Sunitinib malate in previously untreated, nonsquamous, non-small cell lung cancer patients over the age of 70 years: Results of a Phase II trial

Abstract

51 % male, 95 % white, median age 78 years (range, 70-88), 73 % ECOG=1, 97 % Stage IV, 83 % adenocarcinoma, 44 % prior surgery, 19 % prior radiation. With a median of 2 cycles (range, 1-16), DCR=63 %, OR=7 % (0 CR, 4 PR). Median follow-up=5.8 months (all; 15.9 months survivors), median PFS =3.0 months (range, <1-25.1), median TTP=4.5 months (range, <1-25.1), and 1-year survival=26.4 % [95 % CI: 15.9, 38.2]. QOL declined initially, but improved over time. TREATMENT-related adverse events included: fatigue (48.3 %); diarrhea (38.3 %); thrombocytopenia (33.3 %), anorexia (26.7 %), mucositis (25.0 %); nausea (25.0 %), dysgeusia (20.0 %), and neutropenia (20.0 %). Conclusions The study met its primary endpoint. S produced acceptable DCR and QOL improved; however, OR was disappointing (7 %) and toxicity was greater than expected. A biomarker to identify patients more likely to benefit from S is needed.

Congestive heart failure risk in cancer patients treated with vascular endothelial growth factor tyrosine kinase inhibitors: a systematic review and meta‐analysis of 36 clinical trials

“…According to the inclusion criteria of each trial, patients were required to have adequate hepatic, renal and haematological function. Underlying malignancies included renal cell cancer (12 trials), breast cancer (six trials), sarcoma (four trials), thyroid cancer (three trials), gastro‐intestinal stromal tumour (GIST) (two trials), primitive neuroectodermal tumour (PNET) (one trial), hepatocellular carcinoma (one trial), pancreatic cancer (one trial), cervical cancer (one trial), colorectal cancer (one trial) , gastric cancer (one trial), prostate cancer (one trial), non‐small cell lung cancer (NSCLC) (one trial) and advanced neuroendocrine tumours (one trial). The most commonly reported adverse event meeting our criteria was LVEF decline (16 studies), with congestive failure in 12 studies and LV dysfunction in eight studies.…”

Identification of Kinase Inhibitor Targets in the Lung Cancer Microenvironment by Chemical and Phosphoproteomics

“…(23) Importantly, like dasatinib, sunitinib is in advanced clinical development for NSCLC. (7, 24, 25) For both drugs, we have recently described the design, synthesis and validation of close structural analogues suitable for chemical proteomics (c-dasatinib and c-sunitinib, Figure 1B). These drugs retain activity for the primary kinase targets c-ABL and PDGFRα, respectively, as well as for a plethora of other validated targets.…”

Effects of local irradiation combined with sunitinib on early remodeling, mitochondria, and oxidative stress in the rat heart

“…Because of its broad targeting, sunitinib is an effective anti-cancer agent, but it also carries a possibility of side effects that may result from inhibition of off-target kinases. Sunitinib is currently in use for the treatment of several solid tumors, including gastrointestinal stromal tumors, and is tested in clinical trials for breast cancer and non–small cell lung cancer [9;10;13]. Since the cardiotoxic effects of sunitinib have been studied in previous animal models [22–24] that may provide results for comparison, we selected sunitinib as our model TKI.…”