Tuesday, March 03, 2009
Cancer Cell - Accelerated Metastasis after Short-Term Treatment with a Potent Inhibitor of Tumor Angiogenesis - Sunitinib/SU11248
definition: orthotopic = in the normal position
Accelerated Metastasis after Short-Term Treatment with a Potent Inhibitor of Tumor Angiogenesis
John M.L. Ebos,Christina R. Lee,William Cruz-Munoz,Georg A. Bjarnason,James G. Christensen and Robert S. Kerbel1
Molecular and Cellular Biology Research, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada
Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 2M9, Canada
Sunnybrook Odette Cancer Centre, Toronto, ON M5G 2M9, Canada
Pfizer Global Research and Development, La Jolla Labs, La Jolla, CA 92121, USA
Herein we report that the VEGFR/PDGFR kinase inhibitor sunitinib/SU11248 can accelerate metastatic tumor growth and decrease overall survival in mice receiving short-term therapy in various metastasis assays, including after intravenous injection of tumor cells or after removal of primary orthotopically grown tumors. Acceleration of metastasis was also observed in mice receiving sunitinib prior to intravenous implantation of tumor cells, suggesting possible metastatic conditioning in multiple organs. Similar findings with additional VEGF receptor tyrosine kinase inhibitors implicate a class-specific effect for such agents. Importantly, these observations of metastatic acceleration were in contrast to the demonstrable antitumor benefits obtained when the same human breast cancer cells, as well as mouse or human melanoma cells, were grown orthotopically as primary tumors and subjected to identical sunitinib treatments.
Epithelial ovarian cancer: Does the time interval between primary surgery and postoperative chemotherapy have any prognostic importance?
Worldwide, much effort is used every day to perform optimal surgery in the treatment of epithelial ovarian cancer. Treatment of ovarian cancer is a combination of surgery with optimal debulking followed by chemotherapy. However, the optimal timing of postoperative chemotherapy for ovarian cancer remains poorly defined. The literature is made up of seven studies performed in different ways and which have included varying prognostic factors. The general supposition is that the time interval (TI) does not have a prognostic influence but experimental studies have shown that it does affect the prognosis of the cancer. This commentary focuses on the importance of the TI between surgery and postoperative chemotherapy in this horrible disease.
At least 296 distinct processes are required for phase III trial activation: at least 239 working steps, 52 major decision points, 20 processing loops, and 11 stopping points. Of the 195 trials activated during the January 1, 2000, to December 31, 2007, study period, a sample of 167 (85.6%) was used for gathering timing data. Median calendar days from initial formal concept submission to CTEP to trial activation by a cooperative group was 602 days (interquartile range, 454 to 861 days). This time has not significantly changed over the past 8 years. There is a high variation in the time required to activate a clinical trial.