42nd Annual Meeting: Cetuximab plus FOLFOX 6 Beneficial as First-Line Therapy in Metastatic Colorectal Cancer

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Speaker: Shaker Dakhil, MD, President, The Cancer Center of Kansas, Wichita, Kansas

Preliminary results from a phase 2 study suggest that the combination of cetuximab (Erbitux, Bristol-Myers Squibb/ ImClone), an epidermal growth factor receptor (EGFR) targeting monoclonal antibody, with FOLFOX 6 (Oxaliplatin [Eloxatin, Sanofi-Aventis]), when added to simplified bimonthly leucovorin (Leucovorin, Roxane) and a 5-fluorouracil (5-FU) regimen, was safe and effective as a first-line therapy in EGRF-positive patients with metastatic colorectal cancer.

Eighty-two patients who were 18 years of age or older with locally advanced or metastatic colorectal cancer and no prior therapy for advanced disease were treated with cetuximab 400 mg/m² as a two-hour infusion on day one and 250 mg/m² on day eight. For all subsequent cycles, the patients received a one-hour infusion.

A modified FOLFOX 6 infusion was administered, consisting of oxaliplatin 85 mg/m² given as a two-hour infusion on day one, leucovorin 400 mg/m² given as a two-hour infusion simultaneously with oxaliplatin, and a 5-FU bolus 400 mg/m² given on day one, followed by a 5-FU continuous infusion of 2,400 mg/m² over 46 hours. Cycles were repeated every 14 days.

The study’s objectives were response rate, progression-free survival, overall survival, and the overall safety profile.
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Of the 82 patients, 66 were positive for EGFR expression; the median number of treatment cycles administered was 10. In the EGFR-positive group, the best outcomes were complete responses in three patients (6%), partial responses in 31 patients (57%), and stable disease in 16 patients (30%), for an overall response rate of 63%.

At the time of this report, 74 of the 82 patients (90%) were no longer in the study: five patients died during the study; 19 patients discontinued therapy because of toxicity; 34 patients discontinued therapy for disease progression; and four patients completed therapy.

Vorinostat Shows Promise in Advanced Colorectal Cancer

Speaker: Marwan Fakih, MD, Assistant Professor, Department of Medicine, University at Buffalo School of Medicine and Biomedical Sciences, and Staff Physician, Roswell Park Cancer Institute, Buffalo, New York

Vorinostat (Zolina, Merck), a novel histone deacetylase inhibitor, may have a role in the treatment of highly refractory advanced colorectal cancer.

In a phase 1 study, a group of patients with metastatic colorectal cancer received vorinostat twice daily orally at investi-gational dose levels of 100 mg, 200 mg, and 300 mg. None of these patients had responded to a previous combination of irinotecan (Camptosar, Pharmacia & Upjohn), cetuximab (Erbitux), FOLFOX (5-FU) leucovorin (Leucovorin), or oxali-platin (Eloxatin).

Vorinostat was given three days prior to FOLFOX and was administered for one week, followed by a one-week break. FOLFOX was administered at a fixed dose every two weeks, and leucovorin 400 mg/m² and oxaliplatin 85 mg/m² were given over two hours. This regimen was followed by a bolus of 5-FU 400 mg/m² and a 50-FU infusion of 2,400 mg/m² over 46 hours.

The primary endpoint of the study was to determine the recommended dose of this combination of vorinostat and FOL-FOX. canadian pharmacy viagra

In the eight patients evaluable for safety, no dose-limiting tox-icities were noted and no grade 3 toxicities were reported in the early cycles of treatment. Of the six patients evaluable for efficacy, four patients (one patient receiving vorinostat 100 mg and three patients receiving vorinostat 200 mg) experienced disease stabilization at more than five months and at two months, respectively. Two other patients receiving vorinostat 100 mg with biopsies showing liver metastases experienced a major decrease in thymidylate synthetase expression, the main target of 5-FU, after four days of vorinostat therapy.