Oxaliplatin with Weekly Bolus 5-Fluorouracil and Leucovorin in Pretreated Advanced Colorectal Cancer Patients: A Phase II Study

Abstract

Background: The purpose of this study was to determine the efficacy and toxicity of oxaliplatin in combination with weekly bolus 5-fluorouracil (5-FU) and leucovorin (LV) in patients with 5-FU-pretreated advanced colorectal cancer. Methods: A total of 39 patients with documented 5-FU-resistant advanced colorectal cancer were enrolled. All 39 patients had previously received weekly high-dose 5-FU/LV (2,600 mg/m² 5-FU plus 100 mg/m² LV as 24-hour infusion) as first-line chemotherapy for metastatic disease. Oxaliplatin (85 mg/m²) was delivered as an intravenous infusion over 2 h on days 1 and 15, while 5-FU (500 mg/m²) and LV (20 mg/m²) were administered as an intravenous bolus on days 1, 8 and 15. One treatment course consisted of 3 consecutive weeks of therapy followed by a 1-week rest. Results: In an intent-to-treat analysis, the objective response rate for the 39 patients was 20.5% (95% confidence interval, 7.2–33.8%). The disease was stable in 19 patients (48.7%), and progressive in 11 (28.2%). The median survival for all 39 patients was 8.9 months. The median time to progression was 5.0 months. Grade 3/4 neutropenia occurred in only 1 patient (2.6%), and grade 2 and 3/4 peripheral neuropathy occurred in 10 (25.6%) and 5 (12.8%) patients, respectively. Conclusion: Oxaliplatin in combination with weekly bolus 5-FU/LV is also active in patients with advanced colorectal cancer where first-line treatment has failed.

The Irinotecan/5-Fluorouracil Combination Induces Apoptosis and Enhances Manganese Superoxide Dismutase Activity in HT-29 Human Colon Carcinoma Cells

“…The combination therapy with 5-FU/LV and CPT-11 or oxaliplatin demonstrated to be more active than 5-FU/LV as a first-line treatment. Oxaliplatin and CPT-11 combined, or not, with other agents are also active in the second-line treatment of colorectal carcinoma [2,47]. Hence, resistance to current therapies still remains one of the major problems in the treatment of colon cancers.…”

Irinotecan Combined with Infusional 5-Fluorouracil and High-Dose Leucovorin for the Treatment of Advanced Gastric Carcinoma as the First-Line Chemotherapy

“…Meanwhile, the combination of this kind of regimens with newer active drugs has provided good results without decreases in doses of both drugs [10][11][12] . In the context of colorectal cancer, regimens such as LV5FU2 were combined with irinotecan (CPT-11) or oxaliplatin, and these combinations were active in patients pretreated with 5-FU alone and improved the prognosis without a signifi cant increase in toxicity [10,11,13] .…”

Combined Systemic Chronotherapy and Hepatic Artery Infusion for the Treatment of Metastatic Colorectal Cancer Confined to the Liver

“…However, these protocols carry some degree of morbidity with moderate side effects relating especially to L-OHP as grade 3/4 neutropenia or neurotoxicity occurring in 41.7 and 68% of the patients, respectively [19,21] . The high reported response rate mentioned above was very disappointing when treating patients who were refractory to 5FU/folinic acid and irinotecan amounting to between 15 and 25% [22,23] . Our trial demonstrated a 40% partial response rate and stable disease for at least 4 months in 13% of the patients.…”