HOLLYWOOD, FLA. — New guidelines have broadened the options for adjuvant chemotherapy in colon cancer patients who are at high risk of recurrence to include the alkylating agent oxaliplatin and the antimetabolite drug capecitabine.
In the adjuvant setting, patients with stage III colon cancer (tumor-node-metastasis T1-3, N1-2 [any lymph node involvement], M0) should receive oxaliplatin with 5-fluorouracil (5-FU) and leucovorin (the FOLFOX regimen); or capecitabine (Xeloda); or 5-FU and leucovorin without oxaliplatin, Paul Engstrom, M.D., said when presenting the updated guidelines at the annual conference of the National Comprehensive Cancer Network (NCCN).
The updates reflect large-scale clinical trial findings, said Dr. Engstrom, chair of the NCCN colon cancer guideline panel.
The oxaliplatin recommendation is based on findings from the Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) study in which investigators compared the toxic effects and efficacy of the three-drug FOLFOX regimen against that of the 5-FU/-leucovorin regimen. The study, which included about 2,200 patients with resected stage II or stage III colon cancer randomized to 6 months of treatment with one of the two regimens, showed stage III patients receiving FOLFOX had a 24% reduction in their relative risk of disease recurrence after 3 years, compared with the non-oxaliplatin group.
The data showed a significant disease-free survival benefit for stage III patients, but not for stage II patients, said Dr. Engstrom of the Fox Chase Cancer Center, Philadelphia.
Given the incidence of oxaliplatin-associated toxicities—41% of patients experienced neutropenia higher than grade III, and 12.4% experienced reversible grade III peripheral sensorial neuropathy—the new guidelines do not recommend the FOLFOX regimen for most stage II patients, Dr. Engstrom said.
The oxaliplatin-containing regimen may be an option for patients with stage II colon cancer who are considered to be at high risk for cancer recurrence based on primary tumor staging, the guidelines state.
The capecitabine recommendation reflects the findings of the Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) trial of nearly 2,000 patients with stage III disease randomized to receive capecitabine or intravenous 5-FU/leucovorin following tumor resection. Taken orally, capecitabine is converted by the body into 5-FU. The X-ACT results showed capecitabine had better disease-free survival and overall survival rates than the 5-FU/leucovorin regimen and caused significantly fewer serious side effects, although hand-and-foot syndrome was significantly more common in the capecitabine group, he said.
The added options for adjuvant colon cancer therapy have contributed to a sense of optimism in treatment. Because the guidelines give equal weight to the adjuvant therapy recommendations, the choice of which regimen to use should depend on the risk to the patient, he said.
Last updated in 2004, the colon cancer guidelines also include these changes:
▸ Distinctions between three levels of stage III disease (stages IIIA, IIIB, and IIIC) to better target therapeutic decisions.
▸ The recommendation that radiotherapy be considered for use in combination with 5-FU/leucovorin for patients with advanced stage III disease with tumors that have invaded other organs or structures or have perforated the visceral peritoneum, and those with one or two regional metastases.
▸ The inclusion of a restructured treatment algorithm that includes chemotherapy with bevacizumab (Avastin) for patients with advanced colon cancer, giving equal weight to all of the commonly used regimens, including FOLFOX, FOLFIRI (5-FU/leucovorin/irinotecan), irinotecan and bolus 5-FU/leucovorin—all with or without bevacizumab—and 5-FU/leucovorin with bevacizumab.
▸ A recommendation that computed tomography be explored in the surveillance period for those at high risk of recurrence.
▸ A suggestion that laparoscopic surgery be considered instead of open surgery for resection of limited disease.
▸ A recommendation that staging of disease following primary resection of the tumor should be based on results from sampling a minimum of 12 lymph nodes.
▸ The addition of a section regarding risk assessment for stage II disease that recommends physician/patient discussion about treatment options and factors to consider when determining whether adjuvant therapy should be administered.
The NCCN is an alliance of 19 institutions designated comprehensive cancer centers by the National Cancer Institute.