Treatment of low-risk gestational trophoblastic neoplasia comparing biweekly eight-day Methotrexate with folinic acid versus bolus-dose Actinomycin-D, among Brazilian women.

PURPOSE: To compare two single-agent chemotherapy (ChT) regimens evaluating, in first-line treatment, response and side effects and, in final single-agent treatment, the outcomes, among Brazilian patients with low-risk gestational trophoblastic neoplasia (GTN), according to International Federation of Gynecology and Obstetrics (FIGO) 2002. METHODS: Retrospective analysis of two concurrent cohorts with 194 low-risk GTN patients: from 1992 to 2012, as first-line treatment, 115 patients received 4 intramuscular doses of methotrexate alternated with 4 oral doses of folinic acid (MTX/FA) repetead every 14 days and, since 1996, 79 patients received an endovenous bolus-dose of actinomycin D (Act-D), biweekly. At GTN diagnosis, patient opinion was taken into consideration when defining the initial single-agent ChT regimen, and when there was resistance or toxicity to one regimen, the other drug was used preferentially. This study was approved by the Irmandade da Santa Casa de Misericórdia de Porto Alegre Ethical Committee. RESULTS: Both groups were clinically similar (p>0.05). In first-line treatments, frequency of complete response was similar (75.7% with MTX/FA and 67.1% with bolus Act-D); the number of ChT courses -median 3 (range: 1-10) with MTX/FA and 2 (range: 1-6) with bolus Act-D - and the time to remission -median 9 weeks (range: 2-16) with MTX/FA and 10 weeks (range: 2-16) with bolus Act-D) - were not different between the groups. In both groups, first-line side effects frequency were high but intensity was low; stomatitis was higher with MTX/FA (p<0.01) and nausea and vomit with Act-D (p<0.01). Final single-agent ChT responses were high in both groups (94.8% with MTX/FA and 83.5% with bolus Act-D; p<0.01) and 13% higher in the group initially treated with MTX/FA. Rates of hysterectomy and of GTN recurrence were low and similar. No patient died due to GTN. CONCLUSION: The two regimens had similar first-line ChT response. Final single-agent response rates were high and similar in both groups but the final single-agent remission rate was higher in the MTX/FA group.

Treatment of low-risk gestational trophoblastic neoplasia comparing biweekly eight-day Methotrexate with folinic acid versus bolus-dose Actinomycin-D, among Brazilian women / Tratamento da neoplasia trofoblástica gestacional de baixo-risco, comparando aplicação quinzenal de oito dias de Metotrexato com ácido folínico versus Actinomicina D em bolo, em mulheres brasileiras

PURPOSE: To compare two single-agent chemotherapy (ChT) regimens evaluating, in first-line treatment, response and side effects and, in final single-agent treatment, the outcomes, among Brazilian patients with low-risk gestational trophoblastic neoplasia (GTN), according to International Federation of Gynecology and Obstetrics (FIGO) 2002. METHODS: Retrospective analysis of two concurrent cohorts with 194 low-risk GTN patients: from 1992 to 2012, as first-line treatment, 115 patients received 4 intramuscular doses of methotrexate alternated with 4 oral doses of folinic acid (MTX/FA) repetead every 14 days and, since 1996, 79 patients received an endovenous bolus-dose of actinomycin D (Act-D), biweekly. At GTN diagnosis, patient opinion was taken into consideration when defining the initial single-agent ChT regimen, and when there was resistance or toxicity to one regimen, the other drug was used preferentially. This study was approved by the Irmandade da Santa Casa de Misericórdia de Porto Alegre Ethical Committee. RESULTS: Both groups were clinically similar (p>0.05). In first-line treatments, frequency of complete response was similar (75.7% with MTX/FA and 67.1% with bolus Act-D); the number of ChT courses -median 3 (range: 1-10) with MTX/FA and 2 (range: 1-6) with bolus Act-D - and the time to remission -median 9 weeks (range: 2-16) with MTX/FA and 10 weeks (range: 2-16) with bolus Act-D) - were not different between the groups. In both groups, first-line side effects frequency were high but intensity was low; stomatitis was higher with MTX/FA (p<0.01) and nausea and vomit with Act-D (p<0.01). Final single-agent ChT responses were high in both groups (94.8% with MTX/FA and 83.5% with bolus Act-D; p<0.01) and 13% higher in the group initially treated with MTX/FA. Rates of hysterectomy and of GTN recurrence were low and similar. No patient died due to GTN. CONCLUSION: The two regimens had similar first-line ChT response. ...

