ITT Group Research Articles

Fatigue survival and failure resistance of titanium versus zirconia implant abutments with various connection designs

Statement of problemData regarding the effect of connection design and abutment material on the fatigue survival and failure resistance of implant abutments are scarce. PurposeThe purpose of this in vitro study was to investigate the effect of connection design and abutment material on the fatigue survival and failure resistance of implant abutment assemblies. Material and methodsThree types of implants (n=18, N=54) and 6 groups of abutments (n=9, N=54) with different connection designs—internal conical (IC), internal tri-channel (IT), and external hexagonal (EH)—and abutment materials—titanium (T) and zirconia (Z)—were investigated. All the abutments were restored with identical central incisor crowns. Fatigue testing, including thermal and mechanical aging, was performed in a mastication simulator (Esetron Smart Robotechnologies) for up to 1.2×106 cycles with a load of 50 N at an angle of 45 degrees. Then, the surviving specimens were subjected to failure resistance testing in a universal testing machine (Shimadzu AG-IS; Shimadzu Corp) at a crosshead speed of 1.0 mm/min. The maximum loads to failure (N) were recorded. Survival performance of the specimens throughout the fatigue testing was examined by the Kaplan-Meier survival analysis. The failure loads were analyzed by using the Kruskal-Wallis test followed by the Mann-Whitney U tests with Bonferroni-Holm correction (α=.05). ResultsAll the specimens of groups ICT, ITT, ITZ, and EHT survived fatigue testing, whereas 2 specimens from group ICZ and 3 specimens from EHZ failed. Statistically significant differences were found among the groups, based on the results of maximum failure loads (P<.05). The highest mean failure load was obtained in the ICT group (1069 ±182 N), followed by the ITT (926 ±197 N), EHT (873 ±126 N), ITZ (568 ±81 N), EHZ (311 ±45 N), and ICZ (287 ±63 N) groups. ConclusionsAbutment material and connection design affected the fatigue survival of implant abutment assemblies. Implant abutment assemblies with a titanium-titanium interface revealed higher failure resistance than the implant abutment assemblies with a titanium-zirconia interface.

Ixazomib in Combination with Thalidomide and Dexamethasone for Induction and Ixazomib Maintenance Therapy Overcomes High-Risk Cytogenetics (but not of 1q21 Gain) in Relapsed/Refractory Multiple Myeloma — AGMT_MM1

Ixazomib in Combination with Thalidomide and Dexamethasone for Induction and Ixazomib Maintenance Therapy Overcomes High-Risk Cytogenetics (but not of 1q21 Gain) in Relapsed/Refractory Multiple Myeloma — AGMT_MM1

Home-Based, Therapist-Assisted, Therapy for Young Children With Primary Complex Motor Stereotypies

BackgroundComplex motor stereotypies (CMS) typically begin before age three years and include rhythmic, repetitive, fixed movements that last for seconds to minutes and can be interrupted with distraction. ObjectiveWe evaluated the effectiveness of a home-based, parent-provided therapy accompanied by scheduled telephone calls with a therapist, in five- to seven-year old children with primary CMS. MethodsEligible families received an instructional digital versatile disk (DVD) written instructions, and scheduled telephone contacts with a therapist at baseline (DVD receipt), one, three, and eight weeks later. At each call, parents completed outcome measures and received feedback. Outcome scales Stereotypy Severity Scale (SSS) Motor and Impairment scales and a Stereotypy Linear Analogue Scale (SLAS) were also completed via the Iinternet (REDCap)—at screening, one and two months post-baseline call. At study conclusion, participants were divided into an intent-to-treat (ITT; had at least one call) or a lost-to-follow-up (LTF) group. ResultsThirty-eight children (mean = 6 years ± 11 months) were enrolled. The LTF group (n = 14) had significantly higher scores than the ITT (n = 24) group on all attention-deficit/hyperactivity disorder ratings (P < 0.01), but not stereotypy severity. Primary outcome scores, acquired by telephone and REDCap, showed a significant reduction in SSS Motor and Impairment scores between the initial and the last completed evaluation (P ≤ 0.001). Calculated change ratios were SSS Motor −0.23/−0.30 (cal/REDCap); SSS Impairment −0.31/−0.32; and SLAS −0.54 (REDCap). Clinical improvement was further supported by results from a parent improvement scale and end of study questionnaires. ConclusionsHome-based, parent-administered behavioral therapy supplemented by telephone contact with a therapist is effective in reducing complex motor stereotypies in children.

