Average Number Of Cycles Research Articles

Biomechanical Investigation of an Integrated 2-Screw Cephalomedullary Nail Versus a Sliding Hip Screw in Unstable Intertrochanteric Fractures.

To compare the efficacy of 2 intertrochanteric (IT) fracture fixation devices in conferring mechanical stability to unstable IT femur fractures. Nine pairs of cadaveric female femurs with a groupwise average bone quality indicative of osteopenia were used. An unstable IT fracture without calcar support (OTA/AO 31-A2) was created and stabilized with either a sliding hip screw and side plate (SHS) or a cephalomedullary nail using an integrated dual-screw fixation [InterTAN (ITN)]. Constructs were evaluated under stepwise and increasing cyclic loading up to 50,000 cycles (1500 N) or by failure in a test model that may best simulate hip joint contact forces at heel strike. Number of cycles to failure, failure load, and femoral head rotation about the screw axis were compared between groups. The average number of cycles in the ITN group was greater compared with that in the SHS group (48,383 vs. 31,403 cycles, P = 0.046). Similarly, the average maximum load survived by the ITN group was greater than that of the SHS group (1456 vs. 1113 N, P = 0.046). The number of constructs that survived up to the maximum applied load of 1500 N was greater in the ITN group (8/9, 89%) when compared with that of the SHS constructs (3/9, 33%) (P = 0.049). Finally, the ITN group conferred greater rotational control of the femoral head compared with the SHS constructs (1.5 vs. 5.5 degrees, P = 0.018), and reduced the amount of varus collapse (11.1 vs. 31.1 degrees, P = 0.038). The integrated dual-screw construct appeared to confer significantly greater fracture stability compared with a sliding hip screw and side plate using a worst-case model that simulates heel strike during gait. Study data provide biomechanical evidence that the ITN device may provide more stability and rotational resistance than a sliding hip screw in the elderly female patient population with an unstable IT fracture and compromised bone quality.

Insights from outside BJOG

Insights from outside BJOG

Performance Analysis of the EM Algorithm in Conjunction with Algorithms for Determining an Optimal Number of Clusters and Their Centroids, Which Allows Estimating Parameters of Non-Gaussian Interference in Mobile Communication Systems

In this article, the “elbow method” and the “average silhouette” algorithms are used for determining an optimal number of clusters. A “shifted” EM algorithm adapted to the number of clusters is put forward, which allows increasing accuracy of the Gaussian mixture distribution approximation that determines the probabilistic structure of the interference distribution. Dependencies of an average number of cycles and the Kullback–Leibler divergence on a number of clusters in an initial mixture are obtained via mathematical modeling with a preset range of parameters. A comparative analysis of the EM algorithm results is carried out.

Systemic therapy with calcitonin has positive clinical effects on systemic sclerosis in patients with cutaneous manifestations.

Calcitonin gene-related peptide (CGRP) is a vasodilatory neuropeptide that plays an important role in the blood vessels of heart and peripheral circulation, a lack of which may cause vasculopathies. In this study, the clinical course of disease, as well as the efficacy, side effects, and patient satisfaction of systemic calcitonin therapy in patients with systemic sclerosis (SSc), was evaluated. Forty-nine patients received repetitive intravenous calcitonin infusions as first-line treatment. The average number of cycles was 12.2±10.3 over a period of 30 months (each cycle: 100U/day over 10 days). Clinical examinations, laboratory tests, and organ imaging were performed before the start of, and at regular intervals during therapy in order to evaluate organ manifestations and the clinical course of the disease. In addition, patients' own experiences of the therapy, side effects, and therapy success were evaluated with standardized questionnaires. Over the course of the treatment, seven patients experienced improvements in their condition with a considerable reduction in digital ulceration and improved movement (14.3%). Pulmonary function in seven patients improved during the therapy (14.3%). With regards to side effects, nausea (41.7%), headaches (33.3%), fluctuations in blood pressure (29.2%), and flushing (29.2%) were observed. Overall, 45.8% of patients evaluated the therapy as good and 58.3% would undergo further courses of therapy with calcitonin. Systemic calcitonin treatment seems to have positive clinical effects on SSc and contributes to relieving symptoms, especially in patients with cutaneous manifestations. No severe side effects were reported during this study.

