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Andreas Schneeweiss - One of the best experts on this subject based on the ideXlab platform.
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intense dose dense epirubicin paclitaxel cyclophosphamide versus weekly paclitaxel liposomal doxorubicin plus carboplatin in triple negative breast cancer for neoadjuvant treatment of high risk early breast cancer geparocto gbg 84 a randomised phase iii trial
European Journal of Cancer, 2019Co-Authors: Andreas Schneeweiss, Volker Mobus, H Tesch, Claus Hanusch, Carsten Denkert, K Lubbe, Jens Huober, P Klare, Sherko Kummel, Michael UntchAbstract:Abstract Background GeparOcto compared efficacy and safety of two chemotherapy regimens in high-risk early breast cancer (BC): sequential treatment with intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) and weekly treatment with paclitaxel plus non-pegylated liposomal doxorubicin (M, Myocet®) with additional carboplatin (PM(Cb)) in triple-negative BC (TNBC). Patients and methods Patients with cT1c-cT4a-d and centrally assessed human epidermal growth factor receptor (HER)2-positive BC or TNBC were eligible, irrespective of nodal status, luminal B-like tumours only if pN+. Patients were randomised (stratified by BC subtype, Ki67, lymphocyte-predominant BC) to receive 18 weeks of E (150 mg/m2) followed by P (225 mg/m2) followed by C (2000 mg/m2), each q2w for 3 cycles or weekly P (80 mg/m2) plus M (20 mg/m2) plus, in TNBC, Cb (area under curve (AUC) 1.5). HER2-positive BC patients additionally received trastuzumab (6 [loading dose 8]mg/kg q3w) and pertuzumab (420 [840]mg q3w) with all P and C cycles. Primary end-point was pathological complete response (pCR, ypT0/is ypN0), secondary end-points included other pCR definitions, pCR in stratified subpopulations, tolerability and compliance. This trial is registered with ClinicalTrials.gov number NCT02125344 . Results 945/961 randomised patients started treatment. The median age was 48 years; 7.6% had cT3-4, 46% cN+, 66% G3, 40% HER2-positive, 43% TNBC. pCR rate with iddEPC was 48.3%, with PM(Cb) 48.0%, respectively (PM(Cb) versus iddEPC odds ratio 0.99; 95% confidence interval 0.77–1.28, P = 0.979) with no significant differences observed in TNBC, HER2-positive, luminal B-like subtypes. 16.4% with iddEPC and 34.1% with PM(Cb) discontinued treatment (P Conclusions In high-risk early BC there is no difference in pCR rates following neoadjuvant treatment with iddEPC or weekly PM(Cb), respectively. iddEPC is one of the effective dose-dense regimens feasible in daily practice.
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survival analysis of carboplatin added to an anthracycline taxane based neoadjuvant chemotherapy and hrd score as predictor of response final results from geparsixto
Annals of Oncology, 2018Co-Authors: S Loibl, Andreas Schneeweiss, Carsten Denkert, K Weber, Kirsten Timms, E P Elkin, Eric Hahnen, Peter A Fasching, Bianca Lederer, Sascha D BraunAbstract:Abstract Background In the neoadjuvant GeparSixto study, adding carboplatin to taxane- and anthracycline-based chemotherapy improved pathological complete response (pCR) rates in patients with triple-negative breast cancer (TNBC). Here, we present survival data and the potential prognostic and predictive role of homologous recombination deficiency (HRD). Patients and methods Patients were randomized to paclitaxel plus nonpegylated liposomal doxorubicin (Myocet®) (PM) or PM plus carboplatin (PMCb). The secondary study end points disease-free survival (DFS) and overall survival (OS) were analyzed. Median follow-up was 47.3 months. HRD was among the exploratory analyses in GeparSixto and was successfully measured in formalin-fixed, paraffin-embedded tumor samples of 193/315 (61.3%) participants with TNBC. Homologous recombination (HR) deficiency was defined as HRD score ≥42 and/or presence of tumor BRCA mutations (tmBRCA). Results A