Back-solving Unobservable Trademark Royalty Rates—The Case of ITT vs Xylem Group

Intangible assets like trademarks and patents are typically not traded on active markets, and the measurement of their fair values is based on valuation models that use significant unobservable (Level 3) inputs (i.e., guideline royalty rates under the relief-from-royalty method). Although widely accepted, all authors and lecturers emphasize the difficulties when determining guideline royalty rates under this method. Often, royalty rate analyses fail to survive audit, appeal, or other scrutiny. In developing robust Level 3 inputs, the appraiser must take into account all information that is reasonably available. A new approach is discussed, one that illustrates an alternative method with which to overcome difficulties in identifying and interpreting guideline license agreements. This approach was first introduced in a largely unnoticed lawsuit.

The antiviral effect of poly-gamma-glutamic acid (γ-PGA) in HPV-positive patients.

e14623 Background: Poly-gamma-glutamic acid (γ-PGA), as a signaling regulator of Toll-like receptor 4 (TLR4), has been shown to induce innate immune responses. In previous non-clinical study, we showed that γ-PGA induces signaling pathway of Type 1 interferon, which consequently eliminates various viruses such as SARS, hepatitis C virus, influenza virus, etc. To evaluate the clinical efficacy of γ-PGA, we’ve investigated the antiviral effect of γ-PGA on human. In retrospective study to evaluate, the clinical significance of g-PGA treatment for vaginal intraepithelial neoplasia (VAIN), γ-PGA may be helpful for the cytological regression and reduction of viral load in patients with high-risk HPV-positive VAIN. Since previous human studies showed the possibility of a drug, we have completed a phase I dose escalation study to determine the safety, tolerance and pharmacokinetics of γ-PGA in healthy adult male subjects. Methods: In the current study, we designed a human study of γ-PGA orally treated daily (75 mL) for 24 weeks to demonstrate the antiviral effect of γ-PGA in female HPV-positive patients. HPV viral load and cell-mediated immune responses were measured during 24 weeks to compare HPV clearance rates between the γ-PGA-treated group and the placebo-controlled group and to evaluate immunological parameters, respectively. Results: . In phase IIb clinical trial to evaluate the efficacy and safety of γ-PGA for the fertile women with cervical intraepithelial neoplasia grade 1 (CIN1) patients, regression rate by the treatment of γ-PGA was 45.65%, whereas the placebo controls were 30.23% in ITT group with statistically significance ( p= 0.0247). Conclusions: γ-PGA may be helpful for the cytological regression and reduction of viral load in patients with high-risk HPV-positive CIN I.

Ixazomib, Thalidomide and Dexamethasone (IxaThalDex) in Relapsed/Refractory Multiple Myeloma (RRMM): An Interim Analysis of a Phase II Trial

Ixazomib, Thalidomide and Dexamethasone (IxaThalDex) in Relapsed/Refractory Multiple Myeloma (RRMM): An Interim Analysis of a Phase II Trial

Randomized Trial of Interpersonal Psychotherapy and Cognitive Behavioral Therapy for Major Depressive Disorder in a Community-Based Psychiatric Outpatient Clinic.

