Originally published as JCO Early Release 10.1200/JCO.2008.19.4670 on November 3 2008

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In Reply

James Brugarolas

Department of Internal Medicine (Oncology Division) and Department of Developmental Biology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX

Lunardi et al provide the first report of an evaluation of temsirolimus pharmacokinetics in patients with metastatic renal cell carcinoma (RCC) on hemodialysis (HD). While the analysis is limited to two patients, their results show that the administration of 25 mg of temsirolimus intravenously 24 hours before HD, results in pharmacokinetics for both temsirolimus as well as its active metabolite sirolimus that are not significantly different than those previously reported in RCC patients not receiving HD.^1,2 The authors also measured temsirolimus and sirolimus levels before and 1 hour after three HD sessions (data not shown). While it is difficult to interpret the data with respect to temsirolimus after the third HD session, as temsirolimus circulating levels at this time are quite low, their data suggest that HD does not substantially decrease circulating levels of either temsirolimus or sirolimus. It would be fitting to extend these observations to a larger number of patients. However, at the present time and in the absence of other data, these data suggest that in patients with metastatic RCC in whom temsirolimus may offer the best treatment option, such as in previously untreated patients at high risk (as defined by at least three of six risk factors including five Memorial Sloan-Kettering Cancer Center criteria³ and multiple sites of metastasis) in whom temsirolimus has been shown to improve median overall survival,⁴ and more broadly, in patients with non clear-cell RCC, and in particular papillary RCC,⁵ for whom temsirolimus appears to be the most efficacious drug available in the market, temsirolimus may be administered regardless of whether the patient is on HD and no adjustments are needed in the dose or the regimen.

AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

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

ACKNOWLEDGMENTS

Supported by Physician-Scientist KO8 Award (1K08NS051843); Clinical Scientist Development Award, Doris Duke Charitable Foundation; and V Scholar Award, V Foundation for Cancer Research.

NOTES

published online ahead of print at www.jco.org on November 3, 2008

REFERENCES

1. Atkins MB, Hidalgo M, Stadler WM, et al: Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol 22:909-918, 2004[Abstract/Free Full Text]

2. Boni JP, Leister C, Bender G, et al: Population pharmacokinetics of CCI-779: Correlations to safety and pharmacogenomic responses in patients with advanced renal cancer. Clin Pharmacol Ther 77:76-89, 2005[CrossRef][Medline]

3. Motzer RJ, Bacik J, Murphy BA, et al: Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 20:289-296, 2002[Abstract/Free Full Text]

4. Hudes G, Carducci M, Tomczak P, et al: Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271-2281, 2007[Abstract/Free Full Text]

5. Dutcher JP, Szczylik C, Tannir N, et al: Correlation of survival with tumor histology, age, and prognostic risk group for previously untreated patients with advanced renal cell carcinoma (adv RCC) receiving temsirolimus (TEMSR) or interferon-alpha (IFN). J Clin Oncol 26:243s, 2007 (suppl; abstr 5033)

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Related Correspondence

• Temsirolimus in Patients With Renal Cancer on Hemodialysis
  Gianluigi Lunardi, Maria Ornella Vannozzi, Andrea Armirotti, Maurizio Nicodemo, Marco Venturini, and Lucia Cavallini
  JCO 2008 26: 5652-5653 [Full Text]

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