tbuckley/cabot-search huggingface dataset:
Treatment of advanced glioma with an energy restricted ketogenic diet: Case report and literature summary.
Authors: Kenneth A. Schwartz, Mary Noel, Michele Nikolai, Howard T. Chang, Lawrence Karl Olson, Peter C. Kurniali, Joseph Pernicone, Norman Hord, Charles Sweeley
Journal: Journal of Clinical Oncology (2013)

e13047 Background: We initiated a pilot study to evaluate an energy restricted ketogenic diet (ERKD) as treatment for patients with glioblastoma multiforme (GBM) whose brain tumor had progressed with standard therapy. Methods: This reports documents our experience using an ERKD with an IRB approved, clinical trials #NCTO1535911 registered treatment protocol and briefly summarizes the 5 published case reports that document favorable responses with ERKD. Results: Our patient, a 55-year-old white male, presented with a left sided visual field cut, decreased analytical mental skills, a slow methodical wide based gait and a right posterior brain mass with a histological diagnosis of GBM. After documented progression following surgery, radiation therapy and TMZ the patient was treated with ERKD. He was hospitalized to induce a decrease in glucose and an increase in ketones using Ketocal 20-25 Cal/Kg. Adherence and efficacy to the diet was monitored using AM and PM measurements of blood glucose and ketones. Initial treatment with Ketocal decreased his blood glucose so that his PM glucose was &lt;80mg/dl and increased his PM ketones to &gt;3mm(our protocol’s target concentrations). However, his AM glucose was still &gt;80mg/dl and his AM ketones decreased to &gt;2mM. Because of the low palatability of the Ketocal, the patient was switched to a ketogenic regular food diet with a 3:1 ratio of fat to proteins and carbohydrates. Out of the hospital and on this diet his PM ketones remained &gt; 3mM and his AM &gt; 2mM, but his AM and PM blood glucose increased to &gt; 80mg/dl. After 4 weeks of treatment with the ERKD, the patient’s disease advanced; his vision, mobility and cognition decreased and MRI demonstrated tumor growth and he withdrew from the study. Five patients with advanced brain tumors and favorable responses to ERKD have been reported. The best response was a C.R. 5 years after diagnosis. In 4 of the 5 patients ERKD was combined with one of the standard modalities of treatment. At last report 3 of the 5 patients were C.R. and 2 had documented disease progression after stopping the ERKD. Conclusions: Investigation of ERKD in patients with malignant brain tumors using an approved, registered protocol under the guidance of a dietician is feasible.
Development of dosing recommendation of S-1 for patients with impaired renal function by prospective pharmacokinetic study.
Authors: Eisuke Booka, Chiyo K. Imamura, Yasuo Hamamoto, Takuro Mizukami, Daisuke Gomi, Takashi Ichiyama, Kazunari Tateishi, Tsunehiro Takahashi, Hirofumi Kawakubo, Kenzo Soejima, HIROYA TAKEUCHI, Narikazu Boku, Yusuke Tanigawara, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2015)

e13578 Background: S-1 is an oral key drug for gastrointestinal tumors widely used in Asia and Europe that contains tegafur (FT), which is a prodrug of fluorouracil (5-FU); 5-chloro-2,4-dihydroxypyridine (CDHP), which inhibits the rate-limiting enzyme (dihydropyrimidine dehydrogenase; DPD) of 5-FU for retaining a high concentration of 5-FU; and potassium oxonate (Oxo), which inhibits phosphorylation of 5-FU for reducing gastrointestinal toxicity. Although 5-FU elimination is not affected by renal function, more than 50% of CDHP is excreted in urine, thus the renal dysfunction causes high exposure of CDHP, which results in sustained high concentration of 5-FU inducing severe adverse reactions. However, there is no definite information on optimal dose of S-1 adjusted by renal function. Methods: A prospective pharmacokinetic study in cancer patients with varying degrees of renal function was conducted at three institutions in Japan. Sixteen enrolled patients received a single dose of S-1 at 40 mg/m2. A series of blood samples were taken at predefined times over 24 hours to assess the plasma concentrations of 5-FU, CDHP and FT, and the relationships between these pharmacokinetic parameters and creatinine clearance (CLcr) estimated by the Cockcroft-Gault equation were investigated. Results: The AUC0-24 of 5-FU were as follows: 537.4±210.3 ng*h/mL in patients with CLcr > 80 mL/min (n = 4), 750.7±180.4 ng*h/mL in those with CLcr = 60 to 79 mL/min (n = 5), 775.8±359.4 ng*h/mL in those with CLcr = 30 to 59 mL/min (n = 5) and 1866.4 ng*h/mL in those with CLcr = 15 to 29 mL/min (n = 2). The AUC0-24of 5-FU was correlated with the CLcr as well as that of CDHP. Conclusions: Based on the concept of exposure matching to full dose of S-1 (40mg/m2, twice daily) for patients with normal renal function (CLcr > 80mL/min), we propose recommendation of adjusting S-1 dose according to renal function as follows: 70 % dose for patients with mild and moderate renal impairment (CLcr = 30 to 79 mL/min) and 30 % dose for patients with severe renal impairment (CLcr = 15 to 29 mL/min). For the next step, prospective validation study is planned to evaluate clinical outcomes of treatment with S-1 at our recommended dose. Clinical trial information: 000011708.
