A phase I/II trial of non-pegylated liposomal doxorubicin, docetaxel and trastuzumab as first-line treatment in HER-2-positive locally advanced or metastatic breast cancer

D. Amadori, C. Milandri, G. Comella, S. Saracchini, S. Salvagni, C. Barone, R. Bordonaro, V. Gebbia, A. Barbato, P. Serra, D. Gattuso, O. Nanni, B. Baconnet, G. Gasparini

Research output: Contribution to journalArticle

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Abstract

Aim: To assess the activity and safety of non-pegylated liposomal doxorubicin (Myocet®) in combination with docetaxel and trastuzumab as first-line treatment of patients with HER-2/neu-positive metastatic breast cancer (MBC). Patients and methods: The maximum tolerated dose of the combination was defined in the phase I part of the study. In the phase II part, 45 HER-2/neu-positive MBC patients were enrolled to receive 6-8 cycles of Myocet® 50 mg/m 2 (day 1), docetaxel 30 mg/m 2 (days 2 and 9) plus trastuzumab (day 2, 4 mg/kg followed by 2 mg/kg/week) every 21 d until unacceptable toxicity or progression occurred. Objective response (primary end-point) and treatment tolerability were assessed according to World Health Organisation criteria. Cardiotoxicity was defined as signs and/or symptoms of congestive heart failure and/or a decrease in left ventricular ejection fraction (LVEF). Results: The overall response rate was 55.6% (complete response 8.9%, partial response 46.7%), with a median time-to-progression of 10.9 months (C.I. 8.7-15.0). Median overall survival was not reached. The most frequent grade 3-4 adverse events were granulocytopaenia (60.0%), leukocytopenia (43.2%) and alopecia (35.6%). Grade 3-4 diarrhoea, pain, oral and skin toxicity (4.4%, each) and nausea/vomiting, thrombocytopenia and elevated alkaline phosphatase (2.2%, each) were also reported. In 2 patients LVEF fell to 15%. LVEF median values remained stable from baseline to the end of the study (60%). Conclusions: The combination of Myocet®, docetaxel and trastuzumab is safe and shows promising activity as first-line treatment of HER-2-positive MBC.

Original languageEnglish
Pages (from-to)2091-2098
Number of pages8
JournalEuropean Journal of Cancer
Volume47
Issue number14
DOIs
Publication statusPublished - Sep 2011

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docetaxel
Stroke Volume
Doxorubicin
Breast Neoplasms
Maximum Tolerated Dose
Alopecia
Leukopenia
Therapeutics
Thrombocytopenia
Nausea
Signs and Symptoms
Vomiting
Alkaline Phosphatase
Diarrhea
Heart Failure
Safety
Pain
Skin
Survival
liposomal doxorubicin

Keywords

  • Metastatic breast cancer
  • Non-pegylated liposomal doxorubicin
  • Phase I/II trial

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A phase I/II trial of non-pegylated liposomal doxorubicin, docetaxel and trastuzumab as first-line treatment in HER-2-positive locally advanced or metastatic breast cancer. / Amadori, D.; Milandri, C.; Comella, G.; Saracchini, S.; Salvagni, S.; Barone, C.; Bordonaro, R.; Gebbia, V.; Barbato, A.; Serra, P.; Gattuso, D.; Nanni, O.; Baconnet, B.; Gasparini, G.

In: European Journal of Cancer, Vol. 47, No. 14, 09.2011, p. 2091-2098.

Research output: Contribution to journalArticle

Amadori, D, Milandri, C, Comella, G, Saracchini, S, Salvagni, S, Barone, C, Bordonaro, R, Gebbia, V, Barbato, A, Serra, P, Gattuso, D, Nanni, O, Baconnet, B & Gasparini, G 2011, 'A phase I/II trial of non-pegylated liposomal doxorubicin, docetaxel and trastuzumab as first-line treatment in HER-2-positive locally advanced or metastatic breast cancer', European Journal of Cancer, vol. 47, no. 14, pp. 2091-2098. https://doi.org/10.1016/j.ejca.2011.05.005
Amadori, D. ; Milandri, C. ; Comella, G. ; Saracchini, S. ; Salvagni, S. ; Barone, C. ; Bordonaro, R. ; Gebbia, V. ; Barbato, A. ; Serra, P. ; Gattuso, D. ; Nanni, O. ; Baconnet, B. ; Gasparini, G. / A phase I/II trial of non-pegylated liposomal doxorubicin, docetaxel and trastuzumab as first-line treatment in HER-2-positive locally advanced or metastatic breast cancer. In: European Journal of Cancer. 2011 ; Vol. 47, No. 14. pp. 2091-2098.
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abstract = "Aim: To assess the activity and safety of non-pegylated liposomal doxorubicin (Myocet{\circledR}) in combination with docetaxel and trastuzumab as first-line treatment of patients with HER-2/neu-positive metastatic breast cancer (MBC). Patients and methods: The maximum tolerated dose of the combination was defined in the phase I part of the study. In the phase II part, 45 HER-2/neu-positive MBC patients were enrolled to receive 6-8 cycles of Myocet{\circledR} 50 mg/m 2 (day 1), docetaxel 30 mg/m 2 (days 2 and 9) plus trastuzumab (day 2, 4 mg/kg followed by 2 mg/kg/week) every 21 d until unacceptable toxicity or progression occurred. Objective response (primary end-point) and treatment tolerability were assessed according to World Health Organisation criteria. Cardiotoxicity was defined as signs and/or symptoms of congestive heart failure and/or a decrease in left ventricular ejection fraction (LVEF). Results: The overall response rate was 55.6{\%} (complete response 8.9{\%}, partial response 46.7{\%}), with a median time-to-progression of 10.9 months (C.I. 8.7-15.0). Median overall survival was not reached. The most frequent grade 3-4 adverse events were granulocytopaenia (60.0{\%}), leukocytopenia (43.2{\%}) and alopecia (35.6{\%}). Grade 3-4 diarrhoea, pain, oral and skin toxicity (4.4{\%}, each) and nausea/vomiting, thrombocytopenia and elevated alkaline phosphatase (2.2{\%}, each) were also reported. In 2 patients LVEF fell to 15{\%}. LVEF median values remained stable from baseline to the end of the study (60{\%}). Conclusions: The combination of Myocet{\circledR}, docetaxel and trastuzumab is safe and shows promising activity as first-line treatment of HER-2-positive MBC.",
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AU - Amadori, D.

