Irinotecan: A New Antineoplastic Agent for the Management of Colorectal Cancer

Abstract

Spanish

French

OBJECTIVE:

To review the pharmacologic, pharmacokinetic, therapeutic, and safety aspects of irinotecan, a new antineoplastic agent, and to assess its role in the treatment of colorectal and lung cancer.

DATA SOURCES:

English-language articles from the MEDLINE database, January 1990–March 1998; Pharmacia & Upjohn Company; published articles and meeting abstracts.

STUDY SELECTION:

Studies in humans with cancer, clinical case reports, and open clinical studies were reviewed. Efficacy studies were limited to trials with at least 20 evaluable patients.

DATA EXTRACTION:

Relevant data were extracted from published reports and abstracts.

DATA SYNTHESIS:

Irinotecan is an effective agent for the treatment of advanced colorectal cancer. It demonstrates significant activity as a first-line agent and in patients with disease that is refractory to fluorouracil-containing regimens. Activity against lung cancer has also been demonstrated. Limited data indicate activity against cancers of the ovary, cervix, stomach, and in non-Hodgkin's lymphomas. Major toxicity consists of myelosuppression and diarrhea.

CONCLUSIONS:

Irinotecan is a useful addition to the antineoplastic drug family and offers significant efficacy for treatment of patients with fluorouracil-refractory colorectal cancer.

Keywords

irinotecan cancer colorectal lung

Get full access to this article

View all access options for this article.

References

Gottlieb

Guarino

Call

Oliverio

Block

. Preliminary pharmacokinetic and clinical evaluation of camptothecin sodium (NSC-100880). Cancer Chemother Rep 1970;54: 461–70.

Schaeppi

Fleischman

Cooney

. Toxicity of camptothecin (NSC-100880). Cancer Chemother Rep 1974;58: 25–36.

Takimoto

Arbuck

. The camptothecins. In: Chabner

Longo

, eds. Cancer chemotherapy and biotherapy. 2nd ed. Philadelphia: Lippincott-Raven, 1996: 463–84.

Package insert. Camptosar (irinotecan). Kalamazoo, MI: Pharmacia & Upjohn Co., December 1997.

Kawato

Aonuma

Hirota

Kuga

Sato

. Intracellular role of SN-38, a metabolite of the camptothecin derivative, CPT-11, in the antitumor effect of CPT-11. Cancer Res 1991;51: 4187–91.

Rowinsky

Grochow

Ettinger

Sartorius

Lubejko

Chen

T-L

Phase I and pharmacological study of the novel topoisomerase I inhibitor 7-ethyl 1–1 0-[4-(1-piperidino)-1-piperidino] carbonyloxy camptothecin (CPT-11) administered as a ninety-minute infusion every 3 weeks. Cancer Res 1994;54:427–36.

Chabot

Abigerges

Catimel

Culine

deForni

Extra

J-M

Population pharmacokinetics and pharmacodynamics of irinotecan (CPT-11) and active metabolite SN-38 during Phase I trials. Ann Oncol 1995;6:1141–51.

Rothenberg

Kuhn

Burris

III Nelson

Eckardt

Tristan-Morales

Phase I and pharmacokinetic trial of weekly CPT-11. J Clin Oncol 1993;11:2194–204.

deForni

Bugat

Chabot

Culine

Extra

J-M

Gouyette

Phase I and pharmacokinetic study of the camptothecin derivative irinotecan, administered on a weekly schedule in cancer patients. Cancer Res 1994;54:4347–54.

10.

Ohe

Sasaki

Shinkai

Eguchi

Tamura

Kojima

Phase I study and pharmacokinetics of CPT-11 with a 5-day continuous infusion. J Natl Cancer Inst 1992;84:972–4.

11.

Gupta

Mick

Ramirez

Wang

Lestingi

Vokes

Pharmacokinetic and pharmacodynamic evaluation of the topoisomerase inhibitor irinotecan in cancer patients. J Clin Oncol 1997;15:1502–10.

