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Camptosar as First-line Treatment for Metastatic Colorectal Cancer

Camptosar

Brand Name Drug: Camptosar
Active Ingredient Drug: irinotecan
Indication: Currently indicated as second-line treatment of metastatic colorectal cancer; soon to be approved for first-line treatment when administered with 5-fluorouracil and leucovorin
Company Name: Pharmacia & Upjohn
Availability: Approved by FDA for second-line therapy in 1998; FDA recommended approval as first-line therapy in March 2000

Introduction

In 1998, Pharmacia & Upjohn’s Camptosar (irinotecan hydrochloride injection, or CPT-11) was approved by the FDA for the treatment of metastatic colorectal cancer in patients whose disease has recurred or progressed following treatment with 5-fluorouracil (5FU). The drug was hailed by cancer specialists because it was the first new chemotherapy drug approved for colorectal cancer in more than 40 years.

Camptosar may soon be approved for first-line treatment of metastatic colorectal cancer when administered in conjunction with 5FU and leucovorin. The FDA’s Oncologic Drugs Advisory Committee unanimously recommended approval of Camptosar for this indication on March 16, 2000. Clinical studies show that patients with metastatic colorectal cancer who received Camptosar, leucovorin, and 5FU experienced an improvement in objective tumor response, time to tumor progression, and prolonged survival compared to patients who received 5FU and leucovorin alone. Camptosar is administered via intravenous infusion.

How It Works

Camptosar, a derivative of camptothecin, works by inhibiting the enzyme topoisomerase I, which relieves torsional strain in DNA by inducing reversible single-strand breaks. Camptosar prevents religation of these single-strand breaks. The cytotoxicity of Camptosar is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either Camptosar or its active metabolite (SN-38).

Camptosar (irinotecan): Clinical Study Results

One study evaluated 387 patients with metastatic colorectal cancer who received 5FU/leucovorin plus Camptosar or 5FU/leucovorin alone. Infusion schedules were once weekly or every 2 weeks. Patients who received the Camptosar combination treatment had significantly prolonged median survival (17.4 vs. 14.1 months), a significantly higher overall objective tumor response rate (49% vs. 31%), and significantly longer time to tumor progression (6.7 vs. 4.4 months).

“The combination regimen containing Camptosar (irinotecan) may represent a new standard of care for first-line treatment of metastatic colorectal cancer which should be the measurement against which future therapies are tested,” added Dr. Jean-Yves Douillard, Assistant Professor of Medical Oncology at Centre Rene Gauducheau in Nantes, France, and lead author of this study.

In another study, Camptosar was evaluated in 178 patients with metastatic colorectal cancer, 77.5% of whom had had prior chemotherapy with one 5FU-based regimen. Camptosar was administered 350 mg/m2 every 3 weeks. The response rate was 17.7% in the patients who had received prior 5FU and 18.8% in the patients who had not received prior chemotherapy. The median duration of objective response (9.1 months) and median time to achievement of a response (9.3 weeks) did not differ between the two patient groups.

A third study was conducted to assess the response to Camptosar in 41 patients with metastatic colorectal cancer who had not been treated with prior chemotherapy. Patients received a 90-minute infusion of Camptosar 125 mg/m2 weekly for 4 weeks every 6 weeks. Thirty-two percent of the patients achieved a partial response. The median response duration was 8.1 months and the median survival time was 12.1 months.

Camptosar is also being evaluated in clinical trials in patients with lung, ovarian, and pancreatic cancers.

What the Patient Should Know
Camptosar (irinotecan) can induce both early and late forms of diarrhea that appear to be mediated by different mechanisms. Both forms of diarrhea may be severe. Early diarrhea (occurring during or within 24 hours of administration of Camptosar) may be preceded by complaints of diaphoresis and abdominal cramping and may be ameliorated by atropine. Late diarrhea (occurring more than 24 hours after administration of Camptosar) can be prolonged, may lead to dehydration and electrolyte imbalance, and can be life-threatening. Late diarrhea should be treated promptly with loperamide; patients with severe diarrhea should be carefully monitored and given fluid and electrolyte replacement if they become dehydrated. Administration of Camptosar should be interrupted if severe diarrhea occurs. Other gastrointestinal complaints associated with Camptosar include nausea and vomiting. An antiemetic agent may be administered prior to Camptosar infusion.

Severe myelosuppression may occur with Camptosar treatment. Therapy with Camptosar should be temporarily discontinued if neutropenic fever occurs or if the absolute neutrophil count drops below 500/mm3. The dose of Camptosar should be reduced if white blood cell counts fall below levels as indicated in the prescribing information. Physicians may wish to administer G-CSF to boost white blood cell counts in neutropenic patients receiving Camptosar.

Because Camptosar may cause fetal harm, women should not become pregnant while receiving treatment with Camptosar (irinotecan). Women who do become pregnant should be advised of the potential hazard to the fetus.

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