Interpersonal psychotherapy (IPT) and cognitive behavioral therapy (CBT) are both evidence-based treatments for major depressive disorder (MDD). Several head-to-head comparisons have been made, mostly in the United States. In this trial, we compared the two treatments in a small-town outpatient psychiatric clinic in Sweden. The patients had failed previous primary care treatment and had extensive Axis-II comorbidity. Outcome measures were reduction of depressive symptoms and attrition rate. Ninety-six psychiatric patients with MDD (DSM-IV) were randomized to 14 sessions of CBT (n = 48) or IPT (n = 48). A noninferiority design was used with the hypothesis that IPT would be noninferior to CBT. A three-point difference on the Beck Depression Inventory-II (BDI-II) was used as noninferiority margin. IPT passed the noninferiority test. In the ITT group, 53.5% (23/43) of the IPT patients and 51.0% (24/47) of the CBT patients were reliably improved, and 20.9% (9/43) and 19.1% (9/47), respectively, were recovered (last BDI score <10). The dropout rate was significantly higher in CBT (40%; 19/47) compared to IPT (19%; 8/43). Statistically controlling for antidepressant medication use did not change the results. IPT was noninferior to CBT in a sample of depressed psychiatric patients in a community-based outpatient clinic. CBT had significantly more dropouts than IPT, indicating that CBT may be experienced as too demanding. Since about half the patients did not recover, there is a need for further treatment development for these patients. The study should be considered an effectiveness trial, with strong external validity but some limitations in internal validity.

Cyclic loading (vibration) accelerates tooth movement in orthodontic patients: A double-blind, randomized controlled trial

This was a parallel, double-blind, prospective, randomized, controlled trial with the objective to assess the effect of a defined low-level cyclic loading on the rate of orthodontic tooth movement. Overall, 45 orthodontic patients were treated with fixed appliances at the UTHSC San Antonio Orthodontic Department. Inclusion criteria were extraction of maxillary first premolars, maximum maxillary posterior anchorage, and at least 3mm of extraction space after initial alignment. The enrolled subjects were randomized into two groups, vibration ( n = 23) and control ( n = 22) using a third-party computer-generated randomization schedule. All care providers, investigators, and patients were blinded to intervention assignment. Cyclic loading was applied to the vibration group for 20min/day using the AcceleDent ® device, which delivered a force of 0.25N (25g) at a frequency of 30Hz. The control group was assigned to the same protocol, but the device could not be activated to vibrate. The average monthly rate of maxillary canine retraction into an extraction space was analyzed in all 45 subjects (ITT group). The mean rate of movement was significantly higher for the AcceleDent ® group with 1.16mm/month (95% CI: 0.86–1.46) compared to 0.79mm/month (95% CI: 0.49–1.09) in the control group, with the mean difference of 0.37mm/month (95% CI: 0.07–0.81, P = 0.05). These results showed that low-level cyclic loading of 0.25N at 30Hz increases the rate of tooth movement when applied as an adjunct to orthodontic treatment.

Onartuzumab plus bevacizumab versus placebo plus bevacizumab in recurrent glioblastoma (GBM): HGF and MGMT biomarker data.

2015 Background: The phase II GO27819 study assessed the monovalent MET inhibitor, onartuzumab, plus the anti-VEGF antibody, bevacizumab (O+B) versus placebo plus bevacizumab (P+B) in recurrent GBM. Exploratory univariate biomarker analyses correlated efficacy with levels of the MET ligand HGF and MGMT methylation. Methods: GBM patients (pts) at first recurrence after chemoradiation were randomized 1:1 to receive O (15 mg/kg, q3w) + B (15 mg/kg, q3w) or P+B until progression. Primary endpoint: progression-free survival (PFS); secondary endpoints: overall survival (OS), objective response rate (ORR), safety; exploratory endpoint: biomarker analysis. Baseline tumor HGF levels were quantitatively assessed by cobas PCR; MGMT methylation was assessed by Quantitative Methylation Specific PCR. Results: In the ITT group (64 O+B, 65 P+B) no difference in PFS, OS or ORR was seen between the arms. A total of 119 pts (58 O+B, 61 P+B) had HGF-PCR results and 110 (56 O+B, 54 P+B) had MGMT data. Assessing the P+B arm on...