12.

Abigerges

Chabot

Armand

J-P

Hemit

Gouyette

Gandia

. Phase I and pharmacologic studies of the camptothecin analog irinotecan administered every 3 weeks in cancer patients. J Clin Oncol 1995;13: 210–21.

13.

Catimel

Chabot

Guastalla

Dumortier

Cote

Engel

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.

14.

Gupta

Wang

Ramirez

Ratain

. Modulation of glucuronidation of SN-38, the active metabolite of irinotecan, by valproic acid and phenobarbital. Cancer Chemother Pharmacol 1997;39: 440–4.

15.

Lokiec

Canal

Gay

Chatelut

Armand

J-P

Roche

Pharmacokinetics of irinotecan and its metabolites in human blood, bile, and urine. Cancer Chemother Pharmacol 1995;36:79–82.

16.

Armand

J-P

Extra

Catimel

Abigerges

Marty

Clavel

. Rationale for the dosage and schedule of CPT-11 (irinotecan) selected for Phase II studies, as determined by European Phase I studies. Ann Oncol 1996;7: 837–42.

17.

Macdonald

Haller

Mayer

, eds. Manual of oncologic therapeutics. 3rd ed. Philadelphia: JB Lippincott, 1995:526.

18.

Landis

Murray

Boldon

Wingo

. Cancer statistics 1998. CA Cancer J Clin 1998;47: 6–29.

19.

Cohen

Minsky

Schilsky

. Cancer of the colon. In: DeVita

Jr Hellman

Rosenberg

, eds. Cancer principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven, 1997: 1144–97.

20.

Piedbois

Buyse

Rustum

Machove

Erlichman

Carlson

Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: Evidence in terms of response rate. Advanced colorectal cancer meta-analysis project. J Clin Oncol 1993;10: 896–903.

21.

Machover

. A comprehensive review of 5-fluorouracil and leucovorin in patients with metastatic colorectal carcinoma. Cancer 1997;80: 1179–87.

22.

Rougier

Bugat

Pouillard

Culine

Suc

Brunet

Phase II study of irinotecan in the treatment of advanced colorectal cancer in chemotherapynaive patients and patients pre-treated with fluorouracil-based chemotherapy. J Clin Oncol 1997;15:251–60.

23.

Pitot

Wender

O'Connell

Schroeder

Goldberg

Rubin

A Phase II trial of irinotecan in patients with metastatic colorectal carcinoma. J Clin Oncol 1997;15:2910–9.

24.

Shimada

Rougier

Pitot

. Efficacy of CPT-11 (irinotecan) as a single agent in metastatic colorectal cancer. Eur J Cancer 1996;32A(suppl 3):S13–7.

25.

Rothenberg

Eckardt

Kuhn

Burris

III Nelson

Hilsenbeck

Phase II trial of irinotecan in patients with progressive or rapidly recurrent colorectal cancer. J Clin Oncol 1996;14:1128–35.

26.

Conti

Kemeny

Saltz

Huang

Tong

Chou

T-C

Irinotecan is an active agent in untreated patients with metastatic colorectal cancer. J Clin Oncol 1996;14:709–15.

27.

Shimada

Yoshino

Wakui

Nakao

Futatsuki

Sakata

Phase II study of CPT-11, a new camptothecin derivative, in metastatic colorectal cancer. J Clin Oncol 1993;11:909–13.

28.

Von Hoff

Rothenberg

Pitot

Elfring

Mohrland

Schaaf

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;16:238a.

29.

Saltz

Kanowitz

Kemeny

Schaaf

Spriggs

Staton

Phase I clinical and pharmacokinetic study of irinotecan, 5 fluorouracil, and leucovorin in patients with advanced solid tumors. J Clin Oncol 1996;14:2959–67.

30.

