A phase 1 trial of Vorinostat in combination with concurrent chemoradiation therapy in the treatment of advanced staged head and neck squamous cell carcinoma.

Purpose Vorinostat is a potent HDAC inhibitor that sensitizes head and neck squamous cell carcinoma (HNSCC) to cytotoxic therapy while sparing normal epithelium. The primary objective of this Phase I study was to determine the maximally tolerated dose (MTD) and safety of Vorinostat in combination with standard chemoradiation therapy treatment in HNSCC. Patients and Methods Eligible patients had pathologically confirmed Stage III, IVa, IVb HNSCC, that was unresectable or borderline resectable involving the larynx, hypopharynx, nasopharynx, and oropharynx. Vorinostat was administered at the assigned dosage level (100-400 mg, three times weekly) in a standard 3 + 3 dose escalation design. Vorinostat therapy began 1 week prior to initiation of standard, concurrent chemoradiation therapy and continued during the entire course of therapy. Results Twenty six patients met eligibility criteria and completed the entire protocol. The primary tumor sites included tonsil (12), base of tongue (9), posterior pharyngeal wall (1), larynx (4) and hypopharynx (3). Of the 26 patients, 17 were HPV-positive and 9 were HPV-negative. The MTD of Vorinostat was 300 mg administered every other day. Anemia (n = 23/26) and leukopenia (n = 20/26) were the most commonly identified toxicities. The most common Grade3/4 events included leukopenia (n = 11) and lymphopenia (n = 17). No patient had Grade IV mucositis, dermatitis or xerostomia. The median follow time was 33.8 months (range 1.6-82.9 months). Twenty four of 26 (96.2%) patients had a complete response to therapy. Conclusion Vorinostat in combination with concurrent chemoradiation therapy is a safe and highly effective treatment regimen in HNSCC. There was a high rate of complete response to therapy with toxicity rates comparable, if not favorable to existing therapies. Further investigation in Phase II and III trials is strongly recommended.

Interprofessional provider attitudes toward the initiation of epidural analgesia in the laboring patient: are we all on the same page?

BACKGROUND: The timing of initiation of neuraxial labor analgesia should ultimately depend on patient preference although obstetricians, anesthesiologists and nurses may influence decision-making. We hypothesized that provider groups would have similar attitudes toward the timing of epidural placement, but some identifiable differences could be used to improve understanding and communication among providers. METHODS: Anesthesiologists, nurses and obstetricians completed a survey assessing their knowledge and attitudes on the timing of epidural placement in specified clinical circumstances. RESULTS: Anesthesiologists (100%) and nurses (86.2%) reported being more familiar with epidural management than obstetricians (43.3%, P <0.01). The willingness of providers to advocate epidural placement based on the magnitude of cervical dilation was similar, although at 10 cm dilatation obstetricians (73.3%) were significantly more likely to advocate neuraxial block compared to both nurses (27.6%, P <0.01) and anesthesiologists (36.7%, P <0.01). The impact of patient factors and clinical circumstances on the timing of neuraxial block placement showed significant differences among provider groups in five of 24 areas assessed, including patient desire for an epidural, primigravid patients without membrane rupture, oxytocin infusion initiated, labor epidural in a previous pregnancy, and a difficult airway. CONCLUSIONS: There were differences between providers in factors that may impact the timing of epidural placement and in their self-perceived familiarity with epidural management. These present an opportunity for furthering interprofessional education and collaboration.