Clinical and genome-wide analysis of serum platinum levels after cisplatin-based chemotherapy

Matthew R. Trendowski, Omar El-Charif, Mark J. Ratain, Patrick Monahan, Zepeng Mu, Heather E. Wheeler, Paul C. Dinh, Darren R. Feldman, Shirin Ardeshir-Rouhani-Fard, Robert J. Hamilton, David J. Vaughn, Chunkit Fung, Christian Kollmannsberger, Taisei Mushiroda, Michiaki Kubo, Robyn Hannigan, Frederick Strathmann, Lawrence H. Einhorn, Sophie D. Fossa, Lois B. TravisM. Eileen Dolan

研究成果: Article

抄録

Purpose: Serum platinum is measurable for years after completion of cisplatin-based chemotherapy (CBC). We report the largest investigation of serum platinum levels to date of 1,010 testicular cancer survivors (TCS) assessed 1-35 years after CBC and evaluate genetic contributions to these levels. Experimental Design: Eligible TCS given 300 or 400 (15) mg/m2 cisplatin underwent extensive audiometric testing, clinical examination, completed questionnaires, and had crude serum platinum levels measured. Associations between serum platinum and various risk factors and toxicities were assessed after fitting a biexponential model adjusted for follow-up time and cumulative cisplatin dose. A genome-wide association study (GWAS) was performed using the serum platinum residuals of the dose and time-adjusted model. Results: Serum platinum levels exceeded the reference range for approximately 31 years, with a strong inverse relationship with creatinine clearance at follow-up (age-adjusted P ¼ 2.13 103). We observed a significant, positive association between residual platinum values and luteinizing hormone (age-adjusted P ¼ 6.58 103). Patients with high residual platinum levels experienced greater Raynaud phenomenon than those with medium or low levels (age-adjusted ORhigh/low ¼ 1.46; P ¼ 0.04), as well as a higher likelihood of developing tinnitus (age-adjusted ORhigh/low ¼ 1.68, P ¼ 0.07). GWAS identified one single-nucleotide polymorphism (SNP) meeting genome-wide significance, rs1377817 (P ¼ 4.6 108, a SNP intronic to MYH14). Conclusions: This study indicates that residual platinum values are correlated with several cisplatin-related toxicities. One genetic variant is associated with these levels.

元の言語English
ページ(範囲)5913-5924
ページ数12
ジャーナルClinical Cancer Research
25
発行部数19
DOI
出版物ステータスPublished - 01-10-2019

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Platinum
Cisplatin
Genome
Drug Therapy
Serum
Genome-Wide Association Study
Testicular Neoplasms
Single Nucleotide Polymorphism
Survivors
Raynaud Disease
Tinnitus
Luteinizing Hormone
Creatinine
Reference Values
Research Design

