Carboplatin dose capping affects pCR rate in HER2-positive breast cancer patients treated with neoadjuvant Docetaxel, Carboplatin, Trastuzumab, Pertuzumab (TCHP)

Sacha J. Howell, Faye Coe, Xin Wang, Laura Horsley, Maria Ekholm

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Estimated glomerular filtration rate (eGFR) is commonly used to calculate carboplatin doses and capping the eGFR may be used to reduce the risk of excessive dosing and toxicity. We sought to retrospectively examine the impact of our carboplatin guidelines on pathological complete response rates (pCR) and toxicity in women with HER2+ breast cancer receiving neoadjuvant docetaxel, carboplatin, trastuzumab and pertuzumab (TCHP). Methods: The delivered area under the curve (dAUC) was calculated [(actual carboplatin dose at cycle 1 ÷ dose calculated with uncapped/unbanded eGFR) × 6] and dichotomized at the median value. The impact of this and other clinical factors on pCR rate, dose intensity (DI) and toxicity was assessed. Results: 124 eligible patients were identified of whom 63.7% (79/124) achieved pCR. The median dAUC at cycle 1 was 5.75 mg × ml/min. Those with lower dAUC were more frequently younger and overweight/obese. Patients with lower dAUC had significantly inferior pCR rates of 54.8% (34/62) vs 72.6% (45/62), respectively (p = 0.040). Similar results were seen in the ER+ subgroup; 45.2% (19/42) vs 68.3% (28/41), p = 0.037%, whereas no significant difference was seen among ER- patients; 75.0% (15/20) vs 81.0% (17/21), p = 0.72. DI and toxicity were comparable between the two dAUC groups. Conclusions: The overall pCR rate was high in patients with HER2+ breast cancer receiving the TCHP regimen; however, carboplatin dose capping resulted in inferior pCR rates, particularly in the ER+ subgroup. To ensure optimal dosing, isotopic measurement of renal function is warranted in patients who would otherwise have their eGFR and dose capped.

Original languageEnglish
Pages (from-to)481-489
Number of pages9
JournalBreast Cancer Research and Treatment
Volume184
Issue number2
Early online date2020 Aug 29
DOIs
Publication statusPublished - 2020 Nov

Subject classification (UKÄ)

  • Cancer and Oncology

Keywords

  • Administration and dosing
  • Breast neoplasms
  • Carboplatin
  • Neoadjuvant therapy
  • Treatment outcome

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