Time to Definitive Health-Related Quality of Life Score Deterioration in Patients with Resectable Metastatic Colorectal Cancer Treated with FOLFOX4 versus Sequential Dose-Dense FOLFOX7 followed by FOLFIRI: The MIROX Randomized Phase III Trial.

PURPOSE: We previously showed that a sequential chemotherapy with dose-dense oxaliplatin (FOLFOX7) and irinotecan (FOLFIRI; irinotecan plus 5-fluorouracil/leucovorin) is not superior to FOLFOX4 in patients at advanced stage of colorectal cancer with liver metastases. Here we aimed to determine whether time to health-related quality of life (HRQoL) score definitive deterioration (TUDD) differs by study arm. METHODS: HRQoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 at baseline and every 4 cycles until the end of the study or death. Functional scale, symptom scale, global health status, and financial difficulties were analyzed. The TUDD was defined as the time interval between randomization and the first decrease in HRQoL score ≥ 5-point with no further improvement in HRQoL score ≥ 5 points or any further HRQoL data. TUDD was estimated using the Kaplan-Meier method and the long-rank test. Cox regression analyses were used to identify HRQoL items influencing TUDD. Sensitivity analyses were done using a multiple imputation method and different definitions of TUDD. RESULTS: Of the 284 patients, 171 (60.2%) completed HRQoL questionnaires. Cox multivariate analysis showed no statistically significant difference in TUDD for most of the QLQ-C30 scales between treatments. Patients with dyspnea and those without symptoms at baseline had a significantly longer TUDD when there was a delay >12 months between diagnosis of the primary tumor and metastases (HR 0.48 [0.26-0.89]) and when there was diarrhea (HR 0.59 [0.36-0.96]), respectively. CONCLUSION: This study shows that TUDD does not differ significantly according to type of treatment. The TUDD method produces meaningful longitudinal HRQoL results that may facilitate effective clinical decision making in patients with mCRC. TRIAL REGISTRATION: ClinicalTrials.gov NCT00268398.

PEPCOL: a GERCOR randomized phase II study of nanoliposomal irinotecan PEP02 (MM-398) or irinotecan with leucovorin/5-fluorouracil as second-line therapy in metastatic colorectal cancer.

A multicenter, open-label, noncomparative, randomized phase II study (PEPCOL) was conducted to evaluate the efficacy and safety of the irinotecan or PEP02 (MM-398, nanoliposomal irinotecan) with leucovorin (LV)/5-fluorouracil (5-FU) combination as second-line treatment in patients with metastatic colorectal cancer (mCRC). Patients with unresectable mCRC who had failed one prior oxaliplatin-based first-line therapy were randomized toirinotecan with LV/5-FU (FOLFIRI) or PEP02 with LV/5-FU (FUPEP; PEP02 80 mg/m(2) with LV 400 mg/m(2) on day 1 and 5-FU 2400 mg/m(2) on days 1-2). Bevacizumab (5 mg/kg, biweekly) was allowed in both arms. The primary endpoint was 2-month response rate (RR). Fifty-five patients were randomized (FOLFIRI, n = 27; FUPEP, n = 28). In the intent-to-treat population (n = 55), 2-month RR response rate was observed in two (7.4%) and three (10.7%) patients in the FOLFIRI and FUPEP arms, respectively. The most common grade 3-4 adverse events reported in the respective FOLFIRI and FUPEP arms were diarrhea (33% vs. 21%), neutropenia (30% vs. 11%), mucositis (11% vs. 11%), and grade 2 alopecia (26% vs. 25%). FUPEP has activity and acceptable safety profile in oxaliplatin-pretreated mCRC patients.

Randomized trial of simplified LV5FU2 versus FOLFOX7 followed by FOLFIRI (MIROX) in patients with initially resectable metastatic colorectal cancer: a GERCOR study.

OBJECTIVES: To evaluate the MIROX strategy (6 FOLFOX7 cycles followed by 6 FOLFIRI cycles) in patients with resected or resectable metastases from colorectal cancer. METHODS: This trial compared the MIROX strategy to 12 cycles of simplified LV5FU2 (sLV5FU2). Chemotherapy was perioperative or adjuvant, at the investigator's decision, with stratification for this parameter. The primary objective was disease-free survival (DFS). The trial was interrupted in 2004, following the results of the adjuvant MOSAIC trial showing superiority of FOLFOX4 over LV5FU2. RESULTS: Thirty-nine patients were included: 20 in MIROX arm and 19 in sLV5FU2 arm. Median DFS was higher in the MIROX arm (not reached versus 24.8 months, P = 0.044). MIROX regimen was well tolerated; 5/20 patients experienced a Grade 3 sensoryneuropathy. CONCLUSION: The MIROX strategy demonstrated promising efficacy, but this must be considered cautiously due to the small number of patients included. The pragmatic approach adopted for the treatment chronology is feasible.