Citations

Background: Although 50% to 90% of patients who receive epidermal growth factor receptor (EGFR) inhibitors develop a rash, options for rash prevention or palliation remain limited. This issue is particularly important from a palliative care standpoint because these agents are prescribed only to patients with incurable cancer. Here, we report (1) gene expression profiling of skin biopsies from patients with an EGFR inhibitor–induced rash and (2) a randomized, placebo-controlled feasibility trial with the antiandrogen, spironolactone. Both investigations were undertaken to begin to explore the hypothesis that androgens mediate EGFR inhibitor–induced rash and that antiandrogens palliate it. Methods/Results: First, 4 skin biopsies from patients with EGFR inhibitor–induced rash (3 men and 1 woman) were subject to gene expression microarray profiling. A public data set of normal skin gene expression (Gene Expression Omnibus, GSE22998) served as a reference. Sixty percent of commonly interrogated androgen receptor genes (207 of 308 between the 2 data sets) were differentially expressed ( P < .05) in the rash samples. Second, in a 17-patient double-blinded, placebo-controlled trial with topical spironolactone applied to the face, although the primary feasibility end point was not achieved, patients in the spironolactone arm received more doses of EGFR inhibitor, and anecdotal photographic evidence suggested salutatory effects of spironolactone on rash. Conclusions: Epidermal growth factor receptor inhibitor–induced rash appears to be androgen-mediated; antiandrogen therapy merits further study for rash prevention/palliation.

Abstract Background Patients dismissed from the hospital on oral or intravenous antibiotics frequently need follow-up appointments with the Division of Infectious Diseases (ID). Follow-up appointments may be inappropriately scheduled with respect to timing and indication. Suboptimal transitions of care may lead to increased no-shows and ultimately poor patient outcomes. Methods The baseline sample included 102 patients seen by the inpatient ID services at Mayo Clinic’s Rochester Methodist and Saint Mary’s Hospitals between January 1, 2017 and June 30, 2017. Defects in transitions of care were categorized as those pertaining to sign-off templates, sign-off labels, follow-up priority, and timing. The current transfer of care system from our institution is outlined in Figure 1. Results Out of 102 patients, 75 (74%) had at least one defect identified. Root cause analysis revealed multiple factors contributing to this performance gap (Figure 2). Patients often have variable health literacy and social or financial difficulties. There are often multiple ID providers with inadequate time to properly orchestrate follow-up. There are undefined checkpoints and triaging in the department’s scheduling policies. Interventions involved reformatting the ID sign-off template and clarifying the roles of providers in the transitions-of-care process. Analysis after 6 months of implementation revealed improvement of communication among teams, decline in improper sign off by 13% and decrease in antibiotic prescription errors by 2%. Conclusion This study demonstrates that well-designed sign-off templates can help with effective communication of the final treatment plan among providers and possibly improve patient outcomes. The target goal is to reduce the number of improper sign-offs by 50% within 1 year. Disclosures All authors: No reported disclosures.

Objectives: Preclinical studies demonstrated antitumor activity of dovitinib in pancreatic cancer models. This phase Ib study aimed to determine the maximum tolerated dose (MTD) of dovitinib in combination with gemcitabine and capecitabine and to characterize the safety and pharmacokinetic profile in patients with advanced pancreatic and biliary tract cancers and solid malignancies. Materials and Methods: Patients received gemcitabine 1000 mg/m² intravenously on days 1 and 8, capecitabine 1300 mg/m² oral daily from day 1 to 14, and dovitinib oral daily 5 days on and 2 days off, every 21-day cycle. The standard 3+3 dose escalation design was utilized and the study expanded to treat an additional 20 advanced pancreatic and biliary tract cancers patients at MTD. Results: A total of 29 patients were enrolled. One patient experienced dose-limiting grade 3 colitis. Two patients developed clinically significant neuropathy after the first cycle requiring dose reduction. The MTD was not reached and dovitinib 300 mg was declared the recommended dose for expansion. The most frequent grade 2 or worse adverse events were fatigue (45%), neutropenia (41%), thrombocytopenia (34%), anemia (24%), nausea (24%), and palmer-plantar erythrodysaesthesia syndrome (21%). Partial responses were observed in 5 patients. Pharmacokinetic studies showed no drug-drug interaction between dovitinib, capecitabine and gemcitabine. Fibroblast growth factor 23 plasma level increased in 4 of 5 patients during the first cycle of treatment. Conclusions: Dovitinib 300 mg daily is the recommended dose when combined with gemcitabine and capecitabine, achieving clinically relevant plasma concentrations. The study combination demonstrated encouraging efficacy signals in advanced pancreatic cancer.

Endoscopic ultrasound (EUS)-guided pancreatic cyst ablation with alcohol lavage or paclitaxel-based regimens are investigative modalities. To evaluate the safety and efficacy of EUS-guided pancreatic cyst ablation with alcohol lavage or paclitaxel-based regimens. A systematic review of computerized bibliographic databases was carried out for studies of EUS-guided pancreatic cyst ablation with alcohol lavage or paclitaxel-based regimens from January 1980 to February 2018. EUS-guided cyst ablation-related outcomes (cyst resolution) and complications. Data were extracted from six studies (N=207 patients) for EUS-guided cyst ablation with alcohol lavage and eight studies (N=347 patients) for EUS-guided cyst ablation with paclitaxel-based regimens. The pooled proportion of patients with complete cyst resolution was 68/207 (32.8%) for EUS-guided cyst ablation with alcohol lavage and 221/347 (63.6%) for EUS-guided cyst ablation with paclitaxel. Postablation adverse events with EUS-guided ablation with alcohol lavage were 44/207 (21.7%), and those with EUS-guided ablation with paclitaxel-based regimens were 52/347 (15%). Limitations of this study are because of the variability in study design and regimens tested, paucity of randomized trials, and differences in pancreatic cyst types receiving treatment. EUS-guided cyst ablation appears to be effective and safe. The effect on pancreatic cancer incidence is unknown; EUS-guided pancreatic cyst ablation modalities require further improvement and validation to determine their role in the treatment of patients with pancreatic cystic lesions.