Irinotecan CPT

Irinotecan (CPT-11) is approved for colorectal tumors. It is given by intravenous infusion. The most severe side effect is diarrhea, which can be severe and needs to be treated by a physician. Temporary liver dysfunction is generally asymptomatic. The other side effects are the same as those produced by topotecan. 

Rivory LP, Bowles MR, Robert J et al. Conversion of irinotecan (CPT-11) to its active metabolite, 7-ethyl-10-hydroxy-camptothecin (SN-38), by human liver carboxylesterase. Biochem Pharmacol 1996 52 1103-1111. 

Rivory LP, Riou JF, Haaz MC et al. Identification and properties of a major plasma metabolite of irinotecan (CPT-11) isolated from the plasma of patients. Cancer Res 1996 56 3689-3694. 

Iyer L, King CD, Whitington PF et al. Genetic predisposition to the metabolism of irinotecan (CPT-11). Role of uridine diphosphate glucuronosyltransferase isoform 1A1 in the glucuronidation of its active metabolite (SN-38) in human liver microsomes. J Clin Invest 1998 101 847-854. 

Iyer L, Janisch L, Das S et al. UGT1A1 promoter genotype correlates with pharmacokinetics of irinotecan (CPT-11). Proc Am Soc Clin Oncol 2000 19 178a (abstract). 

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],... 

Sugiyama, Y., Kato, Y., and Chu, X. (1998) Multiplicity of bdiary excretion mechanisms for the camptothecin derivative irinotecan (CPT-11), its metabolite SN-38, and its glucuronide role of canalicular multispecific organic anion transporter and P-glycoprotein. Cancer Chemother. Pharmacol. 42(suppl), S44-S49. 

Camptothecin is a plant alkaloid obtained from the Camptotheca acuminata tree. It was first evaluated clinically, as a sodium salt, in the 1960s and 1970s, but was abandoned because of severe and unpredictable hemorrhagic cystitis (3,4). Irinotecan (CPT-11) and Rubetecan are semisynthetic, water-soluble derivatives of camptothecin possessing... 

Rothenberg ML, Cox JV, DeVore RF, et al. A multicenter, phase II trial of weekly irinotecan (CPT-11) in patients with previously treated colorectal carcinoma. Cancer 1999 85(4) 786-795. 

Rothenberg ML. The current status of irinotecan (CPT-11) in the United States. AnnN Y Acad Sci 1996 803 272-281. 

Kobayashi K, Shinbara A, Kamimura M, et al. Irinotecan (CPT-11) in combination with weekly administration of cisplatin (CDDP) for non-small-cell lung cancer. Cancer Chemother Pharmacol 1998 42(1 ) 53—58. 

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... 

Mathijssen RH, van Alphen RJ, Verweij J et al. Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clin Cancer Res 2001 21%2-2194. 

Examples of GDEPT include irinotecan (CPT-11), a prodrug of 7-ethyl- 10-hydroxy-camptothecin activated by carboxylesterase 5-fluorocytosine, a prodrug of 5-FU activated by cytosine deaminase and cyclophosphamide, a prodrug of 4-hydroxycyclophosphamide activated by cytochrome P450, which degrades into acrolein and phospho-ramide mustard.112-115... 

Ohtsu T, Sasaki Y, Igarashi T, et al. Unexpected hepatotoxicities in patients with non-Hodgkin s lymphoma treated with irinotecan (CPT-11) and etoposide. Jpn J Clin Oncol 1998 28(8) 502-506. 

Hanioka N, Ozawa S, Jinno H, et al. Interaction of irinotecan (CPT-11) and its active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38) with human cytochrome P450 enzymes. Dmg Metab Dispos 2002 30(4) 391-396. 

Today, several soluble camptothecin derivatives such as topotecan (3), 9-aminocamptothe-cin (4) and irinotecan (CPT-11) (5) are of clinical importance. Positive results were achieved, especially against intestinal, breast and ovarian can-... 

Yamamoto W, Verweij J, de Bruijn P, de Jonge MJ, Takano H, Nishiyama M, Kurihara M, Sparreboom A. Active transepithelial transport of irinotecan (CPT-11) and its metabolites by human intestinal Caco-2 cells. Anticancer Drugs 2001 12(5) 419-32. 

Slatter JG, Schaaf LJ, Sams JP, Feenstra KL, Johnson MG, Bombard PA, Cathcart KS, Verbnrg MT, Pearson LK, Compton LD, Miller LL, Baker DS, Pesheck CV, Lord RS 3rd. Pharmacokinetics, metabolism, and excretion of irinotecan (CPT-11) following I.V. infusion of [(14)C]CPT-11 in cancer patients. Drug Metab Dispos 2000 28(4) 423-33. 

Sparreboom A, de Jonge MJ, de Bruijn P, Brouwer E, Nooter K, Loos WJ, van Alphen RJ, Mathijssen RH, Stoter G, Verweij J. Irinotecan (CPT-11) metabolism and disposition in cancer patients. Clin Cancer Res 1998 4(ll) 2747-54. 

Santos A, Zanetta S, Cresteil T, Deroussent A, Pein F, Raymond E, Vernillet L, Risse ML, Boige V, Gouyette A, Vassal G. Metabolism of irinotecan (CPT-11) by CYP3A4 and CYP3A5 in humans. Clin Cancer Res 2000 6(5) 2012-20. 

Ong SY, Clarke SJ, Bishop J, Dodds HM, Rivory LP. Toxicity of irinotecan (CPT-11) and hepato-renal dysfunction. Anticancer Drugs 2001 12(7) 619-25. 

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