In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 5545-5545
Abstract:
5545^ Background: The PI3K/mTOR/eIF4E pathway is upregulated in many HN cancers, and expression of eIF4E in surgical margins has been associated with increased risk of recurrence (Cancer Res 2007; 67:2160. Clin Cancer Res 2004; 10:5820. JCO 1999; 17:2909). Daily E + weekly CDDP was well tolerated in a phase I study for patients with advanced solid tumors (Cancer Chemother Pharmacol 2011 Sep 13; Epub ahead of print]. E achieves radiosensitization in pre-clinical models. This study evaluated weekly CDDP + daily E given concurrently with IMRT in HN cancer. Methods: This was a single institution phase I study with a standard 3 + 3 dose escalation plan. Patients (pts) received standard definitive IMRT (66 Gy resected tumors, 70 Gy unresected tumors) concurrent with CDDP 30 mg/m 2 weekly X 6 and daily oral E according to the dose escalation plan. Four dose levels (DLs) of daily oral E were planned: 2.5 mg, 5 mg, 7.5 mg, and 10 mg. Toxicities were recorded according to NCI CTCAE v.3. Results: Thirteen (9M, 4F) pts enrolled, with median age 52y (range, 37 – 65y) and median KPS 90 (range, 80-100). Primary sites: oral cavity (4), salivary gland (4), oropharynx (2), nasopharynx (1), scalp (1), unknown primary (1). Stage: IVA (11), IVB (1), II (1). Prior treatment: surgery (10), chemotherapy (2). The most common ≥ G.3 treatment related AEs were mucositis (functional 62%, clinical 31%), oral pain (31%), and lymphopenia (31%). There were no DLTs among 3 patients at DL1 or the first 3 patients at DL2. Among 4 pts at DL3, there were 2 DLTs: grade 3 mucositis with failure to thrive, and grade 3 mucositis with hypoxia. Among 3 additional patients enrolled at DL2, there was one 1 DLT: grade 3 mucositis with inability to tolerate E. There were no treatment-related deaths. With a median follow-up of 8.9 months, 3 patients have experienced recurrent disease, one of whom has died of disease. Median PFS has not been reached. Tissue correlates in process. Conclusions: When administered with weekly CDDP (30 mg/m 2 ) and definitive IMRT for HN cancer, the phase II recommended dose of E is 5 mg/day.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.5545
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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