Docetaxel Combined With Trastuzumab Is an Active Regimen in HER-2 3+ Overexpressing and Fluorescent In Situ Hybridization–Positive Metastatic Breast Cancer: A Multi-Institutional Phase II Trial

Tedesco, Karen L.; Thor, Ann D.; Johnson, David H.; Shyr, Yu; Blum, K. A.; Goldstein, Lori J.; Gradishar, William J.; Nicholson, Brenda P.; Merkel, Douglas E.; Murrey, D.; Edgerton, Susan M.; Sledge, George W.

doi:10.1200/jco.2004.10.046

Cited by 100 publications

(47 citation statements)

References 25 publications

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“…On the contrary, weekly docetaxel in combination with trastuzumab seems to be more toxic, with two independent studies reporting that approximately one quarter of cases were withdrawn because of severe toxicity [28,29].…”

Section: Discussionmentioning

confidence: 99%

Randomized Phase II Trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer

Gasparini

Gion²,

Mariani³

et al. 2006

Breast Cancer Res Treat

129

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Background A randomized Phase II study evaluated the activity of weekly paclitaxel versus its combination with trastuzumab for treatment of patients with advanced breast cancer overexpressing HER-2. Patients and methods Among 124 patients randomized, 123 are assessable for toxicity and 118 for response. Patients received weekly paclitaxel single agent (80 mg/m 2 ) or combined with trastuzumab (4 mg/kg loading dose, then weekly 2 mg/kg). HER-2 overexpression was determined by immunohistochemistry (IHC). Patients with 2+/3+ IHC scores were eligible. IHC was compared with HER-2 serum extracellular domain (ECD). Results Patient characteristics were similar in the two arms. Both treatments were feasible and well tolerated with no grade 4 hematologic toxicity. No patient developed cardiac toxicity. The combined treatment was statistically significant superior for overall response rate (ORR) (75% vs. 56.9%; P = 0.037), particularly in the subset of IHC 3+ patients (84.5% vs. 47.5%; P = 0.00050). A statistically significant better median time to progression was seen in the subgroup with IHC 3+ (369 vs. 272 days; P = 0.030) and visceral disease (301 vs. 183 days; P = 0.0080) treated with combination. Multivariable analysis of predictive factors showed that only IHC score retained statistically significant value for ORR (P = 0.0035). Conclusion Weekly paclitaxel plus trastuzumab is highly active and safe and it is superior to paclitaxel alone in patients with IHC score of 3+.

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Section: Discussionmentioning

confidence: 99%

Randomized Phase II Trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer

Gasparini

Gion²,

Mariani³

et al. 2006

Breast Cancer Res Treat

129

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“…In particular, several phase II studies of trastuzumab in combination with docetaxel, as first-or as second-line treatment for patients with HER2 -overexpressing MBC, have been reported with RR ranging from 45 to 72% (Burris, 2001;Esteva et al, 2002;Montemurro et al, 2004;Tedesco et al, 2004). More recently, the results of a randomised phase II trial evaluating the activity and the efficacy of trastuzumab plus docetaxel in the first-line treatment of HER2 -overexpressing MBC patients have been reported (Marty et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Phase II study of gefitinib in combination with docetaxel as first-line therapy in metastatic breast cancer

Ciardiello¹,

Troiani²,

Caputo³

et al. 2006

Br J Cancer

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We have evaluated the activity and safety of gefitinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in combination with docetaxel as first-line treatment of women with metastatic breast cancer (MBC). In total, 41 patients with MBC were enrolled in a first-line combination therapy study with oral gefitinib (250 mg day À1 ) and intravenous docetaxel (75 mg m À2, the first 14 patients; or 100 mg m À2 , the following 27 patients, on day 1 of a 3-week cycle). Out of 41 patients, 38 received at least one cycle of therapy. There were no differences in activity or tolerability between the two docetaxel doses. G3/4 toxicities were neutropenia (49%), diarrhoea (10%), acne-like rash (5%), and anaemia (2%). Complete plus partial responses (CR þ PR) were observed in 22 out of 41 patients with a 54% response rate (95% confidence interval (CI) 45 -75%). The 22 patients that achieved a response following six cycles of docetaxel plus gefitinib continued gefitinib monotherapy (median duration, 24 weeks; range, 2 -108 þ weeks). Two patients with PR following combination therapy achieved a CR during gefitinib monotherapy. Complete plus partial responses correlated with oestrogen receptor (ER) status, since they occurred in 19 out of 27 (70%) patients with ER-positive tumours as compared to three out of 14 (21%) patients with ER-negative tumours (P ¼ 0.01).