Shimada

Sasaki

Sugano

Shirao

Kondo

Yokota

Combination Phase I study of CPT-11 (irinotecan) combined with continuous infusion 5 fluorouracil (5FU) in metastatic colorectal cancer (abstract). Proc Am Soc Clin Oncol 1993;12:196.

31.

Ducreux

Rougier

Ychou

Seltz

Bonnay

Mignard

Phase I/II study of escalating doses of CPT-11 in combination with LV5FU2 (“DeGramont” regimen) every two weeks in the treatment of colorectal cancer (CRC) after 5-FU failure (abstract). Proc Am Soc Clin Oncol 1997;16:234a.

32.

Yamato

Shimada

Shirao

Kondo

Matsumura

Sugano

Phase I study of CPT-11 combined with sequential 5FU in metastatic colorectal cancer (CRC) (abstract). Proc Am Soc Clin Oncol 1996;15:481.

33.

Barone

Pozzo

Starkhammar

Terzoli

Dinix

Hmblet

CPT-11 alternating with 5-fluorouracil (5FU)/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.

34.

Rothenberg

Pazdur

Rowinsky

Cohn

Alberts

Petit

A Phase II multicenter trial of alternating cycle of irinotecan (CPT-11) and 5FU/LV in patients with previously untreated metastatic colorectal cancer (CRC) (abstract). Proc Am Soc Clin Oncol 1997;16:266a.

35.

Ginsberg

Vokes

Raben

. Non-small cell lung cancer. In: Devita

Jr Hellman

Rosenberg

, eds. Cancer principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven, 1997: 858–911.

36.

Figlin

Holmes

Tumisi

III . Neoplasms of the lung, pleura, and mediastinum. In: Haskell

, ed. Cancer treatment. 4th ed. Philadelphia: Saunders, 1995: 385–413.

37.

Negoro

Fukuoka

Niitani

Suzuki

Nakabayashi

Kimura

A Phase II study of CPT-11, a camptothecin derivative, in patients with primary lung cancer. Jpn J Cancer Chemother 1991;18:1013–9, accessed in Rothenberg

. CPT-11: An original spectrum of clinical activity. Semin Oncol 1996;23 (suppl 3): 21–6.

38.

Fukuoka

Niitani

Suzuki

Monomiya

Hasegawa

Nishiwaki

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.

39.

Baker

Khan

Lynch

Savaraj

Sandler

Feun

Phase II study of irinotecan (CPT-11) in advanced non-small cell lung cancer (NSCLC) (abstract). Proc Am Soc Clin Oncol 1997;16:461a.

40.

Mori

Hirose

Machida

Yokoyama

Tominaga

. A Phase I study of irinotecan and infusional cisplatin with recombinant human granulocyte colony-stimulating factor support in the treatment of advanced non-small cell lung cancer. Eur J Cancer 1997;33: 503–5.

41.

Mori

Suga

Kishiro

Ohta

Tominaga

. A Phase I study of CPT-11 and cisplatin (5-day continuous infusion) for advanced non-small cell lung cancer (abstract). Proc Am Soc Clin Oncol 1994;13:366.

42.

Masuda

Fukuoka

Takada

. CPT-11 in combination with cisplatin for advanced non-small cell lung cancer. J Clin Oncol 1992;10: 1775–80.

43.

Masuda

Fukuoka

Kudoh

Kusunoki

Matsui

Nakagawa

Phase I study of irinotecan and cisplatin with granulocyte colony-stimulating factor support for advanced non-small cell lung cancer. J Clin Oncol 1994;12:90–96.

44.

DeVore

Crawford

Dimery

Eckardt

Kasunic

Phase II trial of irinotecan (CPT-11) plus cisplatin (CDDP) in advanced NSCLC (abstract). Proc Am Soc Clin Oncol 1997;16:466a.

45.

Mori

Hirose

Tominaga

. Phase II study of 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.

46.