Analysis of candidate homologous repair deficiency genes in a clinical trial of olaparib in patients (pts) with platinum-sensitive, relapsed serous ovarian cancer (PSR SOC).
Authors: Brian Dougherty, Jonathan A. Ledermann, Zhongwu Lai, Jane D Robertson, Tony Ho, Darren R Hodgson, Mark J O'Connor, Anitra Fielding, Matthew J. Hawryluk, Tim Brennan, Roman Yelensky, James Sun, J. Carl Barrett
Journal: Journal of Clinical Oncology (2014)

5536 Background: In a randomized trial of 265 pts with PSR SOC, maintenance therapy with the PARP inhibitor olaparib led to a PFS benefit vs placebo in pts with BRCA1/2 mutations (hazard ratio, 0.18; Study 19 [NCT00753545]; Ledermann et al ASCO 2013). A PFS hazard ratio of 0.54 (0.34–0.85; P=0.007) in BRCA wild type/VUS (variant of unknown significance) pts is consistent with preclinical and clinical evidence that homologous recombination repair-associated genes (HRR genes) in addition to BRCA1/2 may contribute to PARP inhibitor response. Objective: Exploratory characterization of genetic changes in tumors from PSR SOC pts to determine the frequency and co-occurrence patterns of mutations in BRCA1/2 and other HRR genes, and the presence of these mutations in pts with a long-term response (LTR; treatment duration >24 mo) (olaparib, 24%; placebo, 4%). Methods: Using Foundation Medicine’s 287-gene, next-generation sequencing test, alterations were categorized based on loss-of-function mutations and BRCA1/2 mutual exclusivity, and analyzed for loss of heterozygosity and tumor heterogeneity. Results: Compared with ovarian pts from The Cancer Genome Atlas (TCGA; n=316), Study 19 pts with sequenced tumors (n=209) had considerably higher mutation rates in BRCA1 (36% vs 12%) and BRCA2 (17% vs 9%). As with TCGA, most HRR genes had low mutation rates, but the proportion of Study 19 pts with BRCA1/2-mutually exclusive mutations was lower for PTEN (2% vs 6%) and higher for HRR genes (14% vs 9%). BRCA1/2-mutually exclusive HRR gene mutations in ≥1 pt were BRIP1 (5 pts), RAD54L (3 pts), CDK12 (3 pts), RAD51B (2 pts). Of 33 sequenced LTR pts, 7 (21%) had no candidate BRCA1/2 loss-of-function mutation: 5 had candidate HRR gene mutations (BRIP1, RAD51B, FANCL, PTEN, MSH2) and 2 had no clear HRR mutation among the genes tested. Conclusions: Prior Study 19 analyses showed a greater clinical benefit in pts with BRCA1/2 mutations. The proportion of pts with non-BRCA1/2 HRR gene mutations is relatively small in Study 19, but could include candidate genes deserving further study for a potential role in prolonged treatment benefit and survival on platinum or PARP inhibitors. Clinical trial information: NCT00753545.
Dose delays, dose reductions, and relative dose intensity in patients with cancer who received (neo)adjuvant chemotherapy in community oncology practices.
