RESUMEN
BACKGROUND: Nab-paclitaxel/gemcitabine (AG) and FOLFIRINOX (FFX) are promising drugs in metastatic pancreatic cancer (MPC). This study evaluated a new first-line sequential treatment (AG followed by FFX) in MPC that might overcome resistance to primary therapy and delay tumor progression. PATIENTS AND METHODS: Patients with histologically/cytologically confirmed MPC were included in a multicentric trial receiving AG (day 1, 8 and 15) followed by FFX (day 29 and 43). In phase Ib, three dose-levels were tested for maximum tolerated dose (MTD) and recommended phase II dose. In phase II, the main outcome was the objective response rate (ORR) and secondarily safety, progression-free survival (PFS) and overall survival (OS). RESULTS: In phase Ib, we included 33 patients (31 assessable) of median age 61.0 years (range 42-75 years) and represented by 54.8% males. Five dose-limiting toxicities were reported without any death. The main grade 3/4 toxicities were neutropenia with spontaneous resolution (35.5%/32.3%), venous thromboembolism (grade 3: 22.6%) and thrombopenia (grade 3: 29.0%), while the MTD was not reached. In phase II, we included 58 patients of median age 60 years (range 34-72 years), 50% males and with Eastern Cooperative Oncology Group stage score 0 and 1 of 37.9% and 62.1%, respectively. They received a median of 4 (1-9) cycles in 8.5 months (0.5-19.8 months). The ORR was 64.9% [95% confidence interval (CI) 51.1% to 77.1%], and neurotoxicity was remarkably low. The main grade 3-4 toxicities were venous thromboembolism, thrombopenia, neutropenia/febrile neutropenia, nausea, diarrhea, weight loss and asthenia without any death. Tumor response was complete in 3.5% and partial in 61.4%, while disease was stable in 19.3% and progressive in 15.8% of patients. The median PFS was 10.5 months (95% CI 6.0-12.5 months) and median OS was 15.1 months (95% CI 10.6-20.1 months). CONCLUSION: Sequential AG and FFX showed acceptable toxicity as first-line treatment with no limiting neurotoxicity, while high response rate and survival justify randomized trials.
Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adulto , Anciano , Albúminas , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Desoxicitidina/análogos & derivados , Femenino , Fluorouracilo , Humanos , Irinotecán , Leucovorina , Masculino , Persona de Mediana Edad , Oxaliplatino , Paclitaxel , GemcitabinaRESUMEN
BACKGROUND: Biweekly schedule of capecitabine combined with irinotecan (XELIRI), consecutively with irinotecan and oxaliplatin (XELIRINOX), was evaluated in patients with metastatic cancer from any solid tumors. PATIENTS AND METHODS: In this two-step phase I trial, seventeen and eleven patients were enrolled in the XELIRI and XELIRINOX stages, respectively. RESULTS: In XELIRI, a total of 136 chemotherapy cycles were administered with a median number of 8 cycles per patient (2-16). Main dose-limiting toxicities (DLT) were grade 3-4 neutropenia, with one toxicity-related death. Maximum tolerated dose (MTD) for capecitabine combined with 180 mg/m(2) of irinotecan was 3,500 mg/m(2)/day. In XELIRINOX, capecitabine starting dose was 2,500 mg/m(2)/day. Fifty-eight chemotherapy cycles were administered with a median of 4 cycles per patient (1-16). DLT included 3 grade 4 neutropenia, associated with 1 grade 3 diarrhea, and 1 grade 4 pneumopathy leading to patient death. MTD for capecitabine with 180 mg/m(2) of irinotecan and 85 mg/m(2) of oxaliplatin was 3,000 mg/m(2)/day. The recommended doses for capecitabine were 3,000 and 2,500 mg/m(2)/day D1-D7 in combination with 180 mg/m(2) of irinotecan in XELIRI, plus 85 mg/m(2) of oxaliplatin in XELIRINOX (D1 = D14), respectively. CONCLUSION: XELIRI and XELIRINOX regimens are feasible and warrant further investigation in combination with targeted therapy in metastatic colorectal cancer patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Camptotecina/farmacocinética , Camptotecina/uso terapéutico , Capecitabina , Cromatografía Líquida de Alta Presión , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacocinética , Desoxicitidina/uso terapéutico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Estudios de Factibilidad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/análogos & derivados , Fluorouracilo/farmacocinética , Fluorouracilo/uso terapéutico , Glucuronosiltransferasa/genética , Humanos , Irinotecán , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Mutación , Metástasis de la Neoplasia , Neoplasias/genética , Neoplasias/patología , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Compuestos Organoplatinos/farmacocinética , Compuestos Organoplatinos/uso terapéutico , Oxaliplatino , Estudios ProspectivosRESUMEN
BACKGROUND AND STUDY AIMS: The aim of this study was to assess whether preoperative endorectal ultrasound (ERUS) is able to predict histological infiltration of the external anal sphincter or the levator ani muscle in patients with a lower-third rectal neoplasm and so the possibility of treatment by sphincter-saving surgery. PATIENTS AND METHODS: Between May 1996 and May 2003, 66 patients with a lower-third rectal neoplasm that was staged as uT2 or greater were entered into a prospective evaluation of ERUS. All patients underwent neoadjuvant treatment before surgery. RESULTS: The first ERUS (ERUS 1) was performed before neoadjuvant treatment; the second ERUS (ERUS 2) was performed between the end of the radiotherapy and the surgery. An abdominoperineal resection was performed mainly when the lower extent of the tumor was within 3.5 cm from the anal verge (P = 0.011), but no correlation was observed between the lateral clearance determined by ERUS 1 and the histological clearance (P = 0.091). After neoadjuvant treatment, the ERUS 2 lateral clearance was significantly correlated with the type of surgery (P = 0.003) and the histological clearance (P < 0.001). With regard to the performance of ERUS 2 for predicting histological infiltration of the external anal sphincter or the levator ani muscle, the sensitivity was 100%, the negative predictive value was 100%, the specificity was 87%, and the positive predictive value was 53%. In a multivariate analysis, the histological clearance and tumor T stage were statistically correlated with disease-free survival (P = 0.035 and P = 0.05, respectively). CONCLUSIONS: ERUS could help oncologists and surgeons in the management of patients with lower rectal carcinomas. Moreover, ERUS is able to predict lateral histological clearance after neoadjuvant treatment.