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Epidemiology

Impact of obesity on chemotherapy dosing of carboplatin and survival of women with ovarian cancer

British Journal of Cancer volume 128, pages 2236–2242 (2023)Cite this article

Subjects

Abstract

Background

The study objective is to examine the impact of obesity on frontline carboplatin dosing in the neoadjuvant and adjuvant settings and to evaluate the association of dosing with survival among epithelial ovarian cancer (EOC) patients.

Methods

We selected 1527 women diagnosed with EOC from January 1, 2011 to October 20, 2021 from a nationwide electronic health record-derived de-identified database. The dose reduction of frontline carboplatin was defined as a relative dose intensity (RDI) < 0.85. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of RDI with survival overall and by histology.

Results

Women with a BMI ≥ 30 kg/m2 versus <30 kg/m2 were more likely to be underdosed (RDI < 0.85) with frontline carboplatin. Underdosing of carboplatin in the neoadjuvant setting was associated with worse survival among women with serous tumours (HR = 1.98, 95% CI = 1.15, 3.42). Underdosing of carboplatin in the adjuvant setting was not associated with survival.

Discussion

In the real-world setting, underdosing of carboplatin in the neoadjuvant setting was associated with inferior survival among women with serous tumours. With the increasing utilisation of neoadjuvant chemotherapy in EOC, actual weight-based dosing of carboplatin may be important to improve outcomes in this patient population.

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Fig. 1: Consort diagram.
Fig. 2: Ridgeline plot of the average carboplatin RDI stratified by type of frontline therapy and pre-treatment BMI.

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Data availability

The data that support the findings of this study have been originated by Flatiron Health, Inc. These de-identified data may be made available upon request and are subject to a license agreement with Flatiron Health; interested researchers should contact “DataAccess@flatiron.com” to determine licensing terms.

References

  1. Siegel R, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7–30.

    Article  PubMed  Google Scholar 

  2. Armstrong D, Alvarez R, Bakkum-Gamez J, Barroilhet L, Behbakht K, Berchuck A, et al. NCCN guidelines insights: ovarian cancer, version 1.2019. J Natl Compr Cancer Netw. 2019;17:896–909.

    Article  CAS  Google Scholar 

  3. Body surface area for adjustment of drug dose. Drug Ther Bull. 2010;48:33–6. https://pubmed.ncbi.nlm.nih.gov/20200147/.

  4. Gurney H. Obesity in dose calculation: a mouse or an elephant? J Clin Oncol. 2007;25:4703–4.

    Article  PubMed  Google Scholar 

  5. Au-Yeung G, Webb P, DeFazio A, Fereday S, Bressel M, Mileshkin L. Impact of obesity on chemotherapy dosing for women with advanced stage serous ovarian cancer in the Australian Ovarian Cancer Study (AOCS). Gynecol Oncol. 2014;133:16–22.

    Article  CAS  PubMed  Google Scholar 

  6. Bandera E, Lee V, Rodriguez-Rodriguez L, Powell B, Kushi L. Impact of chemotherapy dosing on ovarian cancer survival according to body mass index. JAMA Oncol. 2015;1:737–45.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Melamed A, Hinchliff E, Clemmer J, Bregar A, Uppal U, Bostock I, et al. Trends in the use of neoadjuvant chemotehrapy for advanced ovarian cancer in the United States. Gynecol Oncol. 2016;143:236–40.

    Article  PubMed  Google Scholar 

  8. Lheureux S, Braunstein M, Oza A. Epithelial ovarian cancer: evolution of management in the era of precision medicine. CA Cancer J Clin. 2019;69:280–304.

    PubMed  Google Scholar 

  9. Ma X, Long L, Moon S, Adamson B, Baxi S. Comparison of population characteristics in real-world clinical oncology databases in the US: Flatiron Health, SEER, and NPCR. medRxiv [Preprint] 2020. Available from: https://doi.org/10.1101/2020.03.16.20037143.

  10. Birnbaum B, Nussbaum N, Seidl-Rathkopf K, Agrawal M, Estevez M, Estola E, et al. Model-assisted cohort selection with bias analysis for generating large-scale cohorts from the EHR for oncology research. arXiv:2001.09765 [cs.CY].[Preprint]. Available from: https://doi.org/10.48550/arXiv.2001.09765.

  11. Griggs J, Mangu P, Temin S, Lyman G. Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Oncol Pr. 2012;8:e59–e61.

    Article  Google Scholar 

  12. Curtis M, Griffith S, Tucker M, Taylor M, Capra W, Carrigan G. Development and validation of a high-quality composite real-world mortality endpoint. Health Serv Res. 2018;53:4460–76.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Sivakumaran T, Mileshkin L, Grant P, Na L, DeFazio A, Friedlander M, et al. Evaluating the impact of dose reductions and delays on progression-free survival in women with ovarian cancer treated with either three-weekly or dose-dense carboplatin and paclitaxel regimens in the national prospective OPAL cohort study. Gynecol Oncol. 2020;15:47–53.