AT-60 * A RANDOMIZED DOUBLE BLIND PLACEBO-CONTROLLED PHASE 2 TRIAL OF DENDRITIC CELL (DC) VACCINE ICT-107 FOLLOWING STANDARD TREATMENT IN NEWLY DIAGNOSED PATIENTS WITH GBM

BACKGROUND: This double-blinded randomized phase 2 trial of ICT-107 in newly-diagnosed glioblastoma (GBM) patients rigorously tested efficacy, safety, QoL, and immune response. METHODS: HLA-A1+ and/or -A2+ resected patients with residual tumor <1 cm3 received 6wks of concurrent temozolomide (TMZ) and radiation. 124 patients, randomized 2:1, received ICT-107 (autologous DCs pulsed with 6 synthetic peptide CTL epitopes targeting GBM tumor/stem cell-associated antigens MAGE-1, HER-2, AIM-2, TRP-2, gp100, and IL-13Rα2) or matching control (unpulsed DC). Patients then received induction ICT-107 or control QWx4 followed by maintenance TMZ, 5 days/mo for 12mos. Maintenance vaccinations occurred at 1, 3, and 6mos after induction, and every 6mos thereafter until progression. RESULTS: ICT-107 was generally safe and well tolerated, with no AE imbalance between treated and control. At the 67-event trial completion, median OS had not been reached. Follow-up continues: at 79 events, median OS favored ICT-107 by 1.6mos in the ITT and 1.9mos in the PP (117 patients completing induction) groups, although not statistically significant (p = 0.64 two-sided, HR = 0.89, and p = 0.48, HR = 0.84, respectively). Median PFS was significantly improved in the ICT-107 ITT and PP groups by 2.2mos and 2.4mos (p = 0.01, HR = 0.57, p = 0.006, HR = 0.54, respectively). Treatment extended PFS with sustained QoL assessed by FACT-BR, KPS, and steroid usage. The frequency of HLA-A2 primary tumor antigen expression was higher than that for HLA-A1 patients, and HLA-A2 patients had higher vaccine response (via Elispot) than HLA-A1 patients. PP HLA-A2 patients in both the MGMT methylated and unmethylated pre-specified subgroups saw a clinically meaningful ICT-107 effect, although HLA-A1 patients received no benefit from vaccine. CONCLUSIONS: PFS was significantly improved in ICT-107 treated patients with maintenance of QoL. Patients in the HLA-A2 MGMT subgroups show stronger ICT-107 activity clinically and immunologically, and these groups will be studied in a future phase 3 trial.

Abstract 18968: Bromocriptine-QR: A Potential Novel Strategy for Cardiovascular Risk Reduction in Type 2 Diabetes

Type 2 diabetes (T2D) is associated with a substantially increased risk of cardiovascular disease (CVD). Of the available therapies for T2D, none have been conclusively shown to reduce CVD risk. Metformin has long been considered the only agent with some evidence, albeit limited, of a potential CVD benefit. Bromocriptine-QR (BQR), a quick release sympatholytic dopamine agonist, is a newer FDA-approved therapy for T2D. Based on preclinical and clinical study findings, it is postulated that BQR restores the normal circadian peak in central dopaminergic tone diminished in insulin resistant states, which in turn reduces hyperactive sympathetic tone and improves central fuel sensing thereby reducing postprandial hepatic glucose and lipid output as well as reduces vascular resistance, oxidative stress, and inflammation. In a one-year randomized trial of BQR vs. placebo added to standard therapy (diet and/or ≤ 2 diabetes medications including sulfonylureas, TZD, metformin, or insulin) in 3070 T2D subjects (average duration of T2D: 7.9 years), including individuals with pre-existing CVD, BQR therapy resulted in a 40% hazard rate reduction (HRR) in major CVD events, pre-specified as a composite of time to first myocardial infarction, stroke, coronary revascularization, hospitalization for angina or congestive heart failure. In the present study, this CVD effect of BQR was evaluated in a subset of this original study population on metformin +/- another anti-diabetes therapy at baseline (N = 1791). The composite CVD end point occurred in 16/1208 BQR-treated (1.3%) and 18/583 placebo-treated (3.1%) subjects resulting in a 53% CVD HRR (ITT group, Cox regression analysis; HR 0.47, 95% CI 0.24, 0.92, P = 0.028) adjusted by age (HR 1.08, 95% C.I. 1.04, 1.12, P = 0.0003) and pre-existing CVD (HR 2.27, 95% C.I. 1.02, 5.07, P = 0.041). Kaplan-Meier Curves of the cumulative incidence rate yielded a CVD HRR of 58% (HR 0.42, 95% C.I. 0.21, 0.85, Log-Rank = 0.017). These findings reaffirm prior observations of CVD risk reduction with BQR therapy and further demonstrate the potential for a marked additive effect of BQR above any derived from metformin, suggesting a potential novel strategy for CVD risk reduction in T2D.