1123P - The cost of expensive breast cancer drugs

Background: Increasing healthcare costs are a major challenge in medical oncology, since the total costs of oncology can account for up to 30% of the total hospital expenditures. As many novel (expensive) cancer treatments are being developed, it is important to be transparent about drug prices from an early research stage on. To assess the potential financial impact of pipeline drugs, their expected future prices can be deducted from prices of currently used drugs. As an overview of the standard prices of expensive breast cancer treatments in European countries is lacking, this review aimed to synthesize all evidence on costs of approved, expensive breast cancer drugs in the Netherlands. Methods: A literature review was performed to create an overview of all approved, expensive drugs in the Netherlands. Standard drug costs were retrieved via the Dutch administrative health authority (ZINL). Drugs were considered expensive if the standard price of the drug was more than €10 per unit or if the cost of a treatment with that particular drug exceeded €1000 on average per patient. Results: In the Netherlands 25 breast cancer drugs are approved with a standard price of more than €10 per unit. After excluding drugs with expected treatment costs less than €1000, 19 drugs were included in the analysis. The standard drug price is €7,943 on average (range €63 - €45,452), and the average number of cycles per patient is 10.5 (range 4 - 25.3 cycles). This results in average treatment costs per patient of expensive drugs of €17,968 (range €1,103 - €87,123). Four drugs that initially ranked low based on standard drug unit prices (rank 10-19), rank substantially higher (rank 1-10) when ranking total treatment costs. Conclusions: Ranking standard drug prices per unit may not be very informative. It would be valuable to rank drug treatment costs, based on treatment length and dosage estimates. However, in the Netherlands the expected treatment length for a particular drug is not standardly reported in official approval reports. Furthermore, actual prices of expensive drugs may differ from standard drug prices, by which treatment costs might be deviant. Extending standardization of reporting and calculation of drug treatment costs would be valuable and particularly relevant when extending this type of cost calculations to other countries. Legal entity responsible for the study: University of Twente - Health Technology and Services Research Funding: None Disclosure: All authors have declared no conflicts of interest.

Biomechanical Evaluation of Unicortical Stress Risers of the Proximal Humerus Associated With Pectoralis Major Repair.

Proximal humerus fracture after pectoralis major tendon repair has been recently reported. Although this complication is rare, it may be possible to decrease such risk using newer techniques for myotenodesis. This study was designed to evaluate various unicortical stress risers created at the proximal humeral metadiaphysis during myotenodesis for repair of pectoralis major ruptures. A simulated pectoralis major myotenodesis was performed using fourth-generation Sawbones (N=30). Using previously described anatomic landmarks for the tendinous insertion, 3 repair techniques were compared: bone trough, tenodesis screws, and suture anchors (N=10 each). Combined compression and torsional load was sequentially increased until failure. Linear and rotational displacement data were collected. The average number of cycles before reaching terminal failure was 383 for the bone trough group, 658 for the tenodesis group, and 832 for the suture anchor group. Both the tenodesis and the suture anchor groups were significantly more resistant to fracture than the bone trough group (P<.001). The suture anchor group was significantly more resistant to fracture than the tenodesis group (P<.001). All test constructs failed in rotational stability, producing spiral fractures, which incorporated the unicortical defects in all cases. When tested under physiologic parameters of axial compression and torsion, failure occurred from rotational force, producing spiral fractures, which incorporated the unicortical stress risers in all cases. The intramedullary suture anchor configuration proved to be the most stable construct under combined axial and torsional loading. Using a bone trough technique for proximal humerus myotenodesis may increase postoperative fracture risk. [Orthopedics. 2017; 40(5):e801-e805.].

Docetaxel chemotherapy in metastatic castration-resistant prostate cancer: cost of care in Medicare and commercial populations

