Skip to main content

Advertisement

SpringerLink
Log in

Hematological toxicity of carboplatin for gynecological cancer according to body mass index

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

The aim of the present study was to analyze how patient weight affects the hematological toxicity of carboplatin and whether this toxicity is more prevalent in overweight patients.

Methods

We performed a retrospective 2-year study of patients diagnosed with a gynecological cancer and whose treatment regimen contained carboplatin (AUC dose = 5 or 6) and paclitaxel (dose = 175 mg/m2) every 3 weeks (CP scheme). We recorded all severe hematological events (thrombocytopenia, neutropenia, and/or anemia grade III/IV) according to the CTCAE v4.03, as well as treatment modifications and the need for granulocyte colony-stimulating factors (G-CSF) and/or erythropoietin (EPO) or packed red blood cells (PRBC). Patients with a body mass index (BMI) ≥27 kg/m2 were considered as overweight (OW) and those with a BMI <27 kg/m2 were considered as normal weight (NW).

Results

Fifty-two patients met the inclusion criteria (21 patients in the OW group, 31 patients in the NW group). The OW group showed a higher incidence of thrombocytopenia (95% confidence intervals (CI) 1.51–27.72; p < 0.02) and anemia (95% CI 1.06–33.63; p < 0.05). Moreover, this was reflected in a greater number of changes in the usual CP regimen (95% CI 2.19–44.32; p < 0.01). The need for G-CSF and/or EPO/PRBC was also significantly higher in the OW group (95% CI 1.08–12.16; p < 0.04).

Conclusions

Carboplatin dosing based on real weight in obese patients resulted in increased hematologic toxicity, mainly thrombocytopenia. Dose adjustment based on other descriptors of weight, such as adjusted weight, may be better tolerated by patients. However, future studies are needed to demonstrate not only better safety of carboplatin but also improved survival rates.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Ozols RF, Bundy BN, Greer BE, et al. (2003) Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a gynecologic oncology group study. J Clin Oncol 21:3194–3200

    Article  CAS  PubMed  Google Scholar 

  2. Neijt JP, Engelholm SA, Tuxen MK, et al. (2000) Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer. J Clin Oncol 18:3084–3092

    CAS  PubMed  Google Scholar 

  3. Yuichi Ando, Tomoya Shimokata, Yoshinari Yasuda, Yoshinari Hasegawa (2014). Carboplatin dosing for adult Japanese patients. Nagoya J Med Sci 76. 1~9

  4. van der Vijgh WJF (1991) Clinical pharmacokinetics of carboplatin. Clin Pharmacokinet 21(4):242–261

    Article  PubMed  Google Scholar 

  5. Kloft C, Siegert W, Beyer J, Jaehde U (2002) Toxicity of high-dose carboplatin: ultrafiltered and no total plasma pharmacokinetics is of clinical relevance. J Clin Pharmacol 42(7):762–773

    Article  CAS  PubMed  Google Scholar 

  6. Ekhart C, Rodenhuis S, Schellens JHM, Beijnen JH, Huitema ADR (2009) Carboplatin dosing in overweight and obese patients with normal renal function, does weight matter? Cancer Chemother Pharmacol 64:115–122

    Article  CAS  PubMed  Google Scholar 

  7. Chatelut E, Canal P, Bugat R (2000) Pharmacokinetics and individual dose adjustment of carboplatin. Bull Cancer 87:17–23

    PubMed  Google Scholar 

  8. Calvert AH, Newell DR, Gumbrell LA, et al. (1989) Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 7(11):1748–1756

    CAS  PubMed  Google Scholar 

  9. Gaspari F, Perico N, Ruggenenti P, et al. (1995) Plasma clearance of non-radioactive iohexol of glomerular filtration rate. J Am Soc Nephrol 6:257–263

    CAS  PubMed  Google Scholar 

  10. Hernández Ocampo J, Torres Rosales A, Rodríguez Castellanos F (2010) Comparación de cuatro métodos de medición de la tasa de filtración glomerular con depuración de inulina en individuos sanos y en pacientes con insuficiencia renal. Nefrologia 30(3):324–330