OBJETIVO: Em mulheres brasileiras com neoplasia trofoblástica gestacional (NTG) de baixo-risco, de acordo com a Federação Internacional de Ginecologia e Obstetrícia (FIGO) 2002, comparar dois regimes de quimioterapia (Qt) por agente único avaliando resposta e efeitos colaterais no tratamento de primeira linha, e a eficácia no tratamento final por agente único de Qt. MÉTODOS: Análise retrospectiva de duas coortes concorrentes com 194 pacientes com NTG de baixo risco: de 1992 a 2012; como primeira linha, 115 pacientes receberam 4 doses intramusculares de metotrexato alternado com 4 doses orais de ácido folínico (MTX/FA) repetidos a cada 14 dias e, desde 1996, 79 pacientes receberam quinzenalmente dose em bolo de actinomicina D (Act-D) por via endovenosa. No momento do diagnóstico da NTG, a opinião da paciente foi levada em consideração para definir o regime de Qt por agente único inicial e, quando havia resistência ou toxicidade a um regime, o outro fármaco era usado preferentemente. Este estudo foi aprovado pelo Comitê de Ética da Irmandade da Santa Casa de Misericórdia de Porto Alegre. RESULTADOS: Ambos os grupos eram clinicamente semelhantes (p>0,05). Nos tratamentos de primeira linha, a frequência de resposta completa foi semelhante (75,7% com MTX/FA e 67,1% com Act-D em bolo); não houve diferença entre os grupos quanto ao número de séries de Qt - mediana 3 (intervalo: 1-10) com MTX/FA e 2 (intervalo: 1-6) com Act-D em bolo - e ao tempo para remissão - mediana 9 semanas (intervalo: 2-16) com MTX/FA e 10 semanas (intervalo: 2-16) com Act-D em bolo. Em ambos os grupos, foi elevada a frequência de efeitos colaterais no tratamento de primeira linha, mas com intensidade baixa; estomatite foi mais frequente com MTX/FA (p<0.01) e náuseas e vômitos com Act-D (p<0.01). A resposta final à Qt por agente único foi alta nos dois grupos (94,8% com MTX/FA e 83,5% com Act-D em bolo; p<0,01) e 13% maior no grupo inicialmente tratado com ...

Epidemiological report on the treatment of patients with gestational trophoblastic disease in 10 Brazilian referral centers: results after 12 years since International FIGO 2000 Consensus.

OBJECTIVE: To evaluate treatment of Brazilian patients with gestational trophoblastic disease (GTD). STUDY DESIGN: A retrospective cohort study with analysis of medical reports performed in 10 Brazilian referral centers from January 2000 to December 2011. RESULTS: Of 5,250 patients 3 died (0.06%) at the time of uterine evacuation. Spontaneous remission of GTD (group G1) was observed in 4,103 cases, and 1,144 (21.8%) progressed to gestational trophoblastic neoplasia (GTN) (G2). In G1 2,716 (66.2%) had complete hydatidiform mole (HM) and 1,210, partial HM (29.5%); 3,772 patients (92.7%) recovered as noted in December 2012. In G2, of 1,118 patients treated, initial histopathological results of previous gestation were complete HM (77.5% [n = 886]), partial HM (8.8% [n = 100]), and choriocarcinoma (8.0% [n = 92]); 930 (81.3%) were low-risk, 200 (17.5%) were high-risk GTN, and 14 had placental site trophoblastic tumor (PSTT) (1.2%); cure was achieved in 1,078 cases (96.4%), but 26 patients (2.3%) died (4 low-risk [0.4%], 19 high-risk [9.5%], and 3 PSTT [21.4%]). CONCLUSION: The highest death rates were due to high-risk GTN and PSTT. Patients with molar pregnancy should be referred to a referral center for an early diagnosis and prompt treatment of GTN in order to reduce the morbidity and mortality found in advanced stages.

Role of hysterectomy in the management of patients with gestational trophoblastic neoplasia: importance of receiving treatment in reference centers.