Objective: To estimate the healthcare costs and characteristics of docetaxel chemotherapy episodes of care for men with metastatic castration-resistant prostate cancer (mCRPC).Methods: This study used the Medicare 5% sample and MarketScan Commercial (2010–2013) claims data sets to identify men with mCRPC and initial episodes of docetaxel treatment. Docetaxel episodes included docetaxel claim costs from the first claim until 30 days after the last claim, with earlier termination for death, insurance disenrollment, or the end of a 24-month look-forward period from initial docetaxel index date. Docetaxel drug claim costs were adjusted for 2011 generic docetaxel introduction, while other costs were adjusted to 2015 values using the national average annual unit cost increase.Results: This study identified 281 Medicare-insured and 155 commercially insured men, with 325 and 172 docetaxel episodes, respectively. The average number of cycles (unique docetaxel infusion days) per episode was 6.9 for Medicare and 6.3 for commercial cohorts. The average cost per episode was $28,792 for Medicare and $67,958 for commercial cohorts, with docetaxel drug costs contributing $2,588 and $13,169 per episode, respectively. The average cost per episode on docetaxel infusion days was $8,577 (30%) for Medicare and $28,412 (42%) for commercial. Non-docetaxel infusion day costs included $7,074 (25%) for infused or injected drugs for Medicare, $10,838 (16%) for commercial cohorts, and $6,875 (24%) and $9,324 (14%) for inpatient admissions, respectively.Limitations: The applicability is only to the metastatic castration-resistance clinical setting, rather than the metastatic hormone-sensitive setting, and the lack of data on the cost effectiveness of different sequencing strategies of a range of systemic therapies including enzalutamide, abiraterone, radium-223, and taxane chemotherapy.Conclusion: The majority of docetaxel episode costs in Medicare and commercial mCRPC populations were non-docetaxel drug costs. Future research should evaluate the total cost of care in mCPRC.

Development of a Quantifiable Approach in Monitoring the Fatigue Cracks Using Digital Image Correlation

From the viewpoint of engineering, fatigue is an important issue as most of the mechanical failures are associated with fatigue damage. In fact, these disastrous events had occurred unexpectedly during the regular working conditions and most of the time the applied stresses are well below the yield strength of the material. Thus, it makes the prediction of fatigue damage a challenging task in the field of engineering, especially when the manmade structures and machines are getting more complex than before. Even though fatigue has been studied extensively in the past 170 years, many limitations are still being found within the current fatigue analysis, testing and the non-destructive inspection. Hence, there is a great need to develop a precise and yet efficient inspection technique in quantifying the fatigue cracks. Therefore, the objective of this study is to develop a quantifiable approach in monitoring the fatigue cracks using digital image correlation technique. This can be achieved by using a developed two-dimensional sub-pixel accuracy deformation measurement algorithm which determines the deformation parameters of the first-order shape function of a material subjected to cyclic loading. Next, fatigue tests for samples made of mild steel (Grade: JIS G 3101 SS400) were conducted in accordance to the ASTM E466. Simultaneously, an industrial grade camera was used to capture the fatigue crack’s region at a specific interval until the sample broke into two pieces. The captured images were then analysed and the deformation parameters such as translations, normal and shear strains values were determined by using the developed digital image correlation algorithm. Based on the determined deformation patterns, a specific trend was observed throughout the graphs of respective deformation parameters against the number of cycles. Besides, drastic changes were observed when the average number of cycles was approaching 95.5% (min. loading) and 93.8% (max. loading) of the total fatigue life. In conclusion, the digital image correlation technique was proven to be capable in monitoring the severity of a fatigue crack and the proposed monitoring system would serve as an inspection technique in examining the fatigue damage of a structural component throughout its operational period.

Flexor Tendon Repair With Looped Suture: 1 Versus 2 Knots

To assess the strength of flexor tendon repair with looped suture. We hypothesized that, after passing the intact looped suture in the desired repair configuration, splitting the loop and tying 2 independent knots would increase the strength of flexor tendon repair. Thirty-two flexor tendons were harvested and were sharply transected in zone II. The tendons were repaired with a 4-strand core suture repair using 3-0 looped nonabsorbable nylon suture. The harvested tendons were randomly assigned and repaired with either a 1- or a 2-knot construct. The repaired flexor tendons were fixed in a servohydraulic material testing system and were loaded to failure either with uniaxial tension or cyclically. The average force at failure was 43 N for the 1-knot repair and 28 N for the 2-knot repair. The mode of failure of 15 of the flexor tendon repairs that were cyclically loaded to failure was suture pull-out. The average number of cycles and force in cyclic testing that caused failure of flexor tendon repairs was 134 cycles and 31 N for tendons repaired with looped 3-0 suture tied with 1 knot and 94 cycles and 33 N for tendons repaired with looped 3-0 suture tied with 2 knots. Our hypothesis was disproved by the results of this study. This study suggests that, when using looped suture, tying 2 independent knots instead of tying a single knot does not increase the strength of the flexor tendon repair.

