RESUMO
BACKGROUND: The aim of the present study was to demonstrate that radical hysterectomy (RH) leads to improved survival outcomes in FIGO stage IB2-IIB cervical cancer when compared with standard brachytherapy (BCT) after identical external beam chemoradiation (EBRT-CT). PATIENTS AND METHODS: EBRT-CT treatment consisted of six courses of cisplatin at 40 mg/m² and gemcitabine at 125 mg/m² per week concurrent with 50.4 Gy of radiation. In the BCT arm, EBRT-CT was followed by BCT to reach a point A dose of 85 Gy, whereas in the experimental arm, a type III RH with bilateral pelvic lymph node dissection and para-aortic lymph node sampling (RH) was carried out within 4-6 weeks after EBRT-CT. RESULTS: Between May 2004 and June 2009, 211 patients were enrolled (BCT, 100 and RH, 111). At a median follow-up time of 36 months (3-80), progression-free survival (PFS) and overall survival (OS) rates were similar in both the arms. PFS rates were 74.8% and 71.7% in the BCT and RH arms [HR 0.6516 (95% confidence interval (CI) 0.3504-1.2116)], P = 0.186. OS rates were 76.3% in the BCT versus 74.5% in the surgical arm [HR 0.6981 (95% CI 0.3106-1.3439)], P = 0.236. No differences were observed in the pattern of local and systemic failures. CONCLUSIONS: This study failed to demonstrate that RH after EBRT-CT is superior to standard BCT.
Assuntos
Braquiterapia , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Histerectomia , Neoplasias do Colo do Útero , Adulto , Idoso , Quimiorradioterapia , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Radiossensibilizantes/uso terapêutico , Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/cirurgia , Adulto Jovem , GencitabinaRESUMO
INTRODUCTION: This trial aimed to evaluate the safety and efficacy of epigenetic therapy associated with cisplatin chemoradiation in FIGO Stage IIIB patients. METHODS: Hydralazine containing either 182 mg for rapid-, or 83 mg for slow acetylators and magnesium valproate were administered at 30 mg/kg tid. Both drugs were taken until intracavitary therapy was finished. Pelvic external beam radiation and low-dose rate brachytherapy were administered at a total cumulative dose to point A of at least 85 Gy. Weekly cisplatin at 40 mg/m2 was delivered for six cycles. RESULTS: Twenty-two patients were included and 18 (82%) patients completed treatment. Mean dose to point A was 84.6 + 2.2. Median number of cisplatin cycles was 5.5 (range, 1-6). Brachytherapy was delayed for technical reasons; the mean overall treatment time was 11.8 weeks. Grade 3 anemia, leucopenia, neutropenia, and thrombocytopenia were observed in 9%, 45%, 45%, and 9% of patients, respectively. CONCLUSIONS: Hydralazine and valproate are well-tolerated and safe when administered with cisplatin chemoradiation. Unfortunately, the suboptimal administration of brachytherapy for technical reasons in this study, precluded assessing the efficacy of epigenetic therapy. However, the tolerability of this regimen administered concurrent to radiation needs to be further tested.
Assuntos
Antineoplásicos/uso terapêutico , Braquiterapia , Cisplatino/uso terapêutico , Epigênese Genética , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Braquiterapia/efeitos adversos , Cisplatino/efeitos adversos , Terapia Combinada , Feminino , Humanos , Hidralazina/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Ácido Valproico/administração & dosagemRESUMO
Clinical and experimental data demonstrate that local cytokines are able to induce tumor regression and in some cases antitumor systemic immune response. IRX-2 is a cell-free mixture of cytokines obtained from unrelated donor lymphocytes with demonstrated ability to induce immune mediated regression of squamous cell carcinomas of head and neck. The objective of this study was to evaluate the antitumor activity and toxicity of IRX-2 in untreated early stage cervical cancer patients. Ten consecutive patients clinically staged IB1, IB2 and IIA were treated with a neoadjuvant immunotherapy regimen that consisted in a single IV dose of cyclophosphamide at 300 mg/m2 on day 1, oral indomethacin or ibuprofen and zinc sulfate were administered from days I to 21 and 10 regional perilymphatic injections of IRX-2 on days 3 to 14. All patients were scheduled for radical hysterectomy on day 21. The clinical and pathological responses, toxicity and survival were evaluated. Clinical response was seen in 50% of patients (three partial responses, two minor responses). Seven patients underwent surgery and pathological tumor reduction associated with tumor fragmentation was found in five cases. Histological studies demonstrated a rather heterogeneous cell type infiltrating pattern in the tumor which included lymphocytes, plasma cells, neutrophils, macrophages and eosinophils. Immunohistochemical analysis of the surgical specimens demonstrated an increase of tumor infiltrating CD8+ cells. The treatment was well tolerated except for mild pain and minor bleeding during injections and gastric intolerance to indomethacin. At 31 months of maximum follow-up (median 29), eight patients are disease-free. Our results suggest that the immunotherapy approach used induces tumor responses in cervical cancer patients. Further studies are needed to confirm these results as well as to elucidate the mechanisms underlying these effects.
