Purpose/Objective(s): A combined chemotherapy regimen of cisplatin/5- flourouracil (FU) is considered as standard care and routinely used for patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN) with dose of 80/800 (cisplatin 80 mg/m 2 on day 1 in 4-week cycles, and 5-FU 800 mg/m 2 /24 h by continuous intra- venous infusion on days 1 to 5) in Japan, whereas cisplatin/5-FU 100/1000 is widely used globally. This is the first report to evaluate the feasibility of cisplatin/5-FU 100/1000 in a subgroup analysis of Japanese patients in SPECTRUM trial, a randomized, 2 arms, open label, global phase 3 study, and targeted patients with R/M SCCHN. Materials/Methods: We prospectively evaluated the feasibility of cisplatin/5-FU 100/1000 in Japanese patients enrolled in SPECTRUM trial of panitumumab 9 mg/kg combined with cisplatin/5-FU 100/1000 (Arm 1) versus cisplatin/5-FU 100/1000 alone (Arm 2) continued treatment for a maximum of 6 cycles. Results: 20 Japanese patients were enrolled and received treatment (Arm 1, nZ13; Arm 2, nZ7). Grade 3/4 adverse events included neutropenia, hypomagnesemia, stomatitis, hyponatremia, paronychia, febrile neu- tropenia, decreased appetite, and hypokalemia. Notably, the overall inci- dence of serious treatment-emergent AEs in Japanese patients (Arm 1, 38%; Arm 2, 29%) was lower than in the SPECTRUM population (Arm 1, 48%; Arm 2, 43%), and there were no treatment-related deaths among Japanese patients. Median overall survival (OS) was not estimable in Arm 1 (4 patients had died) and was 15.4 months in Arm 2. Median progres- sion-free survival (PFS) was 6.9 months in Arm 1 and 5.7 months in Arm 2. The median number of infusions (cycles) of cisplatin was 5 in Arm 1 and 4 in Arm 2; the median number of infusions (cycles) of 5-FU was 6 in both arms. The mean administered dose for cisplatin was 93.6 mg/m 2 in Arm 1 and 97.2 mg/m 2 in Arm 2, and 3732.6 mg/m 2 and 3880.6 mg /m 2 in Arm 1 and Arm 2, respectively, for 5-FU. Conclusions: This analysis reports the feasibility of cisplatin/5-FU 100/ 1000 in a subgroup analysis of Japanese patients in the SPECTRUM trial. There were no new safety signals in Japanese patients versus the total population in SPECTRUM. The nature of these events and their severity was consistent with those expected for an anti-EGFR agent panitumumab in combination with cisplatin/5-FU. These results suggest the regimen has mostly acceptable toxicity in Japanese patients. Although the number of Japanese patients in SPECTRUM was limited, OS and PFS with cisplatin/ 5-FU 100/1000 were longer than those in the SPECTRUM population, suggesting that the treatment was not associated with unacceptable toxicity. These findings demonstrate the feasibility of including SCCHN patients from Japan in international clinical trials investigating use of cisplatin/5-FU 100/1000. Author Disclosure: M. Tahara: F. Honoraria; Merck Serono Co.,Ltd., Bristol-Myers Squibb Co.,Ltd. J. Funding Other; Eisai Co.,Ltd., Boeh- ringer Ingelheim Co., Ltd., Yakult Honsya Co.,Ltd. Y. Onozawa: None. H. Fujii: None. N. Monden: None. I. Yana: A. Employee; Takeda Bio Development Center Ltd. S. Otani: A. Employee; Takeda Bio Develop- ment Center Ltd. Y. Hasegawa: None. 104 Activity of Temsirolimus Added to Cetuximab in Patients With Cetuximab-Resistant, Recurrent/Metastatic Head-and-Neck Cancer: Results of the Randomized Phase 2 Maestro-HN Study Molecular Biology and Therapeutics T.Y. Seiwert, 1 D. Adkins, 2 F. Worden, 3 J.L. Wade, 4 S. Hu, 5 K. Price, 6 J. Zavala, 1 Y. Lussier, 7 E.E. Vokes, 1 and E.E.W. Cohen 1 ; 1 University of Chicago, Chicago, IL, 2 Washington University, St. Louis, MO, 3 University of Michigan, Ann Arbor, MI, 4 Decatur Memorial Hospital, Decatur, IL, 5 Mercy Hospital, St. Louis, MO, 6 Mayo Clinic, Rochester, MN, 7 University of Illinois at Chicago, Chicago, IL Purpose/Objective(s): Patients with head and neck squamous cell car- cinoma (HNC) progressing on EGFR-targeted therapy have a poor prog- nosis with a median PFS of only 1.8 months (deSouza, CCR 2012). Using bioinformatics and preclinical modeling, we hypothesized synergy be- tween mTOR and EGFR inhibition. Materials/Methods: Patients with