Abstract P3-10-02: Gemcitabine with cisplatin or paclitaxel in metastatic triple-negative breast cancer

Abstract Background: There is still no standard chemotherapy for patients with metastatic triple-negative breast cancer (mTNBC). Our previous phase II pilot trial with first-line gemcitabine and cisplatin combination (GP) in patients with mTNBC (clinicaltrials.gov Identifier: NCT00601159) showed a median progression-free survival (PFS) of 6.2 months. In this Chinese Breast Cancer Study Group (CBCSG) 006 trial (clinicaltrials.gov Identifier: NCT01287624) we explored in a randomized trial the role of the less costly GP regimen versus the standard GT [Gemcitibine + paclitaxel] chemotherapy for the metastatic breast cancer as a first line treatment for mTNBC. Trial objectives: progression free survival [PFS]; overall survival [OS]; and toxicity. Methods: In the trial with a hybrid trial design incorporating a formal test of superiority as well as noninferiority, mTNBC patients with no previous chemotherapy for metastatic disease were randomly assigned to receive either GP regimen (G/P: 1250 mg/m2 d1,8/ 75 mg/m2 d1) or the GT regimen (same G; T: 175 mg/m2 d1). Results: Between Jan. 2011 and Nov., 2013, 236 patients were randomized [118 patients / arm], and all received at least one dose of assigned chemotherapy. As of Mar. 20, 2014, the intent-to-treat analysis showed 201 recurrences and 97 deaths. Objective response rates of GP vs GT were 67.9% vs. 50.4% (P= 0.008), with median PFS of 232 vs. 194 days (HR=0.692, 95% CI 0.523-0.915; P= 0.009). Overall survival of patients from the GP vs. the GT arms was median 672 vs. 556 days (HR=0.902, 95% CI 0.605-1.344; P= 0.611). Significant differences in grade 3/4 adverse events were seen for nausea, vomiting, anemia and thrombocytopenia [GP vs. GT, 6.8 vs. 0.8%; 11.0 vs. 0.8%; 33.1 vs. 51.0%; and 32.2 vs. 2.5%, respectively]. In addition, assessment of adverse events of any grade showed the GP regimen had more anorexia, constipation, hypomagnesemia and hypokalemia, while GT regimen had significantly more alopecia and peripheral neuropathy. The delivered relative dose intensity was &amp;gt; 90% for all three drugs, with the total number of delivered cycles of chemotherapy in GP and GT arms being 654 and 648 [average 5.54 and 5.49 /patient], respectively. Conclusions: 1.The Gemcitabine + Platinum is superior to Gemcitabine + Paclitaxel in terms of objective response rates and duration of PFS. 2.While grade 3 / 4 nausea &amp; vomiting, and anemia, were heavier for the GP combination, the delivery of chemotherapy and average number of cycles delivered were comparable between the two arms. 3.Overall survival data will be updated on the conference to indicate the long-term effect of the somehow more toxic GP regimen, which shows nevertheless superiority of response rates and of the PFS over the more costly GT regimen. Citation Format: Xichun Hu, Binghe Xu, Li Cai, Zhonghua Wang, Biyun Wang, Jian Zhang, Yuee Teng, Zhongsheng Tong, Yueyin Pan, Yongmei Yin, Changping Wu, Zefei Jiang, Xiaojia Wang, Guyin Lou, Donggeng Liu, Jifeng Feng, Jianfeng Luo, Jiong Wu, Zhimin Shao, Joseph Ragaz. Gemcitabine with cisplatin or paclitaxel in metastatic triple-negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-10-02.

