Jesse M.W.,Decatur Memorial Hospital
Critical Reviews in Physical and Rehabilitation Medicine | Year: 2016
Axillary web syndrome (AWS) describes a self-limiting post-axillary node dissection pain syndrome occurring in a subset of breast cancer patients. The documented incidence in the literature varies from 0.6% to 85.4%. Symptomatic AWS presents with pain, feelings of tightness, and restricted shoulder range of motion and/or numbness. Pain is typically described in the ipsilateral axilla with possible radiation in to the arm with shoulder movement. A systematic search was conducted in the PubMed PEDro (Physiotherapy Evidence Database) and CENTRAL (Cochrane Central Register of Controlled Trials) databases. The purpose of this review was to identify the value of physical therapy treatment for patients with AWS. The literature described improvement of symptoms with manual therapy techniques and therapeutic exercise for mobility. These findings suggest that physical therapy may have a useful role in the treatment of AWS. The decrease of symptoms related this syndrome helps to improve the quality of life and allow for continued treatments such as radiation therapy. The results of the review will help healthcare providers make educated clinical decisions in the treatment for AWS and provide precautions to be observed in the treatment of these patients. © 2016 by Begell House, Inc.
Jain N.,University of Chicago |
Curran E.,University of Chicago |
Iyengar N.M.,University of Chicago |
Diaz-Flores E.,University of California at San Francisco |
And 20 more authors.
Clinical Cancer Research | Year: 2014
Purpose: The clinical relevance of targeting the RAS/RAF/MEK/ERK pathway, activated in 70% to 80% of patients with acute myelogenous leukemia (AML), is unknown. Experimental Design: Selumetinib is an oral small-molecule inhibitor of MAP-ERK kinase (MEK)-1/2. Forty-seven patients with relapsed/refractoryAMLor 60 years old or more with untreatedAMLwere enrolled on a phase II study. Patients were stratified by FLT3 ITD mutation status. The primary endpoint was response rate (complete, partial, and minor). Leukemia cells were analyzed for extracellular signal-regulated kinase (ERK) and mTOR phosphorylation. Results: Common drug-related toxicities were grade 1-2 diarrhea, fatigue, nausea, vomiting, and skin rash. In the FLT3 wild-type cohort, six of 36 (17%) patients had a response [one partial response, three minor responses, two unconfirmed minor responses (uMR)]. No patient with FLT3 ITD responded. NRAS and KRAS mutations were detected in 7% and 2% of patients, respectively. The sole patient with KRAS mutation had uMR with hematologic improvement in platelets. Baseline p-ERK activation was observed in 85% of patients analyzed but did not correlate with a response. A single-nucleotide polymorphism (SNP) rs3733542 in exon 18 of the KIT gene was detected in significantly higher number of patients with response/stable disease compared with nonresponders (60% vs. 23%; P = 0.027). Conclusions: Selumetinib is associated with modest single-agent antileukemic activity in advanced AML. However, given its favorable toxicity profile, combination with drugs that target other signaling pathways in AML should be considered. The potential association of SNP rs3733542 in exon 18 of the KIT gene with antileukemic activity of selumetinib is intriguing, but will require validation in larger trials. Clin Cancer Res; 20(2); 490-8. © 2013 American Association for Cancer Research.
PubMed | Alliance Statistics and Data Center, Roswell Park Cancer Institute, National Cancer Institute, New Hampshire Oncology Hematology PA and 7 more.
Type: Journal Article | Journal: JAMA | Year: 2016
Zoledronic acid, a third-generation aminobisphosphonate, reduces the incidence of skeletal-related events and pain in patients with bone metastases. The optimal dosing interval for zoledronic acid is uncertain.To determine whether zoledronic acid administered every 12 weeks is noninferior to zoledronic acid administered every 4 weeks.Randomized, open-label clinical trial conducted at 269 academic and community sites in the United States. Patients (n=1822) with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma who had at least 1 site of bone involvement were enrolled between May 2009 and April 2012; follow-up concluded in April 2014.Patients were randomized to receive zoledronic acid administered intravenously every 4 weeks (n=911) vs every 12 weeks (n=911) for 2 years.The primary end point was the proportion of patients having at least 1 skeletal-related event (defined as clinical fracture, spinal cord compression, radiation to bone, or surgery involving bone) within 2 years after randomization and a between-group absolute difference of 7% as the noninferiority margin. Secondary end points included the proportion of patients with at least 1 skeletal-related event by disease type, pain as assessed by the Brief Pain Inventory (range, 0-10; higher scores indicate worse pain), Eastern Cooperative Oncology Group performance status (range, 0-4; higher scores indicate worse disability), incidence of osteonecrosis of the jaw, kidney dysfunction, skeletal morbidity rate (mean number of skeletal-related events per year), and, in a subset of 553 patients, suppression of bone turnover (assessed by C-terminal telopeptide levels).Among 1822 patients who were randomized (median age, 65 years; 980 [53.8%] women; 855 with breast cancer, 689 with prostate cancer, and 278 with multiple myeloma), 795 completed the study at 2 years. A total of 260 patients (29.5%) in the zoledronic acid every 4-week dosing group and 253 patients (28.6%) in the every 12-week dosing group experienced at least 1 skeletal-related event within 2 years of randomization (risk difference of -0.3% [1-sided 95% CI, -4% to ]; P<.001 for noninferiority). The proportions of skeletal-related events did not differ significantly between the every 4-week dosing group vs the every 12-week dosing group for patients with breast cancer, prostate cancer, or multiple myeloma. Pain scores, performance status scores, incidence of jaw osteonecrosis, and kidney dysfunction did not differ significantly between the treatment groups. Skeletal morbidity rates were numerically identical in both groups, but bone turnover was greater (C-terminal telopeptide levels were higher) among patients who received zoledronic acid every 12 weeks.Among patients with bone metastases due to breast cancer, prostate cancer, or multiple myeloma, the use of zoledronic acid every 12 weeks compared with the standard dosing interval of every 4 weeks did not result in an increased risk of skeletal events over 2 years. This longer interval may be an acceptable treatment option.clinicaltrials.gov Identifier: NCT00869206.
