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Metal complexes have played central roles in the initiation and propagation of many important polymerization reactions.1 Studies of the reactions of metal carbonyl cluster complexes with episulfides have shown sulfur transfer and alkene elimination to be the preferred reaction pathway (e.g., eq l).2 Although thiirane, C2H4S, is able to serve as a ligand through coordination of the sulfur atom,3 very little is known about the nature of the ring opening and eventual elimination of alkene in these reactions. The

Background:The objective of this study was to review the pharmacology, efficacy, and safety of palbociclib, a first-in-class cyclin-dependent kinase 4/6 inhibitor, for the management of advanced breast cancer (ABC).Methods:Pharmacokinetics and drug interactions associated with palbociclib are described. Recent clinical trial data are reviewed, including patient-reported outcomes and subgroup analyses.Results:Palbociclib is indicated in combination with an aromatase inhibitor as initial endocrine therapy (ET) or with fulvestrant for patients with disease progression following ET for hormone receptor positive, human epidermal growth factor receptor 2 negative ABC or metastatic breast cancer. Palbociclib inhibits cyclin-dependent kinases 4/6, resulting in a blockade of phosphorylation of the retinoblastoma protein, which hinders the activation of transcription factors involved in S-phase entry, thereby arresting cell cycle progression at G1 phase. The efficacy and safety of palbociclib in combination with ET was established in three randomized trials (PALOMA-1, -2, and -3); all studies met their primary endpoint of significantly prolonging investigator-assessed progression-free survival versus ET alone. Findings were similar in subgroup analyses of the three PALOMA studies. Palbociclib plus ET also maintained health-related quality of life (QoL) compared with ET alone in PALOMA-2 and -3. A long-term safety profile for palbociclib, up to 3 years, has been established. Neutropenia, the most common any-grade and grade 3 or higher adverse event associated with palbociclib, is consistent with the drug’s mechanism of action and can be effectively managed with dose interruption, dose reduction, or delay in starting treatment cycles.Conclusions:Palbociclib in combination with ET improved progression-free survival and QoL in patients with ABC, including in several patient subgroups.

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