Originally published as JCO Early Release 10.1200/JCO.2009.23.8899 on July 6 2009

This Article 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 Google Scholar Articles by Tannock, I. F. PubMed PubMed Citation Articles by Tannock, I. F. Related Articles Related Articles Related Reply Social Bookmarking                            What's this?

Effects of Food on Bioavailability of Lapatinib: Useful Data, Wrong Conclusion

Division of Medical Oncology and Hematology, Princess Margaret Hospital and University of Toronto, Toronto, Ontario, Canada

To the Editor:

I read with interest the article entitled "Effects of Food on the Relative Bioavailability of Lapatinib in Cancer Patients" by Koch et al.¹ This study of bioavailability of lapatinib in 27 patients, each performed on three occasions after different food intake, found that the area under the concentration-time curve (AUC) was increased 2.67 fold after a low-fat breakfast and 4.25 fold after a high-fat breakfast, compared with those receiving the drug after an overnight fast. In the fed state, increased bioavailability "did not significantly decrease relative variability" but absolute variability was increased. Koch et al conclude, "These large increases in lapatinib bioavailability and absolute variability support the recommendation for dosing in the fasted state to achieve consistent therapeutic exposure."

Koch et al¹ demonstrate a nonsignificant decrease in relative variability of the AUC in the fed compared with the fasting state (coefficients of variation of 52% versus 68%), and it can be seen from their Figure 2 that the AUC after fasting varies from approximately 5 to approximately 30 (six fold) with one outlier, while after a high-fat breakfast the AUC varies from approximately 20 to approximately 120 (six fold), also with one outlier. The relative difference is consistent with the quoted 4.25-fold increase in the geometric mean AUC between the two groups. So assuming that pharmacokinetics are linear, as is suggested by the lack of intergroup variability in half-life despite differing AUC, giving one quarter of the dose of lapatinib after a high-fat meal should achieve the same AUC with similar (or slightly less) interpatient variability as achieved with a standard dose in the fasting state.

Koch et al¹ make no mention of the cost of lapatinib, but the test dose of 1,500 mg used in this study would cost about $3,000 if given daily for a month to fasting patients. If one quarter of the fasting dose were given after a high-fat breakfast, the cost would be less than $1,000 per month. That's a cost-effective breakfast.^2,3

Koch et al¹ declared their potential conflicts of interest in line with Journal of Clinical Oncology (JCO) policy. Three authors, including the first, own stock in GlaxoSmithKline, who market lapatinib, and two others, including the senior author, have received compensation from this company. Publication of a paper with conclusions that could directly influence the profits of a company in which authors own stock seems questionable, but that is for the editors of JCO to decide. Let us hope that is not the reason that led Koch et al to use the same data to come to the opposite conclusion that I would make from them: a dose of lapatinib roughly one quarter of that recommended in the fasting state could be given to patients after a high-fat breakfast, and will likely lead to equal bioavailability with no increase in inter-patient variability (and hence probability of adverse effects). These data are useful to oncologists and their patients, since they may allow lapatinib to be given safely to patients who otherwise could not afford this beneficial drug.

AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Koch KM, Reddy NJ, Cohen RB, et al: Effects of food on the relative bioavailability of lapatinib in cancer patients. J Clin Oncol 27:1191–1196, 2009.[Abstract/Free Full Text]

2. Ratain MJ, Cohen EE: The value meal: How to save $1,700 per month or more on lapatinib. J Clin Oncol 25:3397–3398, 2007.[Free Full Text]

3. Seruga B, Tannock IF: Mathematics in the realm of lapatinib: 500 + 500 = 1,500? J Clin Oncol 26:2940–2942, 2008.[Free Full Text]

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

Related Articles

• Reply to I.F. Tannock
  Kevin M. Koch, Andrew P. Beelen, Nandi J. Reddy, and Lionel D. Lewis
  JCO 2009 27: 43 [Full Text]
• Effects of Food on the Relative Bioavailability of Lapatinib in Cancer Patients
  Kevin M. Koch, Nandi J. Reddy, Roger B. Cohen, Nancy L. Lewis, Bonnie Whitehead, Kathleen Mackay, Andrew Stead, Andrew P. Beelen, and Lionel D. Lewis
  JCO 2009 27: 1191-1196 [Abstract] [Full Text]

Related Reply

• Reply to I.F. Tannock
  Kevin M. Koch, Andrew P. Beelen, Nandi J. Reddy, and Lionel D. Lewis
  JCO 2009 27: 43 [Full Text]

This article has been cited by other articles:

				K. M. Koch, A. P. Beelen, N. J. Reddy, and L. D. Lewis Reply to I.F. Tannock J. Clin. Oncol., August 1, 2009; 27(22): e43 - e43. [Full Text] [PDF]

This Article 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 Google Scholar Articles by Tannock, I. F. PubMed PubMed Citation Articles by Tannock, I. F. Related Articles Related Articles Related Reply Social Bookmarking                            What's this?