Authors: Menaka Bhor, Xiaoyan Li, Anne Favret, Phuong Khanh H. Morrow, Neelima Denduluri, Richard L. Barron, Shanmugapriya Saravanan, Vincent Girardi, Debra A. Patt, Yanli Li, Gary H. Lyman
Journal: Journal of Clinical Oncology (2014)

9606 Background: Neutropenic complications, such as febrile neutropenia (FN), often necessitate delays or reductions in doses of myelosuppressive chemotherapy. The resulting reduced relative dose intensity (RDI) may lead to poorer disease-free survival and overall survival. Methods: Using the McKesson Specialty Health/US Oncology iKnowMed electronic health record database, we retrospectively identified the first course of (neo)adjuvant chemotherapy received by patients without metastases who initiated treatment between 1/1/2007 and 3/31/2011. For each regimen, we estimated mean RDI and the incidences of reduced RDI (< 85% over the course), dose delays (≥ 7 days in any cycle of the course), and dose reductions (≥ 15% in any cycle of the course) relative to the corresponding standard regimens described in the National Comprehensive Cancer Network (NCCN) guidelines or in published phase 3 trials. We also estimated the proportion of patients who received colony-stimulating factor (CSF) prophylaxis in the first 5 days of cycle 1. Results: See Table. Conclusions: The incidences of chemotherapy dose delays, dose reductions, and reduced RDI varied greatly across tumor types and regimens. CSF prophylaxis also varied, but was most frequently associated with regimens with a high risk (> 20%) of FN according to the NCCN guidelines. Further research should evaluate the impact of reduced RDI on long-term survival. Tumor type and regimen Sample size Mean RDI, % (SD) RDI < 85%, % Dose delay ≥ 7 days, % Dose reduction ≥ 15%, % CSF prophylaxis in cycle 1, % Breast cancer TC 3,392 89.8 (18.9) 19.3 22.9 22.3 50.7 TAC* 1,566 85.7 (22.2) 27.1 36.1 34.8 91.8 Dose-dense AC→T* 1,269 93.5 (9.0) 15.6 38.2 27.0 89.1 Ovarian cancer Carboplatin, paclitaxel 314 67.4 (27.0) 66.9 67.2 77.4 21.0 NSCLC Carboplatin, paclitaxel 391 57.1 (32.4) 71.4 61.9 78.3 24.0 Cisplatin, vinorelbine 218 61.4 (24.2) 82.1 61.5 91.3 1.4 Hodgkin lymphoma ABVD 774 69.1 (24.6) 64.1 72.6 69.9 24.8 NHL RCHOP/CHOP (Q3W) 1,443 75.2 (25.3) 52.6 57.2 54.1 73.1 RCVP/CVP 409 76.7 (26.1) 48.9 54.5 46.2 28.9 * High risk of FN according to the NCCN.
Reduced Intensity Conditioning (RIC) with Double Umbilical Cord Blood Transplantation Has Similar Outcomes Compared to RIC Transplantation From Related or Unrelated Adult Donors
Authors: Yi-Bin Chen, Julie Aldridge, Haesook Kim, Karen K Ballen, Corey Cutler, Grace Kao, Deborah Liney, Edwin P Alyea, Philippe Armand, John Koreth, Jerome Ritz, Robert J Soiffer, Thomas Spitzer, Joseph H. Antin, Vincent T Ho
Journal: Blood (2010)
Mucoadhesive clonidine (Clonidine Lauriad) in the prevention of severe radiomucositis in head and neck cancer patients: A phase II randomized trial.
