Myotax: A phase II trial of docetaxel plus non-pegylated liposomal doxorubicin as first-line therapy of metastatic breast cancer previously treated with adjuvant anthracyclines (original) (raw)
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Docetaxel–Anthracycline Combinations in Metastatic Breast Cancer
Breast Cancer Research and Treatment, 2003
The taxanes and anthracyclines have emerged as the most active agents for treating women with advanced breast cancer. As such, investigation of the two drug classes in combination regimens has been eagerly pursued. The rationale for combining docetaxel with an anthracycline includes high clinical activity of each individual agent, lack of complete clinical cross resistance, and non-overlapping toxicity profiles. Phase II trials of the docetaxel combinations with either doxorubicin or epirubicin showed high activity, with acceptable tolerability in patients with metastatic breast cancer. Consequently, three randomized trials have compared docetaxel-anthracycline-based regimens with standard anthracycline-based polychemotherapies as first-line therapy for women with advanced breast cancer. Improved outcome was reported in favor of the docetaxel-anthracycline combinations, with manageable hematologic toxicity and favorable non-hematologic safety profiles. Therefore, docetaxel-anthracycline combinations represent a validated option in first-line treatment for women with advanced breast cancer, and are further evaluated as adjuvant treatment for early stage breast cancer, with already promising prospects and the potential to change the natural history of breast cancer.
Journal of Chemotherapy, 2011
Doxorubicin is highly effective and widely used in breast cancer; however, its use is limited by cardiotoxicity related to its cumulative dose. In previous studies, pegylated liposomal doxorubicin (PLD) has shown an acceptable toxicity profile with minimal cardiotoxicity. Between June 2006 and October 2009, 27 metastatic breast cancer patients were treated with first-line PLD and vinorelbine at the University of Florence, Radiotherapy Unit. PLD (30 mg/m 2) was administered on day 1, and oral vinorelbine (60 mg/m 2) was administered on days 1 and 8 of a 4-week cycle. All patients were previously treated with anthracycline-based adjuvant chemotherapy. Median age was 52 years (range 38-69) and median time to metastasis was 78.5 months. There were no treatment interruptions or discontinuation for cardiac toxicity and no treatment-related deaths. Grade 3 hematological toxicity was observed in 18.6% of patients, and 3.7% had grade 3 non-hematological adverse events. With a median follow-up of 13.2 months (range 3-33), median response duration was 6.1 months, and median PFS was 5.3 months. The overall clinical benefit rate was 55.5%. Our experience adds to evidence supporting the activity and cardiac safety of PLD and vinorelbine in metastatic breast cancer patients previously treated with anthracycline-based adjuvant chemotherapy.
Docetaxel in the treatment of breast cancer: An update on recent studies
Seminars in Oncology, 2002
Recently there has been great interest in developing combination regimens involving taxanes and anthracyclines for the treatment of advanced breast cancer. Docetaxel in particular has substantial activity when combined with doxorubicin. In one randomized trial, the combination of doxorubicin 50 mg/m 2 and docetaxel 75 mg/m 2 showed significantly greater activity than doxorubicin plus cyclophosphamide (AC), producing a higher response rate (60% v 47%) and longer time to progression. In a second study, 484 patients were randomized to receive either docetaxel plus doxorubicin and cyclophosphamide (TAC) or 5-florouracil plus doxorubicin and cyclophosphamide. The response rate was significantly higher in the TAC arm (54% v 42%), including patients with unfavorable prognostic factors. Febrile neutropenia occurred more frequently in patients receiving TAC, but the incidence of infection and septic death was low and no greater than in the 5-florouracil/doxorubicin/cyclophosphamide arm. TAC was not associated with an increased risk of cardiotoxicity. Data on time to progression and survival are not yet available. The TAC and doxorubicin/docetaxel regimens have been compared with non-docetaxel-containing programs in randomized adjuvant trials which have completed accrual but are not yet mature. A second generation of adjuvant trials compares sequential versus synchronous docetaxel-based polychemotherapy. In addition, based on preclinical data suggesting a synergistic interaction between docetaxel, platinum salts, and trastuzumab, as well as preliminary data from pilot studies in patients with HER2-positive metastatic disease showing tolerability and activity, adjuvant studies of this novel three-agent combination are in progress in patients with HER2-positive early breast cancer. Semin Oncol 29 (suppl 12):28-34.
Annals of Oncology, 2004
Background: This study was designed to demonstrate that efficacy [progression-free survival (PFS)] of CAELYX™ [pegylated liposomal doxorubicin HCl (PLD)] is non-inferior to doxorubicin with significantly less cardiotoxicity in first-line treatment of women with metastatic breast cancer (MBC). Patients and methods: Women (n = 509) with MBC and normal cardiac function were randomized to receive either PLD 50 mg/m 2 (every 4 weeks) or doxorubicin 60 mg/m 2 (every 3 weeks). Cardiac event rates were based on reductions in left ventricular ejection fraction as a function of cumulative anthracycline dose. Results: PLD and doxorubicin were comparable with respect to PFS [6.9 versus 7.8 months, respectively; hazard ratio (HR) = 1.00; 95% confidence interval (CI) 0.82-1.22]. Subgroup results were consistent. Overall risk of cardiotoxicity was significantly higher with doxorubicin than PLD (HR = 3.16; 95%CI 1.58-6.31; P <0.001). Overall survival was similar (21 and 22 months for PLD and doxorubicin, respectively; HR = 0.94; 95%CI 0.74-1.19). Alopecia (overall, 66% versus 20%; pronounced, 54% versus 7%), nausea (53% versus 37%), vomiting (31% versus 19%) and neutropenia (10% versus 4%) were more often associated with doxorubicin than PLD. Palmar-plantar erythrodysesthesia (48% versus 2%), stomatitis (22% versus 15%) and mucositis (23% versus 13%) were more often associated with PLD than doxorubicin. Conclusions: In first-line therapy for MBC, PLD provides comparable efficacy to doxorubicin, with significantly reduced cardiotoxicity, myelosuppression, vomiting and alopecia.
Cancer Chemotherapy and Pharmacology, 2006
Background: The aim of the study was to assess the toxicity profile, activity in terms of response rate, time to progression, overall survival, and quality of life of pegylated liposomal doxorubicin (PLD) and gemcitabine combination in chemo-naïve and pretreated metastatic breast cancer (MBC) women. Methods: Patients were eligible if they had disease progression to prior chemotherapy (anthracycline-including or not) for early breast cancer or MBC. Patients received PLD 25 mg/m2 intravenously on day 1 plus gemcitabine 800 mg/m2 intravenously on days 1 and 8 of each 21-day cycle. Results: Of 50 patients enrolled, 37 had received prior adjuvant chemotherapy (24 with an anthracycline) and 23 prior chemotherapy for metastatic disease (6 with an anthracycline). Two complete responses and 20 partial responses were achieved in 46 assessable patients (overall response rate: 47.8%). Responses were observed in 14 (46.6%) of 30 patients with previous anthracycline exposure. Median response duration was 7 months, median duration of clinical benefit 8 months, time to progression 7 months. At a median follow-up of 10 months, 79.4% patients were alive at 1 year. No neutropenic complication was observed. Non-hematological toxicities were mild. One patient previously treated with an anthracycline developed a transient decrease (26%) in the left ventricular ejection fraction, with cardiac function recovering within 6 months. Conclusion: Because of the non-overlapping toxicity profiles of both PLD and gemcitabine, this combination can be regarded as a reliable therapeutic option for patients who have failed previous treatments, including anthracycline, for MBC.