significantly better DFS (hazard ratio 0.56, 95% CI 0.34–0.93; P = 0.022) was observed in patients with TNBC when treated with PMCb. The improvement of OS with PMCb was not statistically significant. Additional carboplatin did not improve DFS or OS in patients with HER2-positive tumors. HR deficiency was detected in 136 (70.5%) of 193 triple-negative tumors, of which 82 (60.3%) showed high HRD score without tmBRCA. HR deficiency independently predicted pCR (ypT0 ypN0) [odds ratio (OR) 2.60, 95% CI 1.26–5.37, P = 0.008]. Adding carboplatin to PM significantly increased the pCR rate from 33.9% to 63.5% in HR deficient tumors (P = 0.001), but only marginally in HR nondeficient tumors (from 20.0% to 29.6%, P = 0.540; test for interaction P = 0.327). pCR rates with carboplatin were also higher (63.2%) than without carboplatin (31.7%; OR 3.69, 1.46–9.37, P = 0.005) in patients with high HRD score but no tmBRCA. DFS rates were improved with addition of carboplatin, both in HR nondeficient (hazard ratio 0.44, 0.17–1.17, P = 0.086) and HR deficient tumors (hazard ratio 0.49, 0.23–1.04, P = 0.059). Conclusions The addition of carboplatin to neoadjuvant PM improved DFS significantly in TNBC. Long-term survival analyses support the neoadjuvant use of carboplatin in TNBC. HR deficiency in TNBC and HRD score in non-tmBRCA TNBC are predictors of response. HRD does not predict for carboplatin benefit.
Michael Untch - One of the best experts on this subject based on the ideXlab platform.
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intense dose dense epirubicin paclitaxel cyclophosphamide versus weekly paclitaxel liposomal doxorubicin plus carboplatin in triple negative breast cancer for neoadjuvant treatment of high risk early breast cancer geparocto gbg 84 a randomised phase iii trial
European Journal of Cancer, 2019Co-Authors: Andreas Schneeweiss, Volker Mobus, H Tesch, Claus Hanusch, Carsten Denkert, K Lubbe, Jens Huober, P Klare, Sherko Kummel, Michael UntchAbstract:Abstract Background GeparOcto compared efficacy and safety of two chemotherapy regimens in high-risk early breast cancer (BC): sequential treatment with intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) and weekly treatment with paclitaxel plus non-pegylated liposomal doxorubicin (M, Myocet®) with additional carboplatin (PM(Cb)) in triple-negative BC (TNBC). Patients and methods Patients with cT1c-cT4a-d and centrally assessed human epidermal growth factor receptor (HER)2-positive BC or TNBC were eligible, irrespective of nodal status, luminal B-like tumours only if pN+. Patients were randomised (stratified by BC subtype, Ki67, lymphocyte-predominant BC) to receive 18 weeks of E (150 mg/m2) followed by P (225 mg/m2) followed by C (2000 mg/m2), each q2w for 3 cycles or weekly P (80 mg/m2) plus M (20 mg/m2) plus, in TNBC, Cb (area under curve (AUC) 1.5). HER2-positive BC patients additionally received trastuzumab (6 [loading dose 8]mg/kg q3w) and pertuzumab (420 [840]mg q3w) with all P and C cycles. Primary end-point was pathological complete response (pCR, ypT0/is ypN0), secondary end-points included other pCR definitions, pCR in stratified subpopulations, tolerability and compliance. This trial is registered with ClinicalTrials.gov number NCT02125344 . Results 945/961 randomised patients started treatment. The median age was 48 years; 7.6% had cT3-4, 46% cN+, 66% G3, 40% HER2-positive, 43% TNBC. pCR rate with iddEPC was 48.3%, with PM(Cb) 48.0%, respectively (PM(Cb) versus iddEPC odds ratio 0.99; 95% confidence interval 0.77–1.28, P = 0.979) with no significant differences observed in TNBC, HER2-positive, luminal B-like subtypes. 16.4% with iddEPC and 34.1% with PM(Cb) discontinued treatment (P Conclusions In high-risk early BC there is no difference in pCR rates following neoadjuvant treatment with iddEPC or weekly PM(Cb), respectively. iddEPC is one of the effective dose-dense regimens feasible in daily practice.
