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Palliative care consultation is the most common model of hospital-based services in the United States, but few studies examine the impact of this model. In a prospective study, we describe the impact of palliative care consultation on symptoms, treatment, and hospital costs. Patients receiving interdisciplinary palliative care consultations from 2002 to 2004 were approached for enrollment; 304 of 395 (77%) patients participated. Measures included diagnosis, treatment decisions, and symptom scores. To test impact on costs, a one-year subset of cases with lengths of stay4 days (n=104) was compared to all available controls (n=1,813) matched on the 3Mtrade mark All Patients Refined Diagnosis Related Group, Version 20, and mortality risk scores. Half of the patients were younger than 65 years, 28% were African American, and 61% had cancer. Median Palliative Performance score was 20 (range, 10-100). Recommendations were implemented in 88% of cases; new "do not resuscitate/do not intubate" orders were written for 34% of patients, new comfort care orders for 44%, and 27% were referred for hospice care. Symptom scores improved from Day 1 to Day 3, with greatest improvement in pain (2.6-1.4, P0.001). Compared to matched controls without palliative care consultation, palliative care cases had lower cost per day ($897 vs. $1004, P=0.03). Per diem variable costs were 10.7% less for all palliative care cases and 20.5% less for those with50% hospital days with palliative care consultation. Palliative care consultation is followed by decisions to forego costly treatment and improved symptom scores, and earlier palliative care intervention results in greater cost-savings.

ContextPrehospital hypertonic saline (HTS) resuscitation of patients with traumatic brain injury (TBI) may increase survival but whether HTS improves neurological outcomes is unknown.ObjectiveTo determine whether prehospital resuscitation with intravenous HTS improves long-term neurological outcome in patients with severe TBI compared with resuscitation with conventional fluids.Design, Setting, and PatientsDouble-blind, randomized controlled trial of 229 patients with TBI who were comatose (Glasgow Coma Scale score

We conducted a phase I study to determine the maximum tolerated dose of docetaxel in combination with gemcitabine for patients with refractory solid tumors.From January 1998 to November 1999, we treated 28 patients on a phase I protocol with gemcitabine given at a constant dose of 800 mg/m2 i.v. over 30 minutes on days 1, 8, and 15. Docetaxel was administered by a phase I schedule over 1 hour on day 1 of a 28-day cycle with a starting dose of 50 mg/m2 and increased by increments of 10 mg/m2 based on dose-limiting toxicity (DLT) that occurred in the first cycle.Neutropenia and thrombocytopenia were the dose-limiting toxicities. The maximum tolerated dose was 60 mg/m2. The most significant nonhematologic toxicities included fatigue, nausea, vomiting, mucositis, and hypersensitivity reactions. There was one partial response at 15 months in a patient with gastric cancer and six patients with stable disease for 4.0 to 15.0 months.The maximum tolerated dose of docetaxel with gemcitabine is 60 mg/m2. A Phase II study in selected primary sites is planned.

Both oxaliplatin and ormaplatin undergo biotransformation to Pt(dach)Cl2 with studies suggesting a predictive relationship between systemic exposure to Pt(dach)Cl2 and the severity of the delayed sensory neuropathy associated with ormaplatin. Studies characterizing the pharmacokinetic parameters of oxaliplatin and Pt(dach)Cl2 in humans have not been reported. This study was conducted to characterize the pharmacokinetic parameters of oxaliplatin and Pt(dach)Cl2 and to determine the extent to which oxaliplatin undergoes biotransformation to Pt(dach)Cl2 in humans.Ten adult patients with metastatic colon cancer received oxaliplatin with or without fluorouracil-based chemotherapy. Blood samples were obtained during cycles 1 and 2. Total platinum, oxaliplatin and Pt(dach)Cl2 in the plasma ultrafiltrate were measured using high performance liquid chromatography and atomic absorption spectrometry. All patients underwent a thorough neurological evaluation after each cycle.The median steady-state concentration (C(SS)) (interquartile range, 25% to 75%) for oxaliplatin 85 mg/m2 was 0.33 microg Pt/ml (0.28 to 0.38 microg Pt/ml). The area under the curve (AUC) was 0.79 microg Pt/ml/h (0.62 to 0.88 microg Pt/ml/h) and the elimination half-life was 0.32 h (0.27 to 0.46 h). The median C(SS) for Pt(dach)Cl2 was 0.008 microg Pt/ml (0.004 to 0.014 microg Pt/ml). The C(SS) ratio of oxaliplatin to Pt(dach)Cl2 was 31 (24 to 51). All patients reported acute cold-induced neuropathy following cycles 1 and 2. Only two patients reported delayed sensory neuropathy (grade 1).The parent drug oxaliplatin is the major active platinum complex detected in plasma ultrafiltrate for at least the first few hours following oxaliplatin infusion in humans. Therefore, the plasma biotransformation products of oxaliplatin are unlikely to contribute to its efficacy or toxicity. In particular, plasma Pt(dach)Cl2 is unlikely to significantly contribute to the delayed sensory neuropathy associated with oxaliplatin, since only a limited amount (3%) of oxaliplatin undergoes biotransformation to Pt(dach)Cl2.

