tbuckley/cabot-search huggingface dataset:
Phase Ib of anticancer stem cell antibody OMP-59R5 (anti-Notch2/3) in combination with nab-paclitaxel and gemcitabine (Nab-P+Gem) in patients (pts) with untreated metastatic pancreatic cancer (mPC).
Authors: Eileen Mary O'Reilly, Lon S. Smith, Johanna C. Bendell, Fatima A. Rangwala, William Schmidt, Joe Stephenson, Ann Kapoun, Lu Xu, Dawn Hill, Lei Zhou, Jakob Dupont, Allen Lee Cohn
Journal: Journal of Clinical Oncology (2014)

220 Background: OMP-59R5, a fully human IgG2 antibody, inhibits signaling of Notch2 and 3 receptors. Tumor regression was seen in Notch3 expressing patient-derived pancreatic cancer xenografts when OMP-59R5 was combined with Nab-P+Gem. The maximum tolerated dose (MTD) of single agent OMP-59R5 was 7.5 mg/kg every other week (Smith, EORTC 2012); the main dose limiting toxicity (DLT) was grade 3 diarrhea. This study is to determine the MTD, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of OMP-59R5 in combination with Nab-P+Gem in mPC. Methods: Cohorts of 3 to 6 pts were treated at each dose level of OMP-59R5. OMP-59R5 is given intravenously every other week (days 1 and 15) with GEM 1,000 mg/m 2 alone (first two cohorts) or nab-P 125 mg/m 2 and GEM 1,000 mg/m 2 on days 1, 8, and 15 of every 28-day cycle. Results: By August 30, 2013, 24 pts were treated. No DLTs have occurred. Frequently reported (≥10%) OMP-59R5 treatment-related adverse events (AEs) were: diarrhea (44%), fatigue (44%), and nausea (16%); most were grade 1 or 2 and managed with supportive care. Frequent chemo-related AEs (≥10%) were cytopenia, fatigue, diarrhea, and nausea. GEM or Nab-P+Gem did not alter PK of OMP-59R5. See table for additional data. Conclusions: OMP-59R5 with Nab-P+ Gem is well tolerated. The MTD has not been reached. Encouraging anti-tumor activity is observed. Updated Safety, PK/PD, and efficacy data will be presented. Clinical trial information: NCT01647828. [Table: see text]
Encouraging regular physical activity for hormone-receptor positive breast cancer patients to improve mental and physical health during treatment and survivorship.
Authors: Corinne Jordan, Alicia Klepsa
Journal: Journal of Clinical Oncology (2015)

91 Background: Physical inactivity has direct effects on risk of chronic diseases, mental health, quality of life, and early mortality. Women that engage in physical activity after a breast cancer diagnosis may reduce the risk of recurrence and death from this disease. This study examines postmenopausal women with clinical stage I or II breast cancer using the Patient Reported Outcome Measurement Information System (PROMIS) 10 – Global Health Survey, Fitbit Flex, and regular Wellness Coaching. Methods: Our prospective study follows clinical stage I/II, postmenopausal, ER+, Her2- women with BMI &gt; or = to 25 beginning at their surgical consultation. Visits occur again post-operatively, six months after consultation, and again at one year. Each patient was given a Fitbit Flex with the expectation to complete 7,000 steps daily, and weekly Wellness Coaching. At each visit, a record of their activity was recorded including steps, heartrate, blood pressure, and body mass index. Quality of life was also assessed using PROMIS 10 - Global Health Survey. Results: 19 patients have enrolled. 100% of patients on study had BMI stay the same or decrease from initial consult to postop visit. 66% gained weight from initial postop visit to 6 months. 47% of patients met the daily goal of 7,000 steps. 80% showed significant increase in mental health scores and 60% increased physical health scores by PROMIS 10. Conclusions: Encouraging regular physical activity during treatment and survivorship for breast cancer can improve mental health and physical well-being during breast cancer treatment. Regular wellness coaching can support patients to reach their physical and mental health goals during treatment and survivorship.
The combination therapy with methylphenidate and American ginseng in cancer-related fatigue.
Authors: Young Chang, Joshua Smith, Diane G. Portman, Ritika Oberoi-Jassal, Sahana Rajasekhara, Mellar P. Davis
Journal: Journal of Clinical Oncology (2016)

