Summary
Irinotecan is a water-soluble camptothecin analogue. Its cytotoxicity effects are exerted through interaction with the topoisomerase I\3-DNA complex, eventually leading to cell death.
In preclinical studies, irinotecan has demonstrated abroad spectrum of activity in vitro and in vivo, and synergistic effects have been observed when it is administered in combination with other antineoplastic agents.
Phase I studies of irinotecan conducted in Europe, Japan and the US have provided useful information on optimal dosage and scheduling, as well as thorough evaluation of the toxicity profile of the drug. Phase II and III trials utilising either irinotecan alone or in innovative combinations with other drugs are currently in progress. Available data indicate that irinotecan alone or in combination with other cytotoxic agents has therapeutic potential in several types of malignancy, including colorectal, lung, ovarian, cervical and gastric cancers and non-Hodgkin’s lymphoma. It is the first drug since fluorouracil to possess consistent antitumour activity against metastatic colorectal cancer.
The principal toxicities associated with irinotecan are diarrhoea and leucopenia. Effective strategies have been developed to circumvent both the early- and delayed-onset diarrhoea induced by irinotecan, thus allowing safer delivery of this promising agent in the clinical setting.
Similar content being viewed by others
References
Wall ME, Wani MC, Cook CE, et al. Plant antitumor agents. I. The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from Camptotheca acuminata. J Am Chem Soc 1966; 88: 3888–90
Gottlieb JA, Luce JK. Treatment of malignant melanoma with camptothecin (NSC-100880). Cancer Chemother Rep 1972; 56: 103–5
Moertel CG, Schutt AJ, Reitemeier RJ, et al. Phase II study of camptothecin (NSC-100880) in the treatment of advanced gastrointestinal cancer. Cancer Chemother Rep 1972; 56: 95–101
Yokokura T, Sawada S, Nokata K, et al. Antileukemic activity of new camptothecin derivatives [abstract]. Proceedings of the Japanese Cancer Association, 40th Annual Meeting: 1981; Sapparo, 228
Yokokura T, Furuta T, Sawada S, et al. Anti-tumor activity of newly synthesized, lactone ring closed and water soluble camptothecin derivative in mice [abstract]. Proceedings of the Japanese Cancer Association, 43rd Annual Meeting: 1984; Fukuoka, 261
Horwitz SB, Horwitz MS. Effects of camptothecin on the breakage and repair of DNA during the cell cycle. Cancer Res 1973; 33: 2834–6
Sparato A, Kessel D. The effects of camptothecin on mammalian DNA. Biochem Biophys Acta 1973; 331: 194–201
Stevnsner T, Bohr VA. Studies on the role of topoisomerases in general, gene and strand specific DNA repair. Carcinogenesis 1993; 14: 1841–50
Tsao YP, Russo A, Nyamuswa G, et al. Interaction between replication forks and topoisomerase I\3-DNA cleavable complexes: studies in a cell free SV40 DNA replication system. Cancer Res 1993; 53: 5908–14
Slichenmyer WJ, Rowinsky EK, Donehower RC, et al. The current status of camptothecin analogues as antitumor agents. J Natl Cancer Inst 1993; 85: 271–91
Li LH, Fraser TJ, Olin EJ, et al. Action of camptothecin on mammalian cells in culture. Cancer Res 1972; 32: 2643–50
D’Arpa P, Beardmore C, Liu LF. Involvement of nucleic acid synthesis in cell killing mechanisms of topoisomerase poisons. Cancer Res 1990; 50: 6919–24
