A Phase II Randomized Study of Cisplatin-Pemetrexed plus either Enzastaurin or Placebo in Chemonaive Patients with Advanced Non-Small Cell Lung Cancer.
Summary of "A Phase II Randomized Study of Cisplatin-Pemetrexed plus either Enzastaurin or Placebo in Chemonaive Patients with Advanced Non-Small Cell Lung Cancer."
Objectives: Enzastaurin is a serine/threonine kinase inhibitor that targets protein kinase C and AKT pathways. Enzastaurin and pemetrexed demonstrated synergy in preclinical studies. This trial was designed to evaluate the safety and efficacy of first-line enzastaurin plus cisplatin-pemetrexed in advanced non-small cell lung cancer (NSCLC). Methods: A safety lead-in phase (n = 13) of enzastaurin 125 or 250 mg twice daily was added to cisplatin-pemetrexed. A subsequent randomized, placebo-controlled phase II study (n = 22) of the combination was conducted to evaluate efficacy. Results: The combination was well tolerated and showed activity, with 7 (53.8%, 95% CI 26.7-80.9) confirmed partial responses and 2 stable diseases in 13 treated patients in the lead-in phase. However, the study was terminated early based on interim results from two phase II NSCLC studies of enzastaurin plus cytotoxic chemotherapy, which indicated no efficacy improvement. Conclusions: Enzastaurin and cisplatin-pemetrexed is tolerable with preliminary activity in patients with advanced NSCLC, but because of a lack of efficacy improvement in other phase II NSCLC studies, the study was terminated early.
University Hospital Gasthuisberg, Leuven, Belgium.
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Medical and Biotech [MESH] Definitions
An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.
The interval between two successive CELL DIVISIONS during which the CHROMOSOMES are not individually distinguishable. It is composed of the G phases (G1 PHASE; G0 PHASE; G2 PHASE) and S PHASE (when DNA replication occurs).
Metabolic Detoxication, Phase I
Functionalization of exogenous substances to prepare them for conjugation in PHASE II DETOXIFICATION. Phase I enzymes include CYTOCHROME P450 enzymes and some OXIDOREDUCTASES. Excess induction of phase I over phase II detoxification leads to higher levels of FREE RADICALS that can induce CANCER and other cell damage. Induction or antagonism of phase I detoxication is the basis of a number of DRUG INTERACTIONS.
The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.
Clinical Trial, Phase Iii
Work that is a report of a pre-planned, usually controlled, clinical study of the safety and efficacy of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques after phase II trials. A large enough group of patients is studied and closely monitored by physicians for adverse response to long-term exposure, over a period of about three years in either the United States or a foreign country.
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