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e23064 Background: The current exploratory cross-sectional study was designed to better characterize survivorship issues among patients treated with radiation for head and neck cancer with regard to dental health, shoulder-neck dysfunction, and overall quality of life. Methods: Patients (n = 58) being seen for follow-up at a radiation oncology clinic at least one year beyond the end of treatment completed three survey questionnaires: the EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30), the EORTC Head and Neck module (EORTC QLQ-H&N35), and an original 18-item Dental Health and Shoulder Function questionnaire. The questionnaires were scored and univariate analyses were performed using the variables of age, radiation dosage, definitive radiation + neck dissection vs. definitive surgery + postoperative radiation, and chemotherapy. Results: Median follow-up was 2.5 years. Of patients surveyed, 35% reported having more problems with their general dental health as compared to before treatment and 38% reported having pain at night in the neck and shoulder; 79% of patients reported being counseled about their dental health prior to treatment while 31% reported being counseled about possible shoulder-neck dysfunction. Patients younger than 65, patients receiving higher doses of radiation, and patients undergoing definitive surgery + postoperative radiation reported a higher burden of functional and symptomatic issues. Conclusions: Patients treated with radiation for head and neck cancer face a number of survivorship issues, including problems with dental health and shoulder-neck dysfunction, and many do not feel that they are adequately counseled about these issues prior to treatment. Subsets of patients who may experience a higher burden of functional and symptomatic issues include patients younger than 65, patients receiving higher doses of radiation, and patients undergoing definitive surgery + postoperative radiation. Increasing pre-treatment counseling for all patients and placing a particular emphasis on supportive care for these subsets of patients may allow us to better support this growing population of cancer survivors.

9081 Background: Vismodegib (VISMO) (Erivedge) is a first-in-class Hedgehog pathway inhibitor (HPI) approved for advanced basal cell carcinoma (aBCC). In the ERIVANCE trial, VISMO-treated patients ...

2595 Background: Body surface area (BSA)-based dosing of FU results in up to 100-fold inter-individual PK variability. PK-guided FU compared to BSA-based dosing resulted in higher response rates and decreased rate of toxicities in two randomized clinical trials. A paucity of data exists on PK-guided FU dosing in the clinical setting. Methods: A total of 70 colorectal cancer (CRC) patients (pts) from 6 academic and community sites received mFOLFOX6 (FU 2,400 mg/m2over 46 h every 2 wks) +/- bevacizumab. Peripheral blood was obtained 2-44 h after start of FU infusion and AUCs were estimated using an immunoassay at Myriad Genetics. FU doses for cycles 2-4 (C2-4) were adjusted algorithmically to target an area under the concentration-time curve (AUC) of 20-25 mg*h/L. The primary outcome was the % of pts within target AUC by C4, with a secondary outcome of toxicity rates compared to historical data. Comparisons between cycles were made using generalized linear models, accounting for repeated observations within pt. Results: The % of pts within target AUC post C1 and C4 was 30% (17/57, 95%CI: 18-43%) and 46% (24/52, 95%CI: 32-61%), respectively (OR=2.16, p=0.05). For each subsequent cycle, the odds of a pt being within range increases by 28% (p=0.04) (Table). The median dose needed to achieve target AUC at C4 was 2,580 (range 1,920-3,484) mg/m2. The median AUC post C1 and C4 was 19 and 21 mg*h/L, respectively. Less grade 3/4 mucositis and diarrhea were seen compared to historical data (3 v 15% and 6 v 12%, respectively); however, no difference in grade 3/4 neutropenia was noted (27 v 33%). Nine pts were non-evaluable by protocol for PK analysis, largely due to sampling/processing errors. Conclusions: PK-guided FU resulted in a greater number of pts achieving the targeted AUC and fewer pts under-dosed at C4 compared to C1. Individualization of FU dosing in the front-line, community and academic, setting is achievable for the treatment of CRC; however, larger clinical trials are needed to define the clinical utility of PK-guided FU. Clinical trial information: NCT01164215. [Table: see text]