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“…In previously treated patients with MBC, other phase II studies have demonstrated response rates of 11 to 15% with trastuzumab as a monotherapy (6,7) and 24 to 65% for combinations of trastuzumab with platinum salts (8), taxanes (10,13,14,24), vinorelbine (25,26), or a triplet of trastuzumab with taxanes and platinum salts (27). Preliminary analysis of a randomized study of trastuzumab and paclitaxel vs the same regimen in combination with carboplatin demonstrated an improvement in time to progression with the triplet association The optimal trastuzumab-based chemotherapy regimen has not been identified, even though there is a trend favoring weekly schedules of cytotoxic agents compared to standard dosages given every 3-4 weeks (32).…”

Section: Discussionmentioning

confidence: 99%

“…This led to the development of alternative trastuzumab-based combinations for HER-2/neu-positive MBC. Several studies have assessed the antitumoral activity and tolerability of the trastuzumab and taxanes combination, an active first-line therapy for this setting of patients (10)(11)(12)(13)(14). However, when first-line chemotherapy fails, non-crossresistant treatments with minimal toxic effects that could be easily administered on an outpatient basis are warranted.…”

Section: Introductionmentioning

confidence: 99%

Trastuzumab in combination with gemcitabine and vinorelbine as second-line therapy for HER-2/neu overexpressing metastatic breast cancer

Morabito,

Longo,

Gattuso

et al. 2006

Oncol Rep

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Abstract. The aim of this study was to evaluate the safety and efficacy of combined treatment with trastuzumab (T), gemcitabine (gem) and vinorelbine (vin) as second-line therapy for HER-2 overexpressing metastatic breast cancer, pretreated with anthracyclines and/or taxanes and/or trastuzumab. Eligible patients had HER-2/neu-positive disease (IHC 2+ or 3+), performance status (PS) ≤2 and normal L-VEF. Patients were treated with weekly T (4 mg/kg on day 0, then 2 mg/kg), in combination with gem (800 mg/m 2 ) and vin (25 mg/m 2 ) on days 1 and 8, every 21 days. Patients were restaged every 3 cycles. A total of 30 patients (median age, 58 years; range, 41-74) were enrolled in the study. Fifteen patients were HER-2 3+ and 26 (86.7%) presented ≥2 metastatic sites. Of the patients, 7 (23.3%) had received trastuzumab as first-line therapy. Treatment was welltolerated with grade 4 neutropenia in 6 patients, grade 3 thrombocytopenia and grade 3 anemia in 1 patient, and grade 3 asthenia in 4 patients. Fifteen patients obtained an objective response (response rate, 50%; C.I. 95%, range, 31.3-68.7%). Among the patients with HER-2/neu 3+, the response rate was 73.3%. Noteworthy were 4 objective responses observed in patients with brain metastasis. Also, 7 patients had stable disease (23.3%). Median progression-free survival was 7 months (range 5-10), and median overall survival was 15 months (range 5-33). T-gem-vin is a safe and active regimen in this subgroup of patients with poor prognosis, and the efficacy of such a schedule was particularly satisfactory in patients with HercepTest 3+.

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Docetaxel Combined With Trastuzumab Is an Active Regimen in HER-2 3+ Overexpressing and Fluorescent In Situ Hybridization–Positive Metastatic Breast Cancer: A Multi-Institutional Phase II Trial

Abstract: Trastuzumab plus docetaxel is an active and well-tolerated regimen in women with HER-2 3+ overexpressing or FISH-positive metastatic breast cancer.

Cited by 100 publications

References 25 publications

Randomized Phase II Trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer

Randomized Phase II Trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer

Phase II study of gefitinib in combination with docetaxel as first-line therapy in metastatic breast cancer

Trastuzumab in combination with gemcitabine and vinorelbine as second-line therapy for HER-2/neu overexpressing metastatic breast cancer

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