No Improvement in Local Tumor Response by adding Oxaliplatin to Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer

A large, multicenter Italian study has found that adding oxaliplatin (Eloxatin, Sanofi-Aventis) to standard preoperative radiochemotherapy in patients with locally advanced rectal cancer does not improve tumor shrinkage.

However, preliminary and exploratory data from the study, presented on Saturday, May 30, 2009 by Carlo Aschele, MD, PhD, E.O. Ospedali Galliera, (Mura delle Cappuccine, 1416128 Genova (Ligurie), Italy, Phone +39 010 5 6321) during the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO) being held from May 27 – June 2, 2009 in Orlando, Florida, suggest that it may reduce the number of distant metastases.

Chemotherapy and radiation are often administered before surgery for rectal cancer to shrink the tumor and make it easier to remove. Previous results from this study showed that although adding oxaliplatin to standard chemotherapy increased some side effects, especially diarrhea, it did not affect the ability to deliver the full course of radiation therapy or to perform surgery. Oxaliplatin has been found effective and is commonly used in patients with more advanced colon and rectal cancer.

In this phase III trial, 747 patients with locally advanced rectal cancer were randomized to receive standard preoperative chemoradiotherapy or the standard plus oxaliplatin. Researchers found no significant difference between the two groups in terms of tumor reduction: 16 percent of patients in both groups had no tumor present at the time of surgery, and 29 percent in the oxaliplatin group had mildly invasive tumors (T1 or T2) without nodal involvement, compared with 30 percent in the control group. There was also no significant difference in the number of patients who had cancer in the lymph nodes (27 percent in the oxaliplatin group versus 25 percent in the control group). Consistently, the proportions of patients who could have conservative surgery were similar between the two arms.

In an unplanned analysis, when looking at intra-abdominal disease spread at the time of surgical removal of the primary tumor, only 0.5 percent of patients in the oxaliplatin group (2 patients) had distant metastases, versus 3 percent in the control group (11 patients), a difference that was statistically significant.

“Although adding oxaliplatin to the current standard of care did not improve tumor response rates, we found this course of treatment was associated with a reduced number of early distant metastases in the abdomen in a very small number of patients,” said Carlo Aschele, MD, PhD, attending physician and lead clinician in Colorectal/Gastrointestinal Cancer in the Department of Medical Oncology and Cancer Prevention at E.O. Ospedali Galliera in Genoa, Italy, and the study’s first author.

“Although the numbers are very small and the analysis of distant metastases was unplanned and exploratory, the difference is significant and indicates that the lack of an effect on local tumor shrinkage does not necessarily imply a lack of effect on micrometastases at distant sites. Longer follow-up is necessary to assess whether treatment with oxaliplatin will have an effect on recurrence rates or survival.”

Note: This article contains updated data not published in the original ASCO 2009 abstract

For more information:

• Aschele C, Pinto C, Cordio S, Rosati G, Tagliagambe A, Artale S, Rosetti P, Lonardi S, Boni L, Cionini L. Preoperative fluorouracil (FU)-based chemoradiation with and without weekly oxaliplatin in locally advanced rectal cancer: Pathologic response analysis of the Studio Terapia Adiuvante Retto (STAR)-01 randomized phase III trial. Abstract: CRA4008
• American Society of Clinical Oncology (ASCO)