Prognostic Significance of MUC-1 in Circulating Tumor Cells in Patients With Metastatic Pancreatic Adenocarcinoma.

OBJECTIVES: Development of targeted therapies for pancreatic cancer could be enhanced by a reliable method for noninvasive tumor cell assessment. In this pilot study, we isolated and phenotypically characterized circulating tumor cells (CTCs) from patients with metastatic pancreatic cancer and explored their relationship to clinical outcome. METHODS: Peripheral blood from 50 patients was collected at treatment initiation and first disease evaluation for CTC enumeration and phenotyping by CellSearch® system. Expression of human mucin 1 (MUC-1) was performed. RESULTS: Forty-eight and 37 patients had evaluable samples at baseline and first disease evaluation, respectively. The cohort was 62% male, with a median age of 63 years. At least 1 CTC per 7.5 mL was detected in 23 patients (48%) pretreatment and 11 patients (30%) at first disease evaluation. No difference was seen in overall survival between patients with 1 or more CTCs versus no CTC at baseline (P = 0.14). Patients with MUC-1 expressing CTC (n = 10) had shorter median overall survival compared with those with MUC-1 negative CTC (n = 13; 2.7 vs 9.6 m; P = 0.044). CONCLUSIONS: Circulating tumor cell enumeration and phenotypic characterization from metastatic pancreatic cancer patients are feasible. No correlation was found between CTC isolation and survival. However, the presence of MUC-1 expressing CTC demonstrated a trend toward inferior survival.

Phase I and pharmacokinetic study of the cytotoxic ether lipid ilmofosine administered by weekly two-hour infusion in patients with advanced solid tumors.

PURPOSE: A Phase I trial was performed to determine the dose-limiting toxicity and maximum tolerated dose, and to describe the pharmacokinetics of the alkyl-lysophospholipid, ilmofosine, when administered as a weekly 2-h infusion in patients with solid tumors. EXPERIMENTAL DESIGN: Thirty-nine patients were entered into a trial of ilmofosine administered weekly for 4 weeks followed by a 2-week rest period. Dose escalation occurred in 10 levels from 12 to 650 mg/m(2). RESULTS: Thirty-six patients were evaluable for toxicity. The median number of cycles per patient was 1 (range, 1-4). Dose-limiting gastrointestinal toxicity occurred at 650 mg/m(2) with grade 3 nausea in two patients and grade 3 vomiting and diarrhea in one patient. Grade 2 diarrhea was observed in four of six patients treated at 550 mg/m(2). In addition, two patients treated at 550 mg/m(2) and two patients treated at 650 mg/m(2) experienced a decline in performance status of two or more levels that was determined to be due to treatment. There were no tumor responses. Stabilization of disease for at least 8 weeks occurred in six patients. Plasma concentrations of ilmofosine and its sulfoxide metabolite were evaluated by high-pressure liquid chromatography. The elimination of both compounds was biexponential with terminal half-lives of approximately 40 h for ilmofosine and 48 h for the sulfoxide. The area under the concentration-time curve was dose-proportional for each compound, and there was no evidence of saturable kinetics. CONCLUSIONS: The dose-limiting toxicity of ilmofosine is gastrointestinal and the recommended dose for Phase II trials is 450 mg/m(2) as a 2-h weekly infusion. The relatively long half-life of ilmofosine and its active metabolite support the use of this intermittent schedule.

Characteristics of female smokers attending a lung cancer screening program: a pilot study with implications for program development.

Anticipating the development of lung cancer early detection programs, we examined the: (1) feasibility of a lung cancer early detection program; (2) characteristics of enrollees (e.g. motivation to quit smoking); (3) correlates of enrollee motivation to quit smoking; and (4) rates of smoking cessation following screening. Brief surveys were completed before and after screening, which involved sputum cytology, chest X-ray, bronchoscopy, spiral CT, and a meeting with an oncologist to discuss smoking cessation. Of the 168 eligible women who were heavy smokers recruited via newspaper and cancer center advertisements, 55 agreed to undergo screening. Enrollees showed low-to-moderate levels of quit motivation and high levels of nicotine addiction; enrollees were interested in a range of smoking cessation treatments; 20% of enrollees exhibited clinical-levels of emotional distress; 64% of enrollees reported low levels of self-efficacy (i.e. self-confidence) to quit; 24% of enrollees reported low levels of quitting pros and 25% reported high levels of quitting cons; 31% of enrollees showed high levels of fatalistic beliefs about cancer; and all enrollees recognized their elevated lung cancer risk. Greater motivation to quit smoking was related to: greater age, lower nicotine addiction, fewer health symptoms, and higher quitting self-efficacy and quitting pros. Finally, 16% of enrollees quit smoking after screening. Overall, many women eligible for screening refused to undergo comprehensive screening that included bronchoscopy and spiral CT. Screening may represent an opportunity for quitting smoking, although more intensive smoking cessation interventions that target nicotine addiction and self-efficacy may be needed to maximize the health benefits of an early detection program.