Lu C.,University of Texas M. D. Anderson Cancer Center |
Lee J.J.,University of Texas M. D. Anderson Cancer Center |
Komaki R.,University of Texas M. D. Anderson Cancer Center |
Herbst R.S.,University of Texas M. D. Anderson Cancer Center |
And 10 more authors.
Journal of the National Cancer Institute | Year: 2010
Background AE-941 is a standardized aqueous shark cartilage extract with antiangiogenic properties that has previously been evaluated in phase I and II clinical trials. Our objective was to determine the effect of adding AE-941 to chemoradiotherapy on overall survival of patients with unresectable stage III non-small cell lung cancer (NSCLC). Methods A randomized, double-blinded, placebo-controlled, phase III clinical trial was designed to test the efficacy of AE-941 in unresectable stage III NSCLC patients who were treated with chemoradiotherapy. Between June 5, 2000, and February 6, 2006, 379 eligible patients were enrolled in community and academic oncology centers across the United States and Canada. In February 2006, the trial was closed to new patient entry before meeting the target sample size because of insufficient accrual. All subjects received induction chemotherapy followed by concurrent chemotherapy with chest radiotherapy. Each participating center administered one of the two chemotherapy regimens, either carboplatin and paclitaxel, or cisplatin and vinorelbine. The primary endpoint was overall survival, and secondary endpoints were time to progression, progression-free survival, tumor response rate, and toxic effects. Event-time distributions were estimated by the Kaplan-Meier method. All statistical tests were two-sided. Results There was no statistically significant difference in overall survival between the chemoradiotherapy plus AE-941 group (n = 188; median survival = 14.4 months, 95% confidence interval = 12.6 to 17.9 months) and the chemoradiotherapy plus placebo group (n = 191; median survival = 15.6 months, 95% confidence interval = 13.8 to 18.1 months) (P =. 73). Time to progression, progression-free survival, and tumor response rates were not statistically significantly different between the AE-941 and the placebo groups. No differences between the two groups were observed in common grade 3 or higher toxic effects attributable to chemoradiotherapy. Conclusions The addition of AE-941 to chemoradiotherapy did not improve overall survival in patients with unresectable stage III NSCLC. This study does not support the use of shark cartilage-derived products as therapy for lung cancer. © 2010 The Author.
Roscoe J.A.,University of Rochester |
Morrow G.R.,University of Rochester |
Colagiuri B.,University of Sydney |
Heckler C.E.,University of Rochester |
And 4 more authors.
Supportive Care in Cancer | Year: 2010
Purpose To identify risk factors for chemotherapy-related nausea. Methods We examined risk factors for nausea in 1,696 patients from three multicenter studies conducted from 1998 to 2004. All patients were beginning a chemotherapy regimen containing cisplatin, carboplatin, or doxorubicin. Nausea was assessed on a 1-7 scale four times a day for 4 days by diary. Results First, average nausea for breast cancer patients receiving doxorubicin (mean=2.31) was significantly greater than for other patients receiving doxorubicin (mean= 1.82), patients receiving cisplatin (mean=1.88), and patients receiving carboplatin (mean=1.45), Ps<0.01. Second, mean nausea decreased steadily with age, P< 0.0001. Third, patients rating themselves more susceptible to nausea had significantly more nausea (adjusted mean= 2.51) than patients rating themselves less susceptible (adjusted mean=1.92) and were 2.8 times more likely to experience severe nausea, Ps<0.0001. Fourth, expected nausea was a significant predictor of average nausea, P= 0.034, but not severe nausea, P=0.31. Last, no evidence that gender is a significant predictor of nausea in 299 patients with gender neutral cancers, P=0.35. Conclusions Specific patient characteristics, especially younger age and perceived susceptibility to nausea, can help clinicians in the early identification of patients who are more susceptible to treatment-related nausea. © Springer-Verlag 2009.
