Radiochemotherapy with short daily infusion of low-dose oxaliplatin, leucovorin, and 5-FU in T3-T4 unresectable rectal cancer: a phase II IATTGI study.

PURPOSE: Oxaliplatin (OXA)/5-fluorouracil (5-FU) have confirmed their preclinical synergy in advanced colorectal cancer patients. Chemoradiotherapy with 5-FU + leucovorin (LV) is considered the standard treatment in unresectable rectal cancer patients. The objective was to evaluate OXA with 5-FU + LV and concurrent radiotherapy in unresectable rectal cancer patients. TREATMENT: OXA 25 mg/m(2)/day in 30-min infusions, followed by bolus LV 20 mg/m(2)/day and bolus 5-FU 375 mg/m(2)/day. All drugs were given on 4 days during Weeks 1 and 5 of a standard radiotherapy cycle (50.4 Gy). A single OXA dose (50 mg/m(2)) was also given on the third week of radiotherapy. A cycle of OXA with 5-FU + LV was administered 4 weeks after chemoradiotherapy, with surgery planned 4 weeks later. RESULTS: Between March 1998 and April 2000, 22 patients with T3-T4 unresectable rectal cancer were accrued. Patient characteristics included the following: 11 females, 11 males, median age 58 (range: 18-76). Performance status ECOG (PS) 0: 2 patients, PS 1: 7 patients, and PS 2: 13 patients. The following RTOG Grade 3-4 toxicities were reported: diarrhea, 6 patients; cutaneous, 3 patients; neutropenia-leukopenia, 2 patients; and thrombocytopenia, 1 patient; 1 treatment-related death resulted (febrile neutropenia-sepsis after chemoradiotherapy). Only 1 patient had neurosensory Grade 2 (OXA-specific Levi's scale) toxicity. Nine patients had PS worsening during treatment. Five patients had chemoradiotherapy delay (median: 6 days). Of 22 patients, 16 underwent surgery (without serious surgical complications); 12/16 had a complete resection (5/12 had sphincter preservation). Pathologic examination revealed 3/12 complete remissions, 2/12 minimal microscopic residual disease, 2/12 T2N0, 1/12 T3N0, and 4/12 positive nodes; 4/16 had unresectable disease. Median follow-up was 15 months (range: 3.0-43.4 months), median time to progression was 15.7 months (CI 95%, 0, 31.7), and median overall survival was 19.5 months (CI 95%, 18.0, 21). CONCLUSIONS: Outpatient treatment with low-dose, 30-min daily OXA infusion was feasible and very active, with acceptable toxicity.

Radioquimioterapia concurrente en pacientes con tumores digestivos localmente avanzados y diseminados / Radiochemotherapy in patients with locally advanced digestive tumors

Objetivos: Evaluamos en forma retrospectiva: factibilidad, toxicidad, respuesta, paliación de síntomas (Pal S) y sobrevida en 41 pacientes (PTS) con tumores digestivos (TD) localmente avanzados (LA) y avanzados (AV) tratados con radioquimioterapia. Pacientes y Métodos: Entre 7/94 y 4/96, y basados en un esquema de la Mayo Clinic (J Clin Oncol 12, 1994), losPTS recibieron: radioterapia (1,8 Gy/d, 5d x semana) + quimioterapia concurrente (5FU 400 mg/m al cuadrado/d + leucovorina-LV-20 mg/m al cuadrado/d, ambos en bolo i.v. por 4 d en la primera semana y por 3 ó 4 d en la última semana de radioterapia) y 2 cursos posteriores de quimioterapia con 5FU + LV. Veintiocho PTS tenían TD altos: 22 LA y 6 AV, 13 PTS tenían TD bajos: 9 LA y 4 AV. Resultados: La Pal S para PTS LA-AV fue del 68 por ciento-33 por ciento en TD altos y 44 por ciento-75 por ciento en TD bajos. Las respuestas completas y parciales en PTS LA con TD altos fueron 18 por ciento-41 por ciento y en TD bajos 22 por ciento-44 por ciento. Con una mediana de seguimiento para PTS LA-AV de 6 - 4 m en TD altos y de 11 - 11 m en TD bajos están vivos: 68 por ciento - 33 por ciento y 66 por ciento - 75 por ciento de los PTS. TOXICIDAD MAS FRECUENTE: RADIOQUIMIOTERAPIA: G1-2: anemia 54 por ciento, fatiga 49 por ciento, diarrea 34 por ciento, náuseas 29 por ciento, leucopenia 20 por ciento, eritema 12 por ciento; G3: diarrea 10 por ciento. QUIMIOTERAPIA: G1-2: anemia 27 por ciento, náuseas 27 por ciento, diarrea 27 por ciento, mucositis 23 por ciento. Conclusiones: en nuestro medio, este plan ambulatorio fue sencillo, factible y de toxicidad aceptable. Es un esquema recomendable para el manejo paliativo de PTS con TD y para el tratamiento neoadyuvante de PTS con tumores rectales (favoreciendo la resecabilidad)