Phase II study of a 3-weekly liposome-encapsulated doxorubicin/docetaxel/pegfligrastrim in combination with weekly trastuzumab as primary treatment in HER2 positive early stage breast cancer patients (II-IIIa). GEICAM 2003-03 study.

Abstract

#5117 Objective: To assess the safety and efficacy of Myocet (M), Docetaxel (T), Trastuzumab (H) with prophylactic Pegfilgrastrim (N) as neoadjuvant chemotherapy in operable breast cancer patients (pts). The primary efficacy end point was pathologic complete response in the breast. Methods: Eligible pts had pathologically confirmed stage II or IIIA untreated breast cancer and HER2 overexpression determined by FISH in a central laboratory. M 50 mg/m2 and T 60 mg/m2 were given on day 1 and N on day 2 every 3 weeks for 6 cycles (Cy); H (4mg/Kgr loading dose, then 2 mg/Kgr/week) was given intravenously for 17 weeks, recommended dose in a phase I study (Proc ASCO 2007,25:596s Abstr.# 11.032). After all chemotherapy was completed, clinical responses were assessed. After surgery, pathological responses were evaluated using the Miller Payne scoring scale (MPSS). Results: 59 pts have been evaluated. Median age was 47.6 years (range 24-71) and median clinical tumour size 47.5 mm (range, 10-80). 19 pts (32.2%) presented with stage IIIA disease and 40 pts (67.8%) with stage II, 36 pts (61.0%) were premenopausal; 50 pts (84.8%) had histological grade 2-3 tumours; and 29 (49.2%) were ER-PgR-negative. All the pts received M and T 6 Cy with medium relative doses intense of 98.9% and 99.1% respectively. Objective clinical response rate was 84.7% (CI: 75.5-93.9) with 31 (52.5%) complete responses and 19 (32.2%) partial responses. 42 pts (71.2%) underwent conservative surgery, 17 pts (28.8%) achieved a pathological complete response in breast (Grade 5 in MPSS), of these, 16 pts (27.1%) achieved a pathological complete response in breast and axilar (Grade 5A+Grade 5D). Main grades (G) toxicities during MTHN treatment: leucopenia G3/4 was present in 18 pts (30.5%); neutropenia G3/4 in 17 pts (28.8%); febrile neutropenia G3 in 3 pts (5.1%); diarrhea G3 was present in 3 pts (5.1%); G2 rash in 2 pts (3.4%); G3 asthenia in 5 pts (8.5%) and stomatitis G3 in 1 pt (1.7%). 8 pts (13.6%) experienced asymptomatic and reversible cardiac left ventricular function G2. Conclusions: Concomitant administration of M plus THN is highly effective and active regimen with little toxicity in pts with HER2+ and early stage breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5117.

Substituting Doxorubicin with Nonpegylated Liposomal Doxorubicin for the Treatment of Early Breast Cancer: Results of a Retrospective Study

“…In addition, substituting NPLD for conventional doxorubicin as the standard anthracycline in early breast cancer (EBC) may help address the growing concerns regarding the longer-term impact of treatment on cardiac function [ 1 , 2 ]. Current evidence on the use of NPLD in early disease is restricted to two phase II trials [ 8 , 9 ], both of which report limited cardiac data for NPLD.…”

“…The results of two small phase II studies [8, 9] suggest that the benefits observed in metastatic patients may be maintained in early breast cancer, but further data are required. The objective of our study, therefore, was to assess the use of NPLD in place of conventional doxorubicin in standard regimens as a novel therapeutic option for the treatment of patients with early breast cancer.…”

“…In addition, substituting NPLD for doxorubicin as the standard anthracycline in early breast cancer may help address the growing concerns regarding the longer-term impact of treatment on cardiac function, a key survivorship issue [ 1 , 2 ]. However, whilst NPLD has been extensively studied in metastatic breast cancer and is licensed in this regard [ 3 – 7 ], data on its use in early disease are currently scarce [ 8 , 9 ].…”

“…Data from the metastatic setting, which demonstrate that NPLD is equally efficacious but significantly less cardiotoxic than conventional doxorubicin [ 3 , 4 , 6 ], provide a good rationale to postulate that NPLD may help achieve this delicate balance in the adjuvant setting. The results of two small phase II studies [ 8 , 9 ] suggest that the benefits observed in metastatic patients may be maintained in early breast cancer, but further data are required. The objective of our study, therefore, was to assess the use of NPLD in place of conventional doxorubicin in standard regimens as a novel therapeutic option for the treatment of patients with early breast cancer.…”