    Article  Google Scholar 

  14. Liutkauskiene S, Janciauskiene R, Jureniene K, Grizas S, Malonyte R, Juozaityte E. Retrospective analysis of the impact of platinum dose reduction and chemotherapy delays on the outcomes of stage III ovarian cancer patients. BMC Cancer. 2015;15:105.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Nagel C, Backes F, Hade E. Effect of chemotherapy delays and dose reduction on progression free and overall survival in the treatment of epithelial ovarian cancer. Gynecol Oncol. 2012;124:221–4.

    Article  CAS  PubMed  Google Scholar 

  16. Anuradha S, Donovan P, Webb P, Brand A, Goh J, Friedlander M, et al. Variations in adjuvant chemotherapy and survival in women with epithelial ovarian cancer—a population-based study. Acta Oncol. 2016;55:226–33.

    Article  PubMed  Google Scholar 

  17. Hanna R, Poniewierski M, Laskey R, Lopez M, Shafer A, Van Le L, et al. Predictors of reduced relative dose intensity and its relationship to mortality in women receiving multi-agent chemotherapy for epithelial ovarian cancer. Gynecol Oncol. 2013;129:74–80.

    Article  CAS  PubMed  Google Scholar 

  18. Earle C, Schrag D, Neville B, Yabroff K, Topor M, Fahey A, et al. Effect of surgeon speciality on processes of care and outcomes for ovarian cancer patients. J Natl Cancer Inst. 2006;98:172–80.

    Article  PubMed  Google Scholar 

  19. Engelen M, Kos H, Willemse P, Aalder J, de Vries E, Schaapveld M, et al. Surgery by consultant gynecologic oncologists improves survival in patients with ovarian carcinoma. Cancer. 2006;106:589–98.

    Article  PubMed  Google Scholar 

  20. Bouchard-Fortier G, Gien L, Sutradhar R, Chan W, Krzyzanowska M, Liu S, et al. Impact of care by gynecologic oncologists on primary ovarian cancer survival: a population-based study. Gynecol Oncol. 2022;164:522–8.

    Article  PubMed  Google Scholar 

  21. Matulonis U, Sood A, Fallowfield L, Howitt B, Sehouli J, Karlan B. Ovarian cancer. Nat Rev Dis Prim. 2016;2:16061.

    Article  PubMed  Google Scholar 

  22. Peres L, Cushing-Haugen K, Köbel M, Harris H, Berchuck A, Rossing MA, et al. Invasive epithelial ovarian cancer survival by histotype and disease stage. J Natl Cancer Inst. 2019;111:60–68.

    Article  PubMed  Google Scholar 

  23. Lisio M, Fu L, Goyeneche A, Gao A, Telleria C. High-grade serous ovarian cancer: basic sciences and therapeutic standpoints. Int J Mol Sci. 2019;20:952.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Jelovac D, Armstrong D. Recent progress in the diagnosis and treatment of ovarian cancer. CA Cancer J Clin. 2011;61:183–203.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Pectasides D, Pectasides E, Psyrri A, Economopoulos T. Treatment issues in clear cell carcinoma of the ovary: a different entity? Oncologist. 2006;11:1089–94.

    Article  PubMed  Google Scholar 

  26. Hess V, A’Hern R, Nasiri N, King D, Blake P, Barton D, et al. Mucinous epithelial ovarian cancer: a separate entity requiring specific treatment. J Clin Oncol. 2004;22:1040–4.

    Article  CAS  PubMed  Google Scholar 

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Funding

This publication is supported by a 2019 Moffitt Team Science Award and the Cancer Centre Support Grant P30 CA 076292. This work was also supported by the Collaborative Data Services Core at Moffitt Cancer Centre (P30 CA 076292).

Author information

Author notes

  1. Alexandra L. Martin

    Present address: University of Tennessee Health Sciences Center, Department of Gynecologic Oncology, 920 Madison Ave, Memphis, TN, 38163, USA

  2. Sweta K. Sinha

    Present address: Cedars-Sinai, Inflammatory Bowel and Immunobiology Research Institute, 110 George Burns Rd., Davis Building D4094B, Los Angeles, CA, 90048, USA

  3. These authors contributed equally: Jing-Yi Chern, Lauren C. Peres.

Authors and Affiliations

  1. H. Lee Moffitt Cancer Center and Research Institute, Department of Gynecologic Oncology, 12902 Magnolia Dr, Tampa, FL, 33612, USA

    Alexandra L. Martin & Jing-Yi Chern

  2. H. Lee Moffitt Cancer Center and Research Institute, Department of Cancer Epidemiology, 13131 Magnolia Dr, Tampa, FL, 33612, USA

    Christelle M. Colin-Leitzinger, Sweta K. Sinha & Lauren C. Peres

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  1. Alexandra L. Martin
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  5. Lauren C. Peres
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Contributions

LCP and JC designed the research study. CCL and LCP analysed the data. CCL and LCP created the tables and figures. ALM and LCP wrote the manuscript. All authors reviewed and approved the final manuscript.

Corresponding author

Correspondence to Lauren C. Peres.

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The authors declare no competing interests.

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Institutional Review Board approval of the study protocol was obtained prior to the study conduct and included a waiver of informed consent.

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Martin, A.L., Colin-Leitzinger, C.M., Sinha, S.K. et al. Impact of obesity on chemotherapy dosing of carboplatin and survival of women with ovarian cancer. Br J Cancer 128, 2236–2242 (2023). https://doi.org/10.1038/s41416-023-02259-1

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