    PubMed  Google Scholar 

  11. Brenner and Rector’s The Kidney (2008) (8.ª ed). Saunders, Philadelphia, p 686

  12. Cameron JS, R. G (1998) Renal function and testing of function. In: Oxford textbook of clinical nephrology, vol 1. Oxford University Press, London, p. 39

    Google Scholar 

  13. Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16(1):31–41

    Article  CAS  PubMed  Google Scholar 

  14. Demirovic JA, Pai AB, Pai MP (2009) Estimation of creatinine clearance in morbidly obese patients. Am J Health Syst Pharm 66:642–648. doi:10.2146/ajhp080200

    Article  CAS  PubMed  Google Scholar 

  15. Spinler SA, Nawarskas JJ, Boyce EG, Connors JE, Charland SL, Goldfarb S (1998) Predictive performance of ten equations for estimating creatinine clearance in cardiac patients Iohexol Cooperative Study Group. Ann Pharmacother 32(12):1275–1283

    Article  CAS  PubMed  Google Scholar 

  16. Brown DL, Masselink AJ, Lalla CD (2013) Functional range of creatinine clearance for renal drug dosing: a practical solution to the controversy of which weight to use in the Cockgroft-Gault equation. Ann Pharmacother 47. doi:10.1345/aph.1S176

  17. NCCN Guidelines Version 2: Ovarian cancer. (2015) Consulted august 2015

  18. Hamwi GJ (1964) Therapy: changing dietary concepts. In: Danowski TS (ed) Diabetes mellitus: diagnosis and treatment. American Diabetes Association, New York, pp. 73–78

    Google Scholar 

  19. Benezet S, Guimbaud R, Chatelut E, Chevreau C, Bugat R, Canal P (1997) How to predict carboplatin clearance from standard morphological and biological characteristics in obese patients. Ann Oncol 8(6):607–609

    Article  CAS  PubMed  Google Scholar 

  20. Keys A, Fidanza F, Karvonen MJ, et al. (1972) Indices of relative weight and obesity. J Chronic Dis 25:325–343

    Article  Google Scholar 

  21. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Published: May 28, 2009 (v4.03: June 14, 2010)

  22. Bandera EV, Lee VS, Rodirguez-Rodriguez L, Powell CB, Kushi LH (2015) Impact of chemotherapy dosing on ovarian cancer survival according to body mass index. JAMA Oncol 1(6):737–745

    Article  PubMed  Google Scholar 

  23. Hunter RJ, Navo MA, Thaker PH,, Bodurka DC, Wolf JK, Smith JA (2009). Dosing chemotherapy in obese patients: actual versus assigned body surface area (BSA). Cancer Treat Rev 35: 69–78

    Article  CAS  PubMed  Google Scholar 

  24. Green B, Duffull SB (2004) What is the best size descriptor to use for pharmacokinetic studies in the obese? Brit J Clin Pharmacol 58:119–133

    Article  Google Scholar 

  25. Madarnas Y, Sawka CA, Franssen E, Bjarnason GA (2001) Are medical oncologists biased in their treatment of the large woman with breast cancer? Breast Cancer Res Treat 66:123–133

    Article  CAS  PubMed  Google Scholar 

  26. Jennifer J. Griggs, Pamela B. Mangu, Holly Anderson et al (2012) Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology Clinical Practice Guideline 2012

  27. Lexicomp’s drug reference handbooks (2012) 10th edn. p. 216

  28. Davis RL, Quenzer RW, Bozigian HP, Warner CW (1990) Pharmacokinetics of ranitidine in morbidly obese women. DICP 24(11):1040–1043

    CAS  PubMed  Google Scholar 

  29. Louin RA, Warren GW (1999) Pharmacokinetic considerations in obesity. J Pharm Sci 88(1):1–7

    Article  Google Scholar 

  30. Dionne RE, Bauer LA, Gibson GA, Griffen WO Jr, Blouin RA (1981) Estimating creatinine clearance in morbidity obese patients. Am J Hosp Pharm 38(6):841–844

