HOLLYWOOD, FLA. — The goal of chemotherapy for metastatic colorectal cancer is shifting, with greater emphasis now on reducing tumor size to allow for curative resection, Paulo Hoff, M.D., said at the annual meeting of the American College of Surgeons.
The ever-expanding arsenal of chemotherapeutic agents is increasing the likelihood that this goal will be met in a greater number of patients.
“The future is very bright—we have been able to improve dramatically the efficacy of chemotherapy for colorectal cancer,” said Dr. Hoff, deputy chairman of gastrointestinal medical oncology at M.D. Anderson Cancer Center, Houston.
Reducing tumor size would make more patients eligible for surgical resection, which is important, because it has long been known that patients with single or localized metastases who are able to undergo surgery have a 25%–35% chance of cure. However, only 10%–30% of patients are operable at the time of presentation, Dr. Hoff explained.
Data show that chemotherapy can indeed change a patient's status from nonresectable to resectable. In one retrospective study, an oxaliplatin-based regimen used in more than 700 previously nonresectable patients with liver metastases reduced tumor size enough to allow resection in 14% of the patients. Overall 5-year survival rates among 87 patients for whom 5 years of follow-up data were available were similar to those in patients who were resectable at presentation.
In several other studies, oxaliplatin as part of a combination regimen known as FOLFOX, which also includes fluorouracil and leucovorin, was consistently associated with a doubling of the rate of patients whose tumors shrunk by at least 50%, compared with any single drug. Survival also was improved.
Similar outcomes have been shown with irinotecan used in combination with 5FU-LV (a combination known as FOLFIRI).
Even more impressive results were seen when the monoclonal antibody bevacizumab was added to any of these regimens, Dr. Hoff said.
When bevacizumab was added to an irinotecan-based regimen, response rates climbed about 10% to a response rate of 45%, and median survival increased by about 5 months to a median survival of more than 20 months.
Another monoclonal antibody, cetuximab, also showed promise in preliminary trials. In a phase II study that combined the drug with the FOLFOX regimen, the response rate was 81%.
Another benefit of these emerging chemotherapeutic regimens for colorectal cancers is improved treatment of micrometastatic disease. Micrometastases that may remain following resection can lead to recurrence.
Several studies have shown that there is no significant improvement in survival or cure rates following incomplete resection, but tumor reduction may improve the chances of complete resection, Dr. Hoff said.
When tumor reduction isn't possible, the traditional goals of chemotherapy, including promoting survival, delaying tumor progression, and preventing tumor-related complications, still apply.
But with the recent advances—especially if they are combined with advances in surgery and radiation therapy techniques, as well as with systemic chemotherapy agents that target metastases beyond the liver—a major impact will be made on the treatment of colorectal cancer, Dr. Hoff said.