Irinotecan metastatic

Clinical uses Topotecan ovarian cancer, small cell and non-small cell lung cancer Irinotecan metastatic colon and rectal carcinoma Small cell and non-small cell lung cancer, gastric cancer, germ cell cancers, leukemias and lymphomas. 

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. 

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],... 

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. 

UGTIAI has an important role in the metabolism of irinotecan, etoposide, epiru-bicine, and tipifamib. Irinotecan is a camptothecin derivative used in the treatment of metastatic colon cancer. Irinotecan is a prodrug since it is activated to Ethyl-10-hydroxycamptothecin (SN-38) by carboxyl esterase to exert its antitumor activity mediated by the inhibition of topoisomerase I. SN-38 undergoes UGTIAI-catalyzed glucuronide conjugation to form the inactive SN-38 glucuronide (SN-38G). 

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... 

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. 

They cause substantial DNA damage in tumor cells, preventing tumor growth. Topotecan has been evaluated in metastatic ovarian cancer. Irinotecan is a prodrug that is metabolized to a topoisomerase I inhibitor it has been used in the treatment of colon and... 

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. 

Toffoli G., Cecchin E, Corona G et al. The role of UGT1A1 28 polymorphism in the pharmacodynamics and pharmacokinetics of irinotecan in patients with metastatic colorectal cancel. J Clin.Oncol 2006 24 3061-3068. 

Marcuello E, Altes A, Menoyo A et al. UGTIAI gene variations and irinotecan treatment in patients with metastatic colorectal cancer. Br JCancer 2004 91 678-682. 

Irinotecan is a prodrug that is converted mainly in the liver by the carboxylesterase enzyme to the SN-38 metabolite, which is 1000-fold more potent as an inhibitor of topoisomerase I than the parent compound. In contrast to topotecan, irinotecan and SN-38 are mainly eliminated in bile and feces, and dose reduction is required in the setting of liver dysfunction. Irinotecan was originally approved as second-line monotherapy in patients with metastatic colorectal cancer who had failed fluorouracil-based therapy. It is now approved as first-line therapy when used in combination with 5-FU and leucovorin. Myelosuppression and diarrhea are the two most common adverse events. There are two forms of diarrhea an early form that occurs within 24 hours after administration and is thought to be a cholinergic event effectively treated with atropine, and a late form that usually occurs 2-10 days after treatment. The late diarrhea can be severe, leading to significant electrolyte imbalance and dehydration in some cases. 

Jaeger, E., D. Jaeger, J. Orth, and A. Knuth. 2000. Irinotecan in second-line therapy of metastatic colorectal cancer. Onkologie 23 15-17. 

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