Dose-finding study of docetaxel and doxorubicin in first-line treatment of patients with metastatic breast cancer

Misset, Jean-Louis; Dièras, Véronique; Gruia, G.; Bourgeois, H.; Cvitkovic, Esteban; Kalla, S.; Bozec, Laurence; Beuzeboc, Philippe; Jasmin, C; Aussel, J.P.; Riva, A.; Azli, N.; Pouillart, P

doi:10.1023/a:1026418831238

Cited by 119 publications

(50 citation statements)

References 18 publications

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“…The doses of AD were based on the preliminary recommendations available from the (then unpublished) dose-finding study of this combination in first-line treatment of patients with metastatic breast cancer [14]. The doses of AC were those used in primary chemotherapy studies in breast cancer at that time, both in the USA [16] and UK [17].…”

Section: Chemotherapy Treatmentmentioning

confidence: 99%

“…At the time of development of this study, docetaxel had been shown to have significant activity in patients with metastatic breast cancer, including those patients with anthracycline-resistant disease [12,13]. The single-agent activity of docetaxel and of the anthracyclines, and the absence of complete cross-resistance between them, provided a rationale to develop these drugs in combination in patients with breast cancer [14]. Furthermore, AD gave superior response rates and time to progression, but not superior OS, compared with AC as first-line chemotherapy in patients with metastatic breast cancer.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Five-year outcome for women randomised in a phase III trial comparing doxorubicin and cyclophosphamide with doxorubicin and docetaxel as primary medical therapy in early breast cancer: an Anglo-Celtic Cooperative Oncology Group Study

Mansi¹,

Yellowlees²,

Lipscombe³

et al. 2010

Breast Cancer Res Treat

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To compare the long-term outcome of women with primary or locally advanced breast cancer randomised to receive either doxorubicin and cyclophosphamide (AC) or doxorubicin and docetaxel (AD) as primary chemotherapy. Eligible patients with histologic-proven breast cancer with primary tumours C3 cm, inflammatory or locally advanced disease, and no evidence of distant metastases, were randomised to receive a maximum of 6 cycles of either doxorubicin (60 mg/m 2 ) plus cyclophosphamide (600 mg/m 2 ) i/v or doxorubicin (50 mg/m 2 ) plus docetaxel (75 mg/m 2 ) i/v every 3 weeks, followed by surgery on completion of chemotherapy. Clinical and pathologic responses have previously been reported. Time to relapse, site of relapse, and all-cause mortality were recorded. This updated analysis compares long-term disease-free (DFS) and overall survival (OS) using stratified log rank methods. A total of 363 patients were randomised to AC (n = 181) or AD (n = 182). A complete pathologic response was observed in 16% for AC and 12% for AD (P = 0.43). The number of patients with positive axillary nodes at surgery with AC was 61% and AD 66% (P = 0.36). At a median follow-up of 99 months there is 123Breast Cancer Res Treat (2010) 122:787-794 DOI 10.1007 no significant difference between the two groups for DFS (P = 0.20) and OS (P = 0.24). Deaths were due to metastatic breast cancer in 96% of patients. Our data do not support a clinical benefit for simultaneous administration of AD compared with AC. However, the data do not exclude a smaller benefit than the study was powered to detect and are consistent with an increase in both diseasefree and overall survival of about 5% for AD compared with AC. Outcome is consistent with the pathologic complete response following surgery.

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Section: Chemotherapy Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Five-year outcome for women randomised in a phase III trial comparing doxorubicin and cyclophosphamide with doxorubicin and docetaxel as primary medical therapy in early breast cancer: an Anglo-Celtic Cooperative Oncology Group Study

Mansi¹,

Yellowlees²,

Lipscombe³

et al. 2010

Breast Cancer Res Treat

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“…Several phase I studies were performed, with combinations including docetaxel and doxorubicin (Misset et al, 1999), docetaxel+doxorubicin+cyclo-phosphamide (Nabholtz et al, 1997), docetaxel and epidoxorubicin (Pagani et al, 1999), docetaxel and cisplatin (Crown et al, 1997), docetaxel and vinorelbine (Fumoleau et al, 1996b), and docetaxel and 5-fluorouracil (Lortholary et al, 1997).…”

Section: Docetaxelmentioning

confidence: 99%

Phase I study of docetaxel in combination with cyclophosphamide as first-line chemotherapy for metastatic breast cancer

et al. 2002

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This phase I was study conducted to establish the maximum tolerated dose, dose-limiting toxicity, and recommended dose of docetaxel in combination with cyclophosphamide as first-line chemotherapy for metastatic breast cancer. Twenty-six patients were treated with cyclophosphamide (600 mg m 72 , intravenous bolus) followed by docetaxel (60, 75 or 85 mg m 72, 1-h intravenous infusion) every 3 weeks. The maximum tolerated dose was docetaxel 85 mg m 72 with cyclophosphamide 600 mg m 72 , the dose-limiting toxicity being febrile neutropenia. Grade 4 neutropenia was experienced by all patients, but was generally brief. Otherwise, the combination was well tolerated with few acute and no chronic non-haematological toxicities of grade 3/4. Activity was observed at all dose levels and disease sites, and the overall response rate was 42% (95% confidence interval 22 -61%). The pharmacokinetics of docetaxel were not modified by cyclophosphamide coadministration. These findings establish a recommended dose of docetaxel 75 mg m 72 in combination with cyclophosphamide 600 mg m 72 every three weeks for phase II evaluation.

