General Information

Camptosar (irinotecan) is a topoisomerase inhibitor. 

Camptosar is specifically indicated for the following:

• First-line therapy in combination with 5-fluorouracil and leucovorin for patients with metastatic carcinoma of the colon or rectum.
• Patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed following initial fluorouracil-based therapy.

Camptosar is supplied as a solution for intravenous injection. Administer Camptosar as a 90-minute intravenous infusion followed by LV and 5-FU. 

Mechanism Of Action

Camptosar (Irinotecan) is a derivative of camptothecin. Camptothecins interact specifically with the enzyme topoisomerase I, which relieves torsional strain in DNA by inducing reversible single-strand breaks. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks. Research has suggested that the cytotoxicity of irinotecan 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 irinotecan or SN-38. Mammalian cells cannot efficiently repair these double-strand breaks.

Side Effects

Adverse effects associated with the use of Camptosar may include, but are not limited to, the following:

• nausea
• vomiting
• abdominal pain
• diarrhea 
• constipation
• anorexia
• mucositis
• neutropenia
• leukopenia (including lymphocytopenia)
• anemia
• thrombocytopenia
• asthenia
• pain
• fever
• infection
• abnormal bilirubin
• alopecia

The Camptosar drug label comes with the following Black Box Warning: Early and late forms of diarrhea can occur. Early diarrhea may be accompanied by cholinergic symptoms which may be prevented or ameliorated by atropine. Late diarrhea can be life threatening and should be treated promptly with loperamide. Monitor patients with diarrhea and give fluid and electrolytes as needed. Institute antibiotic therapy if patients develop ileus, fever, or severe neutropenia. Interrupt Camptosar and reduce subsequent doses if severe diarrhea occurs. Severe myelosuppression may occur.

Clinical Trial Results

The FDA approval of Camptosar was based on three clinical trials enrolling 304 patients. Thirty-nine patients (12.8%) responded, 2 with a complete response and 37 with partial responses. Time to progression was 6 months for those with stable disease and median survival was 9 months with a range of up to nearly 3 years. The most consistent responses were observed in subjects beginning treatment at the recommended 125 mg/m2 starting dose. Of the 193 subjects treated at this dose level, 29 experienced a positive response for an overall response rate of 15%. Response refers to the complete disappearance of a tumor (two of the 29 subjects) or a reduction of its size by at least 50% (27 of the 29 patients).