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1.  Phase I Trial of Neoadjuvant Conformal Radiotherapy plus Sorafenib for Patients with Locally Advanced Soft Tissue Sarcoma of the Extremity 
Annals of surgical oncology  2014;21(5):1616-1623.
Despite effective local therapy with surgery and radiation (RT), approximately 50% of patients with high grade soft tissue sarcoma (STS) will relapse and die of disease. Since experimental data suggest a significant synergistic effect when anti-angiogenic targeted therapies, such as sorafenib, are combined with RT, we chose to evaluate preoperative combined modality sorafenib and conformal RT in a Phase I/II trial among patients with extremity STS amenable to treatment with curative intent.
For the Phase I trial, eight patients with intermediate or high grade STS > 5 cm in maximal dimension or low grade STS > 8 cm in maximal dimension received concomitant sorafenib (dose escalation cohort 1:200 bid, cohort 2:200/400 daily) and preoperative RT (50 Gy in 25 fractions). Sorafenib was continued during entire period of RT as tolerated. Surgical resection was completed four to six weeks following completion of neoadjuvant sorafenib/RT. Three sorafenib dose levels were planned. Primary endpoints of the Phase I trial were maximal tolerated dose and dose-limiting toxicity (DLT).
Eight patients were enrolled in the Phase I (5 female, median age 44, 3 high grade pleomorphic, 2 myxoid/round cell liposarcoma, 3 other). Median tumor size was 16 cm (range 8–29), and all tumors were located in the lower extremity. Two of 5 patients treated at dose level 2 developed DLT consisting of grade 3 rash not tolerating drug reintroduction. Other grade 3 side effects included anemia, perirectal abscess, and SVT. Radiation toxicity (grade 1 or 2 dermatitis, N=8) and post-surgical complications (3 grade 3 wound complications) were comparable to historical controls and other series of preoperative RT monotherapy. Complete pathologic reponse (≥ 95% tumor necrosis) was observed in 3 patients (38%).
Neoadjuvant sorafenib in combination with RT is tolerable and appears to demonstrate activity in locally advanced extremity STS. Further study to determine efficacy at dose level 1 is warranted. (NCT#00805727,
PMCID: PMC4153793  PMID: 24554062
Soft Tissue Sarcoma; Preoperative Radiotherapy; Sorafenib; Pathologic Response
2.  Phase I Study Evaluating the Combination of Lapatinib (a Her2/Neu and EGFR Inhibitor) and Everolimus (an mTOR Inhibitor) in Patients with Advanced Cancers: South West Oncology Group (SWOG) Study S0528 
Cancer chemotherapy and pharmacology  2013;72(5):1089-1096.
Everolimus, an oral inhibitor of mTOR, can augment the efficacy of HER inhibitors in pre-clinical studies. This study was conducted to determine the safety and pharmacokinetics (PK) of the combination of lapatinib, a Her1 and 2 inhibitor, and everolimus, and to describe its antitumor activity in the Phase I setting.
In Part I, dose escalation to define the maximum tolerated dose (MTD) was performed. In Part II, PK of both drugs were analyzed to assess drug-drug interaction.
Twenty-three evaluable patients with advanced cancers were treated on six different dose levels in Part I of the study. The dose-limiting toxicities were diarrhea, rash, mucositis and fatigue. The MTD of the combination was 1250 mg of lapatinib and 5 mg of everolimus once daily. In Part II of the study, 54 patients were treated with the combination at the MTD. The mean everolimus time to maximum concentration was increased by 44% and mean clearance was decreased by 25% when co-administered with lapatinib, though these differences were not statistically significant. There was no significant influence on the PK of lapatinib by everolimus. Two patients achieved a partial response (thymic cancer (45+ months) and breast cancer (unconfirmed PR; 7 months); eleven patients attained stable disease of at least 4 months
Lapatinib and everolimus are well tolerated at doses of 1250 mg and 5 mg po daily, respectively. Stable disease >4 months/PR was achieved in 13 of 78 patients (17%).
PMCID: PMC4072025  PMID: 24057042
everolimus; lapatinib; phase I; mTOR; Her2
Background and Purpose:
The potential adverse effects of static stretching on athletic performance are well documented, but still appears to be controversial, especially as they relates to sprinting. The prevalence of this practice is demonstrated by the number of competitive and recreational athletes who regularly engage in stretching immediately prior to sprinting with the mindset of optimizing their performance. The purpose of this study was to examine the effects of acute static, dynamic, and ballistic stretching, and no stretching of the iliopsoas muscle on 40‐yard sprint times in 18‐37 year‐old non‐competitive, recreational runners.