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“…These data and those of comparable series suggest that the combination of epirubicin and docetaxel is tolerable and active, and that it should be further developed clinically. The Oncologist 2001;6(suppl 3): [13][14][15][16] The Oncologist 2001;6(suppl 3):13-16 www.TheOncologist.com Correspondence: Cristiana Sessa, M.D., Oncology Institute of Southern Switzerland, Ospedale San Giovanni, Bellinzona CH-6500, Switzerland. Telephone: 41-91-820-90-39; Fax: 41-91-820-90-44; e-mail: csessa@ticino.com Received February 6, 2001; accepted for publication March 5, 2001.…”

Section: Introductionmentioning

confidence: 99%

“…This followed publication of data suggesting that the administration of paclitaxel in patients with a greater than 360 mg/m 2 cumulative exposure to doxorubicin might result in a 20% or greater incidence of congestive heart failure [9][10][11][12]. However, with the docetaxel/anthracycline combination, docetaxel did not appear to increase the incidence or severity of cardiotoxicity observed with doxorubicin alone [6,8,[13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Docetaxel and Epirubicin in Advanced Breast Cancer

Sessa

Pagani

2001

The Oncologist

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In an International Breast Cancer Study Group phase I/II program, 70 patients with advanced breast cancer received up to eight courses of 75 mg/m 2 docetaxel combined with 90 mg/m 2 epirubicin, every 3 weeks. G-CSF was not administered prophylactically. Grade 4 neutropenia occurred in 88% of cycles that were not supported by G-CSF. However, febrile neutropenia affected only 24% of cycles. It occurred after the first cycle in 56% of cases and was managed by oral antibiotics in 52% of cases. When supportive G-CSF was administered, the incidence of febrile neutropenia fell to 3% and grade 4 neutropenia to 41%. Only 6% of patients experienced a greater than 20% reduction in left ventricular ejection fraction and no severe, irreversible cardiotoxicity was observed. The overall response rate (RR) was 66% and median time to progression was 4.5 months. The RR was similar in patients with prior adjuvant chemotherapy and patients with predominantly visceral disease. These data and those of comparable series suggest that the combination of epirubicin and docetaxel is tolerable and active, and that it should be further developed clinically. The Oncologist 2001;6(suppl 3): [13][14][15][16] The Oncologist 2001;6(suppl 3):13-16 www.TheOncologist.com Correspondence: Cristiana Sessa, M.D., Oncology Institute of Southern Switzerland, Ospedale San Giovanni, Bellinzona CH-6500, Switzerland. Telephone: 41-91-820-90-39; Fax: 41-91-820-90-44; e-mail: csessa@ticino.com Received February 6, 2001; accepted for publication March 5, 2001. ©AlphaMed Press 1083-7159/2001 INTRODUCTIONEarly experience suggested that the greater than 40% objective response rate (ORR) seen with anthracyclines in advanced breast cancer could be matched by monotherapy with the taxane, docetaxel [1][2][3][4][5]. It was also suggested that using an anthracycline in combination with a taxane could reliably increase the ORR to 50% or more [5][6][7][8].While the use of docetaxel in combination with doxorubicin is now relatively commonplace, in the mid-1990s there was considerable concern that the combination of a taxane with an anthracycline might result in unacceptable cardiotoxicity. This followed publication of data suggesting that the administration of paclitaxel in patients with a greater than 360 mg/m 2 cumulative exposure to doxorubicin might result in a 20% or greater incidence of congestive heart failure [9][10][11][12]. However, with the docetaxel/anthracycline combination, docetaxel did not appear to increase the incidence or severity of cardiotoxicity observed with doxorubicin alone [6,8,[13][14][15][16]. This paper presents results from the largest study to date of the combination of docetaxel with epirubicin, an anthracycline generally regarded as less cardiotoxic than doxorubicin. It concentrates on the safety aspects of the combined use of epirubicin and docetaxel, attempting to identify the doses that can reasonably be used in clinical practice.

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Dose-finding study of docetaxel and doxorubicin in first-line treatment of patients with metastatic breast cancer

Cited by 119 publications

References 18 publications

Five-year outcome for women randomised in a phase III trial comparing doxorubicin and cyclophosphamide with doxorubicin and docetaxel as primary medical therapy in early breast cancer: an Anglo-Celtic Cooperative Oncology Group Study

Five-year outcome for women randomised in a phase III trial comparing doxorubicin and cyclophosphamide with doxorubicin and docetaxel as primary medical therapy in early breast cancer: an Anglo-Celtic Cooperative Oncology Group Study

Phase I study of docetaxel in combination with cyclophosphamide as first-line chemotherapy for metastatic breast cancer

Docetaxel and Epirubicin in Advanced Breast Cancer

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