Carboplatin dose capping affects pCR rate in HER2-positive breast cancer patients treated with neoadjuvant Docetaxel, Carboplatin, Trastuzumab, Pertuzumab (TCHP)
(2020) In Breast Cancer Research and Treatment 184(2). p.481-489- 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:... (More)
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.
(Less)
- author
- Howell, Sacha J. ; Coe, Faye ; Wang, Xin ; Horsley, Laura and Ekholm, Maria LU
- organization
- publishing date
- 2020-11
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Administration and dosing, Breast neoplasms, Carboplatin, Neoadjuvant therapy, Treatment outcome
- in
- Breast Cancer Research and Treatment
- volume
- 184
- issue
- 2
- pages
- 9 pages
- publisher
- Springer
- external identifiers
-
- pmid:32860550
- scopus:85089968102
- ISSN
- 0167-6806
- DOI
- 10.1007/s10549-020-05868-z
- language
- English
- LU publication?
- yes
- id
- d5154e6e-3ad2-401d-bbf7-aaa7c6095d78
- date added to LUP
- 2020-09-25 13:41:30
- date last changed
- 2024-03-20 17:00:20
@article{d5154e6e-3ad2-401d-bbf7-aaa7c6095d78,
abstract = {{<p>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.</p>}},
author = {{Howell, Sacha J. and Coe, Faye and Wang, Xin and Horsley, Laura and Ekholm, Maria}},
issn = {{0167-6806}},
keywords = {{Administration and dosing; Breast neoplasms; Carboplatin; Neoadjuvant therapy; Treatment outcome}},
language = {{eng}},
number = {{2}},
pages = {{481--489}},
publisher = {{Springer}},
series = {{Breast Cancer Research and Treatment}},
title = {{Carboplatin dose capping affects pCR rate in HER2-positive breast cancer patients treated with neoadjuvant Docetaxel, Carboplatin, Trastuzumab, Pertuzumab (TCHP)}},
url = {{http://dx.doi.org/10.1007/s10549-020-05868-z}},
doi = {{10.1007/s10549-020-05868-z}},
volume = {{184}},
year = {{2020}},
}