neoplasia. J Reprod Med. 2012;57(5-6):219-24.
Feng F, Xiang Y, Wan X, Geng S, Wang T. Salvage combination chemotherapy with floxuridine, dactinomycin, etoposide, and vincristine (FAEV) for patients with relapsed/chemoresistant gestational trophoblastic neoplasia. Ann Oncol. 2011;22(7):1588-94.