Use of the ratio of time to progression following first- and second-line therapy to document the activity of the combination of oxaliplatin with 5-fluorouracil in the treatment of colorectal carcinoma

Background: It has been proposed that the activity of a second-line treatment regimen can be documented by showing that the time to progression (TTP) following second-line therapy is longer than the TTP following first-line therapy in the same patients. Patients and methods: The ratio of TTP during first and second-line therapy, identified as the growth modulation index (GMI), was determined in 34 patients with advanced colorectal cancer. First-line chemotherapy consisted of one of several schedules of leucovorin (LV)-modulated 5-fluorouracil (5-FU) or raltitrexed. Second-line therapy consisted of the combination of LV-modulated 5-FU and oxaliplatin (l-OHP). Patients were switched to second-line therapy upon evidence of progressive disease following first-line therapy. Results: Median TTP following first-line therapy was 13 weeks (95% confidence interval (CI): 7.6-18.7), while median TTP following second-line therapy was 31 weeks (95% CI: 21.3-41.0). Sixteen patients (47%; 95% CI: 35%-59%), showed a GMI greater than or equal to1.33, while the remaining 18 patients (53%; 95% CI: 40%-66%) had a GMI <1.33. Log-rank analysis of the Kaplan-Meier curves of TTP following first- versus second-line therapy demonstrated a statistically significant difference in favour of second-line therapy (P = 0.0081). Conclusions: This study demonstrates the utility of the GMI as a tool for assessing the activity of novel second-line therapeutic programs.