Twenty‐five healthy recreational runners (16 male and 9 female) between the ages of 24 and 35 (Mean = 26.76 yrs., SD = 2.42 yrs.) completed this study. A repeated measures design was used, which consisted of running a 40‐yard sprint trial immediately following each of 4 different stretching conditions aimed at the iliopsoas muscle and lasting 1 minute each. The 4 conditions were completed in a randomized order within a 2‐week time period, allowing 48‐72 hours between each condition. Prior to each 40‐yard sprint trial, a 5‐minute walking warm‐up was performed at 3.5 mph on a treadmill. The subject then ran a baseline 40‐yard sprint. After a 10‐minute self‐paced walk, each subject performed one of the 4 stretching conditions (ballistic, dynamic, static, and no stretch) and then immediately ran a timed 40‐yard sprint.
There was a significant interaction between stretching conditions and their effects on sprint times, F(3,72) = 9.422, p<.0005. To break down this interaction, simple main effects were performed with 2 repeated measures ANOVAs and 4 paired t‐tests using a Bonferroni corrected alpha (α = .0083). There were no significant differences between the 4 pre‐condition times, p = 0.103 (Greenhouse‐Geisser) or the post‐condition times, p = 0.029. In the no stretch condition, subjects improved significantly from pre‐ to post‐ sprint times (p<0.0005). There were no statistically significant differences in pre‐ and post‐stretch condition sprint times among the static (p = 0.804), ballistic (p = 0.217), and dynamic (p = 0.022) stretching conditions.
Sprint performance may show greatest improvement without stretching and through the use of a walking generalized warmup on a treadmill. These findings have clinically meaningful implications for runners who include iliopsoas muscle stretching as a component of the warm‐up.
Level of Evidence:
Level 2
PMCID: PMC3474300  PMID: 23091787
Recreational runners; sprinting; stretching; warm‐up
4.  A Model for Rural Oncology 
Journal of Oncology Practice  2011;7(3):168-171.
The authors describe the development and implementation of a collaborative cancer center serving rural patients.
Small rural hospitals in the United States have had challenging issues developing sustainable oncology programs. This is a report on the development of a successful rural oncology program. In 2006, the Tahoe Forest Health System in Truckee, CA, a remote mountain resort town, started a cancer program that was focused on addressing patient and family fears that are common to all cancer patients but more frightening in the rural setting. Four years later, it is a thriving program with significant community support, a creative academic affiliation, and a central focus of the future of the hospital. The Tahoe Forest Cancer Center developed a sustainable model for high quality cancer care that overcomes geographic, cultural and financial barriers. This structure may serve as a model for national rural health care.
PMCID: PMC3092657  PMID: 21886498
5.  A phase II study of cell cycle inhibitor UCN-01 in patients with metastatic melanoma: a California Cancer Consortium trial 
Investigational New Drugs  2010;30(2):741-748.
Background Genetic abnormalities in cell cycle control are common in malignant melanoma. UCN-01 (7-hydroxystaurosporine) is an investigational agent that exhibits antitumor activity by perturbing the cancer cell cycle. A patient with advanced melanoma experienced a partial response in a phase I trial of single agent UCN-01. We sought to determine the activity of UCN-01 against refractory metastatic melanoma in a phase II study. Patients and methods Patients with advanced melanoma received UCN-01 at 90 mg/m2 over 3 h on cycle 1, reduced to 45 mg/m2 over 3 h for subsequent cycles, every 21 days. Primary endpoint was tumor response. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). A two-stage (17 + 16), single arm phase II design was employed. A true response rate of ≥20% (i.e., at least one responder in the first stage, or at least four responders overall) was to be considered promising for further development of UCN-01 in this setting. Results Seventeen patients were accrued in the first stage. One patient was inevaluable for response. Four (24%) patients had stable disease, and 12 (71%) had disease progression. As there were no responders in the first stage, the study was closed to further accrual. Median PFS was 1.3 months (95% CI, 1.2–3.0) while median OS was 7.3 months (95% CI, 3.4–18.4). One-year and two year OS rates were 41% and 12%, respectively. A median of two cycles were delivered (range, 1–18). Grade 3 treatment-related toxicities include hyperglycemia (N = 2), fatigue (N = 1), and diarrhea (N = 1). One patient experienced grade 4 creatinine elevation and grade 4 anemia possibly due to UCN-01. No dose modification was required as these patients had disease progression. Conclusion Although well tolerated, UCN-01 as a single agent did not have sufficient clinical activity to warrant further study in refractory melanoma.
PMCID: PMC3277821  PMID: 20967484
Metastatic melanoma; UCN-01; 7-hydroxystaurosporine; Cell cycle inhibitor; Phase II; Targeted therapy

Results 1-5 (5)