Irinotecan in the treatment of colorectal cancer: Clinical overview

Purpose and Methods: For more than three decades, the therapeutic options f or patients with advanced colorectal cancer have almost exclusively been ba sed on fluoropyrimidines. With the recognition that topoisomerase-I (TOP-I) is an important therapeutic target in cancer therapy, irinotecan, a semisy nthetic TOP-I-interactive camptathecin derivative, has been clinically esta blished in the treatment of colorectal cancer. Results: Irinotecan was investigated as second-line chemotherapy after prio r treatment with fluorouracil (FU)-based regimens in two large randomized p hase III trials comparing irinotecan with either best supportive care or an infusional FU/leucovorin (LV) regimen. The outcomes of these trials establ ished irinotecan as the standard therapy in the second-line treatment of co lorectal cancer. The therapeutic value of irinotecan in the first-line trea tment of metastatic colorectal cancer was investigated in two large randomi zed phase III trials comparing the combination of irinotecan and FU/LV with FU/LV alone. Both trials demonstrated significant superior efficacy for th e combination of irinotecan and FU/LV in terms of response rate, median tim e to disease progression, and median survival time. Consequently, the combi nation of irinotecan and FU/LV has been approved as first-line chemotherapy for patients with metastatic colorectal cancer and constitutes the referen ce therapy against which other treatment options must be tested in the futu re. Conclusion: In this review, the clinical rationale and update of the presen t clinical status of irinotecan in the treatment of colorectal cancer and f uture prospects of irinotecan-based combinations are discussed. J Clin Onco l 19:1501-1518. (C) 2001 by American Society of Clinical Oncology.