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)

New studies answer key questions about the treatment of gastrointestinal cancers

Findings from a number of large clinical trials of new treatment regimens for gastrointestinal cancers were released today at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO), being held in Orlando, May 29 - June 2, 2009 and will be highlighted in Onco’Zine – The international Cancer Blog.

“The studies presented today answer many important questions about the best care for people with gastrointestinal cancers,” said Nicholas Petrelli, MD, medical director of the Helen F. Graham Cancer Center in Wilmington, Delaware. “These large, conclusive trials tell us what works, and importantly, tell us what doesn’t work. Some settle long-time debates in the field, others demonstrate that the current standard of care is actually superior to experimental treatments, and others will allow patients to avoid unnecessary side effects or surgery.”

The results presented include:

• First-ever data on bevacizumab as adjuvant therapy finds no benefit in colon cancer: A phase III trial finds that adding the targeted therapy bevacizumab (Avastin, Roche), to standard adjuvant chemotherapy did not improve disease free survival for patients with locally advanced colon cancer.
• Surgery unnecessary for majority of patients with advanced colorectal cancer: Most patients with metastatic colorectal cancer can safely avoid surgery on their primary tumors.
• A trial compares common adjuvant treatments for pancreatic cancer: A phase III trial comparing the adjuvant treatments most commonly used for pancreatic cancer in the United States and Europe, gemcitabine (Gemzar, Eli Lilly and Company) and 5-FU/FA, respectively, found that there is no difference in survival between the two regimens, though gemcitabine was associated with fewer side effects.
• The largest study to date on anal cancer supports the current standard: A phase III study finds that the current standard of care for anal cancer should not be changed, and that ongoing maintenance therapy after initial treatment is not effective.
• Oxaliplatin does not improve outcomes for rectal cancer: Adding oxaliplatin (Eloxatin, Sanofi-Aventis) to standard treatment in patients with locally advanced rectal cancer does not improve tumor response. However, a preliminary analysis seems to suggests that the treatment may reduce distant metastases.

For more information:

• American Society of Clinical Oncology
• 2009 ASCO annual meeting abstracts

Reference:

• Medical-Oncology (at Boomja.com)