First-line chemotherapy in low-risk gestational trophoblastic neoplasia
ABSTRACT This is an update of a Cochrane review that was first published in Issue 1, 2009. Gestational trophoblastic neoplasia (GTN) is a rare but curable disease arising in the fetal chorion during pregnancy. Most women with low-risk GTN will be cured by evacuation of the uterus with or without single-agent chemotherapy. However, chemotherapy regimens vary between treatment centres worldwide and the comparable benefits and risks of these different regimens are unclear.
To determine the efficacy and safety of first-line chemotherapy in the treatment of low-risk GTN.
In September 2008, we electronically searched the Cochrane Gynaecological Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL Issue 3, 2008), MEDLINE and EMBASE. In addition, we searched online trial registers, conference proceedings and reference lists of identified studies. We re-ran these searches in February 2012 for this updated review.
For the original review, we included randomised controlled trials (RCTs), quasi-RCTs and non-RCTs that compared first-line chemotherapy for the treatment of low-risk GTN. For this updated version of the review, we included only RCTs.
Two review authors independently assessed studies for inclusion and extracted data to a pre-designed data extraction form. Meta-analysis was performed by pooling the risk ratio (RR) of individual trials.
We included five moderate to high quality RCTs (517 women) in the updated review. These studies all compared methotrexate with dactinomycin. Three studies compared weekly intramuscular (IM) methotrexate with bi-weekly pulsed intravenous (IV) dactinomycin (393 women), one study compared five-day IM methotrexate with bi-weekly pulsed IV dactinomycin (75 women) and one study compared eight-day IM methotrexate-folinic acid (MTX-FA) with five-day IV dactinomycin (49 women).Overall, dactinomycin was associated with significantly higher rates of primary cure than methotrexate (five studies, 513 women; RR 0.64, 95% Confidence Interval (CI) 0.54 to 0.76). Methotrexate was associated with significantly more treatment failure than dactinomycin (five studies, 513 women; RR 3.81, 95% CI 1.64 to 8.86). We consider this evidence to be of a moderate quality.There was no significant difference between the two groups with respect to nausea (four studies, 466 women; RR 0.61, 95% CI 0.29 to 1.26) or any of the other individual side-effects reported, although data for all of these outcomes were insufficient and too heterogeneous to be conclusive. No severe adverse effects (SAEs) occurred in either group in three out of the five included studies and there was no significant difference in SAEs between the groups overall (five studies, 515 women; RR 0.35, 95% CI 0.08 to 1.66; I² = 60%), however, there was a trend towards fewer SAEs in the methotrexate group. We considered this evidence to be of a low quality due to substantial heterogeneity and low consistency in the occurrence/reporting of SAEs between trials.
Dactinomycin is more likely to achieve a primary cure in women with low-risk GTN, and less likely to result in treatment failure, compared with methotrexate. There is limited evidence relating to side-effects, however, the pulsed dactinomycin regimen does not appear to be associated with significantly more side-effects than the low-dose methotrexate regimen and therefore should compare favourably to the five- and eight-day methotrexate regimens in this regard.We consider pulsed dactinomycin to have a better cure rate than, and a side-effect profile at least equivalent to, methotrexate when used for first-line treatment of low-risk GTN. Data from a large ongoing trial of pulsed dactinomycin compared with five- and eight-day methotrexate regimens is likely to have an important impact on our confidence in these findings.
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ABSTRACT: To determine whether single agent chemotherapy with intramuscular methotrexate 50 mg days 1,3,5,7 and oral folinic acid 15 mg days 2,4,6,8 in 2 weekly cycles (IM MTX/FA) is an effective treatment regimen for patients with low risk gestational choriocarcinoma.Gynecologic Oncology 12/2014; 136(2). DOI:10.1016/j.ygyno.2014.12.024 · 3.69 Impact Factor
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ABSTRACT: Gestational trophoblastic disease describes a variety of pregnancy-related diseases including the premalignant conditions of a partial and complete hydatidiform mole and the malignant disorders of invasive mole, choriocarcinoma and the rare placental-site trophoblastic tumour and epithelioid trophoblastic tumour. The availability of a highly sensitive tumour marker in the form of human chorionic gonadotrophin, the chemosensitive character of the disease with effective treatment strategies and centralization of care of a rare group of diseases has resulted in excellent survival rates, which can exceed 98 %. This review gives a general overview of gestational trophoblastic disease, the most recent insights in aetiology and pathology and a summary of the different management strategies.Current Oncology Reports 11/2014; 16(11):408. DOI:10.1007/s11912-014-0408-y · 2.87 Impact Factor
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ABSTRACT: Gestational trophoblastic neoplasm (GTN) is a rare disease which is classified into high- and low-risk groups. While the high-risk patients require combination therapy, the low-risk groups respond to single-agent chemotherapy. We studied resistance to single-agent chemotherapy and its risk factors among the low-risk GTN patients in Iran. We followed 168 low-risk GTN patients who were treated between 2001 and 2011 in Valiasr Hospital, Tehran, Iran. We used a case-control design and studied odds ratios (OR) and corresponding 95% confidence intervals (CI) to evaluate association between drug resistance and different personal and clinical variables. Resistance to sequential single-agent chemotherapy was 19%, although all patients had a complete remission after a combination of chemotherapy and/or surgery. Patients who had International Federation of Gynecology and Obstetrics scores of 5-6 - considered as, the intermediate risk group - had a 14-fold higher resistance compared with the low score patients (OR = 14.28, 95% CI = 5.54-36.81). We found higher risk of resistance among patients with metastasis (OR = 8.42, 95% CI = 2.44-29.07), large tumor size (>3 cm) (OR = 7.73, 95% CI = 1.93-30.91), high β-hCG (>100 000 IU/L) (OR = 5.86, 95% CI = 1.07-32.02) and/or a diagnosis more than 4 months after pregnancy (OR = 3.30, 95% CI = 1.08-10.02), compared with their reference group. We found no priority for the different chemotherapy regimens. Intermediate risk GTN patients had a higher risk of resistance to chemotherapy compared with low-risk patients. Clinical trials and cost-effectiveness studies are needed to suggest a better treatment program for the intermediate risk group. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.Journal of Obstetrics and Gynaecology Research 12/2014; DOI:10.1111/jog.12613 · 0.93 Impact Factor