title: 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.
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/m(2) plus cyclophosphamide 600 mg/m(2) every 4 weeks for four cycles, followed by 80 mg/m(2) 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.
authors.affiliation: Department of Medical Oncology, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Avenida Gran Via 199-201, 08908, Barcelona, Spain, mgilgil@iconcologia.net.
authors.forename: Miguel J
authors.initials: MJ
authors.lastname: Gil-Gil
authors.forename: M
authors.initials: M
authors.lastname: Bellet
authors.forename: S
authors.initials: S
authors.lastname: Morales
authors.forename: B
authors.initials: B
authors.lastname: Ojeda
authors.forename: L
authors.initials: L
authors.lastname: Manso
authors.forename: C
authors.initials: C
authors.lastname: Mesia
authors.forename: E
authors.initials: E
authors.lastname: Garcia-Martínez
authors.forename: N
authors.initials: N
authors.lastname: Martinez-Jáñez
authors.forename: M
authors.initials: M
authors.lastname: Melé
authors.forename: A
authors.initials: A
authors.lastname: Llombart
authors.forename: S
authors.initials: S
authors.lastname: Pernas
authors.forename: P
authors.initials: P
authors.lastname: Villagrasa
authors.forename: C
authors.initials: C
authors.lastname: Blasco
authors.forename: J
authors.initials: J
authors.lastname: Baselga
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D066126:Cardiotoxicity; D015897:Comorbidity; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006331:Heart Diseases / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000008:administration & dosage; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel