Oxaliplatin Added to Simplified Bimonthly Low-Dose Leucovorin and 5-FU for Pretreated Advanced Colorectal Cancer Is Effective and Not Affected by Different Previous 5-FU Regimens

Abstract

This phase II study examined bimonthly oxaliplatin (85 mg/m2) added to a continuous infusion of fluorouracil (3000 mg/m2 for 46 h following a 400 mg/m2 bolus), with leucovorin (LV) (150 mg/m2) administrated in a simplified way to patients with metastatic colorectal cancers (CRC) refractory or resistant to 5-fluorouracil (5-FU). Sixty patients were registered. Of the 52 evaluable patients, 3 (5.8%) achieved a complete response (CR) and 18 (34.6%) achieved a partial response (PR). The overall response rate (CR + PR) was 40.4% (95% confidence interval [CI]: 26.6%-54.2%) for evaluable patients and 35% (95% CI: 22.6%-47.4%) by intention to treat. The median progression-free survival (PFS) was 5.2 months, and the median survival was 14.2 months. No significant differences were seen in response rates and PFS of patient groups pretreated either with high-dose 5-FU/LV by continuous infusion or with intravenous 5-FU/LV by a weekly bolus. From the 421 cycles analyzed, dose-limiting toxicities included cumulative sensory neuropathy and leukopenia, accounting for 11.6% and 10.0%, National Cancer Institute-Common Toxicity Criteria grade 3/4 toxicities per patient, respectively. Two (3.3%) patients experienced hepatic encephalopathy related to high-dose 5-FU. With necessary caution, this regimen was effective for 5-FU-pretreated CRC, regardless of ethnic differences, and it had the advantage of LV being administrated at a low dose in a simplified way.

Phase I study of biweekly gemcitabine followed by oxaliplatin and simplified 48‐h infusion of fluorouracil/leucovorin for advanced pancreatic cancer

“…In the present study, 60% (3/5) of respondants were taken off oxaliplatin because of grade 2 or higher cumulative sensory neuropathy after 5–6 cycles of treatment. This observation is consistent with our earlier experience of oxaliplatin plus infusional 5‐FU/LV in metastatic colorectal cancer 16,21 . It suggests that gemcitabine did not worsen the cumulative sensory neurotoxicity of oxaliplatin, as observed by Alberts et al 22 .…”

“…This observation is consistent with our earlier experience of oxaliplatin plus infusional 5-FU/LV in metastatic colorectal cancer. 16,21 It suggests that gemcitabine did not worsen the cumulative sensory neurotoxicity of oxaliplatin, as observed by Alberts et al 22 However, in contrast to the 42% of grade 1-2 acute laryngopharyngeal dysthesia in patients receiving 100 mg/m 2 of oxaliplatin, 22 the acute neurotoxicity was rarely observed in patients receiving ≤85 mg/m 2 oxaliplatin, 15 as was shown the patients in the present study. These observations further justify the limiting of the oxaliplatin dose to no greater than 85 mg/m 2 in the present study.…”

“…In addition, a fixed‐rate infusion of 1500 mg/m 2 of gemcitabine was shown to have a borderline better clinical outcome than a 30‐minute infusion of 2200 mg/m 2 three times weekly every 4 weeks for advanced pancreatic cancer 14 . The incorporation of oxaliplatin between the gemcitabine and infusional 5‐FU/LV was based on prior preclinical and clinical studies, which showed a synergy between gemcitabine and oxaliplatin being sequence‐dependent with gemcitabine followed by oxaliplatin inhibited cell growth more effectively than the opposite sequence in solid tumors, 12 as well as the synergy between oxaliplatin and infusional 5‐FU/LV 15,16 . The use of a biweekly schedule (as well as the use of 3000 mg/m 2 of 5‐FU and 300 mg/m 2 of LV) rather than the original weekly GemFL 24 regimen was based on our experience of promising efficacy and excellent compliance of a biweekly modified FOLFOX regimen for refractory colorectal cancer patients, 16 and the promising results of a biweekly modified LV5FU2 with gemcitabine for advanced pancreatic cancer 20 …”

Severe anaphylactic reactions in patients receiving oxaliplatin therapy: a rare but potentially fatal complication

“…It is particularly useful in the treatment of colorectal cancer and has shown scheduling flexibility in combination with 5-fluorouracil/ leucovorin (FL), both in advanced disease and adjuvant setting [2,6,9,13]. With the wide application of oxaliplatin, there is increasing concern about its toxicity profile.…”

Phase II Trial Alternating FOLFOX-6 and FOLFIRI Regimens in Second-Line Therapy of Patients with Metastatic Colorectal Cancer (FIREFOX Study)

“…A limiting neurotoxicity occured in 15 percent of the patients. In the Hsieh's Phase II study, a FOLFOX4 regimen administered in 5-FU resistant metastatic CRC achieved a 35 percent RR, with median PFS and OS of 5.2 and 14.2 months, respectively (26). A limiting sensory-neuropathy occured in 11.6 percent of the patients.…”