SAT0333 Efficacy of sodium hyaluronate versus hylan G-F 20 in the treatment of tibiofemoral osteoarthritis

BackgroundCrosslinked hylan is perceived to have longer efficacy than native hyaluronic acid in the treatment of osteoarthritis (OA).ObjectivesTo compare the efficacy of intra-articular injections of native sodium hyaluronate 1% (SH)...

FRI0548 Physical and mental health in ra patients treated with biologic dmards - two-year follow-up data of the german biologics register rabbit

BackgroundHealth-related quality of life (HRQoL) has been identified as a key indicator of disease burden in chronic diseases such as rheumatoid arthritis (RA).ObjectivesTo measure the effectiveness of biologic (b) versus...

A phase II study of cetuximab-based neoadjuvant and adjuvant treatment strategies, with or without surgery, in patients with locally very advanced squamous cell carcinoma of the oral cavity.

e16050 Background: The purpose is to evaluate the efficacy of sequential regimen using cetuximab-based doublet neoadjuvant chemotherapy, followed by surgery, if tumors resectable, and adjuvant cetuximab-based chemoradiotherapy in locally very advanced OSCC patients. Methods: Patients with T4a/b or N2b/c or N3 OSCC were enrolled to determine the response rate of cetuximab, cisplatin, and 5-FU neo-adjuvant chemotherapy. Cetuximab (400 mg/m2 loading, followed by 250 mg/m2 weekly x 6 weeks) was combined with 2 3-weekly cycles of cisplatin (100 mg/m2) and 5-FU (1000 mg/m2 x 3 days) as neo-adjuvant. Patients whose tumors became operable after neoadjuvant underwent radical surgery followed by adjuvant weekly cetuximab (250 mg/m2), cisplatin (30 mg/m2) and XRT (up to 70 Gy). Patients whose tumors remained inoperable after neoadjuvant received weekly cetuximab (250 mg/m2), cisplatin (30 mg/m2) and XRT (up to 70 Gy). Results: 33 patients were enrolled from Dec. 2009 to Jan. 2011. Average age was 47.3 years. 51.5% had primary lesion in buccal mucosa and 21.2% on tongue. 66.7% and 27.2% had T4b or T4a disease respectively, while 72.7% had N2b/N2c/N3 disease. 28/33 completed treatment course. On ITT analysis, 39.4% (13/33) had partial response and 48.5% (16/33) had stable disease after neoadjuvant. 42.4% (14/33) underwent radical surgery after neoadjuvant, while another 9% (3/33) underwent surgery after bio-chemoradiation. The 1 year disease free survival (resected group), progression free survival (ITT group), and overall survival (ITT group) were 48.8%, 73.2%, and 51.7% respectively. The most common grade 3/ 4 adverse event in neo-adjuvant phase was vomiting (16.1%), while mucositis (75%) and dermatitis (42.8%) accounted for major grade 3/ 4 adverse events during bio-chemoradiation. Conclusions: Cetuximab based sequential regimen was efficacious and well tolerated in improving treatment outcomes in locally very advanced OSCC patients with manageable side effects.

