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Background Talactoferrin alfa is an oral dendritic cell (DC)-mediated immunotherapy (DCMI). We tested whether talactoferrin was superior to placebo in advanced non-small-cell lung cancer (NSCLC). Patients and methods An FORTIS-M trial was an international, multicenter, randomized, double-blind comparison of talactoferrin (1.5g p.o. BID) versus placebo BID, in patients with stage IIIB/IV NSCLC whose disease had failed two or more prior regimens. Treatment was administered for a maximum of five 14-week cycles. The primary efficacy end point was overall survival (OS); secondary end points included 6- and 12-month survival, progression-free survival (PFS), and disease control rate (DCR). Results Seven hundred and forty-two patients were randomly assigned (2:1) to talactoferrin (497) or placebo (245). The median OS in the intent-to-treat (ITT) population was 7.66 months in the placebo arm and 7.49 months in the talactoferrin arm [hazard ratio (HR), 1.04; 95% CI, 0.873–1.24; P = 0.6602]. The 6-month survival rates were 59.9% (95% CI, 53.4% to 65.8%) and 55.7% (95% CI, 51.1% to 59.9%), respectively. The 12-month survival rates were 32.2% (95% CI, 26.3% to 38.2%) and 30.9% (95% CI, 26.8% to 35%), respectively. The median PFS rates were 1.64 months and 1.68 months, respectively (HR, 0.99; 95% CI, 0.835–1.16; P = 0.8073). The DCRs were 38.4 and 37.6%, respectively [stratified odds ratio (OR), 0.96; 95% CI, 0.698–1.33; P = 0.8336]. The safety profiles were comparable between arms. Conclusions There was no improvement in efficacy with talactoferrin alfa in patients with advanced NSCLC whose disease had failed two or more previous regimens.

We report on two randomized trials performed in the USA and Europe, which compared methotrexate and nolatrexed as treatment for patients with recurrent head and neck cancer. Eligibility criteria included: histologically confirmed squamous-cell carcinoma, measurable disease, adequate hematological, renal and hepatic functions, failure of a first-line chemotherapy, and informed consent. Methotrexate 40 mg/m(2) was weekly given by short infusion, and nolatrexed 725 mg/m(2) per day was administered as a five-day continuous infusion, every three weeks. A total of 139 patients (63 in the USA, 76 in Europe) were randomized based on a ratio of 2/1: 93 and 46 received nolatrexed and methotrexate, respectively. Patient characteristics included 115 males and 24 females; median age 60 years. In the nolatrexed arm, the following grade 3-4 toxicities occurred: neutropenia (29.9%) with 3.1% of febrile neutropenia, mucositis (33.3%), and vomiting (10.3%). In the MTX arm, the grade 3-4 toxicities were neutropenia (7.1%) and mucositis (6.9%). There was no difference in activity between the nolatrexed and the methotrexate treatment: 3.3% and 10.8% of objective responses, 1.9 versus 1.5 months of disease-free progression and 3.5 versus 3.7 months of overall survival, respectively. Nolatrexed has demonstrated a similar activity to methotrexate.