215 Background: Fatigue is one of common symptoms among patients with cancer. However, little is known about the pathophysiology and effective pharmacologic intervention. Methylphenidate and American Ginseng were recognized for promising results and safe to use as a single therapy. Psycho-stimulants are commonly used and are effective in moderate to severe fatigue. The mechanism behind the evidence for methylphenidate is rebalancing dopamine neurotransmission which is altered in fatigue. The mechanism behind ginseng benefits appears to be improvement in muscle metabolism and reduction in inflammatory responses thought to cause fatigue in cancer. We hypothesized that combination therapy with methylphenidate and American ginseng is superior to single therapy and safe. Methods: We conducted retrospective chart review in the supportive care medicine outpatient clinic between Feb 01, 2015 and Dec 31, 2015. 28 patients were prescribed methylphenidate and American ginseng for 4 weeks. Methylphenidate dosage was between 10-20mg/day. American ginseng dosage was fixed at 2000mg/day (no control of sources). We investigated compliance rate, positive rate and change of fatigue score on ESAS. We also obtained the data for adverse effect ratio and severity as a safety measure. Results: We identified 28 patients (M: F 14/14, Age 50.4) who were prescribed combination therapy with methylphenidate and American ginseng for at least 4 weeks. 18 patients were compliant to combination therapy (Compliance rate 64%). 2 patients (11%) reported Grade 2 adverse effect while on therapy. One patient (5%) became non-compliant during the study period. 15 patients (84%) successfully completed the therapy the average fatigue score of pre and post intervention was 6.93 and 4.13 respectively (mean reduction -2.80, p-Value &lt; 0.0002). 12 patients (80%) showed significant improvement of fatigue (reduced ≥ 2). There was no association between gender and age. Conclusions: Combination therapy with standard dose of methylphenidate and American ginseng were a safe and effective way of treatment for cancer-related fatigue. Further studies to confirm its safety and efficacy are justified.
Chemothherapy using gemcitabine (G) plus cisplatin (C) in locally in stage III and IV gallbladder and biliary tract.
Authors: H. Mahfouf
Journal: Journal of Clinical Oncology (2010)

e14654 Background: The incidence of gallbladder carcinoma in Algiers is 1, 4 /105 in male and 2, 8/105 in female, the incidence of bleary tract is 0.3/105 in male and 0.1/105 in female. Since 2002 GC is the gold standard treatment in locally advanced and metastatic gallbladder and biliary tract carcinoma in Algeria. Methods: To accesses overall response, progressive free survival, delay free survival, toxicity profile, clinical benefit of GC in stage III and IV gallbladder and biliary tract carcinoma. 143 patients (pts) were included, 53M/90F,median age 57.1 (32-75) years, 16 pts with biliary tract carcinoma and 138 with gallbladder carcinoma, and received G 1,250 mg/m2 d1 and d8, C 70 mg/m2 d1(d1 = d21), inclusion criteria was proven histologic gallbladder and biliary tract carcinoma stage III or IV, ECOG performance status (less than or equal to) 1, no prior chemotherapy, measurable disease, adequate renal and liver function, good bone marrow reserve. Results: The overall response evaluated after 4 cycles of GC was 30% (9CR, 34PR, 32SD, 68 PD), the overall survival was 9, 3 months the PFS was, 4, 7 months, and the DFS was 14, 7 months. CTC G 3/4 toxicities non hematological toxicity was vomiting in 20%, fatigue in 2%, hematological toxicity was anemia in 5%, neutropenia in 2%, thrombopénia in 1%. The clinical benefit achieved in 72%. Conclusions: GC therapy showed good response, clinical benefit with moderate toxicity in stage III and IV Galbladder and biliary tract carcinoma. No significant financial relationships to disclose.
Prognostic features and outcomes in primary liver sarcoma.
Authors: Mary L. Guye, Leanne Streja, Steven L. Chen, Lori A. Uyeno, Joseph Kim, Gagandeep Singh
Journal: Journal of Clinical Oncology (2013)