동물 및 인체시험을 통한 Nattokinase의 항응고 작용 및 섬유소 용해능 평가

Bacillus subtilis natto producing high level of a fibrinolytic enzyme was selected and Ultra Nattokinase<TEX>$^{(R)}$</TEX> was manufactured by fermentation and purification. It was performed the evaluation of the antithrombotic effect of Ultra Nattokinase<TEX>$^{(R)}$</TEX> (20,000 FU/g) with rat blood plasma. The maximum aggregation (inhibition ratio) was 71% (0%), 69% (2.8%), 62% (12.7%), 16% (77.5%) and 9% (87.3%), respectively, in the order of 0, 5, 10, 50 and 100 mg/mL of Ultra Nattokinase<TEX>$^{(R)}$</TEX> solutions. Ultra Nattokinase<TEX>$^{(R)}$</TEX> had antithrombotic effect, which was associated with the suppression of collagen-induced platelet aggregation. Ultra Nattokinase<TEX>$^{(R)}$</TEX> in the topic of the FDP (fibrinogen degradation products) in blood coagulation tests showed a significant increasing trend. And based on the daily record of meal 39 people of ITT (what ?) group consisted with 19 people of NP (what ?) group and 20 people of PN (what ?) group except four people, two people who took vitamin K affecting the experiment and two people who took alcohol, finding to be taken Ultra Nattokinase<TEX>$^{(R)}$</TEX> showed an increase in the FDP value after four weeks. In addition, FDP value of 41 people of ITT group except two people having metabolic syndrome was increased by Ultra Nattokinase<TEX>$^{(R)}$</TEX>.

Efficacy and Safety of CVT-E002, a Proprietary Extract of Panax quinquefolius in the Prevention of Respiratory Infections in Influenza-Vaccinated Community-Dwelling Adults: A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Trial

CVT-E002 (a proprietary extract) was found to be effective in the prevention of upper respiratory infections (URIs) in healthy adults, and institutionalized and community-dwelling seniors. A multicenter, randomized, double-blind, placebo-controlled trial was carried out to determine effects of CVT-E002 in the prevention of URIs in influenza-vaccinated community-dwelling adults. 783 community-dwelling adults were randomized to receive placebo, 400 mg or 800 mg treatment/d (1 : 1 : 1) for 6 months. Primary analysis on the incidence of laboratory-confirmed-clinical URIs (LCCUs), including influenza A and B, was performed on those receiving at least one dose. Secondary analysis was performed on study completers and included incidence, severity, and duration of URIs meeting a Jackson-based criteria and safety of CVT-E002. The incidence of LCCUs in the ITT group was 5.5%, 5.2%, and 4.6% in the placebo, 400 mg and 800 mg groups, respectively (P = 0.89). Jackson-confirmed URIs were significantly lower in the treated groups (P < 0.04). CVT-E002 supplementation reduced the severity and duration of Jackson-confirmed URIs. The results indicate that CVT-E002 can be safely used by similar groups and may prevent symptoms of URIs; larger sample size is warranted.

A Novel Nasal Expiratory Positive Airway Pressure (EPAP) Device for the Treatment of Obstructive Sleep Apnea: A Randomized Controlled Trial