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Trendowski, M. R., El-Charif, O., Ratain, M. J., Monahan, P., Mu, Z., Wheeler, H. E., ... Eileen Dolan, M. (2019). Clinical and genome-wide analysis of serum platinum levels after cisplatin-based chemotherapy. Clinical Cancer Research, 25(19), 5913-5924. https://doi.org/10.1158/1078-0432.CCR-19-0113
Trendowski, Matthew R. ; El-Charif, Omar ; Ratain, Mark J. ; Monahan, Patrick ; Mu, Zepeng ; Wheeler, Heather E. ; Dinh, Paul C. ; Feldman, Darren R. ; Ardeshir-Rouhani-Fard, Shirin ; Hamilton, Robert J. ; Vaughn, David J. ; Fung, Chunkit ; Kollmannsberger, Christian ; Mushiroda, Taisei ; Kubo, Michiaki ; Hannigan, Robyn ; Strathmann, Frederick ; Einhorn, Lawrence H. ; Fossa, Sophie D. ; Travis, Lois B. ; Eileen Dolan, M. / Clinical and genome-wide analysis of serum platinum levels after cisplatin-based chemotherapy. :: Clinical Cancer Research. 2019 ; 巻 25, 番号 19. pp. 5913-5924.
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title = "Clinical and genome-wide analysis of serum platinum levels after cisplatin-based chemotherapy",
abstract = "Purpose: Serum platinum is measurable for years after completion of cisplatin-based chemotherapy (CBC). We report the largest investigation of serum platinum levels to date of 1,010 testicular cancer survivors (TCS) assessed 1-35 years after CBC and evaluate genetic contributions to these levels. Experimental Design: Eligible TCS given 300 or 400 (15) mg/m2 cisplatin underwent extensive audiometric testing, clinical examination, completed questionnaires, and had crude serum platinum levels measured. Associations between serum platinum and various risk factors and toxicities were assessed after fitting a biexponential model adjusted for follow-up time and cumulative cisplatin dose. A genome-wide association study (GWAS) was performed using the serum platinum residuals of the dose and time-adjusted model. Results: Serum platinum levels exceeded the reference range for approximately 31 years, with a strong inverse relationship with creatinine clearance at follow-up (age-adjusted P ¼ 2.13 103). We observed a significant, positive association between residual platinum values and luteinizing hormone (age-adjusted P ¼ 6.58 103). Patients with high residual platinum levels experienced greater Raynaud phenomenon than those with medium or low levels (age-adjusted ORhigh/low ¼ 1.46; P ¼ 0.04), as well as a higher likelihood of developing tinnitus (age-adjusted ORhigh/low ¼ 1.68, P ¼ 0.07). GWAS identified one single-nucleotide polymorphism (SNP) meeting genome-wide significance, rs1377817 (P ¼ 4.6 108, a SNP intronic to MYH14). Conclusions: This study indicates that residual platinum values are correlated with several cisplatin-related toxicities. One genetic variant is associated with these levels.",
author = "Trendowski, {Matthew R.} and Omar El-Charif and Ratain, {Mark J.} and Patrick Monahan and Zepeng Mu and Wheeler, {Heather E.} and Dinh, {Paul C.} and Feldman, {Darren R.} and Shirin Ardeshir-Rouhani-Fard and Hamilton, {Robert J.} and Vaughn, {David J.} and Chunkit Fung and Christian Kollmannsberger and Taisei Mushiroda and Michiaki Kubo and Robyn Hannigan and Frederick Strathmann and Einhorn, {Lawrence H.} and Fossa, {Sophie D.} and Travis, {Lois B.} and {Eileen Dolan}, M.",
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Trendowski, MR, El-Charif, O, Ratain, MJ, Monahan, P, Mu, Z, Wheeler, HE, Dinh, PC, Feldman, DR, Ardeshir-Rouhani-Fard, S, Hamilton, RJ, Vaughn, DJ, Fung, C, Kollmannsberger, C, Mushiroda, T, Kubo, M, Hannigan, R, Strathmann, F, Einhorn, LH, Fossa, SD, Travis, LB & Eileen Dolan, M 2019, 'Clinical and genome-wide analysis of serum platinum levels after cisplatin-based chemotherapy', Clinical Cancer Research, 巻. 25, 番号 19, pp. 5913-5924. https://doi.org/10.1158/1078-0432.CCR-19-0113

Clinical and genome-wide analysis of serum platinum levels after cisplatin-based chemotherapy. / Trendowski, Matthew R.; El-Charif, Omar; Ratain, Mark J.; Monahan, Patrick; Mu, Zepeng; Wheeler, Heather E.; Dinh, Paul C.; Feldman, Darren R.; Ardeshir-Rouhani-Fard, Shirin; Hamilton, Robert J.; Vaughn, David J.; Fung, Chunkit; Kollmannsberger, Christian; Mushiroda, Taisei; Kubo, Michiaki; Hannigan, Robyn; Strathmann, Frederick; Einhorn, Lawrence H.; Fossa, Sophie D.; Travis, Lois B.; Eileen Dolan, M.

:: Clinical Cancer Research, 巻 25, 番号 19, 01.10.2019, p. 5913-5924.

研究成果: Article

TY - JOUR

T1 - Clinical and genome-wide analysis of serum platinum levels after cisplatin-based chemotherapy

AU - Trendowski, Matthew R.

AU - El-Charif, Omar

AU - Ratain, Mark J.

AU - Monahan, Patrick

AU - Mu, Zepeng

AU - Wheeler, Heather E.

AU - Dinh, Paul C.

AU - Feldman, Darren R.

AU - Ardeshir-Rouhani-Fard, Shirin

AU - Hamilton, Robert J.