150 Background: Primary liver sarcoma (PLS) is a rare and aggressive hepatic malignancy. Due to the low incidence of PLS, prognostic factors have not been well characterized. The purpose of our study was to evaluate survival outcomes in primary hepatic sarcomas and determine which factors predict survival. Methods: The Surveillance Epidemiology and End Results registry was used to identify patients with PLS from 1988-2009. Patients were evaluated by standard clinical and pathological indices including: age, gender, race, tumor size, tumor grade, histology, and extent of disease. Treatment related factors included surgery and radiation. Overall survival was assessed by Kaplan-Meier method. Univariate and stepwise multivariate Cox proportional hazards analyses were performed to identify prognostic factors. Results: 541 patients with PLS were identified. The mean age was 52 and most patients were male (55%) and white (75%). The most common histology type was blood vessel tumors (50.1%) followed by soft tissue neoplasms (17.7%) and complex mixed-stromal neoplasms (14.6%). Only 33% of patients underwent surgery and most (93%) did not receive radiation. When assessing outcomes, we observed median overall survival (OS) and cancer specific survival (CSS) of 6 months for the entire cohort. When stratified by treatment type, those who received surgery + radiation had the best survival (MS=97mos, p&lt;.001) compared to those who received either radiation alone (MS=5mos) or no treatment (MS=2mos). Stepwise multivariate analysis showed that age, male gender, tumor size, advanced stage, and no surgery were independent predictors of worse survival, all p-values &lt; .005. Conclusions: Primary liver sarcoma is an aggressive hepatic malignancy with low median OS of 6 months. Patients treated with surgery + radiation had the best outcome with a median survival of 97 months. Independent predictors for decreased survival included age, gender, tumor size, advanced stage, and no surgery.
Assessing the frequency of somatic mutations in high-risk clear cell renal cell carcinoma to provide new perspectives.
Authors: Brandon Manley, Daniel Tennenbaum, Jozefina Casuscelli, James Hsieh
Journal: Journal of Clinical Oncology (2016)

548 Background: Previous large collaborative studies have been conducted to characterize the genetic mutations found in Clear Cell Renal Cell Carcinoma (ccRCC). However, these studies have covered all stages of disease. We examine the genetic frequency of mutations in recurrently mutated genes found in ccRCC among patients with advanced localized ccRCC, defined as T3 disease and no known metastasis at presentation. Methods: Reviewing data from The Cancer Genome Atlas (TCGA), The International Cancer Genome Consortium (ICGC), The Cancer Genomics Project Tokyo, Japan and our prospectively collected intuitional database we identified 76 patients with ccRCC and T3 disease. We calculated the frequency of several previously reported recurrently mutated genes including VHL, PBRM1, SETD2, BAP1, KDM5C, TERT (including promoter), TP53, MTOR, and PTEN. .We also reviewed and reported corresponding clinical information for this cohort. Results: Table provides the frequency of somatic mutations as well as demographic information of our cohort. Mutual exclusivity was found between mutations of BAP1 and TERT in all patients studied. Additionally, KDM5Cmutations were found in 20% of our patients. Conclusions: These results describe the frequency of several recurrently mutated genes present in high-risk ccRCC. The mutual exclusivity between BAP1 and TERT, both having been associated with aggressive disease, suggests a possible interesting relationship between the two. Focusing our investigation on a more precise cohort of patients’ staged disease allows for new perspectives on the genetics present. Further investigation into how these mutation burdens differ from lower-risk disease deserves further investigation. [Table: see text]
Docetaxel-induced neutropenia and neutropenic fever in general and elderly patient population: A meta-analysis.
Authors: M. O. Bashir, S. Wu
Journal: Journal of Clinical Oncology (2011)

e19729 Background: Docetaxel is a chemotherapeutic agent widely used for the treatment of many solid malignancies. We did this meta-analysis to evaluate the risk of high- grade neutropenia in general and elderly patients treated with docetaxel monotherapy. Methods: The databases of Pub med and web of Science were searched from January 1966 to December 2010. Abstracts presented at the American Society of Clinical Oncology conferences held between January 2000 and January 2011 was also reviewed. Eligible studies included phase 2 and 3 clinical trials in which docetaxel was used as a single agent at the equivalent dose of 25mg/m2/week. Elderly patients were defined as above 65 years of age in this analysis. Summary incidences and 95% confidence intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: A total of 4332 patients with NSCLC, breast and prostate cancers from 25 clinical trials were included in the analysis. The incidence of high- grade neutropenia with docetaxel monotherapy was 39.3% (95% CI: 32.5-46.4%). There was significant variation among tumor types (p<0.001). No significant variation was found between general and elder patients (p=0.68). The incidence of neutropenic fever was 7.5% (95%CI: 5.6-9.9%) and there was no significant variation between general and elder patients (p=0.78). The incidence of fatal neutropenia was 3.2% (95%CI: 1.2-8.3%), and there was no significant difference between general and elder population (p=0.86). Conclusions: There was significant risk of high-grade neutropenia in general and elderly patients treated with single agent docetaxel at 25 mg/m2 per week, and prophylaxis is recommended.
Impact of breast cancer treatment on body mass index (BMI) over time.
Authors: Raquel E. Reinbolt, Xueliang Jeff Pan, Kaitlin K. Wandell, Robert Pilarski, Rachel M. Layman, Ewa Mrozek, Bhuvaneswari Ramaswamy, Robert Wesolowski, Maryam B. Lustberg
Journal: Journal of Clinical Oncology (2015)