A multicenter phase II study of docetaxel, oxaliplatin, and bevacizumab in first-line therapy for unresectable locally advanced or metastatic non-squamous cell histology non-small-cell lung cancer (NSCLC)
Raez L.E.,Memorial Cancer Institute |
Santos E.S.,Boca Raton Regional Hospital |
Webb R.T.,Genesis Centre |
Wade J.,Decatur Memorial Hospital |
And 4 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2013
Introduction: Platinum-based doublets are standard of care for advanced non-small-cell lung cancer (NSCLC). The combination of docetaxel and oxaliplatin has shown acceptable toxicity and encouraging activity. This phase II study aimed to determine the safety and efficacy of this doublet with bevacizumab as first-line treatment for stage IIIB/IV NSCLC. Methods: Newly diagnosed patients ≥18 years with histologically proven non-squamous NSCLC and Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2 received six 21-day cycles of docetaxel, oxaliplatin, and bevacizumab followed by single-agent bevacizumab for a total of 1 year. Primary efficacy end point was radiographically documented progression-free survival (PFS); secondary end points included objective response rate (ORR), overall survival (OS), time to treatment failure, and safety. Results: Fifty-three patients were enrolled. Median age was 62.0 years, 71.7 % male, 79.2 % Caucasian. A total of 88.7 % had stage IV or recurrent disease; 94.3 % adenocarcinoma; and 94.3 % ECOG PS 0 or 1. Efficacy results are as follows: median PFS 5.6 months, ORR 30.2 % (complete response 1.9 %, partial response 28.3 %); 37.7 % stable disease; and OS 14.0 months. At least one adverse event (AE) was reported in all patients (n = 52); 98.1 % of AEs were treatment related. The most common treatment-emergent grade ≥3 AEs were neutropenia (15.4 %), diarrhea (13.5 %), and fatigue (11.5 %). A serious AE was present in 32.7 %; the most common were pneumonia (7.7 %) and abdominal pain (5.8 %). Dehydration, diarrhea, febrile neutropenia, sepsis, and supraventricular tachycardia each occurred in 3.8 %. Conclusions: The addition of bevacizumab to docetaxel/oxaliplatin is effective with an acceptable safety profile in patients with chemotherapy-naïve advanced NSCLC. © 2013 Springer-Verlag Berlin Heidelberg.
Nimeiri H.S.,University of Chicago |
Oza A.M.,Princess Margaret Hospital |
Morgan R.J.,City of Hope Comprehensive Cancer Center |
Huo D.,University of Chicago |
And 6 more authors.
Gynecologic Oncology | Year: 2010
Objectives: To determine the efficacy and safety of single agent sorafenib, an oral multi-targeted tyrosine kinase inhibitor, in patients with advanced uterine carcinoma and carcinosarcoma. Methods: This multi-institutional non-randomized phase II trial enrolled two cohorts: patients with uterine carcinoma (cohort A) and uterine carcinosarcoma (cohort B). Eligibility criteria included measurable disease, 0-1 prior chemotherapy regimens, and ECOG performance status ≤ 2. Sorafenib at a dose of 400 mg was administered orally twice daily. A cycle was defined as 28 days. Objective tumor response was the primary endpoint and was assessed following every two cycles. Results: Fifty-six patients (40 with carcinoma, 16 with carcinosarcoma) were enrolled between March 2005 and August 2007. Two (5%) patients with uterine carcinoma had a partial response (PR) and 17 (42.5%) achieved stable disease (SD). Five had SD lasting at least 4 months. The 6-month progression-free survival rate for patients with carcinoma was 29%, and the median overall survival was 11.4 months. No patients with carcinosarcoma had an objective response. Four (25%) had SD, and one had SD lasting 18 months. The 6-month progression-free survival rate was 13%, and the median overall survival was 5.0 months. Grade 3/4 drug related toxicities included: hypertension (13%), hand-foot syndrome (13%), hypophosphatemia (7%), anemia (5%), rash (5%), diarrhea (5%), thrombosis (5%), fatigue (5%) and bleeding (5%). Conclusion: Sorafenib had minimal activity in patients with uterine carcinoma. Predictive factors for potential benefit are needed. © 2010 Elsevier Inc.
PubMed | University of Texas Southwestern Medical Center, Penn State Hershey Cancer Institute, Dana-Farber Cancer Institute, Sloan Kettering Cancer Center and 8 more.
