Dose-finding study of epidoxorubicin and docetaxel as first-line chemotherapy in patients with advanced breast cancer

Pagani, Olivia; Sessa, Cristiana; Martinelli, Giovanni; Crivellari, Diana; Buonadonna, Angela; Thürlimann, Beat; Hess, Dagmar; Borner, Markus; Bauer, Jean; Zampino, G.; Zimatore, Matteo; Graffeo, Rossella; Riva, A.; Goldhirsch, Aron

doi:10.1023/a:1026437731354

Cited by 40 publications

(18 citation statements)

References 22 publications

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“…In the phase II study performed by Mavroudis et al (2000), treatment with 70 mg m À2 of epirubicin and 90 mg m À2 of docetaxel resulted in an ORR of 66% with a median TTP of 11 months. The combination of docetaxel and epirubicin without G-CSF support resulted in febrile neutropenia in approximately 15% of cycles in a trial by Pagani et al (1999) and in 4 and 7% of cycles in the trials by Morales et al (2004) and Mavroudis et al (2000), respectively. In our study, febrile neutropenia was not observed.…”

Section: Discussionmentioning

confidence: 99%

Weekly epirubicin plus docetaxel as first-line treatment in metastatic breast cancer

et al. 2007

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This study was designed to evaluate the efficacy and tolerability of a weekly schedule of epirubicin in combination with docetaxel in the first-line treatment of patients with metastatic breast cancer (MBC). A total of 43 women with MBC not previously treated with chemotherapy for metastatic disease received weekly epirubicin 25 mg m À2 and docetaxel 25 mg m À2 for a maximum of five cycles (total cumulative epirubicin dose of p900 mg m À2 ). Dose reduction was not permitted. Objective response and evaluation of toxicity profile were the primary study end points; time to progression and overall survival were secondary end points. Patients were followed for a median of 21 (4 -38) months. Analysis was by intent to treat; 33 patients completed five cycles of therapy, and the median dose of epirubicin administered to the 43 patients was 23 mg m À2 . Twenty-five patients (58%) achieved a partial response and one (2%) achieved a complete response. An additional 12 patients (28%) had stable disease. The median time to progression was 11 months (95% confidence intervals (CI) 7 -14) overall, and 13 months (95% CI 12 -14) in the 26 patients who responded to treatment. Median overall survival was 25 months for responders and 14 months for nonresponders. Grade 3/4 neutropenia occurred in 16% of patients and in 6% of cycles. One patient developed cardiac toxicity (20% reduction in left ventricular ejection fraction). The combination of epirubicin plus docetaxel is highly active in MBC, with a manageable toxicity profile. Such a weekly schedule might provide a valuable treatment option for MBC.

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Section: Discussionmentioning

confidence: 99%

Weekly epirubicin plus docetaxel as first-line treatment in metastatic breast cancer

et al. 2007

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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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“…The dose escalation used, number of patients treated and cycles administered, together with the incidence of febrile neutropenia, are shown in Table 1 [22,23]. Epirubicin was administered as a 15-minute infusion and followed 1 hour later by the 1-hour infusion of docetaxel.…”

Section: Dose-findingmentioning

confidence: 99%

“…Including the 20 patients treated in the dose-finding study and 50 in the phase II trial, a total of 70 patients received the combination of 75 mg/m 2 docetaxel and 90 mg/m 2 epirubicin [22,23]. The dominant site of disease was visceral in 38 patients (54%).…”

Section: Combined Seriesmentioning

confidence: 99%

“…Under the auspices of the International Breast Cancer Study Group (IBCSG), six centers (two in Italy and four in Switzerland) took part in studies of the docetaxel/epirubicin combination. An initial dose-finding study sought to identify the maximum tolerated doses (MTD) of the two agents when used in combination q 3 weeks [22,23]. It also aimed to determine whether safe use of the combination required prophylactic G-CSF.…”

Section: Introductionmentioning

confidence: 99%

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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 epidoxorubicin and docetaxel as first-line chemotherapy in patients with advanced breast cancer

Cited by 40 publications

References 22 publications

Weekly epirubicin plus docetaxel as first-line treatment in metastatic breast cancer

Weekly epirubicin plus docetaxel as first-line treatment in metastatic breast cancer

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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