RESUMEN
BACKGROUND: To investigate the activity and toxicity of high dose (HD) infusional 5-FU in comparison to EAP regimen as first-line chemotherapy in patients with advanced gastric cancer. PATIENTS AND METHODS: Histologically confirmed measurable advanced gastric cancer, age < 72 yr, ECOG performance status 0-2, no prior chemo- and radiotherapy, adequate organ functions. TREATMENT: EAP arm: doxorubicin (40 mg/m(2)), etoposide (360 mg/m(2)), and cisplatin (80 mg/m(2)) every 28 d; HD 5-FU arm: 5-FU 2.6 g/m(2) 24 h infusion, biweekly. RESULTS: Sixty patients were randomized. Patient characteristics (arms EAP/HD 5-FU): Median age 57/55 yr, median PS 1/1, LAD (patients) 3/8, M1 (patients) 27/22. Median number of cycles (range): EAP arm 4 (2-8), HD 5-FU arm 2 (1-8). Worst toxicity per cycle (grade 3 and 4 in%): Neutropenia 20/3, thrombocytopenia 9/0, anemia 9/13, diarrhea 3/10, nausea 17/7, vomiting 10/0 for EAP and HD 5-FU arms, respectively. All patients were eligible for response in both arms. Confirmed response rate (95%CI): EAP arm 34% [16-50%]/HD 5-FU arm 10% (0-21%), no change: 46/40%, progression of disease: 20/50, respectively. Overall survival (range): EAP arm A 7 mo [3-27], HD 5-FU arm 6 mo (4-25). CONCLUSIONS: Infusional HD 5-FU showed a low incidence of severe toxicity. But given the low efficacy of 5-FU in the dosage we applied in the study, it cannot be recommended as a single treatment for further studies. Assessment of higher dose intensity and/or dose density of 5-FU, with introduction of other active drugs in combination, could be an option for further studies.
Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fluorouracilo/administración & dosificación , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/efectos adversos , Cisplatino/uso terapéutico , Progresión de la Enfermedad , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Esquema de Medicación , Etopósido/efectos adversos , Etopósido/uso terapéutico , Femenino , Fluorouracilo/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias Gástricas/mortalidadRESUMEN
As the number of active drugs for colorectal cancer increases, we continually revisit the question of how best to integrate them. We investigated whether sequential chemotherapy consisting of only bolus plus infusional 5-fluorouracil/folinic acid could be comparable, concerning overall survival, to sequential chemotherapy consisting of bolus 5-fluorouracil/folinic acid plus "new-generation" drugs like CPT-11 or oxaliplatin. Patients with histologically verified locally advanced disease and/or metastatic colorectal adenocarcinoma, without possibility for surgical resection, were eligible for the study. The treatments were: Cohort A--Mayo Clinic Regimen (MCR) in first line, "de Gramont" regimen in second line; Cohort B--MCR in first line, CPT-11 (350mg/m2) in second line; Cohort C--MCR in first line, oxaliplatin (85mg/m2) plus "de Gramont" regimen in second line. A total of 89 patients received first plus second line chemotherapy and all of them were analyzed for survival. Number of patients/cohort: A-32 B-27; C-30. The median survival time of the patients was 15, 11, and 17 months for the patients in cohorts A, B, and C, respectively. Survival of the patients in cohort C was significantly better than survival of the patients in cohort B (log-rank test, p=0.04). There was not a significant difference in overall survival between the cohorts A vs. C (log-rank test, p=0.52) and B vs. C (log-rank test, p=0.27). It is conceivable that infusional HD 5-FU could serve as a basis for first and second-line protocols in which other drugs are added to this regimen. Infusional 5-FU plus oxaliplatin in sequential pattern of application after bolus 5-FU has the best overall survival in comparison to other cohorts. CPT-11 applied as a single drug, was not effective enough in comparison to other treatment options.