Faculty Bibliography

INTRODUCTION: The phosphotidylinositol-3 kinase/serine-threonine kinase (AKT)/mammalian target of rapamycin signaling pathway is frequently altered in non-small-cell lung cancer (NSCLC). PX-866 is an oral, irreversible, pan-isoform inhibitor of phosphotidylinositol-3 kinase. Preclinical models revealed synergy with docetaxel and a phase 1 trial demonstrated tolerability of this combination. This randomized phase 2 study evaluated PX-866 combined with docetaxel in patients with advanced, refractory NSCLC. METHODS: Patients with locally advanced, recurrent, or metastatic NSCLC who had received at least one and no more than two prior systemic treatment regimens were randomized (1:1) to a combination of docetaxel (75 mg/m intravenous every 21 days) with or without PX-866 (8 mg orally daily; arms A and B, respectively). The primary end point was progression-free survival (PFS). Secondary end points included objective response rate, overall survival (OS), toxicity, and correlation of biomarker analyses with efficacy outcomes. RESULTS: A total of 95 patients were enrolled. Median PFS was 2 months in arm A and 2.9 months in arm B (p = 0.65). Objective response rates were 6% and 0% in arms A and B, respectively (p = 0.4). There was no difference in OS between the two arms (7.0 versus 9.2 months; p = 0.9). Grade 3 or higher adverse events were infrequent, but more common in the combination arm with respect to diarrhea (7% versus 2%), nausea (4% versus 0%), and vomiting (7% versus 0%). PIK3CA mutations or PTEN loss were infrequently observed. CONCLUSION: The addition of PX-866 to docetaxel did not improve PFS, response rate, or OS in patients with advanced, refractory NSCLC without molecular preselection.

Cancer-associated retinopathy (CAR) is a rare autoimmune condition associated with various cancers, causing significant visual impairment. Visual symptoms in CAR may or may not correlate with the extent of systemic disease or its response to chemotherapy, and must be addressed separately from the management of systemic malignancy. Steroids have been the mainstay of CAR therapy. Various immunomodulatory therapies have also been described with varying responses, but the overall visual prognosis remains poor. Rituximab is a monoclonal antibody used in the treatment of non-Hodgkin's B-cell lymphoma and many autoimmune disorders. This case report describes a patient with small cell uterine cancer who initially presented with visual impairment associated with CAR. The patient's deteriorating visual symptoms were successfully halted for an extended, clinically meaningful period with rituximab.

PURPOSE: Cancer drug shortages have increased considerably over the past 5 years, but quantitative analyses of the scope and effects are limited. We assessed the effects of drug shortages on outpatient medication use in a single New York City university hospital. METHODS: We examined pharmacy records for drug shortages, as defined by the American Society of Health-System Pharmacists. We assessed outpatient records for all patients with cancer treated with infusional antineoplastic medications from April 2010 to September 2010 and April 2011 to September 2011. RESULTS: Twelve medications were in shortage in 2010 and 22 in 2011. Drugs in shortage were used for 170 patients (50.8%) in 2010 and 241 patients (63.6%) in 2011 (P < .001). Of 235 patients treated in August-September 2011, there were 23(9.8%) documented therapy changes due to shortages, compared with zero changes in August-September 2010 (P < .001). Among patients treated in August-September 2010, 24 (11.4%) received paclitaxel and 19 (9.0%) received docetaxel. Among patients treated in August-September 2011, 11 (4.7%) received paclitaxel and 38 (16.2%) received docetaxel, a 69% decrease for paclitaxel and 80% increase for docetaxel from 1 year prior (P = .009, and P = .024, respectively). The estimated cost of a single treatment with paclitaxel for one patient with body-surface area 1.75 was $47.59 versus $858.39 for docetaxel, a 1,704% increase. Surveyed physicians frequently reported lower level evidence (30.4%) and increased risk of toxicity (34.8%) with alternative therapy in drug shortage cases. CONCLUSION: Oncology drug shortages affected the majority of patients in our center and increased at an alarming rate. Drug shortages have substantial economic costs and mandate treatment changes that may affect efficacy and toxicity.