Lani
03-26-2006, 07:20 PM
A multicenter phase II study of epirubicin with low-dose trastuzumab as a first line treatment in Her2 overexpressing metastatic breast cancer: preliminary results
Citation: European Journal of Cancer Supplements Volume 4, No. 2, March 2006, page 165
M. Zilli1, M. De Tursi1, C. Carella1, E. Ricevuto2, P. Marchetti2, A. Gennari3, C. Orlandini3, A. Frassoldati4, P. Conte4, S. Iacobelli1
1Medical Oncology, ``G. D'Annunzio'' University, Chieti, Italy
2Medical Oncology, University of L'Aquila, L'Aquila, Italy
3Medical Oncology, University of Pisa, Pisa, Italy
4Medical Oncology, University of Modena and Reggio Emilia, Modena, Italy
Aims: To evaluate the activity and cardiac safety of the combination of epirubicin (E) with low-dose trastuzumab (LD-H) in patients with HER-2 overexpressing metatatic breast cancer.
Patients and Methods: This was a two step study: In the first step, H was given at a loading dose of 2 mg/kg on day 1, followed by 1 mg/kg weekly; in the second step (?12 objective responses/21 patients), the dose of H was mainatined to 1 mg/kg weekly. E was administered at 90 mg/m2 on day 1 every 3 weeks. After 6–8 courses of this combination, H was administered as a single agent for a maximum of 52 weeks. To assess cardiotoxicity, pts were evaluated for the Left Ventricular Ejection Fraction (LVEF) at baseline, every two cycles during E and LD-H, and every three months during LD-H alone. Either ultrasonography or angioscintigraphy were used. Cardiotoxicity was defined as the appearance of signs or symptoms of congestive heart failure in?10% of patients at an E dose of 720 mg/m2 or in ?20% of patients at an E dose > 720 < 1000 mg/m2.
Results: Twenty-one pts entered the first step: median age was 55 years (41–70 years), hormonal status was positive in 9 pts and negative in 10. Eight pts had received prior adjuvant anthracyclines, and 8 pts prior endocrine therapy. The majority of pts had > 2 organ sites of involvement with visceral lung metastases predominating. A median of 6 cycles (range 1–18) was administered with 134 cycles evaluable for toxicity. The regimen was well tolerated, with grade 3/4 neutropenia, alopecia, and thrombocytopenia occurring in 55%, 25% and 10% of the pts, respectively. Six episodes of cardiotoxicity were observed (an asymptomatic decrease in LVEF ?15% in 4 pts and an asymptomatic decline of LVEF at ? 50% in 2 pts). At the time of analysis, 12 (57%) pts achieved a partial response, 6 (%) had stable disease, and 3 (%) had progressive disease. The median time to progression was 9.8 months (C.I.95%: 5. 5–14.1) and the median overall survival was not reached.
Conclusions: These preliminary results show that the combination of E plus LD-H possesses good antitumor activity, with limited cardiotoxicity. The Protocol Committee recommended to enter the second step of the study, maintaining the dose of H at 1 mg/kg weekly. Accrual is continuing; an update will be presented at the meeting.
Citation: European Journal of Cancer Supplements Volume 4, No. 2, March 2006, page 165
M. Zilli1, M. De Tursi1, C. Carella1, E. Ricevuto2, P. Marchetti2, A. Gennari3, C. Orlandini3, A. Frassoldati4, P. Conte4, S. Iacobelli1
1Medical Oncology, ``G. D'Annunzio'' University, Chieti, Italy
2Medical Oncology, University of L'Aquila, L'Aquila, Italy
3Medical Oncology, University of Pisa, Pisa, Italy
4Medical Oncology, University of Modena and Reggio Emilia, Modena, Italy
Aims: To evaluate the activity and cardiac safety of the combination of epirubicin (E) with low-dose trastuzumab (LD-H) in patients with HER-2 overexpressing metatatic breast cancer.
Patients and Methods: This was a two step study: In the first step, H was given at a loading dose of 2 mg/kg on day 1, followed by 1 mg/kg weekly; in the second step (?12 objective responses/21 patients), the dose of H was mainatined to 1 mg/kg weekly. E was administered at 90 mg/m2 on day 1 every 3 weeks. After 6–8 courses of this combination, H was administered as a single agent for a maximum of 52 weeks. To assess cardiotoxicity, pts were evaluated for the Left Ventricular Ejection Fraction (LVEF) at baseline, every two cycles during E and LD-H, and every three months during LD-H alone. Either ultrasonography or angioscintigraphy were used. Cardiotoxicity was defined as the appearance of signs or symptoms of congestive heart failure in?10% of patients at an E dose of 720 mg/m2 or in ?20% of patients at an E dose > 720 < 1000 mg/m2.
Results: Twenty-one pts entered the first step: median age was 55 years (41–70 years), hormonal status was positive in 9 pts and negative in 10. Eight pts had received prior adjuvant anthracyclines, and 8 pts prior endocrine therapy. The majority of pts had > 2 organ sites of involvement with visceral lung metastases predominating. A median of 6 cycles (range 1–18) was administered with 134 cycles evaluable for toxicity. The regimen was well tolerated, with grade 3/4 neutropenia, alopecia, and thrombocytopenia occurring in 55%, 25% and 10% of the pts, respectively. Six episodes of cardiotoxicity were observed (an asymptomatic decrease in LVEF ?15% in 4 pts and an asymptomatic decline of LVEF at ? 50% in 2 pts). At the time of analysis, 12 (57%) pts achieved a partial response, 6 (%) had stable disease, and 3 (%) had progressive disease. The median time to progression was 9.8 months (C.I.95%: 5. 5–14.1) and the median overall survival was not reached.
Conclusions: These preliminary results show that the combination of E plus LD-H possesses good antitumor activity, with limited cardiotoxicity. The Protocol Committee recommended to enter the second step of the study, maintaining the dose of H at 1 mg/kg weekly. Accrual is continuing; an update will be presented at the meeting.