Gemcitabine/Epirubicin/Paclitaxel as Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer: A Phase II Trial of the NSABP Foundation Research Group
ABSTRACT This phase II protocol of neoadjuvant chemotherapy with gemcitabine/epirubicin/paclitaxel (GET) was designed to determine the pathologic complete response (pCR) rate in the breast, clinical response rate, disease-free survival, and overall survival at 2 years as well as toxicity in patients with locally advanced breast cancer. This trial also evaluated the feasibility of tissue collection for gene-expression profiling.
Seventy-six women with stage IIB, IIIA, and IIIB breast cancer were entered into this trial. Patients received a maximum of 6 cycles of neoadjuvant GET chemotherapy every 21 days (gemcitabine 1000 mg/m2 intravenously [i.v.] on days 1 and 4, epirubicin 90 mg/m2 i.v. bolus on day 1, and paclitaxel 175 mg/m2 i.v. on day 1). After chemotherapy, patients underwent surgery and were assessed for pathologic response.
The pCR rate among the 74 patients evaluable for efficacy was 23% (95% CI, 14%-34.2%). Adverse events among the 76 patients evaluable for toxicity included anemia requiring transfusion (14.5%), infection with grade 3/4 neutropenia (10.5%), febrile neutropenia (7.9%), and platelet transfusion (6.6%). Infectious complications occurred in 24 patients (31.6%), of whom 18.4% were in the setting of neutropenia. High-quality RNA and successful probe synthesis were obtained from all pretreatment core biopsy specimens that contained tumor cells (n=66; 88%).
Neoadjuvant GET chemotherapy is an active regimen but with substantial toxicity. Tissue collection for gene-expression profiling is feasible in a multi-institutional setting.
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ABSTRACT: Epirubicin and docetaxel are two of the most active drugs against breast carcinoma. As the achievement of a pathological complete response (pCR) is important for survival of patients with locally advanced disease, we used both drugs as neoadjuvant chemotherapy. Women with locally advanced or inflammatory breast cancer received epirubicin 120 mg/m2 followed by docetaxel 75 mg/m2, both on day 1, every 21 days for four cycles. Lenograstim was administered for 10 days in all cycles. Of 51 patients included, 50 received a total of 188 cycles, with a median of 4 per patient. The median age was 47 years, tumour stage was IIIA in 14 patients and IIIB in 36. Oestrogen receptors were positive in 65% of tumours. There were 10 clinical complete responses (20%) and 29 partial responses (58%). Surgery consisted of mastectomy in 40 patients and tumorectomy in 6. After surgery, 9 pCR were recorded (18%). One patient progressed and died soon after the end of chemotherapy. After a median follow-up of 22 months, the median disease-free survival was 33.7 months. Grade 3/4 neutropenia was observed in 32% of patients, anaemia in 6%, and thrombocytopenia in 4%. Five patients had febrile neutropenia. There were no toxic deaths or grade 4 nonhaematological toxicities. Docetaxel plus high-dose epirubicin showed promising activity in patients with locally advanced and inflammatory breast cancer, at the cost of moderate toxicity.Cancer Chemotherapy and Pharmacology 01/2005; 54(6):546-52. DOI:10.1007/s00280-004-0830-1 · 2.57 Impact Factor
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ABSTRACT: Neoadjuvant anthracycline/taxane combinations, with or without gemcitabine, produce pathologic complete responses (pCRs) in 15%-25% of patients. In this multicenter phase II study, we attempted to increase efficacy and decrease toxicity of a 3-drug gemcitabine-containing neoadjuvant regimen by administering dose-dense therapy with pegfilgrastim, and including albumin-bound paclitaxel as the taxane. Patients and A total of 123 patients with locally advanced breast cancer were enrolled. Patients were treated with 6 doses of neoadjuvant gemcitabine 2000 mg/m2, epirubicin 50 mg/m2, and albumin-bound paclitaxel 175 mg/m2 intravenously administered at 14-day intervals. Following neoadjuvant chemotherapy, patients underwent either mastectomy or breast conservation surgery; pathologic response to treatment was assessed. Postoperatively, patients received 4 doses of gemcitabine 2000 mg/m2 with albumin-bound paclitaxel 220 mg/m2 at 14-day intervals. Pegfilgrastim 6 mg was administered subcutaneously on day 2 following each dose of chemotherapy. A total of 116 patients (95%) completed neoadjuvant chemotherapy and had subsequent surgical resection. Twenty-three patients (20%) had a pCR. The estimated 3-year progression-free survival (PFS) and overall survival rates were 48% and 86%, respectively. Neoadjuvant treatment was well tolerated; only 11% of the patients had grade 3/4 neutropenia, with 1 episode of neutropenic fever. Other grade 3/4 toxicities occurred in < 10% of the patients. Neoadjuvant biweekly chemotherapy with gemcitabine/epirubicin/albumin-bound paclitaxel with pegfilgrastim is feasible and well tolerated. The pCR rate of 20% and the 3-year PFS rate of 48% are similar to results achieved with other commonly used neoadjuvant regimens.Clinical Breast Cancer 10/2010; 10(5):367-72. DOI:10.3816/CBC.2010.n.048 · 2.63 Impact Factor
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ABSTRACT: Monotherapy with nanoparticle albumin-bound (nab)-paclitaxel has demonstrated improved efficacy and safety compared with solvent-based paclitaxel and docetaxel. A comprehensive review of all reported studies of nab-paclitaxel combinations with other agents in all breast cancer settings was undertaken. Most studies reviewed are small, phase II and non-comparative. Combinations studied included nab-paclitaxel plus trastuzumab and/or bevacizumab (with or without additional cytotoxic agents), gemcitabine, capecitabine, carboplatin, or lapatinib. The majority of metastatic and neoadjuvant studies demonstrated satisfactory efficacy and safety for nab-paclitaxel combinations, although conclusions regarding comparison with solvent-based taxane (SBT) regimens are not possible. The two adjuvant studies confirmed the safety of nab-paclitaxel combinations in this setting. Although results of this review indicate that nab-paclitaxel may be an appropriate substitute for SBTs in combination regimens, additional research is required to confirm the place and cost effectiveness of these combinations before nab-paclitaxel could be recommended routinely in all settings.Breast (Edinburgh, Scotland) 08/2011; 20(5):394-406. DOI:10.1016/j.breast.2011.06.004 · 2.58 Impact Factor