A phase I study of oral LY293111 given daily in combination with irinotecan in patients with solid tumours

Abstract

The recommended phase II dose of LY293111 is 600 mg orally BID in combination with irinotecan 250 mg/m(2) IV every 21-days. Gastrointestinal adverse effects were common but could be well managed.

The role of peroxisome proliferator-activated receptors in carcinogenesis and chemoprevention

“…In two phase II studies, troglitazone had no effect in either patients with breast cancer or colorectal cancer 176, 177 . Some clinical trials examining the effect of PPARγ ligands combined with other therapeutics revealed no effect for some studies 178, 179 , but positive results for patients with thyroid carcinoma and glioma 180–182 . It is also worth noting that a chromosomal translocation that fuses the paired box 8 gene ( PAX8 ) with the PPARG gene is found in some cases of thyroid cancer 183 .…”

Development and validation of a model that predicts early death among cancer patients participating in phase I clinical trials investigating cytotoxics

“…Nevertheless, we enter to a new era of phase 1 clinical trials investigating associations of cytotoxic agents plus molecular targeted therapies. In these new studies, the cytotoxic agents drive the toxicity profile and are the key-element that determines the dose-limiting toxicity and then maximal tolerated dose [28][29][30][31][32]. Phase I trials investigating cytotoxic drugs enroll vulnerable patients not amenable to forms of treatment with established efficacy.…”

Peroxisome Proliferator-Activated Receptor-γLigands Alter Breast Cancer Cell Motility through Modulation of the Plasminogen Activator System

“…One clinical trial in phasetwo investigated the effect of pioglitazone in conjunction with a COX-2 inhibitor in glioma patients and saw moderate results in patients with high-grade glioma, suggesting pioglitazone treatment may be beneficial to a subset of patients [48]. A phase-I trial of a non-TZD PPAR- γ agonist LY29311 studied maximum tolerated dose in a combination regimen in patients with advanced solid tumors and determined there was no limiting toxicity and no disease progression [49]. To date, these advances have not been realized with PPAR- γ agonists in contrast to their preventative benefits in diabetic patients.…”