Addition of receptor tyrosine kinase inhibitor to radiation increases tumour control in an orthotopic murine model of breast cancer metastasis in bone

2008 ◽  
Vol 44 (16) ◽  
pp. 2506-2517 ◽  
Author(s):  
Pawel Zwolak ◽  
Piotr Jasinski ◽  
Kaoru Terai ◽  
Nathan J. Gallus ◽  
Marna E. Ericson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Receptor Tyrosine Kinase ◽  
Murine Model ◽  
Cancer Metastasis ◽  
Kinase Inhibitor ◽  
Breast Cancer Metastasis ◽  
Receptor Tyrosine Kinase Inhibitor ◽  
Tumour Control

Neratinib, an Irreversible ErbB Receptor Tyrosine Kinase Inhibitor, in Patients With Advanced ErbB2-Positive Breast Cancer

2010 ◽  
Vol 28 (8) ◽  
pp. 1301-1307 ◽  
Author(s):  
Harold J. Burstein ◽  
Yan Sun ◽  
Luc Y. Dirix ◽  
Zefei Jiang ◽  
Robert Paridaens ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Receptor Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Erbb Receptor ◽  
Receptor Tyrosine Kinase Inhibitor ◽  
Trastuzumab Treatment ◽  
Erbb Receptor Tyrosine Kinase ◽  
Positive Breast Cancer

Purpose Neratinib is an oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor. The efficacy and safety of neratinib were evaluated in two cohorts of patients with advanced ErbB2-positive breast cancer—those with and those without prior trastuzumab treatment—in an open-label, multicenter, phase II trial. Patients and Methods Patients in the two cohorts (prior trastuzumab, n = 66; no prior trastuzumab, n = 70) received oral neratinib 240 mg once daily. The primary end point was the 16-week progression-free survival (PFS) rate for the evaluable population (prior trastuzumab, n = 63; no prior trastuzumab, n = 64), as assessed by independent review. Results The 16-week PFS rates were 59% for patients with prior trastuzumab treatment and 78% for patients with no prior trastuzumab treatment. Median PFS was 22.3 and 39.6 weeks, respectively. Objective response rates were 24% among patients with prior trastuzumab treatment and 56% in the trastuzumab-naïve cohort. The most common adverse events were diarrhea, nausea, vomiting, and fatigue. Diarrhea was the most frequent grades 3 to 4 adverse event, occurring in 30% of patients with prior trastuzumab treatment and in 13% of patients with no prior trastuzumab treatment, which prompted dose reductions in 29% and 4% of patients, respectively, but treatment discontinuation in only one patient. No neratinib-related, grades 3 or 4 cardiotoxicity was reported. Conclusion Oral neratinib showed substantial clinical activity and was reasonably well tolerated among both heavily pretreated and trastuzumab-naïve patients who had advanced, ErbB2-positive breast cancer. Diarrhea was the most common adverse effect but was manageable with antidiarrheal agents and dose modification.

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