Carsten Denkert - One of the best experts on this subject based on the ideXlab platform.
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intense dose dense epirubicin paclitaxel cyclophosphamide versus weekly paclitaxel liposomal doxorubicin plus carboplatin in triple negative breast cancer for neoadjuvant treatment of high risk early breast cancer geparocto gbg 84 a randomised phase iii trial
European Journal of Cancer, 2019Co-Authors: Andreas Schneeweiss, Volker Mobus, H Tesch, Claus Hanusch, Carsten Denkert, K Lubbe, Jens Huober, P Klare, Sherko Kummel, Michael UntchAbstract:Abstract Background GeparOcto compared efficacy and safety of two chemotherapy regimens in high-risk early breast cancer (BC): sequential treatment with intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) and weekly treatment with paclitaxel plus non-pegylated liposomal doxorubicin (M, Myocet®) with additional carboplatin (PM(Cb)) in triple-negative BC (TNBC). Patients and methods Patients with cT1c-cT4a-d and centrally assessed human epidermal growth factor receptor (HER)2-positive BC or TNBC were eligible, irrespective of nodal status, luminal B-like tumours only if pN+. Patients were randomised (stratified by BC subtype, Ki67, lymphocyte-predominant BC) to receive 18 weeks of E (150 mg/m2) followed by P (225 mg/m2) followed by C (2000 mg/m2), each q2w for 3 cycles or weekly P (80 mg/m2) plus M (20 mg/m2) plus, in TNBC, Cb (area under curve (AUC) 1.5). HER2-positive BC patients additionally received trastuzumab (6 [loading dose 8]mg/kg q3w) and pertuzumab (420 [840]mg q3w) with all P and C cycles. Primary end-point was pathological complete response (pCR, ypT0/is ypN0), secondary end-points included other pCR definitions, pCR in stratified subpopulations, tolerability and compliance. This trial is registered with ClinicalTrials.gov number NCT02125344 . Results 945/961 randomised patients started treatment. The median age was 48 years; 7.6% had cT3-4, 46% cN+, 66% G3, 40% HER2-positive, 43% TNBC. pCR rate with iddEPC was 48.3%, with PM(Cb) 48.0%, respectively (PM(Cb) versus iddEPC odds ratio 0.99; 95% confidence interval 0.77–1.28, P = 0.979) with no significant differences observed in TNBC, HER2-positive, luminal B-like subtypes. 16.4% with iddEPC and 34.1% with PM(Cb) discontinued treatment (P Conclusions In high-risk early BC there is no difference in pCR rates following neoadjuvant treatment with iddEPC or weekly PM(Cb), respectively. iddEPC is one of the effective dose-dense regimens feasible in daily practice.