Plateletapheresis in a low-resource center in Nigeria

Introduction: Apheresis is widely established in developed centers but only very few centers in Nigeria have this facility. The commencement of hematopoietic stem cell transplantation (HSCT) in our facility in 2011 necessitated the development of an apheresis center with its enormous benefits for both HSCT patients and other patients in the hospital. Materials and Methods: A retrospective study at the University of Benin Teaching Hospital on donor plateletapheresis over a 4-year period (January 2011 to December 31, 2014). Apheresis machine used for the plateletapheresis is Haemonetics MCS+ and donors were selected using the European Guidelines for apheresis selection. Result: A total of 150 plateletapheresis were performed for 50 patients with an average of 34.75 per annum. Donors were mainly males (84.9%) and the general indication was thrombocytopenia secondary to some medical condition. The main medical indication was thrombocytopenia for patients undergoing HSCT (38.2%). Others were hematological malignancies/chemotherapy-related thrombocytopenia (33.3%) and bone marrow aplasia (7.2%). Sixty-five (46.8%) of donors were of blood group O, 48.2% were of blood group A, 2.2% were of blood group B, and 2.9% were of blood group AB. The majority of the donors (98.6%) were Rhesus-positive. The average number of cycles was 6.4 ± 0.2, average yield was 3.6 ± 0.1 × 10 11 cells, blood volume was 3,135.2 ± 61.0 mL, acid-citrate-dextrose (ACD) was 409.4 ± 25.4 mL, and platelet volume was 243.9 ± 6.1 mL. Conclusion: Plateletapheresis is a new procedure in most developing centers. We have reported the activities in a single center with enormous benefits to patients with thrombocytopenia. There is a need to improve and subsidize these services to make it readily available to patients who require single platelet concentrate.

Clinical Characteristics and Treatment Outcomes in Patients Diagnosed with Primary Mediastinal Large B-Cell Lymphoma at Princess Margaret Cancer Centre from 1994-2012

Introduction: Primary mediastinal B-cell lymphoma (PMBCL) is a rare clinical entity representing less than 2-4% of Non-Hodgkin lymphomas. PMBCL typically occurs in young adults, more often in females, with early stage disease usually limited to the antero-superior mediastinum. PMBCL tends to have a more locally aggressive clinical course with a substantial percentage of patients with primary refractory disease or early relapse. Patients with primary refractory or relapsed disease have a lower probability response to second-line therapy and proceeding to autologous stem cell transplant (ASCT). The optimum chemotherapy regimen and role of radiation are currently the subject of debate; for this reason we evaluated our experience using a uniform treatment policy of combined modality therapy (CMT), including factors that influence patient outcomes.Methods: We analysed 88 patients (median age 35, range 15-64) diagnosed with PMBCL, treated at Princess Margaret Cancer Centre from 1994-2012. Data on stage, clinical prognostic factors, pathologic characteristics (including presence of sclerosis) treatment and outcome were retrieved from a prospective lymphoma database and pathology reports.Statistical analysis was performed to assess the overall survival (OS) and progression free survival (PFS) at 5 years; PFS events were progressive disease (PD), relapse or death from any cause. Patient characteristics are shown in Table 1Results: All patients received treatment with curative intent. In the majority of patients first-line chemotherapy was cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP, 47 patients) or CHOP + rituximab (R-CHOP, 38 patients) (average number of cycles = 6); standard involved field consolidative radiation was given to 68/83 patients (82%), with a median dose of 35 Gy, usually in 20 fractions. Following the first line treatment, 38 patients achieved CR (complete response), 33 patients had PR (partial response), PD occurred in 18 patients, 10 patients with initial response relapsed. 28/88 patients with PD or relapse received second line chemotherapy (cisplatin-based or Mini-BEAM) and 6/28 went on to ASCT. Twenty one of 88 (24 %) patients died from progressive lymphoma, 2/88 died of other causes. Overall survival (OS) at five years was 72.4%, and five year PFS in was 67.7%.We observed significantly inferior five year-OS and PFS in men by univariate analysis (p=0.019; OS= 51.9% vs 80.2% in women and p=0.022; PFS= 47.6 % vs 75.2% in women, respectively); The presence of sclerosis on tumor biopsy also resulted in inferior OS and PFS (OS= 60.4% vs 89.3 %, p=0.0045; PFS= 56.1% vs 81.7%, p=0.013, respectively);PFS and OS in patients treated with R-CHOP was superior to patients who received chemotherapy without Rituximab( PFS of 84.2% vs 55.8%, p= 0.0099 and OS of 89.2% vs 61.9%, p= 0.012).In multivariate analysis, male gender and tumor pathology (PMBCL with sclerosis) were predictive of inferior OS (p=0.018 and p= 0.022, respectively) and also, inferior PFS (p= 0.0499 and p= 0.024, respectively); age at diagnosis, stage and bulk did not have independent impact on OS or PFS.Conclusions: Current therapy with R-CHOP and radiation result in excellent PFS and OS. The reasons for adverse outcomes in males in our cohort and pathological correlates of extensive sclerosis are being explored.Table 1Patient characteristics at presentation (n=88)VariableN (%)Females62(70.4)Stage I39(44.3)Stage II42(47.7)Stage III-IV8(9.1)B symptoms27(30.7)Elevated LDH44(50)Bulk > 10 cm60 (68.2)Extranodal disease37 (42) DisclosuresKukreti:Celgene: Honoraria. Porwit:Beckman-Coulter: Speakers Bureau.