Medication interactions in palliative care are reviewed. An overview of drug interactions is provided with particular attention to these concepts as they apply in the palliative care setting. Newer information about the role of the CYP 450 system is reviewed. The potential for interactions with individual agents that are used in palliative care is discussed.

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 ...

Cost of analgesic and adjuvant medications used by rural patients with cancer cared for by 29 nurses participating in an in-depth education program were evaluated before and after the program. Across all time periods, the median daily cost was $5.16 across all medications. Average daily cost and maximum and median cost of all medications were $5.36, $74.38 and $3.58, respectively. Average daily cost did not change over time. Average pain intensity did not change over time and was not related to prescribing patterns or daily costs. While professional education was demonstrated to produce change in prescribing practices, further research is needed to evaluate patterns of medication administration and effectiveness patterns using reliable outcome measures other than self report of pain intensity.

This study describes the MR appearances of malignant hypervascular liver lesions pre- and post-hepatic-arterial chemoembolization, with correlation to serial imaging and clinical responses. Eight patients with malignant hypervascular liver lesions underwent pretreatment and posttreatment MR examination on a 1.5-T MR imager. MR sequences included T1-weighted spoiled gradient echo (SGE), T2-weighted fat-suppressed spin echo or turbo spin echo, and dynamic gadolinium-enhanced SGE images. All patients underwent pretreatment, initial posttreatment, and subsequent posttreatment MR studies. The histology of primary tumors included various types of hepatocellular carcinoma (HCC) (four patients: fibrolamellar HCC [one patient], HCC [two patients], mixed HCC/cholangiocarcinoma [one patient]) and liver metastases (four patients: untyped islet cell tumor [two patients], gastrinoma [one patient], carcinoid [one patient]). Response to chemoembolization was determined by three assessments: MR response, serial imaging response, and clinical response. The appearance of MR response to chemoembolization was determined based on the correlation with clinical and serial imaging response. The MR response of lesions that showed good clinical response included: increase in signal intensity on T1-weighted images (three patients), decrease in signal intensity on T2-weighted images (three patients), and negligible or minimal enhancement on immediate postgadolinium images (four patients) after chemoembolization. The most marked change in lesion appearance was observed in lesions < or = 1 cm, which had intense homogeneous enhancement on pretreatment MR studies and negligible enhancement on initial posttreatment MR examinations. MR response of lesions that showed moderate clinical response demonstrated a variety of lesion appearances from substantial change to minimal change. MR response of lesions that showed poor clinical response demonstrated no change in lesion appearances compared with the pretreatment MR study. Our results demonstrated change in appearance of liver lesions between pre- and post-hepatic-arterial chemoembolization MR studies. MR response correlated with response determined by serial imaging studies and clinical findings.

