Cancer chemotherapy and pharmacology
-
Cancer Chemother. Pharmacol. · Mar 2010
Safety, tolerability, and pharmacokinetics of the anti-IGF-1R monoclonal antibody figitumumab in patients with refractory adrenocortical carcinoma.
Insulin-like growth factor 1 receptor signaling through upregulation of the stimulatory ligand IGF-II has been implicated in the pathogenesis of adrenocortical carcinoma. As there is a paucity of effective therapies, this dose expansion cohort of a phase 1 study was undertaken to determine the safety, tolerability, pharmacokinetics, and effects on endocrine markers of figitumumab in patients with adrenocortical carcinoma. ⋯ The side effect profile and pharmacokinetics of figitumumab were similar in patients with adrenocortical carcinoma in comparison to patients with other solid tumors. While hyperglycemia was the most common adverse event, no clear patterns predicting severity were observed. The majority of patients receiving protocol therapy with single agent figitumumab experienced stability of disease, warranting further evaluation.
-
Cancer Chemother. Pharmacol. · Mar 2010
Multicenter StudyPhase II study of oral vinorelbine in combination with capecitabine as second line chemotherapy in metastatic breast cancer patients previously treated with anthracyclines and taxanes.
Effective treatment options for patients with metastatic breast cancer (MBC) resistant/refractory to anthracyclines and/or taxanes are limited. Intravenous and oral combination of vinorelbine (VRL) and capecitabine were shown to be feasible and effective in first-line MBC. In order to evaluate the activity of the combination of an all oral regimen in a more advanced setting, we investigated a regimen combining oral VRL and capecitabine in a phase II study as second-line chemotherapy of MBC patients previously treated with anthracyclines and taxanes. ⋯ In second-line treatment of MBC patients previously treated with anthracyclines and taxanes, oral VRL plus capecitabine is a safe regimen with an efficacy comparable to the other available combination regimens used in this heavily and resistant/refractory (75% of patients) pre-treated patients' population. Moreover, this well-tolerated combination offers the advantages of an all oral regimen.
-
Cancer Chemother. Pharmacol. · Mar 2010
Case ReportsSuccessful rechallenge with erlotinib in a patient with EGFR-mutant lung adenocarcinoma who developed gefitinib-related interstitial lung disease.
Small-molecule tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) pathways are used clinically for patients with non-small cell lung cancer (NSCLC). It is well established that somatic mutations in the kinase domain of the EGFR (Lynch et al. in N Engl J Med 350:2129-2139, 2004; Paez et al. in Science 304:1497-1500, 2004) are strongly associated with the tumor response and clinical outcomes in patients with NSCLC receiving EGFR-TKIs (Mitsudomi and Yatabe in Cancer Sci 98:1817-1824, 2007). ⋯ The precise mechanism underlying the development of drug-related ILD remains unknown. Here, we describe a case of EGFR-mutant NSCLC who was rechallenged with the small-molecule EGFR antagonist erlotinib after developing gefitinib-related ILD.
-
Approximately 20-30% of breast cancer tumors overexpress or amplify human epidermal growth factor receptor 2 (HER2). The role of this receptor in the progression of HER2+ breast cancer and resistance to certain anticancer monotherapies was investigated. The results of several pre-clinical and clinical trials, with the aim of determining the most safe and effective course of treatment for HER2+ breast cancer, were also thoroughly examined. ⋯ While the development and approval of the HER2-targeted recombinant monoclonal antibody trastuzumab (Herceptin) has been efficacious in slowing HER2 cancer progression, combining this and other anti-HER2 therapy with either chemotherapy or endocrine therapy has proven more effective in improving overall and progression free survival.