Giovanella BC, Stehlin JS, Wall ME, et al. DNA topoisomerase I-targeted chemotherapy of human colon cancer in xenografts. Science 1989; 246: 1046–8
Van Der Zee AG, Dejong S, Keith WN, et al. P-glycoprotein expression and DNA topoisomerase I and II activity in benign tumors of the ovary and in malignant tumors of the ovary, before and after platinum/cyclophosphamide chemotherapy. Cancer Res 1991; 51: 5915–20
Takimoto CH, Arbuck SG. The camptothecins. In: Chabner BA, Longo DL, editors. Cancer chemotherapy and biotherapy: principles and practice. 2nd ed. Philadelphia, PA: Lippincott-Raven, 1996: 463–84
Kawato Y, Aonuma M, Hirota Y, et al. Intracellular roles of SN-38, a metabolite of the camptothecin derivative CPT-11, in the antitumor effect of CPT-11. Cancer Res 1991; 51: 4187–91
Kanzawa F, Kondoh H, Kwon SJ, et al. Role of carboxylesterase on metabolism of camptothecin analogue (CPT-11) in non-small-cell lung cancer cell line PC-7 cells [abstract]. Proc Am Assoc Cancer Res 1992; 33: 427
Kaneda N, Nagata H, Furuta T, et al. Metabolism and pharmacokinetics of the camptothecin analogue CPT-11 in the mouse. Cancer Res 1990; 50: 1715–20
Tsuji T, Kaneda N, Kado K, et al. CPT-11 converting enzyme from rat serum: purification and some properties. J Pharmacobiodyn 1991; 14: 341–9
Satoh T, Hosokawa M, Atsumi R, et al. Metabolic activation of CPT-11, 7-ethyl-10-[4-piperidino)-1-piperidino]carbonyloxy camptothecin, a novel anti-tumor agent, by carboxylesterase. Biol Pharm Bull 1994; 17: 662–4
Hertzberg RP, Caranfa MJ, Holden KG, et al. Modification of the hydroxy lactone ring of camptothecin: inhibition of mammalian topoisomerase I and biological activity. J Med Chem 1989; 32: 715–20
Lavelle F, Bissery M-C, Andre S, et al. Preclinical evaluation of CPT-11 and its active metabolite SN-38. Semin Oncol 1996; 23 Suppl. 3: 11–20
Tanizawa A, Fujimori A, Fujimori Y, et al. Comparison of topoisomerase I inhibition, DNA damage, and cytotoxicity of camptothecin derivatives presently in clinical trials. J Natl Cancer Inst 1994; 86: 836–42
Shimada Y, Rothenberg ML, Hilsenbeck SG, et al. Activity of CPT-11 (irinotecan hydrochloride), a topoisomerase I inhibitor, against human tumor colony-forming units. Anticancer Drugs 1994; 5: 202–6
Kunimoto T, Nitta K, Tanaka T, et al. Antitumor activity of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin, a novel water-soluble derivative of camptothecin, against murine tumors. Cancer Res 1987; 47: 5944–7
Matsuzaki T, Yokokura T, Mutai M, et al. Inhibition of spontaneous and experimental metastasis by a new derivative of camptothecin, CPT-11, in mice. Cancer Chemother Pharmacol 1988; 21: 308–12
Kawato Y, Furuta T, Aonuma M, et al. Antitumor activity of a camptothecin derivative, CPT-11, against human tumor xenografts in nude mice. Cancer Chemother Pharmacol 1991; 28: 192–8
Tsuruo T, Matsuzaki T, Matsushita M, et al. Antitumor effects of CPT-11, a new derivative of camptothecin, against pleiotropic drug-resistant tumors in. vitro and in vivo. Cancer Chemother Pharmacol 1988; 21: 71–4
Houghton PJ, Cheshire PJ, Hallman JC, et al. Therapeutic efficacy of the topoisomerase I inhibitor 7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptothecin against human tumor xenografts: lack of cross-resistance in. vivo in tumors with acquired resistance to the topoisomerase I inhibitor 9-dimethylaminomethyl-10-hydroxycamptothecin. Cancer Res 1993; 53: 2823–9
