Trastuzumab and Vinorelbine as First-Line Therapy for HER2-Overexpressing Metastatic Breast Cancer: Multicenter Phase II Trial With Clinical Outcomes, Analysis of Serum Tumor Markers as Predictive Factors, and Cardiac Surveillance Algorithm

2003 ◽  
Vol 21 (15) ◽  
pp. 2889-2895 ◽  
Author(s):  
Harold J. Burstein ◽  
Lyndsay N. Harris ◽  
P. Kelly Marcom ◽  
Rosemary Lambert-Falls ◽  
Kathleen Havlin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Ejection Fraction ◽  
Tumor Markers ◽  
Phase Ii ◽  
Response Rate ◽  
Metastatic Breast ◽  
First Line ◽  
Her2 Positive ◽  
Multicenter Phase

Purpose: Trastuzumab-based therapy improves survival for women with human epidermal growth factor receptor 2 (HER2)–positive advanced breast cancer. We conducted a multicenter phase II study to evaluate the efficacy and safety of trastuzumab combined with vinorelbine, and to assess cardiac surveillance algorithms and tumor markers as prognostic tools. Patients and Methods: Patients with HER2-positive (immunohistochemistry [IHC] 3+-positive or fluorescence in situ hybridization [FISH]-positive) metastatic breast cancer received first-line chemotherapy with trastuzumab and vinorelbine to determine response rate. Eligibility criteria were measurable disease and baseline ejection fraction ≥ 50%. Serial testing for HER2 extracellular domain (ECD) was performed. Results: Fifty-four women from 17 participating centers were entered onto the study. The overall response rate was 68% (95% confidence interval, 54% to 80%). Response rates were not affected by method of HER2 status determination (FISH v IHC) or by prior adjuvant chemotherapy. Median time to treatment failure was 5.6 months; 38% of patients were progression free after 1 year. Concurrent therapy was quite feasible with maintained dose-intensity. Patients received both chemotherapy and trastuzumab on 90% of scheduled treatment dates. Two patients experienced cardiotoxicity in excess of grade 1; one patient experienced symptomatic heart failure. A surveillance algorithm of screening left ventricular ejection fraction (LVEF) at 16 weeks successfully identified women at risk for experiencing cardiotoxicity. Other acute and chronic side effects were tolerable. Lack of decline in HER2 ECD during cycle 1 predicted tumor progression. Conclusion: Trastuzumab and vinorelbine constitute effective and well-tolerated first-line treatment for HER2-positive metastatic breast cancer. Patients with normal LVEF can be observed with surveillance of LVEF at 16 weeks to identify those at risk for cardiotoxicity.

Randomized Phase II Trial of First-Line Trastuzumab Plus Docetaxel and Capecitabine Compared With Trastuzumab Plus Docetaxel inHER2-Positive Metastatic Breast Cancer

2010 ◽  
Vol 28 (6) ◽  
pp. 976-983 ◽  
Author(s):  
Andrew M. Wardley ◽  
Xavier Pivot ◽  
Flavia Morales-Vasquez ◽  
Luis M. Zetina ◽  
Maria de Fátima Dias Gaui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Her2 Positive ◽  
Grade 3

PurposeTo evaluate trastuzumab (H) and docetaxel (T) with or without capecitabine (X) as first-line combination therapy for human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer.Patients and MethodsPatients with HER2-positive locally advanced or metastatic breast cancer were randomly assigned to H (8 mg/kg loading; 6 mg/kg every 3 weeks) plus T (75 mg/m2in HTX arm, 100 mg/m2in HT arm, every 3 weeks) with or without X (950 mg/m2twice per day on days 1 to 14 every 3 weeks). The primary end point was overall response rate (ORR).ResultsIn 222 patients, median follow-up was approximately 24 months. ORR was high with both regimens (70.5% with HTX; 72.7% with HT; P = .717); complete response rate was 23.2% with HTX compared with 16.4% with HT. HTX demonstrated significantly longer progression-free survival: median 17.9 months compared with 12.8 months with HT (hazard ratio, 0.72; P = .045), which translates to a gain of around 5 months. Two-year survival probability was 75% with HTX compared with 66% with HT. Febrile neutropenia (27% v 15%) and grade 3/4 neutropenia (77% v 54%) incidences were higher with HT than HTX. Treatment-related grade 3 hand-foot syndrome (17% v < 1%) and grade 3/4 diarrhea (11% v 4%) occurred more commonly with HTX than HT. One case of congestive heart failure occurred in each arm.ConclusionHTX is an effective and feasible first-line therapy for HER2-positive locally advanced or metastatic breast cancer, although it should be reserved for patients with good performance status who are not receiving long-term steroids.

Phase II Trial of Oral Tegafur and Folinic Acid with Mitoxantrone as First-Line Regimen in Patients with Metastatic Breast Cancer

1996 ◽  
Vol 82 (1) ◽  
pp. 61-64 ◽  
Author(s):  
Vicente Alonso ◽  
Carmen Santander ◽  
Jesús Florián ◽  
Martina Alonso ◽  
Ma Dolores Isla ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Folinic Acid ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Metastatic Breast ◽  
Biochemical Modulation ◽  
Outpatient Basis ◽  
First Line

Background Tegafur acts as a deport form of 5-fluorouracil when administered orally for longs periods of time, since it is an active drug in metastatic breast cancer, with response rates of 29-44%. Biochemical modulation with folinic acid and the addition of mitoxantrone could increase the efficacy of tegafur in patients with metastatic breast cancer. Methods A prospective phase II trial in patients with previously untreated metastatic breast cancer was carried out. The scheme consisted of mitoxantrone, 12 mg/m2 intravenous day 1, oral tegafur, 750 mg/m2/day divided in three equal doses, and leucovorin 15 mg/8 h orally for days 1-21, given in a 4-week schedule. None patient had received chemotherapy for metastatic breast cancer, although 16 patients had received previous adjuvant chemotherapy. Results Thirty-four patients were included. Objective responses were achieved in 20 of 32 patients assessable for response, with 1 complete response and 19 partial responses. The objective response rate was 62.5% (95% confidence intervals, 48-76%). The median duration of response was 10 months. Grade III-IV toxicity according to WHO criteria was digestive (nausea/vomiting) in 12.5%, diarrhea in 25% and stomatitis in 25% of patients. Other toxicities were low. Eight patients required dose-reduction. Conclusions We achieved a significant response rate with the scheme, which was administered on an outpatient basis. It seems to be safe and effective as first-line treatment in metastatic breast cancer, with a short median response duration. The size of the trial does not permit definitive conclusions, and the role of biochemical modulation of tegafur in combination with mitoxantrone remains to be defined.

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