Role of salvage therapy in chemo resistant or recurrent high-risk gestational trophoblastic neoplasm

Abstract

ObjectivesTo assess the importance of salvage therapy in the management of high-risk gestational trophoblastic neoplasia (HR GTN) after failure of first line multiagent chemotherapy.MethodsThis retrospective study involving women with HR GTN treated at Kidwai cancer institute from 2000 to 2015. Initial chemotherapy consisted of etoposide, methotrexate with folinic acid, actinomycin D, cyclophosphamide and vincristine (EMA-CO). Thirty one patients who had incomplete response or relapsed were treated with various drug combinations employing etoposide and platinum agents. Adjuvant surgery and radiation were used in selected patients. Clinical response, survival and factors affecting outcomes were analysed.ResultsThirty one (37.8%) of the 82 patients developed resistance or relapsed after EMA-CO.Of these 25 (80.6%) had lasting complete response to salvage therapy. Salvage chemotherapy included, EMA EP alone in-15, EMA EP followed with BIP in-1, EMAEP followed with VAC in-2, EMA EP followed by TC and VAC in-1, EMA EP followed by TC in-6, TC followed by IA in-1 patient. Irradiation was given to 6 patients for brain metastasis, 1 for spine metastasis, 1 for pelvic tumor, and 1 for mediastinal mass. Operative procedures were hysterectomy in 9, conservative uterine tumour resection in 4 and excision of resistant lung lesion in one. Median follow up 25 (80.6%) patients was 2 years. Complete response to salvage therapy was seen in 25 (80.6%) patients. Overall survival after salvage therapy was 87.1% with median follow up of 2 years. Remission and survival was significantly influenced by βhCG level at the start of salvage therapy (p<0.001 and 0.006) but not with the stage or with WHO score.ConclusionsSalvage therapy with platinum/etoposide based drug regimens in conjunction with surgery and radiation, was successful in achieving significant cure and survival in HR-GTN patients.

Gestational Trophoblastic Neoplasia, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology

“…97,98 The rate of complete response/remission with EMA/EP for disease resistant to EMA/CO has been reported between 75% and 85%. 63,[97][98][99][100] Additional drug combinations containing etoposide and a platinum agent have been effective in patients who have developed disease resistant to methotrexatecontaining regimens. These include TP/TE (paclitaxel and cisplatin alternating weekly with paclitaxel and etoposide), BEP (bleomycin, etoposide, and cisplatin), VIP (etoposide, ifosfamide, and cisplatin), and ICE (ifosfamide, carboplatin, and etoposide).…”

“…These include TP/TE (paclitaxel and cisplatin alternating weekly with paclitaxel and etoposide), BEP (bleomycin, etoposide, and cisplatin), VIP (etoposide, ifosfamide, and cisplatin), and ICE (ifosfamide, carboplatin, and etoposide). 46,96,99,101,102 Additionally, TIP (paclitaxel, ifosfamide, and cisplatin) has been used as a salvage chemotherapy regimen in germ cell tumors, including those with choriocarcinoma components. [103][104][105][106] These etoposide-platinum containing regimens require the use of granulocyte colony-stimulating factor support to prevent neutropenic complications and treatment delays.…”

Identification of the targeted mRNA associated with the miRNA microarray of chemo-sensitive choriocarcinoma using bioinformatics analysis

“…With the effective utilization of chemotherapy, choriocarcinoma (CC) has become a curable human malignancy. However, 30-40% of high-risk or ultra-high-risk CC patients will develop to chemoresistance after initial remission and require treatment with salvage chemotherapy (2,23). Therefore, an increased understanding of the molecular and functional mechanisms of CC development and identi cation of novel biomarkers are needed.…”

Risk Factors That Correlate with Resistance to First-Line Chemotherapy on High-risk Gestational Trophoblastic Neoplasia

“…GTN incidence in developed countries is approximated to be one case per 40,000 pregnancies; meanwhile, in Indonesia, precisely in Hasan Sadikin General Hospital, as many as 730 cases are reported per year [2], [3]. GTN is generally highly sensitive to chemotherapy with a high cure rate of up to 90−100% [2], [4], [5]. Chemotherapy options depend on the risk classification according to the International Federation of Gynecology and Obstetrics (FIGO) prognosis scoring system.…”

“…Etoposide, Methotrexate, Actinomycin-D, Cyclophosphamide, and Vincristine (EMA-CO) are the first-line chemotherapy regimens for high-risk GTN, with a remission rate of 90.6% [2], [6], [7]. In addition to EMA-CO, EMA-EP (Etoposide, Methotrexate, Actinomycin-D, Etoposide, and Cisplatin) is also reported as a second-line chemotherapy regimen with a remission rate of up to 82% [4]. A retrospective study in Korea examined the efficacy of multiagent chemotherapy regimens in 227 high-risk GTN patients.…”