JCO Early Release, published online ahead of print Jun 11 2007
Journal of Clinical Oncology, 10.1200/JCO.2006.09.6115
Received October 26, 2006
Accepted January 17, 2007
Cigarette Smoking and Irinotecan Treatment: Pharmacokinetic Interaction and Effects on Neutropenia
Jessica M. van der Bol, Ron H.J. Mathijssen, Walter J. Loos, Lena E. Friberg, Ron H.N. van Schaik, Maja J.A. de Jonge, André S.Th. Planting, Jaap Verweij, Alex Sparreboom, and Floris A. de Jong*
From the Department of Medical Oncology, Erasmus MC University Medical Center, Daniel den Hoed Cancer Center; Department of Clinical Chemistry, Erasmus MC University Medical Center, Rottendam, the Netherlands; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden; and the Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN
* To whom correspondence should be addressed. E-mail: f.a.dejong{at}erasmusmc.nl
Purpose: Several constituents of cigarette smoke are known to interact with drug metabolizing enzymes and potentially affect treatment outcome with substrate drugs. The purpose of this study was to determine the effects of cigarette smoking on the pharmacokinetics and adverse effects of irinotecan.
Patients and Methods: A total of 190 patients (49 smokers, 141 nonsmokers) treated with irinotecan (90-minute intravenous administration on a 3-week schedule) were evaluated for pharmacokinetics. Complete toxicity data were available in a subset of 134 patients receiving 350 mg/m2 or 600 mg flat-fixed dose irinotecan.
Results: In smokers, the dose-normalized area under the plasma concentration-time curve of irinotecan was significantly lower (median, 28.7 v 33.9 ng · h/mL/mg; P = .001) compared with nonsmokers. In addition, smokers showed an almost 40% lower exposure to SN-38 (median, 0.54 v 0.87 ng · h/mL/mg; P < .001) and a higher relative extent of glucuronidation of SN-38 into SN-38G (median, 6.6 v 4.5; P = .006). Smokers experienced considerably less hematologic toxicity. In particular, the incidence of grade 3 to 4 neutropenia was 6% in smokers versus 38% in nonsmokers (odds ratio [OR], 0.10; 95% CI, 0.02 to 0.43; P < .001). There was no significant difference in incidence of delayed-onset diarrhea (6% v 15%; OR, 0.34; 95% CI, 0.07 to 1.57; P = .149).
Conclusion: This study indicates that smoking significantly lowers both the exposure to irinotecan and treatment-induced neutropenia, indicating a potential risk of treatment failure. Although the underlying mechanism is not entirely clear, modulation of CYP3A and uridine diphosphate glucuronosyltransferase isoform 1A1 may be part of the explanation. The data suggest that additional investigation is warranted to determine whether smokers are at increased risk for treatment failure.
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Facebook  Reddit  Technorati  Twitter What's this?
Related Editorial
- Cigarette Smoking and the Personalization of Irinotecan Therapy
Neal L. Benowitz
JCO 2007 25: 2646-2647
[Full Text]
This article has been cited by other articles:
|
|
|
|
 
D. I. Gregorio, M. Hollenbeck, and H. Samociuk
Who's assessing tobacco use in cancer clinical trials?
Nicotine Tob Res,
November 1, 2009;
11(11):
1354 - 1358.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Kanai, S. Morita, S. Matsumoto, T. Nishimura, E. Hatano, S. Yazumi, T. Sasaki, H. Yasuda, T. Kitano, A. Misawa, et al.
A history of smoking is inversely correlated with the incidence of gemcitabine-induced neutropenia
Ann. Onc.,
August 1, 2009;
20(8):
1397 - 1401.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. H.J. Mathijssen and H. Gurney
Irinogenetics: How Many Stars Are There in the Sky?
J. Clin. Oncol.,
June 1, 2009;
27(16):
2578 - 2579.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. N. Hughes, M. E.R. O'Brien, W. J. Petty, J. B. Chick, E. Rankin, P. J. Woll, D. Dunlop, M. Nicolson, R. Boinpally, J. Wolf, et al.
Overcoming CYP1A1/1A2 Mediated Induction of Metabolism by Escalating Erlotinib Dose in Current Smokers
J. Clin. Oncol.,
March 10, 2009;
27(8):
1220 - 1226.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. van Erp, H. Gelderblom, M. van Glabbeke, A. Van Oosterom, J. Verweij, H.-J. Guchelaar, M. Debiec-Rychter, B. Peng, J.-Y. Blay, and I. Judson
Effect of Cigarette Smoking on Imatinib in Patients in the Soft Tissue and Bone Sarcoma Group of the EORTC
Clin. Cancer Res.,
December 15, 2008;
14(24):
8308 - 8313.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. L. Benowitz
Cigarette Smoking and the Personalization of Irinotecan Therapy
J. Clin. Oncol.,
July 1, 2007;
25(19):
2646 - 2647.
[Full Text]
[PDF]
|
|
|
|