Guichard S, Caliaro MJ, Houin G, et al. Sequential exposure to CPT-1 and 5FU is synergistic in human colon carcinoma HT-29 cell line [abstract]. Proc Am Assoc Clin Res 1996; 37: 292
Funakoshi S, Aiba K, Shibata H, et al. Enhanced antitumor activity of SN-38, an active metabolite of CPT-11, and 5-fluorouracil combination for human colorectal cancer cell lines [abstract]. Proc Am Soc Clin Oncol 1993; 12: 193
Guichard S, Hennebelle I, Cussac D, et al. In vivo evaluation of the irinotecan (CPT-11)/5-fluorouracil (5FU) combination [abstract]. Proc Am Assoc Clin Res 1997; 38: 76
Kudoh S, Takada M, Masuda N, et al. Enhanced antitumor efficacy of a combination of CPT-11, a new derivative of camptothecin, and cisplatin against human lung tumor xenografts. Jpn J Cancer Res 1993; 84: 203–7
Furuta T, Yokokura T. Combination therapy of CPT-11, a camptothecin derivative, with various antitumor drugs against L1210 leukemia. Jpn J Cancer Chemother 1991; 18: 393–402
Kaufmann S. Antagonism between camptothecin and topoisomerase II-directed chemotherapeutic agents in a human leukemic cell line. Cancer Res 1991; 51: 1129–36
Bertrand R, O’Connor PM, Kerrigan D, et al. Sequential administration of camptothecin and etoposide circumvents the antagonistic cytotoxicity of simultaneous drug administration in slowly growing human colon carcinoma HT-29 cells. Eur J Cancer 1992; 28A: 743–8
Kim R, Hirabayashi N, Nishiyama M, et al. Experimental studies on biochemical modulation targeting topoisomerase I and II in human tumor xenografts in nude mice. Int J Cancer 1992; 50: 760–6
Rowinsky EK, Grochow LB, Ettinger DS, et al. Phase I and pharmacological study of the novel topoisomerase I inhibitor 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycampto thecin (CPT-11) administered as a ninety-minute infusion every 3 weeks. Cancer Res 1994; 54: 427–36
Abigerges D, Chabot GG, Armand J-P, et al. Phase I and pharmacologic studies of the camptothecin analog irinotecan administered every 3 weeks in cancer patients. J Clin Oncol 1995; 13: 210–21
Rothenberg ML, Kuhn JG, Burris III HA, et al. Phase I and pharmacokinetic trial of weekly CPT-11. J Clin Oncol 1993; 11: 2194–204
Negoro S, Fukuoka M, Masuda N, et al. Phase I study of weekly intravenous infusion of CPT-11, a new derivative of camptothecin, in the treatment of advanced non-small-cell lung cancer. J Natl Cancer Inst 1991; 83: 1164–8
Rothenberg ML, Eckardt JR, Kuhn JG, et al. Phase II trial of irinotecan in patients with progressive or rapidly recurrent colorectal cancer. J Clin Oncol 1996; 14: 1128–35
Taguchi T, Wakui A, Hasegawa K, et al. Phase I clinical study of CPT-11. Jpn J Cancer Chemother 1990; 17: 115–20
Muggia FM, Creaven PJ, Hansen HH, et al. Phase I clinical trial of weekly and daily treatment with camptothecin (NSC-100880): correlation with preclinical studies. Cancer Chemother Rep 1972; 56: 515–21
Nagata H. Flow cytometric analysis of the effect of an antitumor alkaloid, camptothecin, on cell cycle progression of KB cell. J Aichi Med Univ Assoc 1987; 15: 683–99
Rothenberg ML, Rinaldi DA, Smith LS, et al. Every other week irinotecan (CPT-11): results of a phase I and pharmacokinetic (PK) study [abstract]. Proc Am Soc Clin Oncol 1996; 15:489
Shimada Y, Yoshino M, Wakui A, et al. Phase II study of CPT-11, a new camptothecin derivative, in metastatic colorectal cancer. J Clin Oncol 1993; 11: 909–13
