Chemo-Immunotherapy Regimen Boosts Survival in CRC

June 2011, Vol 2, No 3 -

Orlando, FL—A regimen that combines immunotherapy with chemotherapy doubled the overall survival (OS) time in patients with advanced colorectal cancer (CRC) over a standard chemotherapy regimen alone and improved progression-free survival (PFS), reported Pierpaolo Correale, MD, PhD, of Siena University School of Medicine, Italy.

The immunotherapy involved the combination of recombinant interleukin (IL)-2 and growth factors, an approach that is very experimental in CRC management. Patients with CRC are usually treated with chemotherapy that includes various combinations of fluorouracil or capecitabine (Xeloda), leucovorin, irinotecan (Camptosar), and oxaliplatin (Eloxatin; FOLFIRI or FOLFOX).

Recently, patients have also been routinely treated with bevacizumab (Avastin), cetuximab (Erbitux), or panitumumab (Vectibix); however, this study was initiated in 2005, before these monoclonal antibodies were used.

“These combinations have been successful in inducing tumor regression, retarding disease progression, and increasing overall survival,” said Dr Correale. However, the average PFS and OS “are still no more than 8 to 10 months and 20 to 22 months, respectively,” he noted.

He and his colleagues added gemcitabine to FOLFOX followed by granulocyte- macrophage colony-stimulating factor and low-dose aldesleukin (Proleukin; IL-2; GOLFIG) to boost the immune system. They randomized 130 patients to GOLFIG or to FOLFOX for 12 cycles, followed by a regimen of maintenance therapy.

The study was halted early because of the superior results seen with GOLFIG in the planned interim analysis, Dr Correale said.

Patients who received GOLFIG had a 16.5-month PFS compared with 7.5 months for those receiving FOLFOX—a 9-month improvement over standard treatment. The chemoimmunotherapy regimen was associated with an overall response rate of 63.1% compared with 33.8% with FOLFOX.

Although OS was not a principal outcome, the 30-month median survival in the GOLFIG armrepresented a >60% reduction in risk.

Adverse events were slightly more common in the GOLFIG arm, and 16% receiving the immunotherapy had fever related to IL-2, aswell as self-limiting signs of autoimmunity. “These patients showed the best outcome, a finding that suggests the real involvement of the immune system in conditioning patients’ outcomes,” Dr Correale suggested.

Coinvestigator Piersandro Tagliaferri, MD, commented, “We believe these results confirmthe importance of using the patient’s immune system to treat colon cancer.”

Because biologics have been shown to improve outcomes compared with chemotherapy alone, the GOLFIG regimen would best be compared with regimens containing monoclonal antibodies, the investigators acknowledged.