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

Eur J Clin Pharmacol. 2016 Sep;72(9):1083-9. doi: 10.1007/s00228-016-2080-7. Epub 2016 Jun 10.

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/m(2)) 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/m(2) were considered as overweight (OW) and those with a BMI <27 kg/m(2) 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.

Keywords: Carboplatin; Hematological toxicity; Ovarian cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Body Mass Index
  • Carboplatin / adverse effects*
  • Carboplatin / pharmacokinetics
  • Carboplatin / therapeutic use
  • Female
  • Genital Neoplasms, Female / blood
  • Genital Neoplasms, Female / drug therapy*
  • Hematologic Diseases / blood
  • Hematologic Diseases / chemically induced*
  • Hematologic Diseases / metabolism
  • Humans
  • Middle Aged
  • Overweight / blood
  • Overweight / metabolism*
  • Paclitaxel / therapeutic use

Substances

  • Antineoplastic Agents
  • Carboplatin
  • Paclitaxel