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survival analysis of carboplatin added to an anthracycline taxane based neoadjuvant chemotherapy and hrd score as predictor of response final results from geparsixto
Annals of Oncology, 2018Co-Authors: S Loibl, Andreas Schneeweiss, Carsten Denkert, K Weber, Kirsten Timms, E P Elkin, Eric Hahnen, Peter A Fasching, Bianca Lederer, Sascha D BraunAbstract:Abstract Background In the neoadjuvant GeparSixto study, adding carboplatin to taxane- and anthracycline-based chemotherapy improved pathological complete response (pCR) rates in patients with triple-negative breast cancer (TNBC). Here, we present survival data and the potential prognostic and predictive role of homologous recombination deficiency (HRD). Patients and methods Patients were randomized to paclitaxel plus nonpegylated liposomal doxorubicin (Myocet®) (PM) or PM plus carboplatin (PMCb). The secondary study end points disease-free survival (DFS) and overall survival (OS) were analyzed. Median follow-up was 47.3 months. HRD was among the exploratory analyses in GeparSixto and was successfully measured in formalin-fixed, paraffin-embedded tumor samples of 193/315 (61.3%) participants with TNBC. Homologous recombination (HR) deficiency was defined as HRD score ≥42 and/or presence of tumor BRCA mutations (tmBRCA). Results A significantly better DFS (hazard ratio 0.56, 95% CI 0.34–0.93; P = 0.022) was observed in patients with TNBC when treated with PMCb. The improvement of OS with PMCb was not statistically significant. Additional carboplatin did not improve DFS or OS in patients with HER2-positive tumors. HR deficiency was detected in 136 (70.5%) of 193 triple-negative tumors, of which 82 (60.3%) showed high HRD score without tmBRCA. HR deficiency independently predicted pCR (ypT0 ypN0) [odds ratio (OR) 2.60, 95% CI 1.26–5.37, P = 0.008]. Adding carboplatin to PM significantly increased the pCR rate from 33.9% to 63.5% in HR deficient tumors (P = 0.001), but only marginally in HR nondeficient tumors (from 20.0% to 29.6%, P = 0.540; test for interaction P = 0.327). pCR rates with carboplatin were also higher (63.2%) than without carboplatin (31.7%; OR 3.69, 1.46–9.37, P = 0.005) in patients with high HRD score but no tmBRCA. DFS rates were improved with addition of carboplatin, both in HR nondeficient (hazard ratio 0.44, 0.17–1.17, P = 0.086) and HR deficient tumors (hazard ratio 0.49, 0.23–1.04, P = 0.059). Conclusions The addition of carboplatin to neoadjuvant PM improved DFS significantly in TNBC. Long-term survival analyses support the neoadjuvant use of carboplatin in TNBC. HR deficiency in TNBC and HRD score in non-tmBRCA TNBC are predictors of response. HRD does not predict for carboplatin benefit.
Gerald Batist - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetics of doxorubicin administered i v as Myocet tlc d 99 liposome encapsulated doxorubicin citrate compared with conventional doxorubicin when given in combination with cyclophosphamide in patients with metastatic breast cancer
Anti-Cancer Drugs, 2003Co-Authors: C E Swenson, Gerald Batist, Lauri Welles, Troy H Guthrie, Rupinder Bhamra, Lois E Bolcsak, Katherine Tkaczuk, Harold Boxenbaum, Sheinchung Chow, Philip ChaikinAbstract:Myocet (TLC D-99) is a liposomal formulation of the anti-neoplastic drug doxorubicin with an improved therapeutic index compared with conventional doxorubicin. The objective of this study was to assess the plasma disposition of doxorubicin when administered i.v. as TLC D-99 and to compare this to conventional drug. Metabolite (doxorubicinol) plasma levels were also quantitated in both treatment groups. Plasma was collected during the first course of treatment from 10 patients receiving TLC D-99 60 mg/m and 10 receiving conventional doxorubicin 60 mg/m2, each with cyclophosphamide 600 mg/m2. Samples were assayed for total doxorubicin (all doxorubicin regardless of whether it is encapsulated or not), encapsulated doxorubicin (TLC D-99 group only) and doxorubicinol using high-performance liquid chromatography. Plasma concentrations of total doxorubicin were higher in patients receiving TLC D-99 than in patients receiving conventional doxorubicin. The clearance of total doxorubicin after administration of TLC D-99 was lower (approximately 9-fold) and the volume of distribution at steady state was less (25-fold) than that of doxorubicin after conventional drug. Doxorubicinol was detected in the plasma of all patients in both treatment groups. The mean AUC(0-infinity) of doxorubicinol for patients receiving TLC D-99 (1.5+/-0.4 M x h) was not statistically different than that in patients receiving conventional doxorubicin (1.8+/-0.4 M x h), although the appearance of the peak doxorubicinol concentration occurred later and was lower in patients receiving TLC D-99. There was a correlation between the plasma AUC(0-infinity) of total doxorubicin and the degree of myelosuppression in patients receiving conventional doxorubicin, but this correlation was not found in patients receiving TLC D-99.