OBJECTIVE: To evaluate hysterectomy prevalence, indications and impact on clinical outcomes in a reference center in southern Brazil. STUDY DESIGN: Institutional Ethical Committee approval was granted for this study. In a cohort study spanning 21 years, all patients who underwent hysterectomy for gestational trophoblastic neoplasia (GTN) were included, and technical differences between hysterectomy performed in the reference center and those performed elsewhere were evaluated as well. RESULTS: Of 1,023 patients with gestational trophoblastic disease, 57 (5.6%) underwent hysterectomy (95% CI, 4.3-7.1). Hysterectomy incidence in 230 GTN patients was 17.7% (95%CI, 15.1-23.3). Indications for 41 hysterectomies in the reference center were as follows: primary treatment in 14 (34.1%) cases and secondary treatment in 27 (65.9%); of these, the main indications were GTN recurrence (7 [25.9%] cases), hemorrhage (6 [22.2%]), resistance to single-agent chemotherapy in patients who refused more aggressive treatment (6 [22.2%]), and tumor mass reduction (5 [18.5%]). Twelve (92.3%) of the 13 hysterectomies with bilateral oophorectomy were performed elsewhere (p < 0.001). Thirty-five (85.4%) patients had no complications, and median hospitalization time was short (3 +/- 4 days). None of the 4 deaths were associated with hysterectomy. In the reference center, when associated with hysterectomy, GTN cure rates reached 93% after 63 +/- 87 months of follow-up. CONCLUSION: When treatment is in a reference center, hysterectomy frequency and morbidity may be low, and indications due to hemorrhage are significantly lower. Furthermore, at a reference center there is significantly greater ovarian preservation at the time of hysterectomy, and significantly more patients who undergo hysterectomy have low-risk GTN.

Reproductive outcome after discharge of patients with high-risk hydatidiform mole with or without use of one bolus dose of actinomycin D, as prophylactic chemotherapy, during the uterine evacuation of molar pregnancy.

OBJECTIVE: To evaluate whether prophylactic chemotherapy (P-chem) with one bolus dose of actinomycin D (Act-D) during the uterine evacuation of patients with high-risk hydatidiform mole (Hr-HM) affects reproductive outcomes in subsequent pregnancies. METHODS: From 1987 to 2006, 1090 patients with gestational trophoblastic disease (GTD) were evaluated at a Trophoblastic Disease Center in southern Brazil; 265 with Hr-HM were selected and retrospectively analyzed. From 1996 to 2006, 163 received one bolus dose of Act-D at the time of uterine evacuation (Hr-HM-chem group); 102 with the same risk factors did not get P-chem (Hr-HM-control group). In March 2009, the number of pregnancies, progression of first pregnancy, and association of low age and low parity with subsequent pregnancy were evaluated. RESULTS: The percentage of patients that became pregnant was similar in both groups (Hr-HM-control: 59.5%; Hr-HM-chem group: 45.7%; p=0.069) and independent of HM progression. Percentages of no pregnancies because of age (> or =40 years) or hysterectomy were also similar. Type of subsequent pregnancy was not statistically different between groups, and the rate of live births associated with pregnancies for which US showed a live fetus was high. Frequency of repeat GTD was unexpectedly high in both groups (4.2% and 6.3%; p=1.00). CONCLUSIONS: P-chem did not affect reproductive outcomes for patients with Hr-HM. Patients allowed to become pregnant again in both groups had high rates of live births associated with normal pregnancies. Chances of a subsequent pregnancy were higher in the low age and low parity subgroups.

Prevention of postmolar gestational trophoblastic neoplasia using prophylactic single bolus dose of actinomycin D in high-risk hydatidiform mole: a simple, effective, secure and low-cost approach without adverse effects on compliance to general follow-up or subsequent treatment.

OBJECTIVE: To evaluate the efficacy of actinomycin D (Act-D) as prophylactic chemotherapy (P-Chem) to reduce postmolar gestational trophoblastic neoplasia (GTN) in patients with high-risk hydatidiform mole (Hr-HM). METHODS: From 1987 to 2006, 265 Hr-HM were selected in a retrospective analysis of a nonrandomized clinical trial of 1090 patients with gestational trophoblastic disease (GTD) followed up at a Trophoblastic Disease Center (TDC) in southern Brazil. From 1996 to 2006, 163 received a single bolus dose of Act-D at time of uterine evacuation (Hr-HM-chem group); 102 with the same risk factors did not get P-Chem (Hr-HM-control group). Variables were: number of patients with postmolar GTN who required chemotherapy during follow-up, postmolar GTN morbidity, compliance and operational costs. RESULTS: Postmolar GTN was diagnosed in 18.4% of the Hr-HM-chem patients (95% CI: 12.7-24.7) and in 34.3% of the Hr-HM-control patients (95% CI: 25.1-43.5). Postmolar GTN was 46% lower in P-Chem (RR=0.54; 95% CI: 0.35-0.82; NNT=7). P-Chem adverse effects were occasional and minor. When disease progressed to postmolar GTN, severity was the same, but costs were lower for the Hr-HM-chem group. Compliance with follow-up was high and similar in both groups. CONCLUSIONS: Follow-up of patients with Hr-HM showed that a single bolus dose of prophylactic Act-D reduced the incidence of postmolar GTN. Compliance and postmolar GTN morbidity were not affected. Treatment costs and emotional complications were reduced. This prophylactic approach can be adopted before uterine evacuation in any TDC that treats Hr-HM patients that present with undelivered moles.