Predictive factors associated with resistance to initial methotrexate treatment in women with low-risk gestational trophoblastic neoplasia.

AIM: To compare clinical characteristics and identify factors predictive of resistance to initial treatment with methotrexate-folinic acid (MTX-FA) in women with low-risk gestational trophoblastic neoplasia (GTN). METHODS: Retrospective chart reviews were conducted in patients diagnosed with low-risk GTN who were treated with MTX-FA at Siriraj Hospital between 2002 and 2018. Demographic data, disease characteristics, treatment response, toxicity, and data of the subsequent pregnancy were collected and analyzed. Groups of patients who were responsive or resistant to treatment were compared. Stepwise logistic regression analysis was used to identify factors predictive of resistance to methotrexate chemotherapy. RESULTS: Totally, 113 patients were eligible for analysis. The primary remission rate was 55.8% with first-line MTX-FA. All other patients achieved remission by subsequent treatment with actinomycin D or multiple-agent chemotherapy. Relapse of disease occurred in 4.4% and the overall survival rate was 99.1%. Univariate analysis showed that pretreatment serum hCG, neutrophil-to-lymphocyte ratio at baseline, and serum hCG ratio of the first three consecutive cycles (C) were significantly associated with resistance to MTX-FA. Independent factors that predict failure to respond to first-line MTX-FA were pretreatment serum hCG ≥15,000 IU/L, a less than 4.8-fold reduction of serum hCG between cycle 1 and cycle 2 (C1/C2), and a less than seven-fold reduction of serum hCG from cycle 2 to cycle 3 (C2/C3). CONCLUSIONS: First-line MTX-FA treatment is effective in 55.8% of patients. Pretreatment serum hCG, and serum hCG ratio between consecutive treatment cycles can predict initial treatment failure.

Treatment outcome of gestational trophoblastic neoplasia patients in Egypt.

Background: Gestational trophoblastic neoplasia (GTN) are a spectrum of tumors that develop from placental tissue. We aimed to evaluate the management and treatment outcome of GTN. Methods: Patients diagnosed with GTN presented to Kasr Alainy Center of Clinical Oncology between 2008 and 2017 were included in this study. Patients were assigned to low or high-risk according to the World Health Organization (WHO) scoring system. All data were tabulated and statistically studied by descriptive analysis; comparison between the two groups was done using student t-test for continuous data and Chi-square test for categorical data. Results: A total of 111 patients were studied; the majority of them had WHO low-risk score. In low-risk group, the overall response rate to methotrexate-folinic acid (MTX- FA) or actinomycin D (ActD) was 48.5%, comparable response rate observed between MTX and ActD was 48.2% vs 50%, respectively. Those who received MTX-FA 8-day regimen had higher response rate compared to a weekly schedule, however, no statistical significant difference was observed (51.6% vs 44.4%, respectively, P = 0.586), all low-risk patients who failed MTX or ActD achieved complete remission (CR) with subsequent chemotherapy. Patients with WHO score 5-6 had a significantly lower CR rate compared to patients with scores <5, (28% and 60%, respectively; P = 0.01). Five-years overall survival was significantly lower in high-risk than low-risk patients (79.3% vs 100%, respectively, P = <0.001). Conclusion: Low-risk patients have a survival rate of 100% even if they did not respond to first-line chemotherapy, MTX-FA 8-day regimen seems to be more effective than MTX weekly regimen.

Chemotherapy initiation with single-course methotrexate alone or combined with dactinomycin versus multi-course methotrexate for low-risk gestational trophoblastic neoplasia: a multi-centric randomized clinical trial.

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.

Comparison of weekly methotrexate regimen versus methotrexate folinic acid 8-day regimen for treatment of low-risk gestational trophoblastic neoplasia.

AIM: We aimed to compare weekly methotrexate (MTX) regimen and methotrexate-folinic acid (MTX-FA) 8-day regimen in the first line treatment of low-risk gestational trophoblastic neoplasia (GTN). METHODS: The study included 73 patients with low-risk GTN according to FIGO risk score (FIGO risk score < 7). All patients received either weekly MTX (30-50 mg/m2 intramuscular weekly) or MTX-FA 8-day (MTX 1 mg/kg IV on day 1, 3, 5, and 7, FA 15 mg orally on day 2, 4, 6, and 8 given 24 h after each MTX dose, every 14 days) regimens in the first-line treatment of low-risk GTN. The baseline clinicopathological characteristics and treatment outcomes were analyzed retrospectively. RESULTS: The median age of all patients was 29 (18-51) years, and the median FIGO risk score was 3 (1-6). Of the patients recruited, 53 received MTX-FA 8-day, and 20 had MTX weekly regimens. There was a significant difference between the two groups with respect to FIGO risk scores (3 [1-6] vs. 2 [1-5], p = 0.023, MTX-FA 8-day vs. MTX weekly, respectively). The complete response rate was significantly higher in MTX-FA 8-day group compared to MTX weekly group (83% [44/53] vs. 60% [12/20] p = 0.038). In univariate and multivariate regression analyses, only presence of lung metastasis was found to be an independent risk factor for treatment resistance (OR: 3.959, 95% CI 1.105-14.179, p = 0.035). CONCLUSION: MTX-FA 8-day regimen is more effective than weekly MTX regimen in the first line treatment of low-risk GTN including patients even with higher FIGO risk scores. Treatment resistance may develop especially in patients with lung metastasis.

Influence of oral contraceptives in the development of post-molar trophoblastic neoplasia--a systematic review.

OBJECTIVE: Controversy exists regarding the use of oral contraceptives following hydatidiform mole and possible increased risk of persistent trophoblastic neoplasia. The purpose of this study is to perform a systematic review of the literature to assess the evidence for and against a possible link between oral contraceptive use and the need for chemotherapy after molar evacuation. METHODS: We searched the computerized databases MEDLINE, EMBASE, Popline, Web of Sciences, LILACS and the Cochrane Controlled Trials Register, ISI Proceedings, performed a hand search of references and wrote to experts to identify randomized controlled trials and observational studies comparing oral contraceptives with other methods of contraception. Quality assessment included: concealment of allocation; intention to treat analysis; plus attrition bias for trials; confounding factors and selection bias for observational studies. We collected or calculated risk ratios for the incidence of gestational trophoblastic neoplasia and hCG regression time associated with oral contraceptive use. RESULTS: Two randomized controlled trials were included for analysis. The risk ratios for OC use were similar in both studies: 0.69 (0.12-3.98) and 0.71 (0.46-1.10) respectively. No attempt to summarize these results was made because the studies observed different disease stages. In five of the seven observational studies, the risk ratio ranged from 0.57 (CI = 0.14-2.37) to 1.46 (CI = 0.56-3.79). CONCLUSION: No clear evidence for an association between oral contraceptive use during post-molar follow-up period and the incidence of gestational trophoblastic neoplasia was found. Practitioners should no longer avoid their use because of a supposed effect which we have shown here to be unsupported by evidence in the literature.