The Background Behind The RhoC Triumph

Yip10,11 1Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, Australia, 2Macarthur Cancer Therapy Centre, Campbelltown Hospital, Campbelltown, Australia, 3NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia, 4Cancer Care Centre, St George Hospital, Kogarah, Australia, 5Cancer Therapy Centre, Liverpool Hospital, Liverpool, Australia, 6West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom, 7Department of Surgery, Bankstown Hospital, Bankstown, Australia, 8South Western Sydney Clinical School, Faculty of Medicine, Sydney, Australia, 9Wolfson Wohl Cancer Research Centre, University of Glasgow, Scotland, United Kingdom, 10Department of Medical Oncology, Canberra Hospital, Canberra, Australia, 11ANU Medical School, Australian National University, Canberra, Australia Background:?Combination regimens like G?+?nab-paclitaxel and FOLFIRINOX have recently shown a survival benefit in advanced PC, but these are costly to patients. Galunisertib price There are many trials exploring the effects of GCs over G alone and we have performed a meta-analysis to better inform clinicians about the potential benefit of GCs. Methods:?Randomised clinical trials (RCTs) in patients with advanced PC where GCs were compared with G alone as first-line chemotherapy, were identified by systematically searching databases (MEDLINE, EMBASE, CENTRAL) and conference abstracts from January 1996 �C December 2013. Experimental arms containing chemotherapeutic RhoC agents, biological agents or immune therapies were included. The primary outcome was overall survival (OS), secondary outcomes were progression free survival (PFS), response rates (RR), adverse events (AE) and quality of life (QOL). Hazard ratios (HR), confidence intervals (CI) and p-values were extracted, and pooled HRs were determined using Revman 5.2 software. Subgroup analyses were performed according to treatment type. Results:?Thirty-eight RCTs with 11 896 patients were identified (23 phase III, 15 phase II), 38 with OS data, 29 with PFS data. Overall, GCs improved OS (HR 0.91 [0.87-0.95] p?=?0.0001) and PFS (HR 0.85 [0.80-0.90] p?Z VAD FMK heterogeneity (OS: I2?=?25%, p?=?0.07; PFS: I2?=?46%, p?=?0.003). Pooled HRs (OS) for classes of GCs showed: G?+?topoisomerase inhibitors (HR 1.0 [0.88-1.13] p?=?0.99), G?+?platinums (HR 0.93 [0.84-1.03] p?=?0.16), G?+?taxanes (HR 0.81 [0.66-1.01] p?=?0.06), G?+?fluoropyrimidines (HR 0.84 [0.76-0.92] p?=?0.0003) and G?+?biological agents (HR 0.96 [0.91-1.03] p?=?0.25). Increased toxicity was seen with GCs in 31/37 RCTs. Conclusions:?GCs offer a small benefit over G alone at the cost of increased toxicity in unselected patients. GCs may represent a treatment option for selected patients with advanced PC. P. Hersey1, A. Ribas2, F. S. Hodi3, R. Kefford4, O. Hamid5, A. Daud6, J. D. Wolchok7, W.-J. Hwu8, T. C. Gangadhar9, A. Patnaik10, A. M. Joshua11, J. Weber12, R. Dronca13, H. Zarour14, K.