94 Background: Weight gain concerns breast cancer patients, can impact quality of life, may lead to therapy non-adherence, and is associated with increased recurrence risk and mortality. Early placebo-controlled trials did not identify a clear correlation between Tamoxifen (TAM) and weight gain; gain due to aromatase inhibitors (AIs) is not well characterized. We hypothesized that weight gain occurs more frequently than previously reported in breast cancer patients receiving endocrine therapy. Methods: This is a retrospective chart review investigating body mass index (BMI) change in women after breast cancer therapy. Patients with early stage breast cancer and whom had BMI and treatment data (at least 90 days) from 2003-2012 were identified in The Columbus Breast Cancer Tissue Bank. Patients were separated by treatment received: chemotherapy with and without endocrine therapy vs. endocrine therapy alone (including both TAM and AIs) vs. no other treatment. Results: A total of 970 subjects were included in the analysis. At diagnosis and/or treatment initiation, patients’ mean BMI was 29.2 ± 7.0 kg/m 2 ; mean age 53.7± 11.6 years; and average length of therapy/follow up per patient, 1833 days (range 90-3,990). Patients who received an AI alone had significantly decreased BMIs during therapy (-0.65± 0.29 kg/m 2 , p = 0.025), whereas patients receiving chemotherapy alone, chemotherapy with TAM, or TAM followed by AI therapy, had significantly increased BMIs (0.51 ± 0.25, 0.73 ± 0.26, 1.01 ± 0.51 kg/m 2 ; p = 0.039, 0.005, 0.045, respectively). Both older age and a higher BMI at diagnosis were associated with a significantly greater decline in BMI over treatment time (p &lt; 0.001 and p &lt; 0.001, respectively). In a multivariate regression model, after adjusting for age and initial BMI effect, the BMI change noted among different treatment groups was no longer significantly different (p = 0.43). BMI change was not statistically associated with treatment length (p = 0.26). Conclusions: Our review of a large, early stage breast cancer patient cohort showed no association between weight gain and endocrine therapy after adjusting for the effect of initial BMI and age at diagnosis. Additional study is needed to identify other factors impacting weight in this population.
A novel approach to manage skin toxicity caused by cetuximab and panitumumab.
Authors: R. Berardi, A. Campanati, A. Onofri, A. Bittoni, C. Pierantoni, K. Giuliodori, G. Ganzetti, M. Scartozzi, A. Offidani, S. Cascinu
Journal: Journal of Clinical Oncology (2011)

616 Background: Inhibition of the EGFR represents one of the most important fields for research and development in cancer therapy. Skin rash has been documented as one of the most common adverse reactions in patients receiving EGFR inhibitors. Several approaches have been attempted to manage skin toxicity. Nicotinamide has been shown to be an effective treatment for skin inflammation in various conditions, since nicotinamide inhibits IL-8 production through the NF-kB and MAPK pathways in an in vitro keratinocytes/P. acnes model of inflammation. Furthermore green tea polyphenols could be useful in attenuation of solar UVB light-induced oxidative stress-mediated and MAPK-caused skin disorders in humans. Methods: Therapy protocol for skin toxicity consisted of: topic applications of green tea and a mostouizer and orally given nicotinamide. Patients were monitored weekly and data regarding skin toxicity (NCI-CTC grade, the Dermatology Life Quality Index (DLQI), a global score evaluating all the parameters) were recorded. Results: Between September 2009 and September 2010, 13 colorectal cancer patients receiving anti-EGFR monoclonal antibodies (cetuximab or panitumumab) and developing skin toxicity, were treated by a multidisciplinary team including oncologists, dermatologists, a pathologist, and a nurse. All the patients experienced a significative eduction of erythema, papulo-pustular rash, paronychia, fissuring, xerosis, and itching. A significative improvement of the global score and of DLQI was evident. No toxicity related to the treatment of skin toxicity was observed. Conclusions: Treatment with nicotinamide, green tea, and moisturizer represents a novel effective approach to manage skin toxicity caused by cetuximab and panitumumab. No significant financial relationships to disclose.
Does relative dose intensity of perioperative chemotherapeutic agents correlate survival in patients with pancreatic cancer?
Authors: H. Takamori, H. Tanaka, S. Abe, O. Nakahara, Y. Ikuta, Y. Sakamoto, S. Ida, S. Furuhashi, K. Horino, T. Beppu, H. Baba
Journal: Journal of Clinical Oncology (2011)