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Myocet liposome encapsulated doxorubicin citrate a new approach in breast cancer therapy
Expert Opinion on Pharmacotherapy, 2002Co-Authors: Gerald Batist, C E Swenson, Jeremy Barton, Philip Chaikin, Lauri WellesAbstract:Doxorubicin, either as a single agent or in combination regimens, is considered to be one of the most active chemotherapeutic agents in the treatment of metastatic breast cancer. However, its clinical utility is limited by a cumulative, dose-dependent cardiac myopathy that can lead to potentially fatal congestive heart failure. Considerable research has gone into improving the therapeutic index of doxorubicin-based regimens. A new liposomal formulation of doxorubicin (Myocet™, Elan Pharmaceuticals) has a significantly improved therapeutic index compared with conventional doxorubicin. The development of Myocet, a less cardiotoxic, better tolerated and equally efficacious doxorubicin, extends the therapeutic options in the overall management of breast cancer.
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liposome encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first line therapy of metastatic breast carcinoma
Cancer, 2002Co-Authors: Gerald Batist, Lauri Welles, Eric P Winer, Lyndsay Harris, Robert Belt, Douglas Rovira, Rudolph M Navari, Nozar AzarniaAbstract:BACKGROUND The objective of this study was to compare the efficacy and toxicity of the liposome-encapsulated doxorubicin, TLC D-99 (Myocet, Elan Pharmaceuticals, Princeton, NJ), and conventional doxorubicin in first-line treatment of metastatic breast carcinoma (MBC). METHODS Two hundred twenty-four patients with MBC and no prior therapy for metastatic disease were randomized to receive either TLC D-99 (75 mg/m2) or doxorubicin (75 mg/m2) every 3 weeks, in the absence of disease progression or unacceptable toxicity. The primary efficacy endpoint was response rate. Responses were assessed using World Health Organization criteria and were required to be of at least 6 weeks' duration. The primary safety endpoint was cardiotoxicity. Cardiac function was monitored by multiple-gated radionuclide cardioangiography scan, and the left ventricular ejection fraction (LVEF) was scored at a central laboratory. Patients were removed from study if LVEF declined 20 or more EF units from baseline to a final value of greater than or equal to 50%, or by 10 or more units to a final value of less than 50%, or onset of clinical congestive heart failure (CHF). RESULTS Median age was 54 years in both treatment groups. All relevant prog nostic factors were balanced, with the exception that there were significantly more progesterone receptor positive patients in the doxorubicin-treated group. Protocol-defined cardiotoxicity was observed in 13% of TLC D-99 patients (including 2 cases of CHF) compared to 29% of doxorubicin patients (including 9 cases of CHF). Median cumulative doxorubicin dose at onset of cardiotoxicity was 785 mg/m2 for TLC D-99 versus 570 mg/m2 for doxorubicin (P = 0.0001; hazard ratio, 3.56). The overall response rate was 26% in both treatment groups. The median TTP was 2.9 months on TLC D-99 versus 3.1 months on doxorubicin. Median survival was 16 versus 20 months with a nonsignificant trend in favor of doxorubicin (P = 0.09). Clinical toxicities, commonly associated with doxorubicin, appeared less common with TLC D-99, although the difference was not statistically significant. There was only one report of palmar-plantar erythrodysesthesia (Grade 2) with this liposomal formulation of doxorubicin. CONCLUSIONS Single-agent TLC D-99 produces less cardiotoxicity than doxorubicin, while providing comparable antitumor activity. Cancer 2002;94:25–36. © 2002 American Cancer Society.