    CAS  PubMed  Google Scholar 

  31. Verhave JC, Fesler P, Ribstein J, Du CG, Mimran A (2005) Estimation of renal function in subjects with normal serum creatinine levels: influence of age and body mass index. Am J Kidney Dis 46(2):233–241

    Article  CAS  PubMed  Google Scholar 

  32. Reiss RA, Haas CE, Kar ki SD, Gumbiner B, Welle SL, Carson SW (1994) Lithium pharmacokinetics in the obese. Clin Pharmacol Ther 55(4):392–339

    Article  CAS  PubMed  Google Scholar 

  33. Allard S, Kinzig M, Boivin G, Sorgel F, LeBel M (1993) Intravenous ciprofloxacin disposition in obesity. Clin Pharmacol Ther 54(4):368–373

    Article  CAS  PubMed  Google Scholar 

  34. Herrington JD, Tran HT, Riggs MW (2006) Prospective evaluation of carboplatin AUC dosing in patients with a BMI ≥ 27 or cachexia. Cancer Chemother Pharmacol 57:241–247

    Article  CAS  PubMed  Google Scholar 

  35. Salazar DE, Corcoran GB (1998) Predicting creatinine clearance and renal drug clearance in obese patients from estimated fat-free body mass. Am J Med 84(6):1053–1060

    Article  Google Scholar 

  36. Protocolo para Leucemia Aguda Linfoblástica de la Sociedad Española de Hematología y Oncología Pediátricas (SEHOP) en colaboración con el grupo PETHEMA. Versión LAL/SEHOP PETHEMA 2013 Versión 1.1. 2013

  37. Au-Yeung G, Webb PM, DeFazio A, Fereday S, Bressel M, Mileshkin L (2014) Impact of obesity on chemotherapy dosing for women with advanced stage serous ovarian cáncer in the Australian Ovarian Cancer Study (AOCS). Gynecol Oncol 133(1):16–22

    Article  CAS  PubMed  Google Scholar 

  38. McCune JS, Bemer MJ, Barrett JS, Baker KS, Gamis AS, Holford NHG (2014) Busulfan in infants to adult hematopoietic cell transplant recipients: a population pharmacokinetic model for initial and Bayesian dose personalization. Clin Cancer Res 20(3):754–763

    Article  CAS  PubMed  Google Scholar 

  39. Tham L-S, Wang L-Z, Soo RA, et al. (2008) Does saturable formation of gemcitabine triphosphate occur in patients? Cancer Chemother Pharmacol 63(1):55–64

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Carretera Ofra S/N La Cuesta, San Cristóbal de La Laguna (Tenerife), 38320, Islas Canarias, Spain

    Fernando Gutierrez, Guillermo Antonio Gonzalez-de-la-Fuente, Gloria Julia Nazco, Juana Oramas & Norberto Batista

Authors
  1. Fernando Gutierrez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guillermo Antonio Gonzalez-de-la-Fuente
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gloria Julia Nazco
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Juana Oramas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Norberto Batista
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fernando Gutierrez.

Ethics declarations

The study was conducted in accordance with the principles of the Helsinki Declaration adopted at the 18th World Medical Assembly (Helsinki, Finland) in 1964 and amended in Fortaleza, Brazil (2013), and the laws and regulations in force in Europe and Spain.

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Table S1

(DOCX 84 kb)

Figure S1

(DOCX 46 kb)

Figure S2

(DOCX 39 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gutierrez, F., Gonzalez-de-la-Fuente, G.A., Nazco, G.J. et al. Hematological toxicity of carboplatin for gynecological cancer according to body mass index. Eur J Clin Pharmacol 72, 1083–1089 (2016). https://doi.org/10.1007/s00228-016-2080-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-016-2080-7

Keywords

Search

Navigation