e14564 Background: High probability of systemic and/or local relapses occurs even after curative resection of pancreatic cancer (PC). We have introduced a novel multimodality therapy composed of pancreatic resection and intraoperative radiation therapy (IORT) combined with neoadjuvant (NAC) and postoperative adjuvant (AC) combination chemotherapy using gemcitabine (GEM) + 5-FU for patients with PC since 2001 (Ann Surg Oncol in press). The aim of this study was to assess significance of relative dose intensity (RDI) of the perioperative chemotherapeutic agents. Methods: In eligible patients with PC, 5-FU was administered at a dose of 125 mg/m2 on days 1-5 every week as a continuous pancreatic and hepatic arterial infusion, and GEM was infused intravenously at a dose of 800 mg/m2 for 30 min once weekly for 2 weeks for NAC. Pancreatic resection combined with IORT was performed after the completion of NAC. AC was performed in the same regimen as NAC. Results: This study enrolled 44 pts (stage Ia; 3pts, stage Ib; 1pt, stage IIa; 10pts, stage IIb; 26pts, stage III; 1pt, stage IV; 3pts). Median follow-up time for survivors was 60.5 months. Actual 1-year and 2-year survival rate was 79.5%, 68.2%, respectively. MST was 33.3 months with a 28.5% of the actuarial 5-year survival. Average RDI of total 5-FU and GEM was 54.8% and 72.0%, respectively. Average RDI of 5-FU and GEM for NAC was 93.2% and 83.0%, respectively. Average RDI of 5-FU and GEM for ACwas 43.5% and 70.5%, respectively. Based on Spearman correlation analyses, RDI of total GEM was statistically correlated with survival (p=0.0005). MST was 38.5 months in those who received >50% of the RDI of GEM, significantly longer than 8.0 months in those who received <50% of the RDI (p<0.0001). RDI of total 5-FU was not statistically correlated with survival (p=0.1364). MST was 38.5 months in those who received >50% of the RDI of 5-FU, not significantly longer than 24.0 months in those who received <50% of the RDI (p=0.0717). Conclusions: RDI of GEM was statistically correlated with survival. It indicated that dose intensity of perioperative GEM injection was an important prognostic factor in patients with PC.
Pharmacoeconomic analysis for K-Ras status–based decisions for first-line therapy of metastatic colorectal cancer (mCRC) in Spain.
Authors: Cristobal Belda
Journal: Journal of Clinical Oncology (2012)

438 Background: Personalized medicine is a challenge for current oncology practice. Nowadays there are no pharmacoeconomic analyses in Spain dealing with the clinical and financial impact secondary to K-Ras based decisions for first-line therapy in mCRC patients. So, this study was aimed to assess the cost- effectiveness of K-Ras status based decisions in first- line therapy of mCRC patients in comparison with non- K-Ras based selection of available therapies. Methods: K-Ras mutation prevalence and efficacy of available therapies (measured as response rate and progression free survival) were extracted from randomized clinical trials (RCT) that allowed on-label use of accessible drugs in Spain. Then, we have simulated all possibilities of combination therapies for first-line mCRC based on K-Ras status (wild- type vs mutated) and confronted with all therapies that could be chosen in absence of K-Ras analysis. Prices for all drugs in Spain were used to assume the best- value for each drug including all possibilities to reduce pharmacy costs. For first line, median duration of therapy reported by RCT was used to calculate the final budget. 70 kg and 1.7 m were used as reference for patients dose calculations. Results: First-line therapy that includes a biological drug in absence of K-Ras status based decisions implies an incremental cost per 1% of increased response rate of 1,237 euros for irinotecan based doublets and 3,193 euros for oxaliplatin based doublets. On the opposite, K-Ras based decisions reduce costs per objective response by 69% and 35% for irinotecan and oxaliplatin- based schedules in K-Ras wild-type population incorporating cetuximab as biological agent. These data mimic all calculi based on incremental costs secondary to improved progression free survival measured as HR when all scenarios without prior determination of K-Ras status were confronted with K-Ras based decisions. Conclusions: K-Ras based decisions reduces costs per objective response as well as per improved progression free survival. The most cost- effective scenario among all simulated was cetuximab in combination with chemotherapy for patients that harbor wt K-Ras mCRC.