20508 Background: Most data on treatment of GIST pts were derived from clinical studies, reflecting practice at academic referral centers. The reGISTry, an observational, internet-based database initiated in 2004, was designed to characterize evolving patterns of care for pts with GIST in both community and university practice settings. It also provides site feedback to allow comparison of site management practices to the aggregate reGISTry data. Methods: Physicians may serially enter data on any enrolled pt with confirmed GIST. Pts must give written informed consent. Collected data include pt demographics, clinical characteristics, clinical/economic outcomes and therapy provided for GIST. Analyses are performed every 6 months. Results: As of Oct 2006, there were 353 pts enrolled from 78 centers. 228 pts (65%) were from community-based practices; 184 pts (52%) were male, and 283 pts (80%) were Caucasian, with a median age of 65 years (range 18–92). Median time from diagnosis to enrollment was 1.1 years (range 0–11.7). At diagnosis, 282 pts (80%) had a localized tumor and 71 (20%) presented with metastatic disease. 335 pts (95%) had immunohistochemical KIT testing, and 1% had genotyping. 274 pts had surgery as first-line treatment (78%), including 84% of pts with primary disease and 52% with metastatic cancer. 14 % and 42% of pts with localized and metastatic disease respectively had systemic therapy as initial treatment. Of the 202 pts with follow-up, 170 (82%) retained the same primary decision-maker, usually the medical oncologist and/or surgeon (57%, 56% respectively). 3 patients reported missing days from work or school due to GIST in their first year since diagnosis. Therapeutic efficacy was assessed by tumor size on CT (53%), tumor size and radiodensity on CT (33%), clinical assessment only (14%) and PET (9%). 161 pts (46%) had been treated with imatinib mesylate and 20 pts (6%) sunitinib malate. Conclusions: The reGISTry remains a useful tool for determining evolving patterns in the management of GIST, and it points out important differences in official practice guidelines and community standards. KIT testing is common in the community, but mutational analysis is rare. Assessment by CT is customary, but PET imaging is rarely utilized in clinical practice. [Table: see text]

9543 Background: The management of pts with GIST dramatically changed after the discovery of the biologic role of dysregulated KIT and PDGFR receptor tyrosine kinases. However, published data on the epidemiology and patterns of diagnosis and management of GIST are limited. To fill this gap, the reGISTry, an observational, internet-based database designed to understand evolving patterns of care for pts with GIST, overall and by pt and provider characteristics, was established. Methods: Up to 200 physicians are expected to participate; recruitment of centers is stratified by geographic area and institution size/type. The reGISTry will be active for at least 4 years with expected accrual of 1800 pts. Pts must have a diagnosis of GIST and give written informed consent. Collected data include pt demographics, clinical characteristics, clinical/economic outcomes and medical care provided to treat GIST. Data analyses are performed every 6 months. Results: The first pt was enrolled in Jan 2005. As of Nov 2005 there were 108 pts enrolled from 39 centers. Eighty five pts (79%) were from community-based practices and 23 (21%) from university/academic centers. Fifty-five pts (51%) were male. Median age was 62 years (range 37–85). At diagnosis, 84 pts (78%) had a primary tumor and 24 (22%) metastatic disease. At diagnosis, 101 pts (94%) had immunohistochemical KIT testing, 95% with positive results. Only 2% of pts had genotyping performed. Surgery was the most common first-line treatment (85 pts, 79%). Eighty-nine percent of those with primary disease and 42% of those with metastatic disease underwent surgical resection as their initial therapy. Fifty percent of pts with metastatic disease and 7% of pts with primary disease underwent systemic therapy as their initial treatment. Forty-seven pts (44%) had imatinib mesylate therapy with 400 mg daily the most commonly prescribed dose. Therapeutic efficacy was more commonly assessed by CT size with radiodensity (55.6%) than positron-emission tomography (0%). Conclusions: The reGISTry is a useful tool for determining evolving practice patterns in the management of GIST. Iterative data analyses over the next 4 years will allow for comparison of management patterns as advances in the understanding of GIST evolve. [Table: see text]

We administered 2 g of ceftazidime intravenously every 8 h to cancer patients for the empiric therapy of febrile episodes. Ceftazidime was administered as monotherapy for patients with granulocyte counts in excess of 1,000/microliter. Febrile, neutropenic patients were randomized to also receive either piperacillin or tobramycin. The pharmacokinetic profile of ceftazidime during a steady-state dosing interval was ascertained in 21 patients. No differences were seen between groups for any of the pharmacokinetic parameters examined. As expected, the observed half-life was longer, the serum clearance was smaller, and the volumes of distribution were larger than in previously reported studies of volunteers. Serum concentrations remained above the MIC for inhibition of 90% of strains of the most common bacteremic pathogens seen in our cancer center for the entire 8-h dosing interval.