Phase II Trial of Cediranib in Combination With Cisplatin and Pemetrexed in Chemotherapy-Naïve Patients With Unresectable Malignant Pleural Mesothelioma (SWOG S0905).

PurposeAntiangiogenic agents combined with chemotherapy have efficacy in the treatment of unresectable malignant pleural mesothelioma (MPM). Cediranib (AstraZeneca, Cheshire, United Kingdom), a vascular endothelial growth factor receptor and platelet-derived growth factor receptor inhibitor, demonstrated therapeutic potential in a prior phase I trial. We evaluated a phase II trial for efficacy.Patients and methodsSWOG S0905 (ClinicalTrials.gov identifier: NCT01064648) randomly assigned cediranib or placebo with platinum-pemetrexed for six cycles followed by maintenance cediranib or placebo in unresectable chemotherapy-naïve patients with MPM of any histologic subtype. Primary end point was Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 progression-free survival (PFS). Secondary end points included overall survival, PFS by modified RECIST v1.1, response (modified RECIST and RECIST v1.1), disease control, and safety/toxicity. The trial was designed to detect a difference in RECIST v1.1 PFS at the one-sided 0.1 level using a stratified log-rank test.ResultsNinety-two eligible patients were enrolled (75% epithelioid and 25% biphasic or sarcomatoid). The cediranib arm had more grade 3 and 4 diarrhea, dehydration, hypertension, and weight loss. Cediranib improved PFS by RECIST v1.1 (hazard ratio, 0.71; 80% CI, 0.54 to 0.95; P = .062; 7.2 months v 5.6 months) and increased modified RECIST v1.1 response (50% v 20%; P = .006). By modified RECIST v1.1, cediranib numerically increased PFS (hazard ratio, 0.77; 80% CI, 0.59 to 1.02; P = .12; median, 6.9 months v 5.6 months). No significant difference in overall survival was observed.ConclusionThe addition of cediranib to platinum-pemetrexed improved PFS by RECIST v1.1 and response rate by modified RECIST in patients with unresectable MPM. Whereas adding antiangiogenics to chemotherapy has been a successful strategy for some patients, the cediranib toxicity profile and small incremental survival benefit precludes additional development in MPM

The Political Development of the American Farm Bureau Federation Leading to its Stand on the Wheat Referendum of 01/01/1963 : Factors Influencing the 01/01/1963 Wheat Referendum Vote in Ellis County, Kansas

An attempt has been made in this study to present a concise history of the political development of the American Farm Bureau Federation and to show how economic conditions of the time influenced its formation. Furthermore, a summary of the political development of the AFBF’s policies that led to the Federation\u27s stand against the Wheat Certificate Plan in the 1963 Wheat Referendum is emphasized. Although much of the credit and blame for the defeat of the Wheat Certificate plan has been accredited to the AFBF, it was the purpose of this study to ascertain to what extent the AFBF influenced the outcome of the Wheat Referendum of 1963 in Ellis County, Kansas. This research also considered several other factors which may have influenced the balloting on the county level. While the investigation concerned only one county in Kansas, the results of the questionnaire study could be applied to a certain degree on the state and national levels to better understand the results of the referendum vote in 1963

New directions for evaluation

Publ. comme no 93, spring 2002 de la revue New directions for evaluationBibliogr. à la fin des textesIndex: p. 121-12