Alli (Irinotecan, CPT – 11) We all know that Alli is a derivative of Camptothecin, so what kind of development process did this drug go through? Camptothecin is a plant base extracted from the Camptothecin tree, and its antitumor properties were discovered as early as 1960. Early studies on camptothecin showed that cells exposed to it would undergo DNA breakage, however, the exact mechanism of action was not well understood. It was not until 1980 that the mechanism of its interaction with topoisomerase I was discovered. Because of the relative insolubility of camptothecin in aqueous solution, early clinical trials were conducted with a sodium salt derivative of camptothecin. After a period of application, a high incidence of myelosuppression and hemorrhagic cystitis was observed, and thus the drug was considered too toxic for clinical use. Further studies on camptothecin led to the development of two new water-soluble camptothecin derivatives with lower toxicity: irinotecan and topotecan in 1994 and 1996, respectively. Prior to the advent of irinotecan, 5FU/CF was often used clinically as the treatment of choice for advanced colorectal cancer (ORR 20% – 25%). Since its launch in Japan, irinotecan has been of interest to clinicians around the world because of its proven efficacy. In Europe, a large-scale phase III clinical (V303) study demonstrated that irinotecan combined with 5FU/CF was significantly better than 5FU/CF IV regimen in the treatment of advanced colorectal cancer in terms of remission rate and survival, and established irinotecan combined with 5FU/CF as the preferred first-line treatment for advanced colorectal cancer in Europe. In the United States, the large-scale phase III clinical (0038) study again demonstrated that irinotecan combined with 5FU/CF remains significantly superior to 5FU/CF IV regimens in terms of remission rates and survival in the treatment of advanced colorectal cancer, further establishing irinotecan combined with 5FU/CF as the preferred first-line treatment for advanced colorectal cancer in the United States. There are still a large number of literature reports from all over the world affirming the definitive efficacy of irinotecan for colorectal cancer. Therefore, both European EU and US FDA have approved, irinotecan as a first-line treatment for advanced colorectal cancer.