Background. Induction chemoradiotherapy followed by esophagectomy may provide results superior to those of single-modality treatment in patients with esophageal cancer. The purpose of this study was to review our experience with this approach for esophageal cancer. Methods. From 1988 to 1996, 166 consecutive patients with esophageal cancer were evaluated; 66 entered a protocol of chemotherapy (5-fluorouracil, cisplatin) concurrent with radiation (45 Gy) followed by esophagectomy. Fifty-four patients completed the protocol. Results. Toxicity associated with induction chemoradiotherapy was minimal. The actuarial survival at 12, 24, and 36 months was 59%, 42%, and 32%, respectively. The pathologic complete response (pCR) rate was 41%, with 12-, 24-, and 36-month survivals of 77%, 50%, and 45%, whereas non-pCR patients had survivals of 46%, 35%, and 23%. The difference in survival between pCR and non-pCR patients was not significant ( p = 0.13), but the difference in recurrence-free survival was significant ( p = 0.007). Conclusions. This well-tolerated protocol resulted in a high pCR. Trimodality treatment for esophageal cancer may provide long-term survival in some patients regardless of their pCR status.

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]

A great deal of effort is being expended at national, state and local levels to improve cancer pain management in the United States. The fact that cancer patients continue to experience "unrelieved pain" is of concern to professional caregivers and families, as well as to the patients themselves. This article describes the content and scope of an educational program for nurses who work in predominantly rural areas. Content of the program and the evaluation process are described in detail in order to provide other caregivers with a model that could be implemented in similar settings.

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]

Pentostatin, a novel inhibitor of adenosine deaminase, has shown activity in various lymphoid malignancies of both the T and B cell lineage. This agent has unique side effects and in general myelosuppression has been mild. Interferon has both antiviral and antineoplastic properties. This agent has shown activity in hairy cell leukemia, chronic granulocytic leukemia, low grade lymphoma, and myeloma. Side effects from interferon are in general dissimilar to those that have been seen with pentostatin and in particular myelosuppression has not been a major toxicity with low doses of interferon. This current trial explored the combination of pentostatin and interferon in hematologic malignancies. Fifteen patients were enrolled in this phase I trial at a fixed dose of pentostatin of 4 mg/m2 biweekly and interferon at doses of 0.5, 1, 2, or 4 million units/m2 of interferon. At the first three dose levels of interferon nausea and vomiting were the predominant toxicity and appeared to worsen with time on study. Fatigue also was seen at the lowest level of interferon and was severe enough to cause two individuals to discontinue the study medications. At higher dose levels of interferon, myelosuppression, nausea and vomiting, and fatigue were the predominant toxicities. One patient with hairy cell leukemia had a complete response and a second patient with T cell cutaneous lymphoma had a partial response which lasted for 6 to 7 weeks. The maximum tolerated dose of interferon with pentostatin in this patient population was four million units/m2.

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.

Objectives To measure the efficacy and toxic effects of our chemoradiotherapy regimen by means of response and survival in patients with advanced squamous cell carcinoma of the head and neck (HNSCC) for organ preservation in resectable disease or palliation in unresectable disease. Design All patients underwent evaluation by the multidisciplinary head and neck cancer team, with pathological diagnosis and staging. All patients underwent assessment for response to therapy using results of physical examination and radiologic imaging. Patients were followed up at 3-month intervals for a planned period of 5 years. Setting Academic center. Patients Thirty-eight previously untreated patients with newly diagnosed HNSCC were treated from June 1, 1996, through December 31, 1998, of whom 20 had resectable and 18 had unresectable tumors. Intervention Patients received intravenous cisplatin, 100 mg/m 2 for 1 hour on days 1 and 29; a 24-hour continuous infusion of fluorouracil, 1000 mg/m 2 on days 1 through 4 and 29 through 32; and radiation therapy, 150 rad twice daily for 12 days. The patients were given a 7- to 10-day break, and radiation therapy was restarted on day 29 for 12 additional days (total dose, 7200 rad). Main Outcome Measures Complete, partial, and total response rates; disease-free survival; overall survival; and toxic effects. Results Toxic effects of treatment were moderately severe, including grades III to IV mucositis (89%), neutropenia (71%), and renal toxic effects (8%). In the 18 patients in the unresectable group, complete response in the 17 primary tumors and 15 cervical nodal metastases was achieved in 12 (71%) and 9 (60%), respectively; in the 20 patients undergoing organ preservation, complete response rates were 100% in the 23 primary tumors and 15 cervical nodal metastases. Complete response for all 38 patients was achieved in 31 (82%). In the unresectable group, the Kaplan-Meier relapse-free survival estimate is 56%, with follow-up from 29 to 45 months. In the organ preservation group, 75% of patients are alive without disease, and 8 have been followed up for 36 to 48 months. Of the 5 patients who have died, only 2 died of disease, with recurrences at 13.0 and 16.5 months. Conclusions Chemoradiotherapy consisting of cisplatin, fluorouracil, and twice-daily external beam radiation is highly effective in achieving durable complete responses in patients with resectable HNSCC undergoing organ preservation and patients with unresectable HNSCC undergoing palliation. Toxic effects of this regimen were moderate to severe.