Influence of rotational speed on the cyclic fatigue of Mtwo instruments

To evaluate the effect of rotational speed on cyclic fatigue of Mtwo nickel-titanium files. A total of 120 new Mtwo rotary instruments sizes 10, 0.04 taper; 15, 0.05 taper; 20, 0.05 taper; and 25, 0.06 taper were randomly divided into three groups on the basis of the rotational speed used to shape nine standardized simulated canals: group A=350rpm; group B=250rpm; group C=150rpm. Each group consisted of 40 instruments, 10 for every size. The average preparation time (in seconds) and the average correlated numbers of cycles to instrument (NCI) the nine standardized canals were recorded for each file. The resistance to cyclic fatigue was determined by counting numbers of cycles to failure (NCF) with a rotational speed of 300rpm in a 60° curve with a 5-mm radius. Data were analysed by two-way anova. Preparation time was significantly longer at 150rpm than at 250 or 350rpm. The average number of cycles needed for each file to instrument nine standardized canals was significantly higher at 350 and 250rpm, than at 150rpm. There were no significant differences in the NCF (P>0.05) between A, B and C groups for instruments of the same size. Speed did not affect the cyclic fatigue of Mtwo instruments with the same size and taper. Preparation time was shorter at 350 or 250rpm rather than at 150rpm. However, there was no significant difference between 350 and 250rpm rotational speed, neither in the preparation time of simulated canals nor in the resistance to fatigue fracture.

Broad Overview of a Clinical and Commercial Experience With CoolSculpting

Cryolipolysis has been shown to be a safe and effective noninvasive procedure for the reduction of localized subcutaneous fat. The authors examine the safety, efficacy, and procedural growth of cryolipolysis (via the CoolSculpting device; Zeltiq, Pleasanton, California) in a single plastic surgery practice. A retrospective chart review was conducted for 528 consecutive patients who underwent cryolipolysis treatment from January 2010 to December 2012. The number of patients, the number of treatment cycles, the average number of cycles per patient, all treatment areas, and all procedural complications were recorded and analyzed. Overall practice growth with the device was also analyzed. Over the study period, 1785 anatomic sites were treated with 2729 cycles, primarily in the lower abdomen (28%, n = 490 cycles), upper abdomen (11%, n = 189), left flank (19%, n = 333), right flank (19%, n = 333), inner thigh (6%, n = 111), outer thigh (5%, n = 87), and back (6%, n = 99). The age distribution for men and women was similar (46.6 ± 12.8 years for women and 46.5 ± 12.3 years for men; overall range, 18-79 years). Only 3 cases of mild or moderate pain/neuralgia were reported and resolved in 4 or fewer days. No adverse events were reported. Procedure volume showed consistent growth, with treatment cycles increasing by 823% by 2012. Based on the results in this single plastic surgery practice, cryolipolysis is a safe and effective nonsurgical body contouring method associated with high patient satisfaction that can generate steady, significant business growth.

Methotrexate and cetuximab for metastatic advanced head and neck squamous cell carcinoma.

