No abstract

Six months of induction chemotherapy with FOLFOXIRI is associated with a clinically significant improvement in the long-term outcome compared with FOLFIRI with an absolute benefit in survival at 5 years of 7%.

Purpose: AZD2014 is a novel, oral, m-TORC 1/2 inhibitor that has shown in vitro and in vivo efficacy across a range of preclinical human cancer models.Experimental Design: A rolling six-dose escalation was performed to define an MTD (part A), and at MTD a further cohort of patients was treated to further characterize toxicities and perform pre-and posttreatment biopsies (part B). AZD2014 was administered orally twice a day continuously. Flow cytometry, ELISA, and immunohistochemistry were used to quantify pharmacodynamic biomarkers. Pharmacokinetic analysis was carried out by mass spectrometry.Results: A total of 56 patients were treated across a dose range of 25 to 100 mg. The MTD was 50 mg twice daily. The dose-limiting toxicities were fatigue and mucositis. At the MTD, the most common adverse events (AE) were fatigue (78%), nausea (51%), and mucositis (49%), but these were equal to or greater than grade 3 in only 5% of patients. Drug levels achieved at the MTD (AUC ss 6686 ngÁh/mL, C max ss 1,664 ng/mL) were consistent with activity in preclinical models. A reduction in p-S6 levels and Ki67 staining was observed in 8 of 8 and 5 of 9 evaluable paired biopsy samples. Partial responses were seen in a patient with pancreatic cancer and a patient with breast cancer, who were found to have a PDGFR and ERBB2 mutation, respectively.Conclusions: The recommended phase II dose for further evaluation of AZD2014 is 50 mg twice daily, and at this dose it has been possible to demonstrate pharmacologically relevant plasma concentrations, target inhibition in tumor, and clinical responses.

Small cell lung cancer (SCLC) is a significant health problem worldwide because of its high propensity for relapse. This review discusses existing and future therapies for the treatment of SCLC.

BACKGROUNDTo better inform clinical practice, this study was aimed at capturing patients' motivations for enrolling in phase 1 trials and at quantifying their expectations of the benefits, risks, and commitment associated with clinical trials and the impact of the initial consultation on their expectations.METHODSThis was a single‐center, prospective, quantitative study of newly referred adult patients considering their first phase 1 oncology trial. Participants completed questionnaires before they were seen and an abbreviated follow‐up version after their consultation.RESULTSQuestionnaires were completed by 396 (99%) and 301 (76%) before and after the clinic, respectively. Participants ranked the possibility of tumor shrinkage (84%) as the most important motivation for considering a phase 1 trial; this was followed by no alternative treatments (56%), their physician's recommendation (44%), and the fact that the research might benefit others (38%). When they were asked about the potential personal benefit, 43% predicted tumor shrinkage initially. After the consultation, this increased to 47%. Fourteen percent of patients expected a cure. When asked about risks, 71% of the participants expected moderate side effects. When asked about expectations of time commitments, a majority of patients did not anticipate weekly visits, although this was understood by 93% of patients after the consultation. Overall, patients were keen to consider trials and when asked before and after the consultation 72% and 84% were willing to enroll in studies, respectively.CONCLUSIONSThis study reports that more than 80% of patients enroll in early‐phase clinical oncology trials motivated by the potential of a clinical benefit, with approximately half expecting tumor shrinkage and approximately a tenth anticipating a cure. The typical phase 1 response rate is 4% to 20%, and this discrepancy exemplifies the challenges faced by patients and healthcare professionals during their interactions for phase 1 studies. Cancer 2016;122:3501–3508. © 2016 American Cancer Society