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Screening pharmaceuticals for possible carcinogenic effects: initial positive results for drugs not previously screened

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Abstract

Objective

To screen commonly used prescription drugs for possible carcinogenic effects.

Methods

In a large health care program we identified 105 commonly used drugs, not previously screened. Recipients were followed for up to 12½ years for incident cancer. Nested case–control analyses of 55 cancer sites and all combined included up to ten matched controls per case, with lag of at least 2 years between drug dispensing and cancer. Positive associations entailed a relative risk of 1.50, with p ≤ 0.01 and higher risk for three or more, than for one prescription. Evaluation included further analyses, searches of the literature, and clinical judgment.

Results

There were 101 associations of interest for 61 drugs. Sixty-six associations were judged to have involved substantial confounding. We found evidence that of the remaining 35, the following associations may not be due to chance: sulindac with gallbladder cancer and leukemia, hyoscyamine with nonHodgkin lymphoma, nortriptyline with esophageal and hepatic cancer, oxazepam with lung cancer, both fluoxetine and paroxetine with testicular cancer, hydrochlorothiazide with renal and lip cancer, and nifedipine with lip cancer.

Conclusions

These preliminary findings suggest that further studies are indicated regarding sulindac, hyoscyamine, nortriptyline, oxazepam, fluoxetine, paroxetine, hydrochlorothiazide, and nifedipine.

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Acknowledgments

This study was supported by Grant R01 098838 from the National Cancer Institute. Dr. Friedman served on an advisory committee to Roche Laboratories in June 2008 and in the past 3 years has consulted for law firms serving both plaintiffs and Ortho-McNeil-Janssen Pharmaceuticals regarding litigation concerning celecoxib and Ortho-Evra, respectively. During the last 5 years, Dr. Habel has had research support through contracts with Kaiser Foundation Research Institute from Eli Lilly, Inc.; Genomic Health, Inc.; Takeda; Merck; AviaraDx; Genentech; and Roche. None of these sponsors had any role in this manuscript; they did not sponsor the research, have any role in its study design, data collection, analysis, interpretation of results, or drafting.

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Authors and Affiliations

  1. Division of Research, Kaiser Permanente Medical Care Program, 2000 Broadway, Oakland, CA, 94612, USA

    Gary D. Friedman, Natalia Udaltsova, Charles P. Quesenberry Jr & Laurel A. Habel

  2. Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA

    Gary D. Friedman

  3. Pharmacy Outcomes Research Group, Kaiser Permanente Medical Care Program, 1800 Harrison, Oakland, CA, USA

    James Chan

Authors
  1. Gary D. Friedman
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  2. Natalia Udaltsova
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  3. James Chan
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  4. Charles P. Quesenberry Jr
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  5. Laurel A. Habel
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Corresponding author

Correspondence to Gary D. Friedman.

Additional information

This work performed at Division of Research, Kaiser Permanente Medical Care Program, Oakland, California.

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Friedman, G.D., Udaltsova, N., Chan, J. et al. Screening pharmaceuticals for possible carcinogenic effects: initial positive results for drugs not previously screened. Cancer Causes Control 20, 1821–1835 (2009). https://doi.org/10.1007/s10552-009-9375-2

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  • DOI: https://doi.org/10.1007/s10552-009-9375-2

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