RESUMO
The efficacy and adverse events of neoadjuvant chemotherapy with irinotecan hydrochloride and nedaplatin were evaluated in patients with bulky stage Ib2 to IIb cervical squamous cell carcinoma. Eligibility included patients who received irinotecan (60 mg/m2) on days 1 and 8 and nedaplatin (80 mg/m2) on day 1 of a 21-day cycle. After 1-3 courses of chemotherapy, radical hysterectomy was performed. Sixty-eight patients were enrolled. Sixty-six were included in the full analysis set. Their median age was 47 years (range 22-71), the FIGO stage was Ib2 in 18 patients, IIa in 10, and IIb in 38. Radical hysterectomy was performed after NAC in 63 patients (95.5%). The number of administered courses of NAC was 1 in 13 patients, 2 in 43, and 3 in 10. The response rate, the primary endpoint of this study, was 75.8% (CR in 2 patients, PR in 48, SD in 12, PD in 0, and NE in 4). The mean number of treatment courses required for a response was 1.42 (1 course in 30 patients, 2 courses in 19, and 3 courses in 1). The incidences of grade 3 or 4 hematological toxicities were: neutropenia 72.2%, leukopenia 16.7%, anemia 13.6%, thrombocytopenia 7.6%, febrile neutropenia 1.5%, and elevations of alanine aminotransferase and aspartate aminotransferase 1.5%. Grade 3 or 4 non-hematologic toxicities were as follows: diarrhea 6.1%, nausea 3%, anorexia 1.5%, vomiting 1.5%, fever 1.5%, allergic reactions 1.5%, ileus 1.5% and vesicovaginal fistula 1.5%. Neoadjuvant chemotherapy with irinotecan and nedaplatin was an effective and well-tolerated treatment for patients with bulky stage Ib2 to IIb squamous cell carcinoma of the uterine cervix.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/cirurgia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Carcinoma de Células Escamosas/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Histerectomia/métodos , Irinotecano , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Neoplasias do Colo do Útero/patologia , Adulto JovemRESUMO
The aim of this study (JGOG1063) was to determine the recommended dose (RD) for combination chemotherapy with irinotecan hydrochloride (CPT-11) and nedaplatin (NDP) for advanced cervical squamous cell carcinoma. CPT-11 was given intravenously in fixed doses of 60 mg/m2 on days 1 and 8 and NDP, in escalating doses, on day 1, every 4 weeks. A total of 15 patients were enrolled in the study. At level 1 (NDP: 50 mg/m2), one of the 3 patients developed grade 3 diarrhea, so 3 additional patients were enrolled at this level. As none of the 3 additional patients exhibited dose-limiting toxicity, level 1 was elevated to level 2 (NDP: 60 mg/m2). The maximum tolerated dose was not reached, even at the highest dose level (level 4; NDP: 80 mg/m2). No further dose escalation was carried out, and level 4 (CPT-11: 60 mg/m2, NDP: 80 mg/m2) was determined as the RD.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Idoso , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Feminino , Humanos , Irinotecano , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversosRESUMO
BACKGROUND: A phase I study to evaluate combined therapy with irinotecan (CPT-11), mitomycin-C (MMC), and 5-fluorouracil (5-FU) was performed in patients with gynecological malignancy, especially non-squamous cell carcinoma of the uterine cervix. MATERIALS AND METHODS: Eligibility for the study included patients with previously untreated, chemotherapy-naïve cervical and ovarian carcinoma. CPT-11 and MMC were administered on days 1 and 15 by intravenous infusion, while 5-FU was given on days 3 to 7. This regimen was repeated after 5 weeks. Four escalating dose levels were carried out (CPT-11/MMC: 120/5, 120/6, 150/6, and 150/7 mg/m2; 5-FU 600 mg/m2 fixed). RESULTS: Fourteen patients were enrolled in the study. Although all the patients had no previous chemotherapy, three patients had undergone a simple hysterectomy and nine had a radical hysterectomy performed before this chemotherapy. The maximum tolerated dose was not reached by using CPT-11 150 mg/m2, MMC 7 mg/m2, and 5-FU 600 mg/m2 because none of the patients experienced any hematological or non-hematological toxicities of grade 4 during the first cycle. CONCLUSION: The recommended doses of this new regimen are CPT-11 150 mg/m2, MMC 7 mg/m2, and 5-Fu 600 mg/m2 which can be well tolerated for gynecological malignancies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma Mucinoso/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Relação Dose-Resposta a Droga , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Irinotecano , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Mitomicina/efeitos adversosRESUMO
