New colon cancer guide features major changes

A major change in the treatment of advanced or metastatic colon cancer has been made in a new update from the National Comprehensive Cancer Network (NCCN). The network's "Clinical Practice Guidelines in Oncology: Colon Cancer," published in January, were revised to reflect new scientific data and expert judgment.

For one, the update has added the regimen CapeOx, a combination of capecitabine (Xeloda, Roche) and oxaliplatin (Eloxatin, Sanofi-Aventis), as an alternative to FOLFOX for the treatment of advanced or metastatic colon cancer. The FOLFOX regimen includes oxaliplatin, leucovorin, and 5-fluorouracil (5-FU).

"I think many physicians were already gaining experience with this regimen [CapeOx] and are comfortable giving it," said Mark Kirstein, Pharm.D., assistant professor of experimental and clinical pharmacology at the University of Minnesota's Cancer Center and College of Pharmacy. He pointed out that the European head-to-head trial of CapeOx and FOLFOX will likely provide some of the data clinicians have been lacking.

NCCN also recommends discontinuation of oxaliplatin from FOLFOX or CapeOx after three months of therapy-or sooner if significant neurotoxicity develops (>grade 3)-with other drugs maintained until the time of tumor progression. Oxaliplatin may then be reintroduced if it was discontinued previously for neurotoxicity rather than for disease progression.

"There is acute and chronic," said Kirstein of oxaliplatin-associated neurotoxicity. "The chronic is the one that requires a dosage adjustment or stopping the regimen." With FOLFOX, Kirstein explained, some physicians will give oxaliplatin for six cycles and then stop, but continue with the 5-FU.

Following disease progression on a bevacizumab (Avastin, Genentech)-containing regimen, the new guide has now added two new options for treatment: FOLFIRI plus cetuximab (Erbitux, BMS/ImClone), or irinotecan (Camptosar, Pfizer) plus cetuximab. The FOLFIRI regimen includes treatment with 5-FU, leucovorin, and irinotecan. Cetuximab may also be used as a single-agent therapy for patients who cannot tolerate irinotecan. According to NCCN, there are no data to support continued use of bevacizumab with a second-line regimen after first progression on a bevacizumab-containing regimen and, therefore, it is not routinely recommended. Practitioners should keep in mind that there is an increased risk of stroke and other arterial events, especially in the over-65 population. The use of bevacizumab may also interfere with wound healing.

The NCCN colon cancer panel also added panitumumab (Vectibix, Amgen) as an alternate option to cetuximab after first or second progression on previous therapy. Panitumumab has been Food & Drug Administration-approved for the treatment of patients with EGFR (epidermal growth factor receptor)-expressing metastatic colorectal carcinoma with disease progression on or following regimens containing fluoropyrimidine, oxaliplatin, or irinotecan. The NCCN panel stated that patients should not be excluded from this therapy, however, on the basis of EGFR results.

Kirstein believes that pharmacists can manage the supportive care surrounding a regimen, such as emetogenicity and neurotoxicity. "Another issue is the transition of many of our antitumor regimens toward more orally administered agents, like capecitabine. This requires us to counsel our patients, since they will be receiving more of their treatments away from the clinic."

The NCCN "Clinical Practice Guidelines in Oncology: Colon Cancer" can be accessed on-line at http://www.nccn.org/.