Meta-analysis Of Initial Chemotherapy For Low-risk Gestational Trophoblastic Neoplasia

Background:Gestational trophoblastic neoplasia (GTN) is the malignant tumor formed by abnormal proliferated embryonic trophoblast cells. The cure rate of chemotherapy is 100% in low-risk gestational trophoblastic neoplasia,and 86% in high-risk gestational trophoblastic neoplasia. A large number of regimens are used worldwide in the therapy of GTN. Regimens have significant differences in the route of administration and side effects and so have a bearing on the efficacy and safety.Objective:To determine the efficacy and safety of first line chemotherapy in the treatment of low risk GTN.Materials and Methods:1. Search strategy:we searched Pubmed, Medline, Science Direct, CINK, CBM and relevant references.2.Selection criteria:Trials was included if they were randomized or clinical controlled trials of initial chemotherapy for low-risk gestational trophoblastic neoplasia. Languages was restricted to Chinese and English.Retrieval time is limited since January,1990 to March,2010.3.Data collection and analysis:Data extracted and quality assessment was performed by author independently.All the calculations and statistical tests were done with RevMan 4.2 software.4. The outcome measures:(1) Efficacy of initial chemotherapy (complete remission,drug resistance,change chemotherapy due to resistance or toxicity, and relapse after remission). (2) Toxicity due to chemotherapy (toxicity grades will be reported as illustrated below). Grade 4 toxicity was chiefly mucositis and liver function deterioration in this review.Results:1.4 RCT and 4 CCT were indentified and included in this review.There are 989 patients and 7 chemotherapy regimens (5d-MTX,5d-ACT,w-MTX,p-ACT,MTX-CF, MACT,VP-16) in all these 7 studies.2.Quality of included studies:four randomized controlled studies were considered as high-quality studies; three clinical controlled studies were not described the grouping in detail and the use of blinding.3.Effect of the intervention(1) 5d-MTX versus 5d-ACT regimen:There was no significant difference in complete remission, failure of the initial chemotherapy and the incidence of side effects.(2) 5d-MTX versus MACT regimen:There was no significant difference in complete remission,drug resistance and failure of the initial chemotherapy.The incidence of side is higher in MACT regimen (RR= 0.46,95% CI= [0.26,0.81]).(3) 5d-MTX versus MTX-CF regimen:There was no significant difference in complete remission, relapse, failure of the initial chemotherapy and grade 4 toxicity;Drug resistence was higher in MTX-CF regimen (RR= 0.30,95% CI= [0.12,0.75]).(4) 5d-MTX versus VP-16 regimen:VP-16 regimen has higher effects and lower grade 4 toxicity;There was no significant difference in drug resistance and relapse.(5) 5d-ACT versus p-ACT regimen:no significant difference in complete remission.(6) 5d-ACT versus MACT regimen:There was no significant difference in complete remission, failure of initial chemotherapy and drug resistance; Side effects was higher in MACT regimen (RR= 0.30,95% CI= [0.15,0.61]).(7) 5d-ACT versus MTX-CF regimen:5d-ACT regimen has higher complete remission and incidence of mucositis and alopecia. (8) 5d-ACT versus VP-16 regimen:There was no significant difference in effects and grade 4 toxicity.(9) w-MTX versus p-ACT regimen:p-ACT regimen has higher effect, but the occurrence of alopecia is also higher rate.(10) w-MTX versus MTX-CF regimen:There was no significant difference in effects; MTX-CF has higher hepatotoxicity rate.(11) VP-16 versus MTX-CF regimen:VP-16 regimen has higher effects and lower grade 4 toxicity.Conclusion:5d-ACT did not show significant advantage over 5d-MTX; p-ACT was superior to w-MTX in achieving primary complete remission,but increased alopecia;MTX-CF did not show significant advantage over 5d-MTX both in reducing toxicity or primary complete remission,meanwhile increased drug resistance. MTX-CF has higher hepatotoxicity rate versus w-MTX. MACT resulted in significantly increased toxicity without significantly improving primary complete remission.VP-16 showed higher effects and lower grade 4 toxicity than MTX and MTX-CF,but no significant advantage over Act-D.