recurrent/metastatic (R/M) HNC and documented progression on a cetuximab-based treatment were eligible and were randomized to temsirolimus (T) iv 25mg weekly with or without cetuximab (C) (400/250 mg/m 2 ). Response Rate (RR) was assessed by RECIST. Other endpoints included progression-free Survival (PFS), overall Survival (OS), and toxicity. A sample size of 80 patients provided 89% power to detect a PFS increase from 2 to 4 months. Results: 80 patients were enrolled and started treatment across 13 clinical sites as part of the University of Chicago and Mayo Clinic Phase 2 net- works. Median age was 63 years with 49 male and 9 female patients. 60 patients are currently evaluable for response: Five confirmed partial re- sponses were observed exclusively on the TC arm (5/30; RRZ16.7%) while no confirmed responses were observed on T alone (0/30; RRZ0%) (one-sided PZ0.026). All responders on the TC arm had response or prolonged SD to cetuximab prior to entering study. Median duration of response to TC was 5.7 months (range 4-11). Median PFS was 3.5 months (TC) versus 3.2 months (T) (logerank, one-sided PZ0.097). Treatment was tolerable with the most common toxicities being fatigue, skin and hematologic toxicities. Conclusions: Temsirolimus added to cetuximab in cetuximab-refractory patients induces responses in 16.7% of subjects suggesting that PI3K- AKT-mTOR activation represents an acquired mechanism of resistance to EGFR inhibition that can be overcome by combination therapy. Combi- nation therapy with temsirolimus and cetuximab is well tolerated. Current investigation is focused on defining molecular parameters that define this patient subset. Author Disclosure: T.Y. Seiwert: E. Research Grant; Genentech/Roche. F. Honoraria; Boehringer Ingelheim. D. Adkins: None. F. Worden: None. J.L. Wade: None. S. Hu: None. K. Price: None. J. Zavala: None. Y. Lussier: None. E.E. Vokes: None. E.E.W. Cohen: None. 108 Reassessing Locus-Specific DNA Methylation in Head-and-Neck Squamous Cell Carcinoma (HNSCC) With Quantitative Methodology and Correlation With Patient Outcome Molecular Biology and Therapeutics A.M. Lim, 1 I.L.M. Candiloro, 1 N. Wong, 2 M. Collins, 1 H. Do, 1,2 C. Angel, 1 J. Corry, 1 D. Rischin, 1 B. Solomon, 1 and A. Dobrovic 1,2 ; 1 Peter MacCallum Cancer Centre, East Melbourne, Australia, 2 Ludwig Institute of Cancer Research, Austin Hospital, Heidelberg, Australia Purpose/Objective(s): DNA promoter hypermethylation is reported to be a frequent event and a putative prognostic marker in HNSCC that is most commonly evaluated with non-quantitative methylation-specific PCR (MSP). We sought to validate reported hypermethylated genes in a single HNSCC subsite with quantitative methodology and correlate these results with patient outcome. Materials/Methods: Methylation status in bisulfite modified DNA from 115 oral tongue squamous cell carcinoma (OTSCC) samples was assessed by methylation-specific high resolution melting (MS-HRM), sensitive- melting after real time MSP (SMART-MSP) and bisulfite pyrosequencing. Significant levels of methylation were defined as quantities above 10%. Results: In contrast to much of the literature, either no or infrequent locus- specific methylation was identified by MS-HRM for DAPK1, RASSF1A, MGMT , MLH1, APC, CDH1, CDH13, BRCA1, ERCC1, ATM, RUNX3 and ABO. Assessment by SMART-MSP of DAPK1 and RASSF1A loci confirmed insignificant levels of methylation on quantification (median 0.0015% for DAPK1, 0% for RASSF1A). Gel electrophoresis of SMART- MSP products produced bands for both insignificant levels of methylation and false positives, indicating a major cause for overestimation of methylation events with the use of non-quantitative methodology. Patient tumors with hypermethylation of RUNX3 (18/108) and ABO (22/107) detected by MS-HRM, had significantly worse survival (5-year OS: 32% versus 57%, pZ0.01, and 32% versus 57%, pZ0.03; respectively). However, when heterogeneous methylation was quantified with pyrose- quencing, only patients with RUNX3 hypermethylated tumors retained a statistically significantly worse outcome (4 year OS 22% vs 61%, International Journal of Radiation Oncology  Biology  Physics 510