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reduced cardiotoxicity and preserved antitumor efficacy of liposome encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized multicenter trial of metastatic breast cancer
Journal of Clinical Oncology, 2001Co-Authors: Gerald Batist, Gopal Ramakrishnan, Chandra Sekhar Rao, Aruna Chandrasekharan, John Gutheil, Troy H Guthrie, Pankaj Shah, Ali Khojasteh, Madhavan Krishnan Nair, Karen HoelzerAbstract:PURPOSE: To determine whether Myocet (liposome-encapsulated doxorubicin; The Liposome Company, Elan Corporation, Princeton, NJ) in combination with cyclophosphamide significantly reduces doxorubicin cardiotoxicity while providing comparable antitumor efficacy in first-line treatment of metastatic breast cancer (MBC). PATIENTS AND METHODS: Two hundred ninety-seven patients with MBC and no prior chemotherapy for metastatic disease were randomized to receive either 60 mg/m2 of Myocet (M) or conventional doxorubicin (A), in combination with 600 mg/m2 of cyclophosphamide (C), every 3 weeks until disease progression or unacceptable toxicity. Cardiotoxicity was defined by reductions in left-ventricular ejection fraction, assessed by serial multigated radionuclide angiography scans, or congestive heart failure (CHF). Antitumor efficacy was assessed by objective tumor response rates (World Health Organization criteria), time to progression, and survival. RESULTS: Six percent of MC patients versus 21% (including fi...
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reduced cardiotoxicity and preserved antitumor efficacy of liposome encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized multicenter trial of metastatic breast cancer
Journal of Clinical Oncology, 2001Co-Authors: Gerald Batist, Gopal Ramakrishnan, Chandra Sekhar Rao, Aruna Chandrasekharan, John Gutheil, Troy H Guthrie, Pankaj Shah, Ali Khojasteh, Madhavan Krishnan Nair, Karen HoelzerAbstract:Purpose To determine whether Myocet (liposome-encapsulated doxorubicin; The Liposome Company, Elan Corporation, Princeton, NJ) in combination with cyclophosphamide significantly reduces doxorubicin cardiotoxicity while providing comparable antitumor efficacy in first-line treatment of metastatic breast cancer (MBC). Patients and methods Two hundred ninety-seven patients with MBC and no prior chemotherapy for metastatic disease were randomized to receive either 60 mg/m(2) of Myocet (M) or conventional doxorubicin (A), in combination with 600 mg/m(2) of cyclophosphamide (C), every 3 weeks until disease progression or unacceptable toxicity. Cardiotoxicity was defined by reductions in left-ventricular ejection fraction, assessed by serial multigated radionuclide angiography scans, or congestive heart failure (CHF). Antitumor efficacy was assessed by objective tumor response rates (World Health Organization criteria), time to progression, and survival. Results Six percent of MC patients versus 21% (including five cases of CHF) of AC patients developed cardiotoxicity (P =.0002). Median cumulative doxorubicin dose at onset was more than 2,220 mg/m(2) for MC versus 480 mg/m(2) for AC (P =.0001, hazard ratio, 5.04). MC patients also experienced less grade 4 neutropenia. Antitumor efficacy of MC versus AC was comparable: objective response rates, 43% versus 43%; median time to progression, 5.1% versus 5.5 months; median time to treatment failure, 4.6 versus 4.4 months; and median survival, 19 versus 16 months. Conclusion Myocet improves the therapeutic index of doxorubicin by significantly reducing cardiotoxicity and grade 4 neutropenia and provides comparable antitumor efficacy, when used in combination with cyclophosphamide as first-line therapy for MBC.
A Barbato - One of the best experts on this subject based on the ideXlab platform.