Pitot HC, Wender DB, O’Connell MT, et al. Phase II trial of irinotecan in patients with metastatic colorectal carcinoma. J Clin Oncol 1997; 15: 2910–9
Van Cutsem E, Cunningham D, Ten Bokkel Huinink W, et al. CPT-11 in 5-FU-resistant colorectal cancer: patient benefit [abstract]. European Society of Medical Oncology Symposium: 1996 Nov 2–5; Vienna
Rougier P, Bugat R, Douillard JY, et al. Phase II study of irinotecan in the treatment of advanced colorectal cancer in chemotherapy-naive patients and patients pretreated with fluorouracil-based chemotherapy. J Clin Oncol 1997; 15: 251–60
Conti JA, Kemeny NE, Saltz LB, et al. Irinotecan is an active agent in untreated patients with metastatic colorectal cancer. J Clin Oncol 1996; 14: 709–15
Von Hoff DD, Rothenberg ML, Pitot HC, et al. Irinotecan (CPT-11) therapy for patients with previously treated metastatic colorectal cancer (CRC): overall results of FDA-reviewed pivotal US clinical trials [abstract]. Proc Am Soc Clin Oncol 1997; 16: 228a
Nakai H, Fukuoka M, Furese K, et al. An early phase II study of CPT-11 for primary lung cancer. Jpn J Cancer Chemother 1991; 18: 607–12
Negoro S, Fukuoka M, Kusunoki Y, et al. A phase II study of CPT-11, a camptothecin derivative, in patients with primary lung cancer. Jpn J Cancer Chemother 1991; 18: 1013–9
Baker L, Khan R, Lynch T, et al. Phase II study of irinotecan (CPT-11) in advanced non-small cell lung cancer (NSCLC) [abstract]. Proc Am Soc Clin Oncol 1997; 16: 461a
Fukuoka M, Niitani H, Suzuki A, et al. A phase II study of CPT-11, a new derivative of camptothecin, for previously untreated non-small-cell lung cancer. J Clin Oncol 1992; 10: 16–20
Douillard JY, Ibrahim N, Riviere A, et al. Phase II study of CPT-11 (irinotecan) in non-small cell lung cancer [abstract]. Proc Am Soc Clin Oncol 1995; 14: 365
Masuda N, Fukuoka M, Kusunoki Y, et al. CPT-11: a new derivative of camptothecin for the treatment of refractory or relapsed small-cell lung cancer. J Clin Oncol 1992; 10: 1225–9
Le Chevalier T, Ibrahim N, Chomy P, et al. A phase II study of irinotecan (CPT-11) in patients (pts) with small cell lung cancer (SCLC) progressing after initial response to first-line chemotherapy (CT) [abstract]. Proc Am Soc Clin Oncol 1997; 16: 450a
Takeuchi S, Dobashi K, Fujimoto S, et al. A late phase II study of CPT-11 on uterine cervical cancer and ovarian cancer. Research Groups of CPT-11 in Gynecologic Cancers. Jpn J Cancer Chemother 1991; 18: 1681–9
Potkul RK, Price FV, Bailey H, et al. Irinotecan (CPT-11) in advanced squamous cell carcinoma of the cervix (phase II) [abstract]. Proc Am Soc Clin Oncol 1995; 14: 279
Verschraegen CF, Levy T, Kudelka AP, et al. Phase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix. J Clin Oncol 1997; 15: 625–31
Chevallier B, Lhomme C, Dieras V, et al. Phase II trial of CPT-11 in advanced cervical carcinoma [abstract]. EORTC Early Drug Development Meeting: 1995 Jun 21–24; Corfu, 92
Taguchi T, Tominaga T, Ogawa M, et al. A late phase II study of CPT-11 (irinotecan) in advanced breast cancer. CPT-11 Study Group on Breast Cancer. Jpn J Cancer Chemother 1994; 21: 1017–24
Bonneterre J, Pion JM, Adenis A, et al. A phase II study of a new camptothecin analogue CPT-11 in previously treated advanced breast cancer patients [abstract]. Proc Am Soc Clin Oncol 1993; 12: 94
Sakata Y, Shimada Y, Yoshino M, et al. A late phase II study of CPT-11, irinotecan hydrochloride, in patients with advanced pancreatic cancer. CPT-11 Study Group on Gastrointestinal Cancer. Jpn J Cancer Chemother 1994; 21: 1039–46