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.

PURPOSE A prospective study was performed to determine the outcome of patients with esophageal cancer who received preoperative radiation therapy and chemotherapy followed by esophagectomy, and to determine the role of preresection esophagogastroduodenoscopy (EGD) in predicting the patients in whom surgery could possibly be omitted, and the impact of surgery on survival. MATERIALS AND METHODS Thirty-five patients with localized carcinoma of the esophagus received concurrent external-beam radiotherapy and chemotherapy followed by esophagectomy. Patients received 45 Gy in 25 fractions. Chemotherapy consisted of continuous infusion fluorouracil (5-FU; 1,000 mg/m2/d) on days 1 through 4 and 29 through 32 and cisplatin (100 mg/m2) on day 1. Patients underwent an Ivor-Lewis esophagectomy 18 to 33 days after completion of radiotherapy. RESULTS Eighty percent of the patients had squamous cell carcinoma and 20% had adenocarcinoma. In addition, 51% had a pathologic complete response (CR). Twenty-two of the 35 underwent a preresection EGD before resection. Seventeen of the 22 (77%) had negative pathology from the preresection EGD, but seven of the 17 (41%) had residual tumor at surgery. The median survival and disease-free survival rates for all patients were 25.8 months and 32.8 months, respectively. Eighteen patients (51%) had no tumor at resection. The median survival for these patients was 36.8 months; the median disease-free survival time has not been reached. The median survival and disease-free survival rate for the patients with residual tumor in the surgical specimen were 12.9 months and 10.8 months, respectively. CONCLUSION Preresection EGD is not reliable for determining the presence of residual disease or the patients in whom surgery could be omitted. Twenty-five percent of the patients with residual tumor in the resected surgical specimen were long-term survivors; this suggests a benefit from esophagectomy after concurrent radiotherapy and chemotherapy.

A study of predictive factors for locoregional recurrences after curative surgery for breast cancer was undertaken. Specifically, the authors wished to determine whether such recurrences correlated with either hormonal receptor status or a delay between the initial biopsy and the definitive surgery. A retrospective chart review was done on all women with breast cancer who had surgery for cure between 1970 and 1982. Factors analyzed included, among others, size of the tumor, clinical and pathologic status of the axilla, estrogen and progesterone receptors status, and delay between biopsy and definitive surgery. There were 404 patients studied. Pathologic axillary nodal status was the most important predictor of locoregional recurrence, with failures in 36 of 188 (19%) node-positive but only 9 of 216 (4%) node-negative patients (P = 0.0001). In node-positive patients, tumor size was a predictor of local recurrence, with failure in only 4 of 51 (8%) of tumors less than 2 cm, but in 14 of 44 (32%) of tumors greater than 6 cm (P = 0.004). Progesterone receptor (PR) status correlated with locoregional recurrence, but estrogen receptor status did not. In node-positive women, there were 4 of 14 PR-negative but 0 of 15 PR-positive local failures (P = 0.017); this result has not been previously reported. The presence of palpable axillary disease was also found to be a predictor of local recurrence. Finally, no increase in locoregional recurrence could be attributed to the delay between biopsy and definitive surgery. Two new predictors for locoregional recurrence in breast cancer, not previously emphasized, are PR and clinical axillary status. Should these findings be substantiated, patients at high risk for locoregional recurrence could then be more readily identified.