e17033 Background: After the failure of first-line palliative chemotherapy in recurrent non-resectable or metastatic head and neck squamous-cell carcinoma (HNSCC), there is no standard of care second-line treatment that is proven to improve quality of life or prolong survival. Both methotrexate and cetuximab has shown a single-agent activity in advanced HNSCC. We are presenting our institutional experience in using unique combination chemotherapy with methotrexate plus cetuximab (MC). Methods: Retrospectively, single institution’s charts were reviewed from 2004-2010, all patients have documented recurrent non-resectable or metastatic HNSCC. After failing at least one line of palliative chemotherapy, patients received weekly IV methotrexate 25 mg/m2 plus IV cetuximab 400 mg/m2 loading dose at week one followed by 250 mg/m2 maintenance dose weekly. Each cycle is 4 weeks treatments. Patients who completed at least 2 cycles were included in the study. Patients can receive MC as first line if they have poor performance status. Treatment was continued until progression. Results: Total of 34 patients were included in the study, 26 male and 8 female, 18 African American and 16 Caucasian. Median patient age was 60 years old. 18, 6 and 6 patients received MC as second, third and fourth line therapy, respectively. 4 patients received MC as first line because there were not candidates for more aggressive chemotherapeutic regimens. The average received number of weekly treatments was 25 (8-69) and average number of cycles was 6 (2-17). Prior chemotherapy regimens include taxanes, platinum, 5-flurouracil, and gemcitabin. Median progression free survival was 4.9 months and overall survival was 10.7 months. Overall survival based on race was 9.9 months for Caucasians and 10.7 months for African Americans (P=0.0391). Grade I and II skin rash was observed in 41% of patients, no grade III/IV toxicities were noticed. Conclusions: Methotrexate plus cetuximab is a well tolerated regimen with a significant survival benefit. Prospective studies are warranted in order to evaluate this regimen as a second line palliative therapy for patients with advanced non-curable head and neck squamous cell carcinoma.

Phase I clinical trial of the intraperitoneal (IP) administration of a novel nanoparticle formulation of paclitaxel (NTX).

2558 Background: IP therapy is an attractive option for patients with IP carcinomatosis as many of these malignancies remain confined IP. Agents whose plasma clearance rates substantially exceed their rates of uptake from the peritoneal cavity are especially suited for IP administration. Pre-clinical studies of a novel formulation of nanoparticulate paclitaxel in animal tumor models demonstrated superior activity and substantially reduced systemic toxicity. This allowed for significant IP doses and concentrations, yet yielded very low systemic concentrations of paclitaxel. We report here the results of a Phase I trial of IP administered NTX. Methods: Patients (ECOG≤2) had relapsed, treatment refractory solid IP tumors and adequate organ function. NTX was administered IP as a bolus injection after 500 ml saline followed by IP administration of up to 2 L of saline. We utilized an accelerated dose escalation scheme until one DLT occurred during cycle 1, followed by a standard dose escalation (3+3 design) based on CTCAE V3 toxicities. The pharmacokinetics of IP administered NTX were characterized in plasma and ascites fluid. Secondary objectives were to define the recommended phase 2 dose of NTX, and characterize preliminary activity and toxicity. Results: 20 patients were treated at dose levels from 50 – 275 mg/M2 q 28 days. Primary malignancy was ovarian cancer (74%). Treatment was well tolerated at all dose levels. Common toxicities potentially related to NTX were: gastrointestinal (68%), constitutional (42%), and pain (42%). Average number of cycles received was 2 (range 1 to 6). Best response was stable disease (4 patients, 21%). Median length of disease stability was 99 days (range 85 to 151 days); median time on study patients with stable disease was 313 days (range 142 to 740 days). All Cmax in plasma were less than 35 ng/mL, with ascites fluid Cmax generally greater than 1000 ng/mL. Conclusions: IP NTX is well tolerated. MTD has not yet been reached. Pharmacokinetic data demonstrate significant, persistent IP exposure to paclitaxel with minimal systemic exposure. Accrual at the 275 mg/M2 dose level continues; updated results will be presented. Further clinical development of NTX is indicated. Clinical trial information: NCT00666991.

Oral chemotherapy: A focus on interventions and access.