Oshita

Noda

Nishiwaki

Fujita

Kurita

Nakabayashi

Phase II study of irinotecan and etoposide in patients with metastatic non-small cell lung cancer. J Clin Oncol 1997;15:304–9.

47.

Saka

Shimokata

Yoshida

Noda

Nakaboyashi

Tsuchiya

Irinotecan (CPT-11) and concurrent radiotherapy in locally advanced non-small cell lung cancer (NSCLC): A Phase II study of Japan Clinical Oncology Group (JCOG 9504) (abstract). Proc Am Soc Clin Oncol 1997;16:447a.

48.

Masuda

Fukuoka

Kushunoki

Matsui

Takifuji

Kudoh

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.

49.

Negoro

Fukuoka

Niitani

Taguchi

. Phase II study of CPT-11, new camptothecin derivative, in small cell lung cancer (SCLC) (abstract). Proc Am Soc Clin Oncol 1991;10:241.

50.

LeChevalier

Ibrahim

Chomy

Riviere

Monnier

Magherini

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.

51.

Fujiwara

Yamakido

Fukuoka

Kudoh

Furuse

Ikegami

Phase I study of irinotecan (CPT-11) and cisplatin (CDDP) in patients with small cell lung cancer (SCLC) (abstract). Proc Am Soc Clin Oncol 1994;13:335.

52.

Sugiyama

Nishida

Ookura

Yakushiji

Ikeda

Noda

Is CPT-11 useful as a salvage chemotherapy for recurrent ovarian cancer (abstract)?

Proc Am Soc Clin Oncol 1997;16:378a.

53.

Verschraegen

Levy

Kudelka

Llerena

Endes

Freedman

Phase II study of irinotecan in prior chemotherapy treated squamous cell carcinoma of the cervix. J Clin Oncol 1997;15:625–31.

54.

Kambe

Wakui

Nakao

Futasuki

Sakata

Yoshino

A late Phase II study of irinotecan (CPT-11) in patients with advanced gastric cancer (abstract). Proc Am Soc Clin Oncol 1993;12:198.

55.

Tsuda

Takatsuki

Ohno

Masauka

Okada

Shirakawa

A late Phase II trial of a potent topoisomerase I inhibitor, CPT-11, in malignant lymphoma (abstract). Proc Am Soc Clin Oncol 1992;11:316.

56.

Rougier

Bugat

. CPT-11 in the treatment of colorectal cancer: Clinical efficacy and safety profile. Semin Oncol 1996;23 (suppl 3): 34–41.

57.

Kudoh

Fukuoka

Masuda

Yoshikawa

Kusunoki

Matsui

Relationship between the pharmacokinetics of irinotecan and diarrhea during combination chemotherapy with cisplatin. Jpn J Cancer Res 1995;86:406–13.

58.

Gupta

Lestingi

Mick

Ramirez

Vokes

Ratain

. Metabolic fate of irinotecan in humans: Correlation of glucuronidation with diarrhea. Cancer Res 1994;54: 3723–5.

59.

Araki

Ishikawa

Iigo

Koide

Itabashi

Hoshi

. 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.

60.

Kaplan

Jack

Cotler

Alexander

. Utilization of area under the curve to elucidate the disposition of an extensively biotransformed drug. J Pharm Biopharm 1973;1: 201–16.

61.

Mick

Gupta

Vokes

Ratain

. Limited-sampling models for irinotecan pharmacokinetics—pharmacodynamics: Prediction of biliary index and intestinal toxicity. J Clin Oncol 1996;14: 2012–9.

62.

Canal

Gay

Dezeuze

Douillard

Bugat

Brunet

Pharmacokinetics and pharmacodynamics of irinotecan during a Phase II clinical trial in colorectal cancer. J Clin Oncol 1996;14:2688–95.

63.

1998 Drug topics red book. Montvale, NJ: Medical Economics Co., 1998:206,315,382.

64.

Moertel

. Chemotherapy for colorectal cancer. N Engl J Med 1994;330: 1136–42.