Assuntos
Adenocarcinoma/tratamento farmacológico , Carcinoma Adenoescamoso/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Citocinas/uso terapêutico , Terapia Neoadjuvante/métodos , Neoplasias do Colo do Útero/tratamento farmacológico , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Adulto , Carcinoma Adenoescamoso/imunologia , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/estatística & dados numéricos , Projetos Piloto , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologiaRESUMO
Despite the recent progress in the management of cervical carcinoma, treatment failure is quite common and therefore it is necessary to identify predicting factors for tumor response. It is known that both cell proliferation and apoptosis determine the tumor growth index (TGI) which reflects the overall contribution of gene defects. Here we explored whether the TGI index could be a better predictor of response in comparison to cell proliferation or apoptosis as separate phenomena. Twenty-five patients with cervical carcinoma treated with radiation alone or neoadjuvant chemotherapy plus surgery were analyzed. Cell proliferation and apoptosis determined by PCNA immunohistochemical expression and tumor nucleosomes by ELISA, respectively, were used to calculate the TGI, which was analyzed with regard to early tumor response. Our results show that most patients with a negative TGI had early response suggesting increased tumor sensitivity(p = 0.0186). On the other hand, patients with a positive TGI were more resistant to treatment. TGI was not related to age, clinical stage or tumor size. In conclusion, the results of this study show that the determination of the TGI, but no cell proliferation or apoptosis, as separate events, is able to predict an early treatment response to either radiation or chemotherapy in cervical carcinoma.
Assuntos
Adenocarcinoma/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/terapia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Apoptose/fisiologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/terapia , Divisão Celular/fisiologia , Quimioterapia Adjuvante , Feminino , Humanos , Técnicas Imunoenzimáticas , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Antígeno Nuclear de Célula em Proliferação/metabolismo , Dosagem Radioterapêutica , Resultado do Tratamento , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/terapiaRESUMO
BACKGROUND: Cisplatin-based chemoradiation for locally advanced cervical carcinoma is now the standard of care for most patients with cervical carcinoma. However, induction chemotherapy followed by surgery, particularly with newer agents or combinations remains to be explored. This study was undertaken to evaluate the antitumor activity and toxicity of gemcitabine in combination with cisplatin for untreated locally advanced cervical carcinoma. PATIENTS AND METHODS: Open-label, single center, phase II, non-randomized study of neoadjuvant gemcitabine plus cisplatin. Forty-one patients with histologic diagnosis of cervical carcinoma, with no previous treatment and staged as IB2 to IIIB, were treated with three 21-day courses of cisplatin 100 mg/m2 day I and gemcitabine 1000 mg/m2 days 1 and 8, followed by locoregional treatment with either surgery or concomitant chemoradiation. Response and toxicity were evaluated before each course and at the end of chemotherapy. RESULTS: All patients were evaluated for toxicity and 40 for response. The overall objective response rate was 95% (95% confidence interval (CI): 88%-100%) being complete in 3 patients (7.5%) and partial in 35 (87.5%). A complete pathological response was found in 6 (26%) of the 23 patients that underwent surgery. Granulocytopenia grades 3-4 occurred in 13.8% and 3.4% of the courses, respectively, whereas non-hematological toxicity was mild. CONCLUSIONS: Induction chemotherapy with the combination of gemcitabine and cisplatin is highly active for untreated cervical cancer patients and has an acceptable toxicity profile.