6042 Background: Appropriate use of oral antineoplastics (OA), especially those with a food-effect, is a challenge for patients and clinicians. Patient adherence is essential to optimize outcomes, minimize toxicity, minimize bias in clinical trials, and reduce health care costs. As the use of OA grows, due to the narrow therapeutic margin, it is critical to understand the barriers to patient adherence. The purpose of this study was to analyze cancer patients’ use of OAs and identify opportunities to improve patient adherence. Methods: We developed and tested a 30-question survey to address frequency and reasons for reducing/skipping doses; sources of information for OA use; perceived importance of food-drug effects, and ease of understanding directions on vial label. Surveys, consisting of Likert scale and multiple choice questions, were distributed to adult cancer patients on OAs at the UNC Cancer Hospital clinics. Results: Seventy-seven patients taking OAs with CML, RCC, breast cancer, and GI tumors completed the survey with a response rate of 97%. This was a well-educated population with 71% having completed some college; 54% female and 58% older than 50 years. Forty-three percent of patients taking drugs with a significant food-drug effect (sorafenib, pazopanib, lapatinib, imatinib, nilotinib, and capecitabine) did not think about the last time they ate before taking their OA and 23% did not know that their OA had a food-drug effect. In addition, 21% of patients indicated they intentionally skipped/cut back on their OAs and 38% of those did not inform their physician. Although 97% reported no difficulty reading instructions on drug vial, nearly 20% had some difficulty understanding the directions. Conclusions: There are three main barriers associated with appropriate use of OAs: confusion or misunderstanding about the timing of drug with food; reducing/stopping drug without informing MD; and difficulty understanding directions on the drug vial label. A multipronged integrated approach involving the pharmacist, physician and nurse is needed to optimize communication of directions for optimal OA use.

512 Background: mTOR is a controller of cellular growth and other processes that is activated by several oncogenic pathways in cancer. Everolimus is an oral inhibitor of mTOR activation. The mTOR inhibitor, temsirolimus, when combined with high dose 5FU, was limited by significant mucosal toxicity. Purpose: Phase I study to determine the maximum tolerated doses (MTD) and the safety of everolimus combined with 5FU/LV in patients with refractory solid tumors. Methods: Using a standard 3+3 design, starting doses were everolimus 15mg weekly, and q2 weekly 5FU 400mg/m2 bolus and 1800mg/m2 infusion (over 46 hours) and LV 400mg/m2. Daily dosing of everolimus was instituted during level 3 as data emerged about improved target inhibition and adverse event profile with daily dosing. Dose escalation to the maximum planned levels was achieved: everolimus 10mg daily, 5FU 400mg/m2 bolus and 2400mg/m2 infusion, and LV 400mg/m2. Dose limiting toxicities (DLT) were assessed in cycle 1 (4 weeks), defined as any grade 3/4 non-hematologic toxicity (except grade 3 skin rash, nausea and diarrhea), or complicated grade 3-4 heme toxicity. Tumors were measured every 8 weeks. Results: From 03/2008 and 11/2009, 21 patients were treated. Median age 58 (range 35-77), male/female 13/8, PS 0/1 10/11. One DLT was seen at dose level 1 (grade 3 hypersensitivity/angioedema); two at dose level 6 (grade 3 diarrhea, grade 3 hypophosphatemia). As such, dose level 5 is the MTD. Dose reductions were required in 4 patients for mouth sores (2), nasal sores (1), and grade 3 transaminitis (1). Responses are as follows: 11 stable disease and 8 progressive disease; 2 patients were not evaluable. Conclusions: MTD is everolimus 5mg daily, with q2 weekly 5FU 400mg/m2 bolus and 2400mg/m2 infusion and LV 400mg/m2. We are currently expanding the study to evaluate the addition of oxaliplatin and panitumumab to the 5-FU/LV and everolimus base. [Table: see text] [Table: see text]

9166 Background: Since February 2008, we have begun a Supportive Care Consult Service that uses a pharmacist/nurse model of care delivery. Requests are called in from all adult oncology clinics—Hem/Onc; Gyn Onc, Surg Onc, or Rad Onc to the nurse. The team then goes to the individual clinic where the consult is done by either the pharmacist or nurse, with physician backup. A separate half-day clinic was begun in April 2008 to address patients needing ongoing follow-up or complex patients that could not be dealt with as consults only. Methods: We carried out an analysis of the practice with an IRB-approved database using standard descriptive statistical methods. Results: In the first 18 months of the service, 89 new patients were seen. Overall there were 292 encounters, reflecting both new and return visits. Details of the encounters are shown in the Table. Demographics: M/F: 47%/53%; Age: >60 y.o.-45%; 44-59-34%

