These data confirm and extend the primary report of OS, supporting the superior efficacy of nab-paclitaxel plus gemcitabine over gemcitabine alone. Subgroup analyses support the relevance of CA 19-9 and NLR as prognostic markers in metastatic pancreatic cancer.

Of 133 patients with advanced urothelial tract cancer given methotrexate (MTX), vinblastine (VBL), Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (DDP) (M-VAC regimen), significant tumor regression occurred in 72% f 8% of 121 with transitional cell carcinoma (TCC) evaluable for response. Complete remission (CR) was achieved in 36% +-9% of patients, of whom 11% required the addition of surgical resection of residual disease. Although 68% of CR patients have relapsed, CR median survival will exceed 38 months compared with 11 months for partial (36%) and minor (6%) responders, and 8 months for nonresponders: 2-year and 3-year survivals were 68% and 55%, respectively, versus 0% to 7% for the remaining patients. Sixteen percent of responders developed brain lesions, half of whom had no systemic relapse a t the time of progression. Three patients with non-TCC histologies did not respond. In 32 patients who had pathologic restaging, the clinical (T) understaging (T < pathologic [PI restaging) error was 35%. Although all metastatic sites showed evidence of tumor regression, CR was noted more frequently in lung, in intraabdominal lymph nodes and masses, and in bone (24% to 35%); the rate for hepatic lesions was 15%. There were 52% of 21 NS4& patients who achieved CR versus 33% of 100 with No.+M+ lesions. Toxicity was significant with 4 (3%) drug-related deaths, 25% incidence of nadir sepsis, 58% 2 3+ myelosuppression, and 49% with mucositis. Responsiveness of metastasis in various sites, patterns of relapse, and the usefulness of the new CR response criteria are reported, as is the current status of cisplatin and methotrexate combination regimens.Cancer 64:2448-2458, 1989. noma (TCC), complete remission (CR) was achieved in 37% of patients, with 55% alive from 26+ to 49+ months, and partial remission (PR) in 3 1 % of patients. The current Phase I1 study reports the experience of the first 3 years with a follow-up of a minimum of 3 years from patient entry (median follow-up is 54 months), the responsiveness of the primary tumor and metastases at different sites, the relapse patterns, and the accuracy of clinical staging. In 46 cases, serum MTX levels obtained on day 2 were within the expected range.'Patients were hospitalized for 3 to 5 days of each monthly cycle (Table 1) for diagnostic tests and hydration with D5 1/2NS with potassium supplement to assure a urinary output of >lo0 ml/h, and until the blood urea nitrogen (BUN) and creatinine (Cr) returned to pretreatment values. Generally, DDP was given with antiemetics and 12.5 g mannitol. ADR was reduced to 15 mg/m2 in patients who had irradiation equivalent to >20 Gy in 5 2448

Primary Outcome Esophageal eosinophil count: P < .0001 for both dose groups Key Secondary Outcome Dysphagia clinical symptom frequency and severity (DSD): Not statistically significant for both dose groups Safety Assessment AEs All low frequency Headache Upper respiratory tract infection Arthralgia Nasopharyngitis Diarrhea Nausea SAEs All unrelated to treatment RPC4046 180 mg or 360 mg treatment for 16 weeks See editorial on page 545. BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a chronic, esophageal, type 2 inflammatory response associated with increased serum levels of interleukin 13 (IL13), which might contribute to its pathogenesis. RPC4046, a recombinant humanized monoclonal antibody against IL13, prevents its binding to the receptor subunits IL13RA1 and IL13RA2. We performed a phase 2 trial to evaluate the efficacy and safety of RPC4046 in patients with EoE. METHODS: We performed a multicenter, double-blind trial of 99 adults with active EoE randomly assigned (1:1:1) to groups given RPC4046 (180 or 360 mg) or placebo once weekly for 16 weeks, from September 2014 through December 2015. Patients were seen at day 1 (baseline) and weeks 2, 4, 8, 12, and 16. They underwent esophagogastroduodenoscopy and biopsies were collected at baseline and week 16. Patients completed a daily dysphagia symptom diary through week 16 and patient-reported outcome data were collected. The primary outcome was change in mean esophageal eosinophil count in the 5 high-power fields (hpfs) with the highest level of inflammation. RESULTS: At week 16, mean changes in esophageal eosinophil count per hpf were a reduction of 94.8 ± 67.3 in patients who received 180 mg RPC4046 (P < .0001) and a reduction of 99.9 ± 79.5 in patients who received 360 mg RPC4046 (P < .0001) compared with a reduction of 4.4 ± 59.9 in patients who received placebo. The 360-mg RPC4046 group, compared with the placebo group, showed significant reductions in validated endoscopic severity score at all esophageal locations (P < .0001), validated histologic grade and stage scores (both P < .0001), and clinician's global assessment of disease severity (P ¼ .0352); they had a numerical reduction in scores from the dysphagia symptom diary (P ¼ .0733). Significant reductions in esophageal

Background. nab-Paclitaxel in combination with gemcitabine has emerged as a new treatment option for patients with metastatic pancreatic cancer (MPC), based on superiority over gemcitabine demonstrated in the phase III MPACT trial. Previously, Karnofsky performance status (KPS) score and the presence of liver metastases were shown to be predictive of survival with nab-paclitaxel plus gemcitabine treatment. This analysis sought to further explore the relationship between clinical characteristics and survival in the MPACT trial and to identify potential predictors of overall survival and progression-free survival in patients with MPC. Materials and Methods. Cox regression models adjusted for stratification factors and a stepwise multivariate analysis of prespecified baseline prognostic factors were performed. Results. Treatment effect was significantly associated with survival, with a similar magnitude of reduction in risk of

In vitro studies have shown that fluoxetine and paroxetine are more potent inhibitors of cytochrome CYP2D6 than sertraline. The pharmacokinetics of desipramine when coadministered with the selective serotonin reuptake inhibitors (SSRIs) paroxetine and sertraline were studied in 24 healthy male volunteers (CYP2D6 extensive metabolizers). Desipramine (50 mg/day) was administered for 23 days in each phase of the crossover study with a 7-day drug-free period between phases. In addition, subjects were randomly assigned to receive concomitant paroxetine (20 mg/day on days 8 through 17 followed by 30 mg/day on days 18 through 20) or sertraline (50 mg/day on days 8 through 17 and 100 mg/day on days 18 through 20). SSRI treatments were switched between phases. After 10 days of coadministration at the lower dose, mean desipramine maximum concentration in plasma (Cmax) relative to baseline increased from 37.8 to 173 ng/mL (+358%) with paroxetine versus from 36.1 to 51.9 ng/mL (+44%) with sertraline; the mean desipramine 24-hour area under the concentration-time curve (AUC[24]) increased from 634 to 3,305 ng x h/mL (+421%) with paroxetine versus from 611 to 838 ng x h/mL (+37%) with sertraline; and the mean desipramine trough value (C0) increased from 18.5 to 113 ng/mL (+511%) with paroxetine versus from 18.3 to 21.8 ng/mL (+19%) with sertraline (all increases, p < 0.001). An approximately 10-fold increase in the Cmax and AUC(24) of paroxetine and an approximately 2-fold increase in these parameters for sertraline occurred simultaneously with the desipramine concentration changes. Thus, when coadministered with 50 mg/day desipramine, sertraline had significantly less pharmacokinetic interaction than paroxetine with desipramine at the recommended starting dosages of 50 mg/day and 20 mg/day, respectively.