Thirty-nine cancer patients (Ca) and 37 age-and sex-matched healthy controls (Co) evaluated 11 commercially available enteral supplements using a modified wine-tasting scale. The cancer patients were 19 males with lung cancer and 20 females with breast cancer, and their controls consisted of 17 males and 20 females, respectively. Mean evaluation scores for the individual supplements revealed no significant differences (NS) between lung cancer patients and controls. Ensure Plus (strawberry) received the highest score from both groups (Ca 16.0 +/- 3.0 vs Co 17.1 +/- 2.6, N.S.) while Vital received the lowest (Ca 6.3 +/- 4.8 vs Co 4.9 +/- 4.2, NS). Similar results were obtained for breast cancer patients and their controls except that chocolate Sustacal was rated significantly higher by breast cancer patients than by controls (16.6 +/- 2.6 vs 13.3 +/- 4.3, p less than 0.01). Again, Ensure Plus (strawberry) received the highest score from both groups (Ca 17.0 +/- 3.5 vs Co 17.8 +/- 2.3, NS), while Vital was rated lowest by both groups (Ca 5.6 +/- 4.7 vs Co 4.3 +/- 5.0, NS). The modified wine-tasting scale provides a method for quantitating taste preference for various dietary supplements. We report here the numerical rating of 11 supplements by patients with lung cancer and patients with breast cancer as well as their age- and sex-matched controls.

Nausea and vomiting are commonly recognized side effects of chemotherapy. However, the incidence and duration of these effects have not been systematically studied in a large outpatient oncology population. This survey was conducted over two consecutive 6-week periods in the adult oncology clinics of two university teaching hospitals. The objectives were: (1) to document the incidence and duration of chemotherapy-induced nausea and vomiting; (2) to identify variables that influence nausea and vomiting; and (3) to describe patterns of antiemetic prescribing and compliance. One hundred thirty-eight completed patient-maintained diaries were returned (70% response rate). Anticipatory nausea and vomiting were reported by 9.4% and 6.5% of patients, respectively. Fifty percent and 27% of patients reported nausea and vomiting, respectively, on the day chemotherapy was administered (day 1: acute nausea and vomiting phase). Percentages fell to 22% and 11% by day three and 14% and 2.5% on day 5. Of patients who reported nausea and vomiting during the five-day period, 52% and 33% experienced nausea and vomiting, respectively, during the delayed period only (days 2 through 5: delayed emesis phase). Emetogenicity of chemotherapy significantly influenced incidence and duration of those symptoms. Sixty-seven percent of patients reported taking antiemetics on one or more days during the survey period. Of patients who reported antiemetic use, 92% reported antiemetics on day 1, 51% on day 3, and 31% on day 5. At-home antiemetic use was related to the emetogenicity of chemotherapy received. Patients who receive moderate to strong emetogens as defined in this report should receive antiemetic therapy for a minimum of three days. Increasing the dose of antiemetic prescribed both in the clinic and at home may be of benefit.

• Female patients with Hodgkin's disease who undergo staging laparotomy frequently have oophoropexy performed to preserve both fertility and hormone production. Because of recent changes in therapy favoring systemic chemotherapy rather than total nodal irradiation for patients with stage III Hodgkin's disease, the need for oophoropexy may be less than previously described. Thirty-nine women of childbearing age underwent laparotomy at the University of North Carolina, Chapel Hill, from 1970 to 1984. Twenty-seven patients underwent oophoropexy. Only three of these patients would have needed this procedure based on their subsequent therapy. Two patients required additional gynecologic surgery because of complications related to the oophoropexy. The success rate in preservation of menstrual function and fertility is also discussed. We review the previous experience with oophoropexy and suggest an alternative approach to the routine use of this procedure. ( Arch Surg 1986;121:1083-1085)

