Csaky A.G.,Complutense University of Madrid |
Herran G.D.L.,Complutense University of Madrid |
Murcia M.C.,Pharma Mar
Chemical Society Reviews | Year: 2010
The conjugate addition reaction of carbon nucleophiles to electron-deficient olefins is one of the most reliable methods for selective C-C bond formation. However, the conjugate addition to the vinylogous electron-deficient dienes has been much less developed, as there is considerably more difficulty in controlling the regioselectivity of the addition to these extended conjugate systems due to the presence of three electrophilic sites, as well as the stereoselectivity. Although still underdeveloped, new approaches to tackle these challenges are beginning to emerge. Both transition-metal-catalyzed and organocatalytic approaches are currently being developed to cope with the main selectivity issues of this type of process: regioselectivity (1,2-, 1,4-, and 1,6-addition) and stereoselectivity (asymmetric formation of the new C-C bonds). In this tutorial review, we have surveyed representative examples to get an overview of the recent advances obtained in the scope of the conjugate addition reaction of carbon nucleophiles to electron-deficient dienes. © 2010 The Royal Society of Chemistry.
Pharma Mar | Date: 2015-08-18
Pharma Mar | Date: 2015-11-24
Baudin E.,Institute Gustave Roussy |
Droz J.P.,Center Leon Berard |
Paz-Ares L.,Hospital Universitario 12 Of Octubre |
Van Oosterom A.T.,UZ Gasthuisberg |
And 2 more authors.
American Journal of Clinical Oncology: Cancer Clinical Trials | Year: 2010
Objectives: To evaluate the antitumor response, time-to-event efficacy endpoints and toxicity of plitidepsin (Aplidin) 5 mg/m2 as a 3-hour intravenous (i.v.) infusion every 2 weeks in patients with unresectable advanced medullary thyroid carcinoma (MTC). Methods: Sixteen patients with MTC and disease progression or large tumor burden received plitidepsin. Tumor response and time-related parameters were evaluated according to Response Evaluation Criteria in Solid Tumors. Secondary efficacy endpoints were marker response (calcitonin and carcinoembryonic antigen), clinical benefit and quality of life. Safety was assessed using the National Cancer Institute Common Toxicity Criteria. Results: A total of 141 cycles (median, 9 per patient; range, 1-24) were administered. No complete responses or partial responses (PR) were found, and 12 patients had stable disease for >8 weeks. Median follow-up was 15.0 months. Median time to progression was 5.3 months. Median overall survival could not be calculated, but 86.7% and 66.0% of patients were alive at 6 and 12 months. Marker response included 1 unconfirmed PR and 2 stabilizations for calcitonin, and 1 unconfirmed PR and 4 stabilizations for calcitonin and carcinoembryonic antigen. One patient showed clinical benefit. Quality of life scores generally decreased during the study. Most treatment-related adverse events were mild or moderate. Grade 3 lymphopenia was the only severe hematological toxicity found (2 patients). Severe nonhematological toxicities were grade 3 creatine phosphokinase increase (2 patients, with no myalgia or muscular weakness) and transient grade 3 alanine aminotransferase increase (5 patients). Conclusions: Single-agent plitidepsin given as 3-hour i.v. infusions every 2 weeks was generally well tolerated but showed limited clinical activity in patients with unresectable advanced MTC. © 2010 by Lippincott Williams & Wilkins.
Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer: Outcomes in the partially platinum-sensitive (platinum-free interval 6-12 months) subpopulation of OVA-301 phase III randomized trial
Poveda A.,Valencian Institute of Oncology |
Vergote I.,University Hospital |
Tjulandin S.,Russian Cancer Research Center |
Kong B.,Shandong University |
And 12 more authors.
Annals of Oncology | Year: 2011
Background: OVA-301 is a large randomized trial that showed superiority of trabectedin plus pegylated liposomal doxorubicin (PLD) over PLD alone in relapsed ovarian cancer. The optimal management of patients with partially platinum-sensitive relapse [6-12 months platinum-free interval (PFI)] is unclear. Patients and methods: Within OVA-301, we therefore now report on the outcomes for the 214 cases in this subgroup. Results: Trabectedin/PLD resulted in a 35% risk reduction of disease progression (DP) or death [hazard ratio (HR) = 0.65, 95% confidence interval (CI), 0.45-0.92; P = 0.0152; median progression-free survival (PFS) 7.4 versus 5.5 months], and a significant 41% decrease in the risk of death (HR = 0.59; 95% CI, 0.43-0.82; P = 0.0015; median survival 23.0 versus 17.1 months). The safety of trabectedin/PLD in this subset mimicked that of the overall population. Similar proportions of patients received subsequent therapy in each arm (76% versus 77%), although patients in the trabectedin/PLD arm had a slightly lower proportion of further platinum (49% versus 55%). Importantly, patients in the trabectedin/PLD arm survived significantly longer after subsequent platinum (HR = 0.63; P = 0.0357; median 13.3 versus 9.8 months). Conclusion: This hypothesis-generating analysis demonstrates that superior benefits with trabectedin/PLD in terms of PFS and survival in the overall population appear particularly enhanced in patients with partially sensitive disease (PFI 6-12 months). © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology.