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Pegylated liposomal doxorubicin plus cyclophosphamide followed by paclitaxel as primary chemotherapy in elderly or cardiotoxicity-prone patients with high-risk breast cancer: results of the phase II CAPRICE study

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Abstract

Anthracycline and taxane-based primary chemotherapy (PCT) is the standard treatment for high-risk breast cancer (HRBC). However, conventional anthracyclines are not commonly used in elderly patients or those prone to cardiotoxicity. Pegylated liposomal doxorubicin, (PLD) has comparable efficacy, but less cardiotoxicity than conventional anthracyclines. We conducted a phase II single-arm trial to assess the efficacy and safety of PCT based on PLD followed by paclitaxel (PTX) in a HRBC population usually undertreated. Fifty patients with stage II–IIIB breast cancer and at least one risk factor for developing cardiotoxicity initiated PLD 35 mg/m2 plus cyclophosphamide 600 mg/m2 every 4 weeks for four cycles, followed by 80 mg/m2 weekly PTX for 12. Close cardiac monitoring was performed. Primary endpoint was the pathological complete response rate (pCR) in the breast. Treatment delivery and toxicities were assessed. Eighty-four per cent of patients were older than 65 years, 64 % suffered from hypertension, and 10 % had prior cardiac disease. In an intention-to-treat analysis, breast pCR was 32 % (95 % CI 19.5–46.7 %) and pCR in breast and axilla was 24 % (95 % CI 12.1–35.8 %). At diagnosis only, 26 % of patients were candidates for breast conservative surgery, which increased to 58.7 % after PCT. No significant decrease in left ventricular ejection fraction was seen. PLD followed by PTX was feasible in a fragile population of patients who were not candidates for conventional doxorubicin. Moreover, it achieved a pCR similar to standard therapy and could therefore be an option for elderly patients or cardiotoxicity-prone who present HRBC.

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Abbreviations

BCS:

Breast conserving surgery rate

CPM:

Cyclophosphamide

CHF:

Congestive heart failure

ECG:

Electrocardiogram

DOX:

Doxorubicin

HRBC:

High-risk breast cancer

HFS:

Hand–foot syndrome

ITT:

Intention to treat

LVEF:

Left ventricular ejection fraction

MRI:

Magnetic resonance image

ER:

Estrogen receptor

ORR:

Overall response rate

OS:

Overall survival

PTX:

Paclitaxel

pCR:

Pathologic complete response

PLD:

Pegylated liposomal doxorubicin

PCT:

Primary chemotherapy

PFS:

Progression-free survival

US:

Ultrasound

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Acknowledgments

This work was supported by the Schering Plough and Merck Sharp and Dohme. The results of this study were presented in part at SABCS 2011.

Conflict of interest

The authors declare that they have no conflict of interest.

Compliance with Ethical Standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in this study.

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Correspondence to Miguel J. Gil-Gil.

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On behalf of the SOLTI Breast Cancer Research Group.

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Gil-Gil, M.J., Bellet, M., Morales, S. et al. Pegylated liposomal doxorubicin plus cyclophosphamide followed by paclitaxel as primary chemotherapy in elderly or cardiotoxicity-prone patients with high-risk breast cancer: results of the phase II CAPRICE study. Breast Cancer Res Treat 151, 597–606 (2015). https://doi.org/10.1007/s10549-015-3415-2

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  • DOI: https://doi.org/10.1007/s10549-015-3415-2

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