Wagener DJ, Verdonk HER, Dirix LY, et al. Phase II trial of CPT-11 in patients with advanced pancreatic cancer, an EORTC early clinical trials groups study. Ann Oncol 1995; 6: 129–32
Futatsuki K, Wakui A, Nakao I, et al. Late phase II study of irinotecan hydrochloride (CPT-11) in advanced gastric cancer. Jpn J Cancer Chemother 1994; 21: 1033–8
Ohno R, Okada K, Masaoka T, et al. An early phase II study of CPT-11: a new derivative of camptothecin, for the treatment of leukemia and lymphoma. J Clin Oncol 1990; 8: 1907–12
Shimada Y, Sasaki Y, Sugano K, et al. Combination phase I study of CPT-11 (irinotecan) combined with continuous infusion of 5-fluorouracil (5-FU) in metastatic colorectal cancer [abstract]. Proc Am Soc Clin Oncol 1993; 12: 196
Benhammouda A, Bastian G, Rixe O, et al. A phase I and pharmacokinetic (PK) study of CPT-11 (C) and 5-FU (F) combination [abstract]. Proc Am Soc Clin Oncol 1997; 16: 202a
Saltz LB, Kanowitz J, Kemeny NE, et al. Phase I clinical and pharmacokinetic study of irinotecan, fluorouracil, and leucovorin in patients with advanced solid tumors. J Clin Oncol 1996; 14: 2959–67
Parnes HL, Tait N, Conley B, et al. A phase I study of CPT-11, weekly bolus 5-FU and leucovorin in patients with metastatic cancer. Oncol Rep 1995; 2: 1131–4
Rougier Ph, Ychou M, Seitz JF, et al. Phase I/II study of CPT-11 in combination with LV5FU2 (De Gramont-Regimen) every 2 weeks for the treatment of colorectal cancer (CRC) after 5FU failure [abstract]. The European Cancer Conference 9: 1997 Sep 14–18; Hamburg, S169
Ducreux M, Rougier PH, Ychou M, et al. PhaseI/II study of escalating doses of CPT-11 in combination with LV5FU2 (De Gramont-Regimen) every 2 weeks in the treatment of colorectal cancer (CRC) after 5-FU failure [abstract]. Proc Am Soc Clin Oncol 1997; 16: 234a
Sasaki Y, Ohtsu A, Shimada Y, et al. Simultaneous administration of CPT-11 and fluorouracil: alteration of the pharmacokinetics of CPT-11 and SN-38 in patients with advanced colorectal cancer. J Natl Cancer Inst 1994; 86: 1096–8
Karato A, Sasaki Y, Shinkai T, et al. Phase I study of CPT-11 and etoposide in patients with refractory solid tumors. J Clin Oncol 1993; 11: 2030–5
Saltz L, Kanowitz J, Kelsen D, et al. Phase I study of weekly cisplatin (CDDP) plus irinotecan (CPT-11) in patients (PTS) with advanced solid tumors [abstract]. Proc Am Soc Clin Oncol 1996; 15: 484
Masuda N, Fukuoka M, Kudoh S, et al. Phase I and pharmacologic study of irinotecan and etoposide with recombinant human granulocyte colony-stimulating factor support for advanced lung cancer. J Clin Oncol 1994: 12: 1833–41
Masuda N, Fukuoka M, Takada M, et al. CPT-11 in combination with cisplatin for advanced non-small-cell lung cancer. J Clin Oncol 1992; 10: 1775–80
Masuda N, Fukuoka M, Kudoh S, et al. Phase I and pharmacologic study of irinotecan in combination with cisplatin for advanced lung cancer. Br J Cancer 1993; 68: 777–82
Ueoka H, Tabata M, Shibayama T, et al. A phase I study of irinotecan (CPT-11) and cisplatin (CDDP) in advanced lung cancer (ED-SCLC and IIIB/IV-NSCLC) [abstract]. Proc Am Soc Clin Oncol 1996; 15: 385
Kobayashi K, Soma T, Shinbara A, et al. Phase I study of irinotecan (CPT-11) and cisplatin (CDDP) by divided administration in patients with non-small-cell lung cancer [abstract]. Proc Am Soc Clin Oncol 1996; 15: 388
