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Important Information - Camptosar

Date: 2001-05-11

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IMPORTANT DRUG SAFETY INFORMATION

Pharmacia Canada
2233 Argentia Road, 4th Floor
Mississauga, Ontario
L5N 2X7
Tel 905.755.3000
Fax 905.819.9994
 www.pharmaciaoncology.com

May 11, 2001

Dear Doctor,

The purpose of this letter is to inform you that enrollment in two NCI-sponsored cooperative group trials has been suspended because of preliminary safety information about the number and pattern of deaths on the weekly CAMPTOSAR® (irinotecan HCl injection) plus bolus 5-fluorouracil (5-FU) and leucovorin (LV) arms of these studies.

NCCTG Study Evaluating First-Line Therapy for Metastatic Colorectal Cancer (Study N9741, NCIC CTG Trial CO.13) ¹
Following a routine safety evaluation, the North Central Cancer Treatment Group (NCCTG) has temporarily suspended enrollment into their ongoing 3-arm first-line colorectal cancer trial (N9741). The External Data Monitoring Committee (EDMC) noted in April 2001 that the preliminary estimate of the mortality rate from any cause, within 60 days of treatment initiation, was 4.8% (14/289) on the CAMPTOSAR +bolus 5-FU/LV arm compared to 1.8% on each of the other two study arms. Although the control arm mortality rate was not statistically significantly different from the other two arms of this study, the EDMC recommended temporary suspension of enrollment because the absolute number of deaths was higher.

CALGB Study Evaluating Adjuvant Colorectal Cancer Therapy (Study C89803, NCIC CTG Trial CO.15) ²
The Cancer and Leukemia Group B (CALGB) announced the suspension of new patient accrual to study C89803 (weekly CAMPTOSAR plus bolus 5-FU/LV versus weekly bolus 5-FU/LV for adjuvant colorectal cancer, an investigational use of CAMPTOSAR) on April 27, 2001. As a result of the NCCTG recommendation to temporarily suspend accrual to N9741, the CALGB Data Safety Monitoring Board (DSMB) reviewed the safety data from C89803 and found a higher than anticipated incidence of serious adverse events related to sepsis, diarrhea and thromboses. The preliminary estimate of the mortality rate from any cause, within 60 days of treatment initiation, on the CAMPTOSAR +bolus 5-FU/LV arm was 2.2% (14/635) compared to 0.8% (5/628) in the 5-FU/LV arm. There was no statistically significant difference in mortality rates between treatment arms.

On the basis of these developments Pharmacia conducted an additional analysis of mortality in the pivotal study that supported the registration of the weekly CAMPTOSAR plus bolus 5-FU/LV regimen. The mortality rate from any cause within 60 days of treatment initiation on the CAMPTOSAR +bolus 5-FU/LV arm was 7% (15/225) compared to 7% (16/219) in the 5-FU/LV arm. The mortality rate from any cause within 30 days of receiving drug during any cycle on the CAMPTOSAR +bolus 5-FU/LV arm was 9% (21/225) compared to 7% (15/219) in the 5-FU/LV arm. There were no statistically significant differences in mortality rates between treatment arms.

In the United States, since approval of the first-line indication in April 2000, an estimated 15,000 patients have been treated, primarily with the weekly regimen. Recognizing the implicit limitations of any post-marketing surveillance system, no new patterns of toxicity have emerged.

Physicians should be aware that CAMPTOSAR can induce severe myelosupression and both early and late forms of diarrhea that may be life threatening. Rare cases of ileus, complicated colitis, or renal impairment have been observed. CAMPTOSAR is emetogenic and premedication with anti-emetics is recommended. Patients should be instructed to inform their physician and nurses of any signs or symptoms of toxicity at their earliest manifestation so that appropriate supportive care and/or dose modifications can be promptly initiated. It is important to employ careful management of patients in accordance with the supportive care guidelines contained in the product monograph for CAMPTOSAR.

In February 2001, CAMPTOSAR was approved as a component of first-line therapy in combination with 5 FU/LV for patients with metastatic colorectal cancer. Two treatment regimens were approved: 1) Weekly CAMPTOSAR plus bolus 5-FU/LV and 2) CAMPTOSAR plus infusional 5-FU/LV every 2 weeks. Each of these regimens prospectively demonstrated a significant survival benefit over 5-FU/LV. Any modification of the recommended regimens does not assure retention of efficacy or safer delivery.

Pharmacia is committed to the safety and well being of all patients receiving CAMPTOSAR as part of any standard or investigational treatment regimen, and thus felt it was important to inform you of these events. We will continue working with the Cooperative Groups, the National Cancer Institute, the Food and Drug Administration, and the Therapeutic Products Programme to fully evaluate the preliminary data reported by the NCCTG and the CALGB.

If you have any questions, please contact your local Pharmacia representative or Pharmacia Medical Information Services at 1-800-268-7888, or via the Pharmacia Oncology web site ( www.pharmaciaoncology.com).  

Sincerely,

David Cook, MD
Vice President, Medical & Scientific Affairs
Pharmacia Canada

Please see full prescribing information for CAMPTOSAR.

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