e13521 Background: Sorafenib had demonstrated single agent activity in non-small cell and small cell lung cancer. Methods: A non-comparative, two arm phase I trial escalating sorafenib in combination with fixed doses of CE or CbP was performed. A 3-patient cohort design was utilized to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT). Dose level 0 for all pts was a sorafenib dose of 200 mg po BID continuously. Pts on arm A received C (60 mg/m2) on day 1 and E 120 mg/m2 on days 1,2,3 every 3 weeks with escalating doses of sorafenib. On arm B, pts received treatment with Cb (AUC=6) and P 500 mg/m2 every 3 weeks with escalating doses of sorafenib. However, excessive toxicity was observed on arm B, therefore the trial was amended such that Cb dose was lowered to AUC=5 (arm C). DLT were assessed in the 1st cycle and defined as grade (gr.) 4 anemia or thrombocytopenia, gr. 4 neutropenia lasting > 7 days, gr. ≥ 3 non-hematologic toxicity (except nausea, vomiting, and alopecia) and > 2 week dose delay. Response was assessed every 2 cycles according to RECIST, and best response was recorded. Results: Between 9/2007 and 9/2008, 20 pts were treated on the trial; median age 62 (range 47–73), male/female: 12/8, PS of 0/1: 6/14, and median number of prior therapies 2 (range 1–4). The most common tumor types were NSCLC (n=8), SCLC (n=4) and head/neck (n=2). At dose level 0 arm A (200 mg BID), 2 of 4 patients experienced DLT (gr.4 thrombocytopenia, gr.3 fatigue, febrile neutropenia and gr.4 neutropenia for > 7 days, gr.3 febrile neutropenia, diarrhea, hypokalemia, hyponatremia); 2 pts have been enrolled at dose level -1 (200 mg po QD) without DLT. Two of 3 patients enrolled on arm B at dose level 0 had gr.4 thrombocytopenia. On arm C at dose level 0 (200 mg po BID), 1/6 pts experienced DLT (gr.3 hyponatremia, dehydration, hypoglycemia). Enrollment continued at dose level 1 (400 mg po BID), but 2/5 pts experienced a DLT (both gr. 3 fatigue/anorexia). Responses observed were: PR (n=3) (all arm C), and SD (n=6). Conclusions: The MTD of sorafenib in combination with carboplatin (AUC=5) and pemetrexed 500 mg every 3 weeks is 200 mg po BID. The MTD of sorafenib in combination with cisplatin/etoposide has yet to be determined and is currently accruing at dose level -1. [Table: see text]

4604 Background: Hepatocellular carcinomas (HCC) are known to express EGFR, and a ph II study of erlotinib suggested clinical activity of EGFR inhibition. Combinations with EGFR and chemotherapies ...

4595 Background: Radiologic procedures that involve embolizing branches of the hepatic artery lengthen survival for patients with unresectable HCC, but the benefit of administering intrahepatic art...

15522 Introduction: Transarterial chemoembolization (TACE) is a treatment option for patients with unresectable hepatocellular carcinoma (HCC). Prior reports suggest biochemical markers (BM) and ra...

15008 Purpose: Locally advanced pancreatic cancer (LAPC) leads to a poor survival, and current therapies are inadequate. External beam radiotherapy (EBRT) has been used to obtain local control, but the most effective systemic agent, gemcitabine(gem), can be used only at low doses with standard RT. Oxaliplatin (ox) has activity in PC, and has been delivered safely at doses near full systemic doses with EBRT for rectal cancer. We set out to define the maximum tolerated dose (MTD) of ox in combination with gem + upper abdominal EBRT. Methods: Patients (pts) with LAPC or biliary ca were eligible. Prior systemic therapy was allowed. A 3 + 3 design was employed with 4 dose levels (table). Gem + ox was given once weekly. EBRT was given in 1.8 Gy fractions to 50.4 Gy using a multi-field technique. DLT was defined as any grade 4 tox or grade 3 tox resulting in treatment delay > 1 wk. Results: 11 pts have completed therapy (Table). 10 pts had LAPC, 1 had ampullary ca. No pts in the first 2 cohorts had DLT. Pt #3 in cohort 3 had DLT (grade 3 elevated liver enzymes). Cohort 3 was expanded; patients 4 and 5 in the cohort have completed therapy without DLT; pt 6 is not yet evaluable. To date, 43 grade 3 toxic events have occurred in 11 evaluable patients. No grade 4 toxicities have occurred. The most common grade 3 tox are: nausea (63%), metabolic (54%), hyperglycemia (45%), neutropenia (36%), vomiting (27%). SD was best radiographic response in 8 of 8 evaluable pts. One patient with ampullary ca had regression of disease from vessels and was resected, but had positive retroperitoneal margin and died of a post-operative complication. Five pts have died (OS 2.6–12.2 mos). Median OS is currently 9 mos (95% CI 4.6, 12.3). Conclusions: Weekly oxaliplatin can be given safely with weekly gemcitabine (200 mg/m2) during EBRT for LAPC. The ox MTD in this combination is not yet defined, but is at least 30 mg/m2 weekly. Final dose results and updated efficacy results will be presented at the meeting. [Table: see text] [Table: see text]

