Irinotecan colorectal cancer

The clinical trial that resulted in FDA approval of bevacizumab (February 2004) was a randomized, double-blind, phase III study in which bevacizumab was administered in combination with bolus-IFL (irinotecan, 5FU, leucovorin) chemotherapy as first-line therapy for previously untreated metastatic colorectal cancer [3]. Median survival was increased from 15.6 months in the bolus-IFL + placebo arm to 20.3 months in the bolus-IFL + bevacizumab arm. 

Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovor-in for metastatic colorectal cancer. N Engl J Med 350 2335-2342... 

Goldberg RM, Sargent DJ, Morton RF, et al. A randomized, controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004 22 23-30. 

Saltz LB, Cox JV, Blanke C et al. Irino-tecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 2000 343 905-914. 

Vanhoefer U, Harstrick A, Achter-rath W et al. Irinotecan in the treatment of colorectal cancer clinical overview. J Clin Oncol 2001 19 1501-1518. 

First generation of topi inhibitors were developed as drugs from camptothecins, a family of compounds derived from wood and bark of the Chinese tree Camptotheca acuminata) [9, 10], Many of these are already in clinical use or clinical trials, including irinotecan, topotecan, exatecan, rubitecan, and lurtotecan. Irinotecan (CPT-11) is bioactivated in liver by carboxylesterase to the active metabolite SN-38, 1000-fold more active [11]. Irinotecan received in 1998 FDA approval for treatment of metastatic colorectal cancer after failure of treatment with 5FU [12],... 

FDA approves irinotecan as first-line therapy for colorectal cancer. Oncology (Williston Park). 2000 May 14(5) 652, 4. 

Cetuzimab (Erbitux) Monoclonal antibody against EGF receptor Refractory colorectal cancer in combination with irinotecan Randomized Phase II trial... 

Irinotecan refractory EGFR-positive metastatic colorectal cancer 576 screened... 

Cunningham, D. et al.. Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. The Lancet, 352, 1413-1418, 1998. 

Messerer CL, Ramsay EC, Waterhouse D, et al. Liposomal irinotecan formulation development and therapeutic assessment in murine xenograft models of colorectal cancer. Clin Cancer Res 2004 10(19) 6638. 

Irinotecan treatment schedules differ from 125 to 150 mg/m2 once a week for 4 wk followed by a 2-wk drug free interval (United States), to 350 mg/m2 once every 3 wk (Europe), or 100 mg/m2/wk or 150 mg/m2 every 2 wk (Japan). Differing intermittent treatment schedules using cytokine support for neutropenia, or intensive loperamide to counteract diarrhea, have also been reported (14). These tolerable CPT-11 regimens have produced median durations of response that range from 5.6 to 10.6 mo in colorectal patients disease stabilization occurs in 30 to 71 % (40). Response rates of 26% and 32% have been reported for previously untreated colorectal cancer patients higher response rates have been reported for non-5-FU-refractory patients (only 7-21%). Symptoms of diarrhea, nausea, and vomiting are common toxicities other side effects are asthenia, abdominal pain, leukopenia, and neutropenia. In the US trials at least one of these adverse... 

Cetuximab is a chimeric monoclonal antibody, against epidermal growth factor receptor (EGFR). It is given by intravenous injection with weekly intervals for the treatment of metastatic colorectal cancer and head and neck cancer. It is given in combination with the chemotherapeutic agent irinotecan. The... 

Cetuximab has modest activity in relapsed colorectal cancer as a single agent but is more effective with irinotecan and possibly oxaliplatin based regimens where a doubling of the response rate has been observed. There is some evidence that cetuximab may reverse irinotecan resistance. Toxic effects of cetuximab include hypersensitivity reactions, malaise, nausea, headache and an acneiform rash. 

Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A et al. Cetuximab monotherapy or cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004 351 337-45. 

C. Levy-Piedbois, I. Durand-Zaleski, H. Juhel, C. Schmitt, A. Bellanger, P. Piedbois, Cost-effectiveness of second-line treatment with irinotecan or infusional 5-fluorouracil in metastatic colorectal cancer, Ann. Oncol. 11 (2000) 157-161. 

Yu J, Shannon WD, Watson MA et al. Gene expression profiling ofthe irinotecan pathway in colorectal cancer. Clin Cancer Res 2005 11 2053-2062. 

Colorectal cancer (CRC) is the third most common cause of cancer-related death in women and men in the United States. The current therapeutic options for patients with metastatic CRC (mCRC) are 5-fluorouracil (5-FU) based chemotherapy regimens with the addition of irinotecan (CPT-11) or oxaliplatin. It still remains a challenge for oncologists to evaluate the reasons for a wide variation in response and toxicity among patients undergoing systemic 5-FU based chemotherapy. Pharmacogenomics... 

Douillard JY, Cunningham D, Roth AD et al. Irinotecan combined with fluorouraeil eompared with fluorouracil alone as first-line treatment for metastatic colorectal cancer a multieentre randomised trial. Lancet 2000 355 1041-1047. 

Carlini EE, Meropol NJ, Bever J et al. UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan. Clin Cancer Res 2005 11 1226-1236. 

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