AU - Milandri, C.

AU - Comella, G.

AU - Saracchini, S.

AU - Salvagni, S.

AU - Barone, C.

AU - Bordonaro, R.

AU - Gebbia, V.

AU - Barbato, A.

AU - Serra, P.

AU - Gattuso, D.

AU - Nanni, O.

AU - Baconnet, B.

AU - Gasparini, G.

PY - 2011/9

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N2 - Aim: To assess the activity and safety of non-pegylated liposomal doxorubicin (Myocet®) in combination with docetaxel and trastuzumab as first-line treatment of patients with HER-2/neu-positive metastatic breast cancer (MBC). Patients and methods: The maximum tolerated dose of the combination was defined in the phase I part of the study. In the phase II part, 45 HER-2/neu-positive MBC patients were enrolled to receive 6-8 cycles of Myocet® 50 mg/m 2 (day 1), docetaxel 30 mg/m 2 (days 2 and 9) plus trastuzumab (day 2, 4 mg/kg followed by 2 mg/kg/week) every 21 d until unacceptable toxicity or progression occurred. Objective response (primary end-point) and treatment tolerability were assessed according to World Health Organisation criteria. Cardiotoxicity was defined as signs and/or symptoms of congestive heart failure and/or a decrease in left ventricular ejection fraction (LVEF). Results: The overall response rate was 55.6% (complete response 8.9%, partial response 46.7%), with a median time-to-progression of 10.9 months (C.I. 8.7-15.0). Median overall survival was not reached. The most frequent grade 3-4 adverse events were granulocytopaenia (60.0%), leukocytopenia (43.2%) and alopecia (35.6%). Grade 3-4 diarrhoea, pain, oral and skin toxicity (4.4%, each) and nausea/vomiting, thrombocytopenia and elevated alkaline phosphatase (2.2%, each) were also reported. In 2 patients LVEF fell to 15%. LVEF median values remained stable from baseline to the end of the study (60%). Conclusions: The combination of Myocet®, docetaxel and trastuzumab is safe and shows promising activity as first-line treatment of HER-2-positive MBC.

AB - Aim: To assess the activity and safety of non-pegylated liposomal doxorubicin (Myocet®) in combination with docetaxel and trastuzumab as first-line treatment of patients with HER-2/neu-positive metastatic breast cancer (MBC). Patients and methods: The maximum tolerated dose of the combination was defined in the phase I part of the study. In the phase II part, 45 HER-2/neu-positive MBC patients were enrolled to receive 6-8 cycles of Myocet® 50 mg/m 2 (day 1), docetaxel 30 mg/m 2 (days 2 and 9) plus trastuzumab (day 2, 4 mg/kg followed by 2 mg/kg/week) every 21 d until unacceptable toxicity or progression occurred. Objective response (primary end-point) and treatment tolerability were assessed according to World Health Organisation criteria. Cardiotoxicity was defined as signs and/or symptoms of congestive heart failure and/or a decrease in left ventricular ejection fraction (LVEF). Results: The overall response rate was 55.6% (complete response 8.9%, partial response 46.7%), with a median time-to-progression of 10.9 months (C.I. 8.7-15.0). Median overall survival was not reached. The most frequent grade 3-4 adverse events were granulocytopaenia (60.0%), leukocytopenia (43.2%) and alopecia (35.6%). Grade 3-4 diarrhoea, pain, oral and skin toxicity (4.4%, each) and nausea/vomiting, thrombocytopenia and elevated alkaline phosphatase (2.2%, each) were also reported. In 2 patients LVEF fell to 15%. LVEF median values remained stable from baseline to the end of the study (60%). Conclusions: The combination of Myocet®, docetaxel and trastuzumab is safe and shows promising activity as first-line treatment of HER-2-positive MBC.

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