Colon
Oxaliplatin-Bevacizumab Combination Regimen Shows a Better Survival Advantage in Advanced Colorectal Cancer,2 studies show
By Akanksha,Pharmacology Correspondent
Jan 31, 2005, 20:26

Sanofi-aventis announced today preliminary results of two large prospective trials evaluating the safety and efficacy of Eloxatin(R) (oxaliplatin for injection)-based regimens in the treatment of metastatic colorectal cancer.These data were presented at the Gastrointestinal Cancers Symposium, co-sponsored by the American Society of Clinical Oncology (ASCO), the American Gastroenterological Association (AGA), the American Society for Therapeutic Radiology and Oncology (ASTRO), and the Society of Surgical Oncology (SSO).

TREE-2 is the first study to assess the safety of oxaliplatin-based regimens combined with bevacizumab for the first-line treatment of metastatic colorectal cancer. Preliminary efficacy results suggested that adding bevacizumab improved the response rate of all oxaliplatin-based regimens.

Researchers from the Eastern Cooperative Oncology Group (ECOG) also reported results of the E3200 study, which demonstrated a significant 26 percent reduction in the risk of death for patients receiving oxaliplatin-based chemotherapy (FOLFOX4) plus bevacizumab compared to those who received oxaliplatin alone. Although patients in the E3200 study had previously been treated for advanced or metastatic colorectal cancer, median overall survival with oxaliplatin-based chemotherapy plus bevacizumab was 12.5 months compared to 10.7 months with oxaliplatin alone.The difference is statistically significant and corresponds to a 17 percent improvement in median overall survival in this
previously treated patient population.

The randomized, multicenter TREE-2 (A Randomized, Prospective Study Comparing Three Regimens of oxaliplatin Plus Fluoropyrimidine and Bevacizumab for Evaluation of Safety and Tolerability in First-Line Treatment of Patients with Advanced Colorectal Cancer) is the first study evaluating the safety and tolerability of bolus, infusional, and oral fluoropyrimidine + oxaliplatin-based regimens combined with bevacizumab for the first-line treatment of metastatic colorectal cancer.

In the TREE-2 study, 213 adults aged 18 or older with metastatic colorectal cancer were treated with one of three oxaliplatin-containing chemotherapy regimens: oxaliplatin plus infusional 5-fluorouracil/leucovorin,oxaliplatin plus bolus 5FU, and oxaliplatin plus capecitabine,all used in combination with bevacizumab.The preliminary results of TREE-2 assessed the tolerability of the three oxaliplatin/fluoropyrimidine regimens with bevacizumab. There were no unexpected toxicities.The best treatment response rates were seen when bevacizumab was added to oxaliplatin or capecitabine. Full efficacy results are expected to be presented at the 2005 ASCO Annual Meeting in May 2005.

The E3200 study, a phase III randomized study of oxaliplatin, fluorouracil, and leucovorin calcium with or without bevacizumab versus bevacizumab alone in patients with previously treated advanced or metastatic colorectal
adenocarcinoma , was sponsored by the National Cancer Institute (NCI) and conducted by a network of researchers led by the ECOG.A total of 829 patients were enrolled in the study between October 2001 and April 2003.

Preliminary results were announced in December 2004. Sanofi-aventis provided oxaliplatin for the trial under its Cooperative Research and Development Agreement (CRADA) with the NCI for the clinical development of oxaliplatin.

Oxaliplatin, used in combination with infusional 5-FU/LV, is indicated for adjuvant treatment of stage III colon cancer patients who have undergone complete resection of the primary tumor. The indication is based on an improvement in disease-free survival, with no demonstrated benefit in overall survival after a median follow-up of 4 years.

Oxaliplatin, used in combination with infusional 5-FU/LV, is indicated for the treatment of advanced carcinoma of the colon or rectum.

Oxaliplatin should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate diagnostic and treatment facilities are readily available.

Anaphylactic-like reactions to oxaliplatin have been reported and may occur within minutes of oxaliplatin administration. Epinephrine, corticosteroids, and
antihistamines have been employed to alleviate symptoms, and discontinuation of oxaliplatin therapy may be required.

In Adjuvant Colon Cancer Setting,the incidence of grade3 or grade4 events was 70% and 31% on oxaliplatin combination arm and infusional 5-FU/LV arm, respectively. Granulocytopenia,paresthesia, diarrhea, vomiting,and nausea were the most common grade3 or 4 adverse events.Paresthesia was seen in 92% of patients on the oxaliplatin combination; 21% had residual paresthesia at 18-month follow-up.Three percent and 0.5% had grade2 and 3paresthesias,respectively, at 18-month follow-up.Grade 3 or 4 hypersensitivity was noted in 3% and may require discontinuation of therapy. Hepatotoxicity, evidenced by increase in transaminases(57% vs 34%) and alkaline phosphatases (42% vs 20%),was observed more commonly in the oxaliplatin arm.The incidence of increased bilirubin was similar on both arms.Hepatic vascular disorders should be considered and investigated if abnormal liver function tests or portal hypertension are present and cannot be explained by liver metastases or other known etiologies.
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Sanofi-aventis is the world's 3rd largest pharmaceutical company, ranking number 1 in Europe. Backed by a world-class R&D organization, sanofi-aventis is developing leading positions in seven major therapeutic areas:
cardiovascular disease, thrombosis, oncology, diabetes, central nervous system, internal medicine, vaccines. Sanofi-aventis is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).

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