Crystal Trial Confirms Central Role of Irinotecan in Metastatic Colorectal Cancer

New Data Reinforce Importance of Irinotecan Regimen in First Line Setting

BARCELONA--(BUSINESS WIRE)--June 30, 2007--Data presented for the first time in Europe reinforce the position of irinotecan as a key component of first line therapy in the management of patients with metastatic colorectal cancer (mCRC).

Colorectal cancer is the most common cancer in Europe, and the third most common cancer worldwide. Each year, 138,000 Europeans die from the disease. However, colorectal cancer is preventable in most cases and highly treatable if diagnosed in its early stages.

"With colorectal cancer affecting so many people, we as physicians need to understand how each available therapy affects patients, so we can evaluate their benefits when choosing treatment options," said Markus Moehler, Assistant Professor for GI Oncology, Johannes Gutenberg University, Mainz, Germany. "Metastatic disease means patients need a lot of treatment, so we need to consider how well they can cope with each element of therapy. FOLFIRI is an important regimen of choice throughout the world, due to its tolerability as well as its efficacy, and is a valuable backbone on which to deliver targeted therapies to patients."

The CRYSTAL trial, presented this week at the 9th World Congress on Gastrointestinal Cancer, evaluated cetuximab combined with the irinotecan-based chemotherapy regimen FOLFIRI versus FOLFIRI alone, in patients with metastatic colorectal cancer. Results showed that the risk of cancer spreading or growing was reduced by 15% for patients in the FOLFIRI plus cetuximab arm (p=0.0479), and that significantly more patients in this arm experienced a shrink in tumour size (46.9% versus 38.7% in the FOLFIRI only arm, p=0.0038).

Furthermore, in a subgroup analysis of patients who had liver-limited disease (patients who had liver metastases only), the positive effect of the addition of cetuximab was even more pronounced, resulting in a progression-free survival of 11.4 months with cetuximab versus 9.2 months in the control arm, and a 36% reduction in the risk of metastatic colorectal cancer growing or spreading. The number of complete resections of the metastases in the subgroup who had liver metastases only was more than double with cetuximab plus FOLFIRI versus the control arm (9.8% versus 4.5%). The number of complete resections in the overall population was three times higher in the cetuximab plus FOLFIRI arm.

Treatment was generally well-tolerated, and side-effects were similar between the two groups. The most common grade 3/4 adverse events in the FOLFIRI + cetuximab group versus FOLFIRI alone were diarrhea (15.2% versus 10.5%), neutropaenia (26.7% versus 23.3%) and grade 3 skin reactions (18.7% versus 0.2%). These skin reactions showed a strong correlation with cetuximab efficacy.

"The results of this trial confirm the benefits of improving and refining treatment regimens to get better patient outcomes," continued Professor Moehler, who participated actively in the trial. "Additionally, this trial confirms the evidence of the updated BICC-C trial, presented at ASCO in 2007, which assessed first line therapy with FOLFIRI and bevacizumab in patients with mCRC."

The BICC-C trial was divided into two separate study periods. The first demonstrated that FOLFIRI was superior to other chemotherapy regimens studied in the trial, providing improved progression-free survival (7.8 months, compared to 5.9 months and 5.8 months in the other regimens). The second study period showed that after 29 months' follow up, first-line FOLFIRI + bevacizumab significantly improved overall survival compared with mIFL + bevacizumab (p=0.01) - one-year survival was higher in the FOLFIRI + bevacizumab arm (87%) than in the mIFL + bevacizumab arm (61%). Median overall survival was not yet reached in the FOLFIRI plus bevacizumab arm, but was 19.2 months in the mIFL arm. The most frequent serious adverse events in this study were diarrhea, neutropaenia, nausea and vomiting, hypertension and dehydration.

"What we can learn from both these trials is that when combined with new targeted agents, irinotecan is demonstrating improved outcomes in terms of progression-free and overall survival," Professor Moehler added.

The CRYSTAL and BICC-C data continue to reinforce evidence from previous clinical studies, demonstrating the efficacy of irinotecan as a first line therapy of choice for patients with mCRC, as FOLFIRI alone, or combined with these targeted agents.

Irinotecan important safety information

Irinotecan is indicated for the treatment of patients with advanced colorectal cancer:

-- In combination with 5-fluorouracil and folinic acid in patients without prior chemotherapy for advanced disease.

-- As a single agent in patients who have failed an established 5-fluorouracil containing treatment regimen.

Irinotecan in combination with cetuximab is indicated for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer after failure of irinotecan-including cytotoxic therapy.

Irinotecan in combination with 5-fluorouracil, folinic acid and bevacizumab is indicated for first-line treatment of patients with metastatic carcinoma of the colon or rectum.

The most common adverse effects associated with irinotecan therapy are diarrhoea, neutropaenia and myelosuppression.

For full prescribing information, safety information and black box warnings applicable in your country, please contact your local Pfizer affiliate.



Joel Morris, +44 1304 648 922