A phase IB dose-finding trial of liposomal doxorubicin in combination with capecitabine in patients with pretreated metastatic breast cancer (original) (raw)
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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.
Experimental hematology & oncology, 2012
Liposomal formulations of anthracyclines appear to have favorable toxicity profile when compared with conventional anthracyclines in elderly, high risk cardiac patients and patients with prior use of anthracyclines. Randomized controlled trials have evaluated the efficacy and safety profile of liposomal formulations with conventional anthracyclines. Our aim is to evaluate the adverse effects and quantify the relative safety profile of the liposomal and conventional anthracyclines through meta-analysis of the published randomized trials. We conducted a broad search strategy of major electronic databases. We performed a meta- analysis of adverse effects on randomized controlled trials comparing liposomal formulation and conventional anthracyclines on different tumors. The primary outcome was the adverse effects including congestive heart failure (CHF), hematological toxicity, palmar-plantar erythrodysthesias (PPE), alopecia, nausea and vomiting. The odds ratios of the adverse effects ...
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.
Cancer Chemotherapy and Pharmacology, 2017
LVEF remained stable between studies (59 ± 7, 60 ± 9 and 58 ± 10.5% for the latest study, previous, p < 0.79, and most remote study p < 0.9); No change was found in average left ventricular/right ventricular global longitudinal strain as well: −20.8 ± 4.6% at the latest study and −19.3 ± 2.6% for the previous (p < 0.51). Conclusion No prevalent or incident cases of cardiotoxicity were found despite prolonged treatment with large cumulative doses of PLD, adding to previous reports on shorter treatment duration.
Frontiers in Oncology, 2021
Background The CAPRICE trial was designed to specifically evaluate neoadjuvant pegylated liposomal doxorubicin (PLD) in elderly patients or in those with other cardiovascular risk factors in whom conventional doxorubicin was contraindicated. The primary analysis of the study showed a pathological complete response (pCR) of 32% and no significant decreases in LVEF during chemotherapy. Here, we report important secondary study objectives: 5-year cardiac safety, disease-free survival (DFS), overall survival (OS) and breast cancer specific survival (BCSS). Methods In this multicentre, single-arm, phase II trial, elderly patients or those prone to cardiotoxicity and high risk stage II-IIIB breast cancer received PLD (35 mg/m2) plus cyclophosphamide (600 mg/m2) every 4 weeks for 4 cycles, followed by paclitaxel for 12 weeks as neoadjuvant chemotherapy (NAC). Left ventricular ejection fraction (LVEF) monitorization, electrocardiograms and cardiac questionnaires were performed at baseline, ...
Preclinical evaluation of the cardiac toxicity of HMR-1826, a novel prodrug of doxorubicin
British journal of cancer, 1999
Cardiotoxicity represents the major side-effect limiting the clinical use of anthracyclines, especially doxorubicin, in cancer chemotherapy. The use of non-toxic prodrugs, or of liposome-encapsulated drugs, allows a better targeting of the tumours and may, therefore, improve the tolerance to the treatment. Using the model of isolated perfused rat heart, we have evaluated the cardiotoxicity of a novel prodrug of doxorubicin, HMR-1826, which consists of the association of doxorubicin to glucuronic acid. We have compared the cardiac effects (developed pressure, contractility and relaxation of the left ventricle) induced by HMR-1826 to those induced by doxorubicin and Doxil, a liposomal form of doxorubicin. HMR-1826 was administered intravenously every other day for 11 days at doses of 50-200 mg kg(-1) per injection while doxorubicin was administered according to the same protocol at doses of 1-3 mg kg(-1) per injection. Doxorubicin strongly decreased the cardiac functional parameters a...