44 Background: Oral chemotherapies are becoming more predominant with 40% of the currently available oral agents being approved in the last 7 years. Patient self-administration and the costs of these medications raise concerns about monitoring and access. As a result, nonfulfillment rates in the literature have been reported to range from 10-24% with rates directly correlated with cost of the medication. Methods: Patients who utilized the pharmacist-managed oral chemotherapy program were included for evaluation. Patients were excluded if they utilized external mail order pharmacies. Patient charts were audited for documented pharmacist-initiated interventions such as drug-interactions, lab monitoring, and dose adjustments. Patient nonfulfillment rates were evaluated by evaluating percentage of patients referred to number of prescriptions filled. Patients were classified as either filled, mail order, financial assistance or never started. Financial assistance patients were divided into free drug or co-pay assistance. Total amount of free drug obtained was assessed by multiplying the average number of cycles obtained by patients by the average wholesale price (AWP). Results: A total of 702 patients were served by the Oral Chemotherapy program between August 2009 and October 2011. In those patients, 82 drug-drug interactions and 24 patients required dose adjustments up front, mostly due to renal dysfunction. Compared to the 10-24% nonfulfillment rates in the literature, this program was able to keep rates less than 1% for patients who were unable to obtain medication for financial reasons. In this time period, underinsured patients were able to obtain &gt;$1 million in free drug and &gt;$200,000 in co-pay assistance funds thanks to our financial advocates. Conclusions: Collaboration within one health system between oncologists, pharmacists, nurses and social workers/financial advocates was able to ensure better quality of care by helping address medication issues upfront with minimal delays in access. In addition, this program was able to ensure that most patients were able to obtain their medication within a reasonable time period at a reasonable cost, reducing non-fulfillment rates compared to what has previously been reported in the literature.

P204 Fractionated Carboplatin and Vinorebine For Elderly and Poor Performance Status Patients with NSCLC

Patients with advanced NSCLC who are elderly and/or have poor Performance Status are generally considered unsuitable for chemotherapy and usually excluded from the possible benefits of systemic treatment. The outlook...

MK-0457, an Aurora kinase and BCR–ABL inhibitor, is active in patients with BCR–ABL T315I leukemia

MK-0457, an Aurora kinase and BCR-ABL inhibitor, was studied on a Phase I/II study in 77 patients with refractory hematologic malignancies. The average number of cycles per patient was 3 (range 1-21). Maximum tolerated doses for a 5-day short infusion and continuous infusion regimens were 40 mg/m(2)/h and 144 mg/m(2)/h, respectively. Drug-related adverse events (AEs) included transient mucositis and alopecia. Eight of 18 patients with BCR-ABL T315I-mutated chronic myelogenous leukemia (44%) had hematologic responses and one of three patients (33%) with Philadelphia chromosome-positive acute lymphoblastic leukemia obtained complete remission. MK-0457 has important activity in patients with leukemias expressing the highly resistant T315I BCR-ABL mutation.

Methotrexate and cetuximab for metastatic advanced head and neck squamous cell carcinoma: A retrospective study.

e16019 Background: After the failure of first line palliative chemotherapy in recurrent non-resectable or metastatic head and neck squamous-cell carcinoma (HNSCC), there is no standard of care treatment that improves survival or quality of life. Both, methotrexate and cetuximab have single agent activity in metastatic HNSCC. We are presenting our institutional experience in using unique combination chemotherapy with methotrexate plus cetuximab (MC). Methods: Retrospectively, single institution’s charts were reviewed from 2004-2010, all patients have documented recurrent non-resectable or metastatic HNSCC. Patients received weekly IV methotrexate 25 mg/m2 plus IV cetuximab 250 mg/m2. Each cycle is 4 weeks treatments. Patients who completed at least 2 cycles were included. Patients can receive MC as first line if they have poor performance status. Treatment was continued until progression. Results: Total of 39 patients were included, 27 male and 12 female. Median patients’ age was 57 years old. 35 patients received methotrexate plus cetuximab (MC) after failure of prior line of palliative chemotherapy. 17, 10 and 8 patients received MC as second, third and fourth line therapy, respectively. 4 patients received MC as 1st line because they were not candidate for more aggressive therapy. The average received number of weekly treatments was 31 (8-95) and average number of cycles was 7 (2-23). Prior chemotherapy regimens include taxanes, platinum, 5-flurouracil, and gemcitabin. 13 patients received prior cetuximab as single agent or in combination. Median progression free survival was 7.1 months and overall survival was 9.8 months. Considering the line of therapy, the median survival was 6.9, 10.1, 13.5 and 9.9 months for patients received MC as 1st, 2nd , 3rd and 4th line of therapy respectively (P= 0.356). Grade 1 and 2 skin rash and hypomagnesimia were observed in 47% and 36% of patients. Conclusions: Methotrexate plus cetuximab is a well tolerated regimen with a significant survival benefit. Prospective well designed studies are warranted in order to evaluate this regimen as a second line palliative therapy for patients with advanced non-curable head and neck squamous cell carcinoma.