This study evaluated the effect of 2'-deoxy-5-fluorouridine (FUDR) on the regeneration of the liver following partial (68%) hepatectomy in the rat. Male Sprague-Dawley rats weighing between 190 and 240 g underwent partial hepatectomy under ether anesthesia. Twelve hours postoperatively rats received intraperitoneal injections of 2'-deoxy-5-fluorouridine or 0.9% NaCl solution as follows: Group I, 0.9% NaCl solution (n = 49); Group II, 89 mg 2'-deoxy-5-fluorouridine/kg of body weight (n = 25); and Group III, 178 mg 2'-deoxy-5-fluorouridine/kg of body weight (n = 24). Sham groups underwent celiotomy and liver palpation followed by 0.9% NaCl solution injections (n = 5) or low dose 2'-deoxy-5-fluorouridine (n = 5) and high dose 2'-deoxy-5-fluorouridine (n = 5). The regenerative ability of the liver was evaluated by weight and deoxyribonucleic acid synthesis in the liver remnant.Both low and high dose 2'-deoxy-5-fluorouridine delayed the peak of deoxyribonucleic acid synthesis from 36 to 72 hr as compared to control animals which had maximal synthesis at 25 to 36 hr postoperatively (P less than 0.01). Weight of the liver remnants demonstrated a similar pattern.High doses of 2'-deoxy-5-fluorouridine administered intraperitoneally delay, but do not inhibit, liver regeneration following partial (68%) hepatectomy as reflected by DNA synthesis and weight of the remnant.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Prophylactic hypothermia is effective in laboratory models, but clinical studies to date have been inconclusive, partly because of methodological limitations. Our Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury (POLAR) randomised controlled trial is currently underway comparing early, sustained hypothermia versus standard care in patients with severe TBI. We describe our study protocol and the challenges in conducting prophylactic hypothermia research in TBI.We aim to randomise 500 patients to either prophylactic 33°C hypothermia initiated within 3 hours of injury and continued for at least 72 hours, or standard normothermic management. Patients will be enrolled by paramedic services in the prehospital setting, or by emergency department staff at participating sites in Australia, New Zealand and Europe. The primary outcome will be the eight-level extended Glasgow outcome scale (GOSE), dichotomised to favourable and unfavourable outcomes at 6 months after injury. Secondary outcomes will include mortality at hospital discharge and at 6 months, ordinal analyses of 6-month GOSE outcomes, quality of life with health economic evaluations and the differential proportion of adverse events. We will predefine subgroup and interaction analyses.After a run-in phase, recruitment for our main study began in December 2010. When the study is completed, we aim to provide evidence on the efficacy of prophylactic hypothermia in TBI to guide clinicians in their management of this devastating condition.

To develop methods for distinguishing patients with in-hospital cardiac arrest (IHCA) from patients with out-of-hospital cardiac arrest (OHCA) in routinely collected intensive care unit registry data, and to explore the utility of the methods for describing trends in adult ICU cardiac arrest (CA) admissions and outcomes.A retrospective observational analysis of all ICU admissions entered in the Australian and New Zealand Intensive Care Society adult patient database between 2000 and 2011. Trends in admission and survival rates to hospital discharge over time were examined using eight different methods of classifying patients with IHCA and OHCA.There were 1 001 754 admissions to the ICUs between 2000 and 2011. Of these, postarrest admissions comprised 23 857 (2.4%), and increased annually by an average of 135 admissions (95% CI, 120-150 admissions). The annual volume of patients with IHCA as a fraction of total admissions declined by 0.4 patients/1000 admissions (95% CI, 0.3-0.5 patients/1000 admissions). In contrast, for patients with OHCA, each year was associated with an additional 0.2 patients/1000 admissions (95% CI, 0.1-0.4 patients/1000 admissions). This increase occurred in tertiary ICUs and declined in non-tertiary ICUs. Survival to hospital discharge for both groups improved, increasing annually by 1.2% (95% CI, 0.8%-1.6%) for patients with IHCA, and by 1.1% (95% CI, 0.7%-1.4%) for patients with OHCA.Use of routinely collected registry data uncovered important trends in adult ICU admission and survival rates for patients with IHCA and OHCA. The improved survival rates and increased number of admissions to tertiary centres requires further study to understand mechanisms and related factors.