AU - Vaughn, David J.

AU - Fung, Chunkit

AU - Kollmannsberger, Christian

AU - Mushiroda, Taisei

AU - Kubo, Michiaki

AU - Hannigan, Robyn

AU - Strathmann, Frederick

AU - Einhorn, Lawrence H.

AU - Fossa, Sophie D.

AU - Travis, Lois B.

AU - Eileen Dolan, M.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Purpose: Serum platinum is measurable for years after completion of cisplatin-based chemotherapy (CBC). We report the largest investigation of serum platinum levels to date of 1,010 testicular cancer survivors (TCS) assessed 1-35 years after CBC and evaluate genetic contributions to these levels. Experimental Design: Eligible TCS given 300 or 400 (15) mg/m2 cisplatin underwent extensive audiometric testing, clinical examination, completed questionnaires, and had crude serum platinum levels measured. Associations between serum platinum and various risk factors and toxicities were assessed after fitting a biexponential model adjusted for follow-up time and cumulative cisplatin dose. A genome-wide association study (GWAS) was performed using the serum platinum residuals of the dose and time-adjusted model. Results: Serum platinum levels exceeded the reference range for approximately 31 years, with a strong inverse relationship with creatinine clearance at follow-up (age-adjusted P ¼ 2.13 103). We observed a significant, positive association between residual platinum values and luteinizing hormone (age-adjusted P ¼ 6.58 103). Patients with high residual platinum levels experienced greater Raynaud phenomenon than those with medium or low levels (age-adjusted ORhigh/low ¼ 1.46; P ¼ 0.04), as well as a higher likelihood of developing tinnitus (age-adjusted ORhigh/low ¼ 1.68, P ¼ 0.07). GWAS identified one single-nucleotide polymorphism (SNP) meeting genome-wide significance, rs1377817 (P ¼ 4.6 108, a SNP intronic to MYH14). Conclusions: This study indicates that residual platinum values are correlated with several cisplatin-related toxicities. One genetic variant is associated with these levels.

AB - Purpose: Serum platinum is measurable for years after completion of cisplatin-based chemotherapy (CBC). We report the largest investigation of serum platinum levels to date of 1,010 testicular cancer survivors (TCS) assessed 1-35 years after CBC and evaluate genetic contributions to these levels. Experimental Design: Eligible TCS given 300 or 400 (15) mg/m2 cisplatin underwent extensive audiometric testing, clinical examination, completed questionnaires, and had crude serum platinum levels measured. Associations between serum platinum and various risk factors and toxicities were assessed after fitting a biexponential model adjusted for follow-up time and cumulative cisplatin dose. A genome-wide association study (GWAS) was performed using the serum platinum residuals of the dose and time-adjusted model. Results: Serum platinum levels exceeded the reference range for approximately 31 years, with a strong inverse relationship with creatinine clearance at follow-up (age-adjusted P ¼ 2.13 103). We observed a significant, positive association between residual platinum values and luteinizing hormone (age-adjusted P ¼ 6.58 103). Patients with high residual platinum levels experienced greater Raynaud phenomenon than those with medium or low levels (age-adjusted ORhigh/low ¼ 1.46; P ¼ 0.04), as well as a higher likelihood of developing tinnitus (age-adjusted ORhigh/low ¼ 1.68, P ¼ 0.07). GWAS identified one single-nucleotide polymorphism (SNP) meeting genome-wide significance, rs1377817 (P ¼ 4.6 108, a SNP intronic to MYH14). Conclusions: This study indicates that residual platinum values are correlated with several cisplatin-related toxicities. One genetic variant is associated with these levels.

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U2 - 10.1158/1078-0432.CCR-19-0113

DO - 10.1158/1078-0432.CCR-19-0113

M3 - Article

C2 - 31296530

AN - SCOPUS:85072827982

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JO - Clinical Cancer Research

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Trendowski MR, El-Charif O, Ratain MJ, Monahan P, Mu Z, Wheeler HE その他. Clinical and genome-wide analysis of serum platinum levels after cisplatin-based chemotherapy. Clinical Cancer Research. 2019 10 1;25(19):5913-5924. https://doi.org/10.1158/1078-0432.CCR-19-0113