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Open Access Publications from the University of California

Scholarly Works (2 results)

  • Article
Recent Work (2006)

In 2006, two urban universities started a new 6-week, residential program designed to provide a pipeline of qualified disadvantaged students to medical or dental school. Using both qualitative and quantitative techniques, this paper describes an iterative self-study process in which discrepancies in perceptions on program objectives held by students and faculty were detected. Analysis of interviews and a focus group with faculty resulted in eight program objectives. Faculty and students rank-ordered seven of these according to importance using pair-wise comparisons. Although they agreed that “skill building” was the most important program objective, students and faculty differed significantly on others. Some of these differences were attributed to inadequate communication about the program.

    Cover page: Starting a new pipeline program for health sciences: do faculty and students value the same objectives?
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2017)

    Background

    Activation of the mitogen-activated protein kinase pathway is important for growth of pediatric low-grade gliomas (LGGs). The aim of this study was to determine the recommended phase II dose (RP2D) and the dose-limiting toxicities (DLTs) of the MEK inhibitor selumetinib in children with progressive LGG.

    Methods

    Selumetinib was administered orally starting at 33 mg/m2/dose b.i.d., using the modified continual reassessment method. Pharmacokinetic analysis was performed during the first course. BRAF aberrations in tumor tissue were determined by real-time polymerase chain reaction and fluorescence in situ hybridization.

    Results

    Thirty-eight eligible subjects were enrolled. Dose levels 1 and 2 (33 and 43 mg/m2/dose b.i.d.) were excessively toxic. DLTs included grade 3 elevated amylase/lipase (n = 1), headache (n = 1), mucositis (n = 2), and grades 2-3 rash (n = 6). At dose level 0 (25 mg/m2/dose b.i.d, the RP2D), only 3 of 24 subjects experienced DLTs (elevated amylase/lipase, rash, and mucositis). At the R2PD, the median (range) area under the curve (AUC0-∞) and apparent oral clearance of selumetinib were 3855 ng*h/mL (1780 to 7250 ng × h/mL) and 6.5 L × h-1 × m-2 (3.4 to 14.0 L × h-1 × m-2), respectively. Thirteen of 19 tumors had BRAF abnormalities. Among the 5 (20%) of 25 subjects with sustained partial responses, all at the RP2D, 4 had BRAF aberrations, 1 had insufficient tissue. Subjects received a median of 13 cycles (range: 1-26). Fourteen (37%) completed all protocol treatment (26 cycles [n = 13], 13 cycles [n = 1]) with at least stable disease; 2-year progression-free survival at the RP2D was 69 ± SE 9.8%.

    Conclusion

    Selumetinib has promising antitumor activity in children with LGG. Rash and mucositis were the most common DLTs.
      Cover page: A phase I trial of the MEK inhibitor selumetinib (AZD6244) in pediatric patients with recurrent or refractory low-grade glioma: a Pediatric Brain Tumor Consortium (PBTC) study.
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