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Extension of the Calvert formula to patients with severe renal insufficiency

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Abstract

Purpose

The Calvert formula was derived from the study among patients with glomerular filtration rates (GFRs) of 33–135 ml/min, and it remains unclear whether the formula can be used to calculate optimal and safe dosages of carboplatin in patients with severe renal insufficiency. We evaluated the utility of this formula in patients with severe renal insufficiency.

Methods

For pharmacokinetic analysis, we studied nine adult Japanese patients with advanced cancer who had an estimated GFR of lower than 30 ml/min/1.73 m2, as calculated by the Japanese equation for estimating GFR, or who were receiving hemodialysis. The dose of carboplatin was calculated with the Calvert formula, in which GFR was measured by inulin clearance or was assumed to be 0 in patients requiring hemodialysis. Hemodialysis was started 23 h after the end of carboplatin infusion.

Results

Although there was a significant correlation between the estimated and measured carboplatin clearance, the estimated clearance was consistently higher than the measured clearance [mean prediction error ± standard deviation = 41.0 ± 26.3 %] in all seven patients with renal insufficiency (GFR, median 21.4, range 7.8–31.4 ml/min) and in the two hemodialysis patients. Actual areas under the concentration–time curve (AUC) (mg/ml min) were 5.4, 5.7, 6.2, and 9.0 for the four patients with a target AUC (mg/ml min) of 5; 5.7, 6.2, and 7.1 for the three patients with a target AUC (mg/ml min) of 4; and 5.1 and 8.7 for the two hemodialysis patients with a target AUC (mg/ml min) of 5. The measured clearance of carboplatin ranged from 23.0 to 51.3 ml/min in the seven patients not receiving hemodialysis. The pre-hemodialysis carboplatin clearance in the hemodialysis patients was 20.5 and 11.1 ml/min, respectively.

Conclusion

For adult patients with severe renal insufficiency, the Calvert formula causes carboplatin overdosing by overestimating the carboplatin clearance.

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Acknowledgments

We are deeply indebted to Ms. Yuka Murasaki and Miki Sagou for their professional assistance in this study. This study was partly supported by the National Cancer Center Research and Development Fund [23-A-16]. Yoshinari Yasuda and Yoshinori Hasegawa have received research Grants from Pfizer Co. Ltd. and a speaker honorarium from Pfizer Co. Ltd. Yuichi Ando has received research Grants from Nippon Kayaku Co. Ltd. and a speaker honorarium from Pfizer Co. Ltd.

Conflict of interest

All other authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan

    Tomoyo Oguri, Tomoya Shimokata & Yuichi Ando

  2. Department of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan

    Isao Ito & Yoshinari Yasuda

  3. Department of Urology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan

    Naoto Sassa

  4. Research Institute for Drug Discovery, School of Pharmacy, Kumamoto University, 5-1 Oe Chuo-ku, Kumamoto, 862-0973, Japan

    Masami Nishiyama

  5. Department of Clinical Pharmacology Group for Translational Research Support Core, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Akinobu Hamada

  6. Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan

    Yoshinori Hasegawa

Authors
  1. Tomoyo Oguri
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  2. Tomoya Shimokata
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  7. Akinobu Hamada
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  8. Yoshinori Hasegawa
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  9. Yuichi Ando
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Corresponding author

Correspondence to Tomoya Shimokata.

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Oguri, T., Shimokata, T., Ito, I. et al. Extension of the Calvert formula to patients with severe renal insufficiency. Cancer Chemother Pharmacol 76, 53–59 (2015). https://doi.org/10.1007/s00280-015-2769-9

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  • DOI: https://doi.org/10.1007/s00280-015-2769-9

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