This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by de Jonge, M. J. A. Articles by Verweij, J. Search for Related Content PubMed PubMed Citation Articles by de Jonge, M. J. A. Articles by Verweij, J. Social Bookmarking                            What's this?

Phase I Study of 3-Week Schedule of Irinotecan Combined With Cisplatin in Patients With Advanced Solid Tumors

From the Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek) and University Hospital Rotterdam, Rotterdam, the Netherlands; and Rhône-Poulenc Rorer, Antony, France.

Address reprint requests to M.J.A. de Jonge, MD, PhD, Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek) and University Hospital Rotterdam, Groene Hilledijk 301, 3075 EA Rotterdam, the Netherlands.

PURPOSE: To assess the feasibility, pharmacokinetic interaction, and possible sequence-dependent effects of the irinotecan/cisplatin combination given every 3 weeks, and to assess the influence of additional granulocyte colony-stimulating factor (G-CSF) on the hematologic toxicity.

PATIENTS AND METHODS: Patients who had received no more than one prior combination chemotherapy regimen or two single-agent regimens were entered. Treatment consisted of a 90-minute irinotecan infusion followed by a 3-hour cisplatin infusion on day 1, with cycles repeated once every 3 weeks. After the maximum-tolerated dose was determined, the sequence of administration was reversed. In a separate cohort of six patients, we assessed the effect of G-CSF on the experienced hematologic toxicity and dose-intensity. Irinotecan doses ranged from 175 to 300 mg/m² and cisplatin doses ranged from 60 to 80 mg/m².

RESULTS: Fifty-two patients entered the study; one was not eligible, and two were not assessable for response. Twenty-five patients were pretreated, and 26 were not. Fifty-one patients received a total of 223 courses. The dose-limiting toxicity was a combination of neutropenic fever, diarrhea, and fatigue at a dose level combining irinotecan 300 mg/m² with cisplatin 80 mg/m². Neutropenia was common (grades 3 to 4, 68%). Irinotecan pharmacokinetics were linear over the dose range studied. No sequence-dependent side effects were observed. Tumor responses included three complete responses and eight partial responses.

CONCLUSION: For phase II studies, we recommend irinotecan 260 mg/m² combined with cisplatin 80 mg/m² once every 3 weeks for chemotherapy-naive patients in good physical condition, and irinotecan 200 mg/m² combined with cisplatin 80 mg/m² for other patients.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C. Theodore, I. Skoneczna, I. Bodrogi, M. Leahy, J. M. Kerst, L. Collette, K. Ven, S. Marreaud, R. D. T. Oliver, and for the EORTC Genito-Urinary Tract Cancer Group A phase II multicentre study of irinotecan (CPT 11) in combination with cisplatin (CDDP) in metastatic or locally advanced penile carcinoma (EORTC PROTOCOL 30992) Ann. Onc., July 1, 2008; 19(7): 1304 - 1307. [Abstract] [Full Text] [PDF]

				J. M. van der Bol, R. H.J. Mathijssen, W. J. Loos, L. E. Friberg, R. H.N. van Schaik, M. J.A. de Jonge, A. S.Th. Planting, J. Verweij, A. Sparreboom, and F. A. de Jong Cigarette Smoking and Irinotecan Treatment: Pharmacokinetic Interaction and Effects on Neutropenia J. Clin. Oncol., July 1, 2007; 25(19): 2719 - 2726. [Abstract] [Full Text] [PDF]

				C. Pozzo, C. Barone, J. Szanto, E. Padi, C. Peschel, J. Bukki, V. Gorbunova, V. Valvere, J. Zaluski, M. Biakhov, et al. Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study Ann. Onc., December 1, 2004; 15(12): 1773 - 1781. [Abstract] [Full Text] [PDF]

				R. H. J. Mathijssen, F. A. de Jong, R. H. N. van Schaik, E. R. Lepper, L. E. Friberg, T. Rietveld, P. de Bruijn, W. J. Graveland, W. D. Figg, J. Verweij, et al. Prediction of Irinotecan Pharmacokinetics by Use of Cytochrome P450 3A4 Phenotyping Probes J Natl Cancer Inst, November 3, 2004; 96(21): 1585 - 1592. [Abstract] [Full Text] [PDF]

				M. Michael, M. Brittain, J. Nagai, R. Feld, D. Hedley, A. Oza, L. Siu, and M. J. Moore Phase II Study of Activated Charcoal to Prevent Irinotecan-Induced Diarrhea J. Clin. Oncol., November 1, 2004; 22(21): 4410 - 4417. [Abstract] [Full Text] [PDF]

				F. A. de Jong, S. Marsh, R. H. J. Mathijssen, C. King, J. Verweij, A. Sparreboom, and H. L. McLeod ABCG2 Pharmacogenetics: Ethnic Differences in Allele Frequency and Assessment of Influence on Irinotecan Disposition Clin. Cancer Res., September 1, 2004; 10(17): 5889 - 5894. [Abstract] [Full Text] [PDF]

				J. D. Chester, S. P. Joel, S. L. Cheeseman, G. D. Hall, M. S. Braun, J. Perry, T. Davis, C. J. Button, and M. T. Seymour Phase I and Pharmacokinetic Study of Intravenous Irinotecan Plus Oral Ciclosporin in Patients With Fluorouracil-Refractory Metastatic Colon Cancer J. Clin. Oncol., March 15, 2003; 21(6): 1125 - 1132. [Abstract] [Full Text] [PDF]

				A.-K. Souid, R. L. Dubowy, S. M. Blaney, L. Hershon, J. Sullivan, W. D. McLeod, and M. L. Bernstein Phase I Clinical and Pharmacologic Study of Weekly Cisplatin and Irinotecan Combined with Amifostine for Refractory Solid Tumors Clin. Cancer Res., February 1, 2003; 9(2): 703 - 710. [Abstract] [Full Text] [PDF]

				R. H.J. Mathijssen, J. Verweij, M. J.A. de Jonge, K. Nooter, G. Stoter, and A. Sparreboom Impact of Body-Size Measures on Irinotecan Clearance: Alternative Dosing Recommendations J. Clin. Oncol., January 1, 2002; 20(1): 81 - 87. [Abstract] [Full Text] [PDF]

				F. E. de Jongh, J. Verweij, W. J. Loos, R. de Wit, M. J.A. de Jonge, A. S.T. Planting, K. Nooter, G. Stoter, and A. Sparreboom Body-Surface Area-Based Dosing Does Not Increase Accuracy of Predicting Cisplatin Exposure J. Clin. Oncol., September 1, 2001; 19(17): 3733 - 3739. [Abstract] [Full Text] [PDF]

				R. H. J. Mathijssen, R. J. van Alphen, J. Verweij, W. J. Loos, K. Nooter, G. Stoter, and A. Sparreboom Clinical Pharmacokinetics and Metabolism of Irinotecan (CPT-11) Clin. Cancer Res., August 1, 2001; 7(8): 2182 - 2194. [Abstract] [Full Text] [PDF]

				M. J. A. de Jonge, J. Verweij, P. de Bruijn, E. Brouwer, R. H. J. Mathijssen, R. J. van Alphen, M. M. de Boer-Dennert, L. Vernillet, C. Jacques, and A. Sparreboom Pharmacokinetic, Metabolic, and Pharmacodynamic Profiles in a Dose-Escalating Study of Irinotecan and Cisplatin J. Clin. Oncol., January 5, 2000; 18(1): 195 - 195. [Abstract] [Full Text] [PDF]