Type: Journal Article | Journal: Cancer | Year: 2016
Preclinical targeting of the hedgehog pathway by vismodegib and of insulin-like growth factor 1 receptor by cixutumumab enhances the efficacy of chemotherapy and also demonstrates activity against the tumor cell fraction responsible for disease recurrence in small cell lung cancer.Patients with newly diagnosed extensive-stage small cell lung cancer (SCLC-ED) were randomized to receive four 21-day cycles of cisplatin and etoposide alone (cisplatin at 75 mg/m(2) on day 1 and etoposide at 100 mg/m(2) on days 1-3; arm A) or in combination with either vismodegib (150 mg/d by mouth; arm B) or cixutumumab (6 mg/kg/wk intravenously on day 1; arm C). The primary endpoint was progression-free survival (PFS). Circulating tumor cells (CTCs) were isolated/enumerated with the Veridex CellSearch platform at the baseline.One hundred fifty-two eligible patients were treated. Patient demographics and disease characteristics were well balanced between the 3 arms except for the higher rate with a performance status of 0 in arm B (P = .03). The median PFS times in arms A, B, and C were 4.4, 4.4, and 4.6 months, respectively; the median overall survival (OS) times were 8.8, 9.8, and 10.1 months, respectively; and the response rates were 48%, 56%, and 50%, respectively. None of the comparisons of these outcomes were statistically significant. The median OS was 10.5 months for those with low CTC counts (100/7.5 mL) at baseline and 7.2 months for those with high CTC counts (hazard ratio, 1.74; P = .006).There was no significant improvement in PFS or OS with the addition of either vismodegib or cixutumumab to chemotherapy in patients with SCLC-ED. A low baseline CTC count was associated with a favorable prognosis. Cancer 2016;122:2371-2378. 2016 American Cancer Society.
Jesse M.,Decatur Memorial Hospital
Critical Reviews in Physical and Rehabilitation Medicine | Year: 2014
Elevated joint loads during walking have been associated with pathophysiol-ogy and symptoms affecting the performance of physical activities. Specifically, the ground reaction forces, center of pressure, and joint kinetics in the lower body directly affect mechanical factors in lower extremity joints. In some situations these biomechanical forces are responsible for the pathogenesis and progression of disease, such as osteoarthritis (OA). OA is a common arthritic condition, and symptoms can be a source of disability and impaired quality of life. Studies have shown that elevated joint loads correspond with radiographic severity, disease progression, and pain, and reduction of loading may provide symptomatic benefits. The design of footwear has the potential to affect the loading patterns of the lower extremity joints and therefore lessen the impact at symptomatic junctions. Although footwear may be designed for foot support and comfort, the mechanical effects on the hips and knees should also be a consideration. A systematic search of PubMed, the Physiotherapy Evidence Database, and the Cochrane Central Register of Controlled Trials was conducted. The purpose of this review was to identify shoe types and their effect on lower extremity joint loading. Several aspects of footwear may affect joint loading, including heel height, flexibility, wedge and arch support, and sensory input. The findings suggest that footwear may have a significant effect on the mechanical loading of the lower extremity joints and therefore the overall disease process that is occurring. The results of this review will help health care providers make educated suggestions for footwear that may help symptoms associated with lower extremity joint loading. By altering dynamic loading at affected joints, OA management may be more successful. © 2014 by Begell House, Inc.
Willis J.S.,Southern Illinois University Carbondale |
Hoy R.H.,Decatur Memorial Hospital |
Jenkins W.D.,Southern Illinois University Carbondale
Journal of Community Health | Year: 2011
The use of multiple medications, in persons 65 years and older, has been linked to increased risk for cognitive impairment, falls, hip fractures, hospitalizations, adverse drug reactions, and mortality. The purpose of this study was to determine if trained undergraduate students, in conjunction with pharmacists, could provide in-home medication reviews and demonstrate benefit to the health and welfare of a senior population affiliated with a primary care facility. Students received training in the completion of an in-home medication inventory, assessing a home for fall risk, and performing blood pressures. Once trained and proven proficient students performed the assessments in homes of Decatur Family Medicine Residency patients 65 years and older. Collected medication inventories were reviewed by a hospital pharmacist for fall risk medications, major drug interactions, or duplicate therapy. Changes to patient management were made by the primary care provider as needed. In all, 75 students visited 118 patients in Fall 2010. Findings from the medication review include: 102 (86%) patients were prescribed at least one fall risk medication; 43% were prescribed 3 or more; 14% had the potential for a major drug interaction; and 7% were prescribed duplicate therapies. Fifty-seven patients had a subsequent change made to their clinical medication list. The results demonstrate that an in-home outreach can be successfully performed by student volunteers and provide data of high clinical relevance and use. This application of the patient-centered medical home can readily and directly improve patient safety. © 2011 Springer Science+Business Media, LLC.