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nonpegylated liposomal doxorubicin Myocet combination r comp chemotherapy in elderly patients with diffuse large b cell lymphoma dlbcl results from the phase ii eur018 trial
Annals of Oncology, 2010Co-Authors: Stefano Luminari, S Bologna, Martin J S Dyer, Antonella Montanini, Dolores Caballero, M Notter, A Chiappella, J Briones, Mario Petrini, A BarbatoAbstract:Abstract Background To evaluate the activity and safety of nonpegylated liposomal doxorubicin (Myocet™) when substituted for doxorubicin in the R-CHOP regimen (R-COMP). Patients and methods Seventy-five elderly patients with diffuse large B-cell lymphoma (DLBCL) were studied. Only patients with left ventricular ejection fraction (LVEF) ≥50% were allowed. R-COMP regimen was administered every 3 weeks for three cycles, followed by additional five cycles in case of complete response (CR) or partial response. Results From November 2002 to April 2005, 75 patients were registered, of which 72 were evaluated. Median age was 72 years (range 61–83); 56% of patients had high or high–intermediate International Prognostic Index score. Median LVEF at baseline was 61%. Thirty-eight patients had history of abnormal cardiovascular conditions. The overall response rate was 71%, with a CR rate of 57%. After a median follow-up of 33 months, the 3-year overall survival, failure-free survival, and progression-free survival rates were 72%, 39%, and 69%, respectively. Neutropenia (54%) was the most frequent grade 3–4 adverse event (AE); 21% of patients experienced cardiac AEs, graded as 3–4 in 4% of the cases. Conclusion R-COMP is an effective regimen for the treatment of DLBCL in elderly patients, with an acceptable tolerability profile.
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phase ii study of liposomal doxorubicin Myocet docetaxel and trastuzumab combination as first line treatment of patients with her 2 neu positive locally advanced or metastatic breast cancer
Cancer Research, 2009Co-Authors: Dino Amadori, Roberto Bordonaro, Giampietro Gasparini, Andrea Ardizzoni, Giuseppe Comella, Silvana Saracchini, Carlo Barone, K Djazouli, A BarbatoAbstract:Abstract #3149 Objective: the aims of the study are to assess activity and safety of liposomal doxorubicin (Myocet®) in combination with Docetaxel and Trastuzumab as first-line treatment of patients with HER-2/neu positive MBC. Methods: forty-six (46) non treated patients with metastatic HER2-overexpressing BC were planned to receive Myocet 50 mg/m 2 (d1) and Docetaxel 30 mg/m 2 (d2 and d9) plus Trastuzumab (d2, 4 mg/kg followed by 2 mg/kg weekly) for at least 6 cycles (up to a maximum of 8 unless occurrence of unacceptable toxicity or PD). Cycles were repeated every 21 days. Objective response was assessed according to WHO criteria every 3 cycles. To evaluate the tolerability WHO grading toxicity events were assessed at each cycle. Cardiotoxicity was defined as signs and/or symptoms of CHF and/or a decrease in LVEF below normal limit ( Results : we reported preliminary results of 46 patients enrolled. 41 patients completed at least 3 cycles and at first response evaluation Complete Response was seen in 2 pts (CR=4,9%), Partial Response in 22 pts (PR=53,7%), Stable Disease in 15 pts (SD=36,6%) and Progression Disease in 2 pts (PD=4,9%). The Overall Response Rate (ORR) was 58,6%. 36 pts completed the planned chemotherapy (6 cycles): Complete Response was seen in 4 pts (CR=11,1%), Partial Response in 15 pts (PR=41,7%), Stable Disease in 9 (SD=25,0%) and Progression Disease in 8 pts (PD=22,2%). The Overall Response Rate (ORR) was 52,8%. 12 pts were entered in the follow up and for this subgroup median TTP was 13 months. All 46 enrolled patients were included in the safety analysis. Most frequent toxicity events occurred during the study were: granulocytopenia Grade 4 in 16 pts (30.4%), leukocytopenia Grade 3 in 15 pts (32.6%), increase of transaminase levels Grade 1 in 14 pts (30.4%), alopecia Grade 4 in 16 pts (34.8%) and nausea Grade 2 in 13 pts (28.3%). In 2 patients LVEF dropped 15% with respect to baseline value. In the whole population LVEF mean value changed from 62.6 ± 4.9 at baseline to 61.0 ± 5.5 at cycle 3, to 62.9 ± 6.4 (cycle 6) and to 60.0 ± 8.1 (cycle 8). Conclusion: these preliminary results suggest that the combination of non-pegylated liposomal doxorubicin, docetaxel and trastuzumab has shown a promising activity in first line MBC. The combination is safe with no significant change in LVEF values from baseline to the end of therapy. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3149.