Investigate the efficacy of a novel nasal expiratory positive airway pressure (EPAP) device as a treatment for obstructive sleep apnea (OSA). A prospective, multicenter, sham-controlled, parallel-group, randomized, double-blind clinical trial. 19 sites including both academic and private sleep disorder centers Obstructive sleep apnea with a pre-study AHI ≥10/hour Treatment with a nasal EPAP device (N=127) or similar appearing sham device (N=123) for 3 months. Polysomnography (PSG) was performed on 2 non-consecutive nights (random order: device-on, device-off) at week 1 and after 3 months of treatment. Analysis of an intention to treat group (ITT) (patients completing week 1 PSGs) (EPAP N=119, sham N=110) was performed. At week 1, the median AHI value (device-on versus device-off) was significantly lower with EPAP (5.0 versus 13.8 events/h, P<0.0001) but not sham (11.6 versus 11.1 events/h, P=NS); the decrease in the AHI (median) was greater (-52.7% vs. -7.3%, P<0.0001) for the ITT group. At month 3, the percentage decrease in the AHI was 42.7% (EPAP) and 10.1% (sham), P<0.0001. Over 3 months of EPAP treatment the Epworth Sleepiness Scale decreased (9.9 ± 4.7 to 7.2 ± 4.2, P<0.0001), and the median percentage of reported nights used (entire night) was 88.2%. The nasal EPAP device significantly reduced the AHI and improved subjective daytime sleepiness compared to the sham treatment in patients with mild to severe OSA with excellent adherence. ClinicalTrials.gov. Trial name: Randomized Study of Provent Versus Sham Device to Treat Obstructive Sleep Apnea (AERO). URL: http://www.clinicaltrials.gov/ct2/show/NCT00772044?term=Ventus&rank=1. NCT00772044.

Geriatric subgroup of AGITG MAX trial: International randomized phase III trial of capecitabine (C), bevacizumab (B), and mitomycin C (M) in first-line metastatic colorectal cancer (CRC).

510 Background: In an aging population a greater proportion of geriatric patients will be considered for systemic chemotherapy. CRC is a common cancer and will be a major health issue in geriatrics. Methods: MAX, a three arm study of C v CB v CBM, found an improvement in PFS with addition of B (± MMC) to C (Tebbutt NC et al. JCO 2010; 28(19): 3191–3198). This analysis assesses effect of adding B (± MMC) to C on PFS, OS, RR and toxicity in geriatric patients (age &gt;75y). Results: 99 patients (21%) were &gt;75y. Number/Median age: C 37/78.5y (75.2–86), CB 32/78.7y (75.2–84.9), CBM 30/80.2y (75.2–83.4). Baseline characteristics were well balanced. 88% commenced C dose of 2000mg/m2/day, d1–14, q21 (61% for &lt;75y). ECOG 0–1 for 88%. Comorbidities were: (%) Ex/smoker 13/2, diabetes 15, HT 56, IHD 15, CVA/TIA 10. These are similar to reported rates ( http://www.aihw.gov.au/cdarf/data_pages/incidence_prevalence/index.cfm ) in this population. Proportion receiving all three chemotherapy drugs at some time (5FU/oxaliplatin/irinotecan) was 10% &gt;75y v 20% &lt;75y. RR, median PFS &amp; OS reported in Table. Interaction test for OS, RR and PFS revealed no impact of age. Gd 3-4 tox for &gt;75y C/CB/CBM respectively was (%); vomiting 5/13/3, diarrhea 19/22/20, stomatitis 3/0/3, HT 0/3/3, thrombosis/thrombus/embolism 5/6/13, cardiac 0/6 (3 Gd5)/3. There was one perforation (Gd5) in C. Grade 2/3 HFS (%) was 38/59/53. One Gd 3-4 neutropenia episode in CB, no Gd 3-4 thrombocytopenia. Overall, toxicity rate similar to &lt;75 y. Conclusions: Significant improvement in PFS with addition of B to C was seen in this geriatric population, similar to results of ITT group and those &lt;75yrs. Treatment was well tolerated with no signal of increased toxicity when compared to those &lt;75yrs, including VTE/ATE. [Table: see text] [Table: see text]

Results of pooled analyses from two phase III trials of 1,085 patients (pts) with advanced melanoma: Oblimersen (OBL) plus dacarbazine (DTIC) versus DTIC alone.