8579 Background: Level of consciousness (LOC) often varies in the palliative care patient population. Tools are needed to reliably rate symptoms. The purpose of our analysis was to describe the patient demographics and rating distributions elicited by two distinct measurement tools, one for those able to self-rate (SR) and one for proxy-rated (PR) patients. Methods: Data obtained prospectively over the time period 1/2002–12/2004 was reviewed. A symptom distress scale using 11 items on a 5 point Likert-type scale (5=most severe) was adapted from the revised McCorkle symptom distress scale and used for alert and oriented patients. Symptoms evaluated included nausea, mood, appetite, shortness of breath (SOB), insomnia, pain, mobility, fatigue, constipation, decreased LOC, and delirium. For patients unable to SR, an advanced practice nurse rated symptoms using the Detroit Medical Center non-verbal pain scale and proxy symptom distress measures adapted from the Common Toxicity Criteria Manual, version 2. Rated symptoms included pain, vomiting, constipation, tachypnea, depressed LOC, and agitated delirium. Results: A total of 259 patients with data from visits 1 and 2 were included in the analysis. On visit 1, 46% (61/133) of PR patients were male, 70% (94/134) were ≥60yrs and 73% (98/134) were Caucasian. Symptom distress scores varied by rater and visit (Table). Conclusions: There is a need for proxy symptom distress measurement in the palliative care patient population as LOC fluctuates. Variability in symptom distress ratings between the SR and PR groups, with a trend toward lower scores in PR patients, is in accordance with the current literature. Of note, there was a consistent improvement in scores, regardless of rater, when visit 2 was compared to visit 1. We plan a prospective study of inter-rater reliability and validity of this novel symptom scoring system. [Table: see text] No significant financial relationships to disclose.

PURPOSE: To determine the maximum-tolerated dose, dose-limiting toxicities, and potential antitumor activity of twice-weekly gemcitabine and concurrent radiation in patients with locally advanced pancreatic cancer. PATIENTS AND METHODS: Nineteen patients with histologically confirmed adenocarcinoma of the pancreas were studied at the Wake Forest University Baptist Medical Center and the University of North Carolina at Chapel Hill. The initial dose of gemcitabine was 20 mg/m2 by 30-minute intravenous infusion each Monday and Thursday for 5 weeks concurrent with 50.4 Gy of radiation to the pancreas. Gemcitabine doses were escalated in 20-mg/m2 increments in successive cohorts of three to six additional patients until dose-limiting toxicity was observed. RESULTS: The dose-limiting toxicities at 60 mg/m2 given twice-weekly were nausea/vomiting, neutropenia, and thrombocytopenia. Twice-weekly gemcitabine at a 40-mg/m2 dose was well tolerated. Of the eight patients eligible for a minimum follow-up of 12 months, three remain alive, one of whom has no evidence of disease progression. CONCLUSION: A dose of twice-weekly gemcitabine at 40 mg/m2 produced mild thrombocytopenia, neutropenia, nausea, and vomiting when delivered with concurrent radiation to the upper abdomen in patients with advanced pancreatic cancer. These data suggest this regimen is well tolerated and may possess significant activity. These data and other observations have resulted in a phase II Cancer and Leukemia Group B study to ascertain the efficacy of this treatment regimen in patients with locally advanced pancreatic cancer.