BACKGROUND: The efficacy and toxicity of combined therapy with irinotecan (CPT-11) and mitomycin-C (MMC) in a neoadjuvant setting were evaluated in patients with locally advanced squamous cell carcinoma (SCC) of the uterine cervix. PATIENTS AND METHODS: Eligibility included patients with previously untreated cervical carcinoma. CPT-11 (100 mg/m2) was administered on days 1, 8 and 15 intravenously (i.v.), while MMC (10 mg/m2 i.v.) was given on day 1. Survival curves were generated using the Kaplan-Meier method. RESULTS: Among 35 eligible patients, 3 showed a complete response and 27 a partial response, with an overall response rate of 85.7%. No patient showed progressive disease. Thirty-three patients were able to undergo radical surgery after neoadjuvant chemotherapy and only 2 patients (stage IIIb) received radiotherapy without the optimal surgery. The median disease-free survival (DFS) period was 42 months (range 5-73). The median overall survival (OAS) period was 44 months (range 17-74). Two-year DFS and OAS rates were 74.3% and 91.4%, respectively. Of the 58 treatment cycles administered, grade 3 or 4 neutropenia and thrombocytopenia were observed in 50% and 9% of the treatment cycles, respectively. Grade 3 or 4 diarrhea was observed in 6%. CONCLUSION: Neoadjuvant chemotherapy with CPT-11 and MMC can be effective and well-tolerated against locally advanced SCC of the uterine cervix.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico , Adulto , Idoso , Análise de Variância , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Feminino , Humanos , Irinotecano , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Mitomicina/efeitos adversos , Terapia Neoadjuvante , Estadiamento de NeoplasiasRESUMO
BACKGROUND: This study was designed to investigate the relationship between apoptosis and Bcl-2 and Bax expressions in uterine cervical cancer after balloon-occluded arterial infusion (BOAI). MATERIALS AND METHODS: Twenty-four specimens were obtained before and after BOAI. The occurrence of apoptosis was examined with molecular biochemical techniques. The expressions of Bcl-2 and Bax proteins were investigated by immunohistochemical staining. RESULTS: Labelling of DNA in situ indicated that apoptotic cells were sporadically seen before BOAI (6.1 +/- 1.9). Apoptotic cells apparently increased at 5 days (25.1 +/- 6.4) after BOAI The autoradiographic analysis revealed that the DNA-ladder was identified at 5 days after BOAI. Although Bcl-2 immuno-reactivity was faintly detected, the expression of Bax increased at 3 days (49.4 +/- 10.4%) after BOAI. CONCLUSION: The results indicated that treatment with BOAI resulted in transient increases of apoptosis in cervical cancer in association with the increased expression of Bax.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Fragmentação do DNA/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/metabolismo , Cateterismo , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Feminino , Humanos , Imuno-Histoquímica , Infusões Intra-Arteriais , Pessoa de Meia-Idade , Peplomicina/administração & dosagem , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Neoplasias do Colo do Útero/metabolismo , Proteína X Associada a bcl-2/biossínteseRESUMO
BACKGROUND: Intravenous leiomyomatosis is a rare variant of leiomyoma. CASE: The patient was a 49-year-old gravida 3, para 3 woman with menopause at age 46. She presented with a history of syncope. Vaginal examination revealed an enlarged and elastic-soft mass of the uterus. A pelvic ultrasound, computed tomography scan, and magnetic resonance imaging showed a heterogeneous, irregularly shaped 8- to 10-cm tumor. In addition, the inferior vena cava was almost completely occluded. Cardiac ultrasound demonstrated a mobile mass in the right atrium. The serum estradiol was 208 pg/mL (normal 0-59). Intravenous leiomyomatosis with cardiac extension was diagnosed preoperatively. A resection of the intracardiac and intracaval mass and a subtotal hysterectomy with bilateral salpingo-oophorectomy were performed. The uterine tumor weighed 600 g, and the cordlike intravascular tumor extending from the internal iliac vein into the right ventricle was 40 cm long and weighed 60 g. Pathologic examination confirmed intravenous leiomyomatosis with no evidence of atypia. The level of estrogen receptor in the tissue was 140 fmol/mg protein. The postoperative course was uneventful, and she has been in good health for 17 months after the operation. CONCLUSION: We report a case of intravenous leiomyomatosis extending into the right ventricle treated with a one-stage operation. It is possible that a high concentration of serum estradiol and high level of tissue estrogen receptor are related to the intravenous leiomyomatosis.