8573 Background: We conducted two phase III trials (GM301 and AGENDA) of DTIC ± OBL in pts with advanced melanoma. Overall survival (OS) was a primary or co-primary endpoint in both studies. The AGENDA analysis plan prospectively specified a “pooled analysis” of OS in both studies. As AGENDA data on OS and durable response are still being collected, we conducted exploratory analyses of early OBL effects using data available from both trials. Methods: A total of 771 and 314 chemotherapy-naïve pts were randomized in GM301 and AGENDA, respectively. Entry criteria were similar in both studies. AGENDA was a double-blind study limited to pts with low-normal baseline LDH levels (≤ 0.8 × ULN), whereas GM301 was open-label and had no LDH restriction. All pts received DTIC ± OBL every 3 weeks. Data from AGENDA were pooled with data of (1) the ITT group in GM301 and (2) the 274 pts with low-normal baseline LDH in GM301 and compared by treatment. PFS was assessed by the log-rank test; ORR was assessed by the Cochran-Mantel-Haenszel test. Results: In DTIC-OBL-treated pts, the ITT ORR in GM301 and AGENDA was 13.5% and 17.2%, respectively, and 20.8% in the GM301 low-normal LDH group. In DTIC-treated pts, the ITT ORR in GM301 and AGENDA was 7.5% and 12.1%, respectively, and 7.2% in the GM301 low-normal LDH group. Response data combined from both trials show an ITT ORR of 14.5% in DTIC-OBL pts vs. 8.9% for DTIC pts (p = 0.004) and a low-normal LDH ORR of 19.0% vs. 9.9% (p = 0.002), respectively. PFS hazard ratio for the ITT group in GM301 and AGENDA was 0.75 and 0.85, respectively, and for the GM301 low-normal LDH group, 0.58. In DTIC-OBL-treated pts, PFS data combined from both trials show a median increase in PFS of 1 month in ITT pts (HR = 0.78; p = 0.0004) and of 1 month in the low-normal LDH group (HR = 0.71; p = 0.0004). Conclusions: Pooled analysis confirms OBL + DTIC is associated with an increase in ORR and modest improvement in PFS, compared with DTIC alone. In the ITT analysis, absolute and proportional improvement in ORR is 5%-6% and 42%-80%, respectively. As ORR and PFS are not established as clinical benefit endpoints in this population, pt follow-up for OS and durable response is ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genta Abraxis BioScience, Bristol-Myers Squibb, Genta, ImClone Systems, Novartis Genta Genta, ImClone Systems Genta Genta

Use of a liquid nicotine delivery product to promote smoking cessation

BackgroundDespite access to various pharmacotherapies and counseling support to aid cessation, smokers typically demonstrate quit rates below 50%. This report describes the results of a Phase 2a study exploring the efficacy of a liquid nicotine delivery system as an aid to smoking cessation assessed after 12 weeks of therapy.MethodsA single-arm Phase 2a study was conducted. Community-based smokers (ages 18+ years, smoking at least 10 cigarettes daily for the past year and interested in making a quit attempt) were recruited and completed clinic visits at 2 week intervals over the 12 week study period where carbon monoxide levels were assessed and the Smoke-Break product was rated on taste and overall satisfaction. Participants were provided with a supply of liquid nicotine cigarettes (e.g., Smoke-Break) at each clinic visit. A total of 69 smokers were enrolled and received the intervention product (intention to treat group, ITT) and 52 smokers verified participation (according to protocol group, ATP).ResultsThe cessation rate at 12 weeks after the baseline visit, assessed as the bioverified point prevalence of abstinence, was 71.1% (95% confidence interval [CI] 58.8%-83.5%) in the ATP group and 53.6% (41.8%-65.4%) in the ITT group. Participants rated the liquid nicotine delivery system highly and also expressed general satisfaction. Few adverse events were identified with no serious adverse events.ConclusionsThese results support the efficacy of the liquid nicotine delivery system in smoking cessation. If this nicotine delivery product proves to be effective in larger trials, it could represent an inexpensive, readily accessible and well-tolerated agent to promote smoking cessation.Trial RegistrationThis trial is registered at clinicaltrials.gov as study NCT00715871.