Fatores prognósticos de resposta à quimioterapia em tumores avançados do colo uterino: o papel da neoangiogênese / Prognostic factors for response to chemotherapy in advanced tumors of the uterine cervix: the role of neoangiogenesis

RESUMO Objetivo: analisar a expressão do Fator de Crescimento do Endotélio Vascular (VEGF), seu receptor (VEGFR-2), idade e tipo histológico de carcinomas avançados de colo uterino com relação à resposta clínica à quimioterapia neoadjuvante. Métodos: foram incluídas 40 pacientes com diagnóstico de carcinoma de colo uterino (IB2 e IVA), com biópsias prévias ao tratamento. Todas as pacientes foram submetidas à quimioterapia neoadjuvante e avaliadas quanto à resposta clínica e à expressão do VEGF. Considerou-se boa resposta clínica uma regressão tumoral total ou maior do que 50%. Resultados: em relação à resposta à quimioterapia, 18 pacientes (45%) apresentaram boa resposta e 22 (55%), má resposta. Quanto à expressão do VEGF, em 16 pacientes foi considerada positiva e em 24, negativa. Quando os casos foram analisados separadamente em relação à resposta à quimioterapia, somente a expressão positiva de VEGF foi associada à boa resposta clínica (p=0,0157). Conclusão: a expressão de VEGF mostrou ser isoladamente, um importante marcador de boa resposta ao tratamento quimioterápico neoadjuvante das pacientes com carcinoma avançado de colo uterino.

ABSTRACT Objective: to analyze the expression of Vascular Endothelial Growth Factor (VEGF), its receptor (VEGFR-2), age and histological type of advanced cervical carcinomas with respect to the clinical response to neoadjuvant chemotherapy. Methods: we studied 40 patients with cervical carcinoma (IB2 and IVA) diagnosed by biopsies prior to treatment. All patients underwent neoadjuvant chemotherapy and evaluation for clinical response and expression of VEGF. We considered a tumor regression greater than 50% as a good clinical response. Results: eighteen patients (45%) had good response to chemotherapy, and 22 (55%), poor response. VEGF expression was positive in 16 patients and negative in 24. When analyzed separately for response to chemotherapy, only the positive expression of VEGF was associated with good clinical response (p=0.0157). Conclusion: VEGF expression alone was an important marker of good response to neoadjuvant chemotherapy in patients with advanced carcinoma of the cervix.

Weekly versus three-weekly cisplatin as an adjunct to radiation therapy in high-risk stage I-IIA cervical cancer after surgery: a randomized comparison of treatment compliance.

OBJECTIVES: To compare weekly and three-weekly cisplatin as an adjunct to radiation therapy in high-risk early-stage cervical cancer after surgery with regard to treatment compliance. MATERIAL AND METHOD: From June 1st, 2003 to February 29th, 2004, the authors performed a randomized trial of radiotherapy in combination with two concurrent chemotherapy regimens - weekly or three-weekly cisplatin--in patients with high-risk cervical cancer FIGO stage I-IIA after surgery. Women with primary invasive squamous-cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix were enrolled. The patients also had to have an absolute neutrophil count of at least 1,500 cells per cubic millimeter, a platelet count of at least 75,000 cells per cubic millimeter, a creatinine clearance higher than 40 milliliter per minute, and adequate hepatic function. All patients received external-beam radiotherapy according to a strict protocol. Patients were randomly assigned to receive one of two chemotherapy regimens: 75 mg per square meter of cisplatin on days 1, 22, 43 and 64 or every three weeks for 4 cycles (group 1) or 40 mg per square meter of cisplatin per week for six cycles (group 2). RESULTS: The analysis included 40 women. The first group that received three-weekly cisplatin had a higher rate of incomplete and delayed treatments than the second group that received weekly cisplatin (p < 0.001 and p = 0.0236 respectively). The relative risks of delayed courses were 2.06 (95 percent confidence interval, 1.15 to 3.68) for group 1, compared with group 2. The toxicity-related incomplete treatments rate and G-CSF doses used were significantly higher in group 1 than in group 2. CONCLUSION: Concurrent chemoradiation with weekly cisplatin regimen has more complete treatment rate and less delayed courses than that with three- weekly cisplatin among women with high-risk cervical cancer after surgery.