Masuda N, Fukuoka M, Kudoh S, et al. Phase I study of irinotecan and cisplatin with granulocyte colony-stimulating factor support for advanced non-small-cell lung cancer. J Clin Oncol 1994; 12: 90–6
Mori K, Ohnishi T, Yokoyama K, et al. A phase I study of irinotecan and infusional cisplatin for advanced non-small-cell lung cancer. Cancer Chemother Pharmacol 1997; 39: 327–32
Shinkai T, Arioka H, Kunikane H, et al. Phase I clinical trial of irinotecan (CPT-ll), 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy-camptothecin, and cisplatin in combination with fixed dose of vindesine in advanced non-small cell lung cancer. Cancer Res 1994; 54: 2636–42
Shirao K, Shimada Y, Kondo H, et al. Phase I–II study of irinotecan hydrochloride combined with cisplatin in patients with advanced gastric cancer. J Clin Oncol 1997; 15: 921–7
Rothenberg ML, Pazdur R, Rowinsky EK, et al. A phase II multicenter trial of alternating cycles of irinotecan (CPT-11) and 5-FU/LV in patients with previously untreated metastatic colorectal cancer (CRC) [abstract]. Proc Am Soc Clin Oncol 1997; 16: 266a
Barone C, Pozzo C, Starkhammar H, et al. CPT-11 alternating with 5-fluorouracil (5-FU)/folinic acid (FA): a multicentre phase II study in first-line chemotherapy (CT) of metastatic colorectal cancer (CRC) [abstract]. Proc Am Soc Clin Oncol 1997; 16: 270a
Oshita F, Noda K, Nishiwaki Y, et al. Phase II study of irinotecan and etoposide in patients with metastatic non-small-cell lung cancer. J Clin Oncol 1997; 15: 304–9
DeVore R, Crawford J, Dimery I, et al. Phase II trial of irinotecan (CPT-11) plus cisplatin (CDDP) in advanced NSCLC [abstract]. Proc Am Soc Clin Oncol 1997; 16: 466a
Mori K, Hirose T, Tominaga K. Phase II study irinotecan and infusional cisplatin with recombinant human granulocyte colony-stimulating factor support in the treatment of advanced non-small cell lung cancer [abstract]. Proc Am Soc Clin Oncol 1997; 16: 476a
Saka H, Shimokata K, Yoshida K, et al. Irinotecan (CPT-11) and concurrent radiotherapy in locally advanced non-small cell lung cancer (NSCLC): a phase II study of Japan Clinical Oncology Group (JCOG9504) [abstract]. Proc Am Soc Clin Oncol 1997; 16: 447a
Kudoh S, Fujiwara Y, Takada Y, et al. Phase II study of irinotecan combined with cisplatin in patients with previously untreated small-cell lung cancer. J Clin Oncol 1998; 16: 1068–74
Sugiyama T, Nishida T, Ushijima K, et al. Irinotecan hydrochloride (CPT-11) combined with cisplatin (CDDP) in patients with relapsed or metastatic ovarian cancer [abstract]. Proc Am Soc Clin Oncol 1996; 15: 291
Shimizu Y, Umezawa S, Hasumi K. Combination of CPT-11 (CPT) with mitomycin-C (MMC) is active for clear cell adenocarcinoma of the ovary (OCA) which is intrinsically CDDP-resistant [abstract]. Proc Am Soc Clin Oncol 1996; 15: 282
Boku N, Ohtsu A, Shimada Y, et al. Phase II study of a combination of CDDP and CPT-11 in metastatic gastric cancer: CPT-11 study group for gastric cancer [abstract]. Proc Am Soc Clin Oncol 1997; 16: 264a
Poon MA, O’Connell MJ, Wieand HS, et al. Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therpeutic efficacy in advanced colorectal cancer. J Clin Oncol 1991; 9: 1967–72
Gandia D, Abigerges D, Armand JP, et al. CPT-11-induced cholinergic effects in cancer patients. J Clin Oncol 1993; 11: 196–7
Bleiberg H, Cvitkovic E. Characterisation and clinical management of CPT-11 (irinotecan)-induced adverse events: the European perspective. Eur J Cancer 1996; 32A Suppl. 3: S18–23
