Mo'iad Alazzam1, John Tidy, Barry W Hancock, Raymond Osborne. 1. Obstetrics & Gynaecology, Sheffield Teaching Hospitals Foundation NHS Trust, Royal Hallamshire Hospital, Glossop Road, Sheffield, UK, S10 2JF. Moiad.Alazzam@sth.nhs.uk
Abstract
BACKGROUND: Gestational trophoblastic neoplasia (GTN) is a rare but curable disease. The incidence in Europe and North America is nearly 1.5 per 1000 live births but much higher rates are reported from Africa and Asia. The majority of the patients respond to evacuation of the uterus plus or minus chemotherapy, however, occasional patients will die. Patients are categorised into low or high risk groups using a variety of scoring systems. A large number of regimens are used worldwide in the management of low risk GTN; there are reports of 14 different regimens in the English literature. The choice of the regimen is usually dependent on geographic location, prior training and current experience with the specific regimen. Regimens have significant differences in the route of administration, hospitalisation and side effects and so have a bearing on healthcare cost. Patients are therefore exposed to different regimens with the potential for different response rates and different side effect profiles. OBJECTIVES: To determine the efficacy and safety of first line chemotherapy in the treatment of low risk GTN. SEARCH STRATEGY: We electronically searched Cochrane Gynaecological Cancer Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3 2008), MEDLINE and EMBASE in September 2008. We performed additional searching of online trial registers and conference proceedings. We cross examined article references to identify relevant papers not detected by the electronic search. SELECTION CRITERIA: The review included randomised controlled trials (RCTs) , quasi-RCTs and non-RCTs (cohort and case control studies (CCS)) for the treatment of low risk GTN. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion in the review using a data extraction form. Meta-analysis was performed by pooling the relative risk (RR) of individual trials. MAIN RESULTS: Eight studies met the review entry criteria (n = 769). There were four RCTs and four CCS. Six different treatment regimens were identified; weekly methotrexate, 5-day methotrexate, 8-day methotrexate-folinic acid, "pulsed" dactinomycin, 5-day dactinomycin and the combination of methotrexate and dactinomycin. "Pulsed" dactinomycin was superior to weekly methotrexate in achieving primary cure without significantly increasing toxicity (three studies, RR 3.00, 95% CI 1.10 to 8.17, n = 392) . Eight-day methotrexate-folinic acid did not show significant advantage over 5-day methotrexate both in reducing toxicity or primary cure rate (two studies, RR 1.07, 95% CI 0.91 to 1.25, n = 169). The combination of methotrexate-dactinomycin resulted in significantly increased toxicity without significantly improving primary cure rate. AUTHORS' CONCLUSIONS: Based on the available evidence from the included RCTs, the authors conclude that "pulsed" dactinomycin is superior to weekly parenteral methotrexate at the reported dosages. However, the authors believe that rigorously designed, multicentred, randomised double-blind trials are required to evaluate other combinations of chemotherapy regimens, most importantly "pulsed" dactinomycin with the widely used 8-day methotrexate-folinic acid.
BACKGROUND:Gestational trophoblastic neoplasia (GTN) is a rare but curable disease. The incidence in Europe and North America is nearly 1.5 per 1000 live births but much higher rates are reported from Africa and Asia. The majority of the patients respond to evacuation of the uterus plus or minus chemotherapy, however, occasional patients will die. Patients are categorised into low or high risk groups using a variety of scoring systems. A large number of regimens are used worldwide in the management of low risk GTN; there are reports of 14 different regimens in the English literature. The choice of the regimen is usually dependent on geographic location, prior training and current experience with the specific regimen. Regimens have significant differences in the route of administration, hospitalisation and side effects and so have a bearing on healthcare cost. Patients are therefore exposed to different regimens with the potential for different response rates and different side effect profiles. OBJECTIVES: To determine the efficacy and safety of first line chemotherapy in the treatment of low risk GTN. SEARCH STRATEGY: We electronically searched Cochrane Gynaecological Cancer Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3 2008), MEDLINE and EMBASE in September 2008. We performed additional searching of online trial registers and conference proceedings. We cross examined article references to identify relevant papers not detected by the electronic search. SELECTION CRITERIA: The review included randomised controlled trials (RCTs) , quasi-RCTs and non-RCTs (cohort and case control studies (CCS)) for the treatment of low risk GTN. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion in the review using a data extraction form. Meta-analysis was performed by pooling the relative risk (RR) of individual trials. MAIN RESULTS: Eight studies met the review entry criteria (n = 769). There were four RCTs and four CCS. Six different treatment regimens were identified; weekly methotrexate, 5-day methotrexate, 8-day methotrexate-folinic acid, "pulsed" dactinomycin, 5-day dactinomycin and the combination of methotrexate and dactinomycin. "Pulsed" dactinomycin was superior to weekly methotrexate in achieving primary cure without significantly increasing toxicity (three studies, RR 3.00, 95% CI 1.10 to 8.17, n = 392) . Eight-day methotrexate-folinic acid did not show significant advantage over 5-day methotrexate both in reducing toxicity or primary cure rate (two studies, RR 1.07, 95% CI 0.91 to 1.25, n = 169). The combination of methotrexate-dactinomycin resulted in significantly increased toxicity without significantly improving primary cure rate. AUTHORS' CONCLUSIONS: Based on the available evidence from the included RCTs, the authors conclude that "pulsed" dactinomycin is superior to weekly parenteral methotrexate at the reported dosages. However, the authors believe that rigorously designed, multicentred, randomised double-blind trials are required to evaluate other combinations of chemotherapy regimens, most importantly "pulsed" dactinomycin with the widely used 8-day methotrexate-folinic acid.