O’Reilly S, Rowinsky R. The clinical status of irinotecan (CPT-11), a novel water soluble camptothecin analogue: 1996. Crit Rev Oncol Hematol 1996; 24: 47–70
Chen G, Portman R, Wickel A. Pharmacology of 1,1-dimethyl-4-phenyl-piperazinium iodide, a ganglion-stimulating agent. J Pharmacol Exp Ther 1951; 103: 330–6
Abigerges D, Armand JP, Chabot GG, et al. Irinotecan (CPT-11) high-dose escalation using intensive high-dose loperamide to control diarrhea. J Natl Cancer Inst 1994; 86: 446–9
Goncalves E, da Costa L, Abigerges D, et al. A new enkephalinase inhibitor as an alternative to loperamide in the prevention of diarrhea induced by CPT-11. J Clin Oncol 1996; 13: 2144–6
Ychou M, Rougier Ph, Oberling F, et al. Aphase II randomized study of CPT-11 (irinotecan) in colorectal cancer (CRC) refractory to 5-FU, with preventive treatment of delayed diarrhea using acetorphan [abstract]. Proc Am Soc Clin Oncol 1996; 15: 212
Hagipantelli R, Saliba F, Misset JL, et al. Pathophysiology and therapy of irinotecan (CPT-11) induced delayed onset diarrhea: a prospective assessment [abstract]. Proc Am Soc Clin Oncol 1995; 14: 464
Ikuno N, Soda H, Watanabe M, et al. Irinotecan (CPT-11) and characteristic mucosal changes in the mouse ileum and cecum. J Natl Cancer Inst 1995; 87: 1876–83
de Forni M, Bugat R, Chabot GG, et al. Phase I and pharmacokinetic study of the camptothecin derivative irinotecan, administered on a weekly schedule in cancer patients. Cancer Res 1994; 54: 4347–54
Catimel G, Chabot GG, Guastalla JP, et al. Phase I and pharmacokinetic study of irinotecan (CPT-11) administered daily for three consecutive days every three weeks in patients with advanced solid tumors. Ann Oncol 1995; 6: 133–40
Sasaki Y, Hakusui H, Mizuno S, et al. A pharmacokinetic and pharmacodynamic analysis of CPT-11 and its active metabolite SN-38. Jpn J Cancer Res 1995; 86: 101–10
Gupta E, Lestingi TM, Mick R, et al. Metabolic fate of irinotecan in humans: correlation of glucuronidation with diarrhea. Cancer Res 1994; 54: 3723–5
Atsumi R, Suzuki W, Hakusui H. Identification of the metabolites of irinotecan, a new derivative of camptothecin, in rat bile and its biliary excretion. Xenobiotica 1991; 21: 1159–69
Rivory LP, Robert J. Identification and kinetics of a β-glucuronide of SN-38 in human plasma after administration of the camptothecin derivative irinotecan (CPT-11). Cancer Chemother Pharmacol 1995; 36: 176–9
Lokiec F, Canal P, Gay C, et al. Pharmacokinetics of irinotecan and its metabolites in human blood, bile, and urine. Cancer Chemother Pharmacol 1995; 36: 79–82
Araki E, Ishikawa M, Iigo M, et al. Relationship between development of diarrhea and the concentration of SN-38, an active metabolite of CPT-11, in the intestine and the blood plasma of athymic mice following intraperitoneal administration of CPT-11. Jpn J Cancer Res 1993; 84: 697–702
Boddy AV, Ratain MJ. Pharmacogenetics in cancer etiology and chemotherapy. Clin Cancer Res 1997; 3: 1025–30
Rothenberg ML. Topoisomerase I inhibitors: review and update. Ann Oncol 1997; 8: 837–55
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Siu, L.L., Rowinsky, E.K. A Risk-Benefit Assessment of Irinotecan in Solid Tumours. Drug-Safety 18, 395–417 (1998). https://doi.org/10.2165/00002018-199818060-00002
Published:
Issue Date:
DOI: https://doi.org/10.2165/00002018-199818060-00002