Authors: Jordi Giralt, Yungan Tao, René-Jean Bensadoun, Rajesh V. Lalla, Esat Mahmut Ozsahin, Gabor Pajkos, Rolf-Dieter Kortmann, Jorge Contreras-Martinez, Philippe Ceruse, Xavier Zasadny, Fernando Arias de la Vega, Pierre Attali, Berangere Vasseur, Michael Henke
Journal: Journal of Clinical Oncology (2015)

6058 Background: Oral mucositis (OM) is the most frequent and severe complication of chemoradiotherapy (CRT) in head and neck cancer patients. There is currently no effective mechanistically-targeted intervention for CRT-induced OM. NF-κB plays a central role in the signaling cascades and pathways responsible for OM. Clonidine reduces NF-κB activation and the subsequent expression of pro-inflammatory cytokines. In preclinical studies, topical clonidine reduced the incidence and duration of severe OM (SOM). The safety and efficacy of 2 doses of clonidine MBT were evaluated in patients with head and neck cancer receiving postoperative CRT. Methods: This phase 2, multicenter, double-blind, randomized, placebo-controlled, 3-arm study compared clonidine MBT 50µg, 100µg, and placebo. Clonidine MBT and matching placebo were applied to the gum once daily 1-3 days prior to RT until the end of CRT. The primary endpoint was the cumulative radiation dose at the onset of SOM (WHO grade 3 or 4) analyzed by the Kaplan-Meier method and the log-rank test. Safety was evaluated by monitoring AEs, clinical laboratory parameters, vital signs, and physical examinations. Results: Clonidine MBT was administered to 121 patients and placebo to 62. SOM developed in 45.3% of patients in the clonidine MBT group and in 60.0% of patients in the placebo group (p = 0.064). Patients developed SOM at a median radiation dose of 60.0 Gy and 48.0 Gy for the clonidine MBT and placebo groups, respectively (HR = 0.754 [0.484; 1.175]; p = 0.211). The percentage of AEs was similar between placebo (98.4%) and clonidine MBT groups (90.8%) with less nausea (49.6% vs 71%) and dysphagia (32.8% vs 48.4%) in the clonidine MBT groups vs placebo. Conclusions: Here, we present for the first time, that clonidine MBT treatment in head and neck cancer patients undergoing postoperative CRT reduces SOM with minimal toxicity. However not statistically significant, the observed differences in the incidence and time to occurrence of SOM support the initiation of future confirmatory studies. Clinical trial information: NCT01385748.
Erratum: Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography (New England Journal of Medicine (1998) 339 (5-11))
Authors: R. J. Adams, V. C. McKie, L. Hsu, B. Files, E. Vichinsky, C. Pegelow, M. Abboud, G. Woods, N. Olivieri, C. Driscoll, S. Miller, D. Brambilla, W. Wang, A. Hurlet, C. Scher, B. Berman, E. Carl, F. T. Nichols, E. S. Roach, A. Kutlar, E. Wright, R. A. Zimmerman, D. Gallagher, M. A. Waclawiw, D. R. Bonds
Journal: New England Journal of Medicine (1998)
A randomized phase II study of carboplatin and bevacizumab in recurrent glioblastoma multiforme (CABARET).
Authors: Kathryn Maree Field, John Simes, Helen Wheeler, Elizabeth J. Hovey, Anna K. Nowak, Lawrence Cher, Chris Brown, Ann Livingstone, Kate Sawkins, Mark Rosenthal
Journal: Journal of Clinical Oncology (2013)

2017 Background: The optimal use of bevacizumab (bev) in recurrent glioblastoma (GBM) remains uncertain including the choice between monotherapy or combination therapy as well as the role of continuing bev beyond disease progression. Methods: This was a sequential stratified two part randomized phase II study. Eligibility criteria included: recurrent GBM after radiotherapy and temozolomide, no other chemotherapy for GBM, ECOG PS 0-2. The primary objective (Part 1) was to determine the effect of bev plus carboplatin versus bev alone on 6 month progression-free survival (6PFS) using modified RANO criteria. Bev was given 2-weekly 10mg/kg, carboplatin 4-weekly AUC5. On progression, patients (pts) able to continue treatment were randomized to continue or cease bev (Part 2). Secondary endpoints included response rate (RR); cognitive function; quality of life; toxicity and overall survival (OS). Results: 122 pts (median age 55) were enrolled from 18 Australian sites. 87 (71.3%) were PS 0-1. The current median follow up is 14.7 months with median on-treatment time 3.7 months. 6PFS was 26% (combination) versus 24% (monotherapy) (HR 0.96, 95%CI (0.66, 1.39), p = 0.82). RR (CR+PR) was 15% versus 13%. Median OS was 6.9 versus 6.4 months (HR 1.08, 95%CI (0.74, 1.59), p = 0.68). There were 2 treatment (bev) related deaths in the combination arm (one GI perforation, one CNS hemorrhage). To date, overall incidence of bev-related AEs is similar to prior literature with 10 (8.3%) venous thromboembolic events and 5 (4.2%) hemorrhages (all grades) reported. There were 3 episodes of G3-4 neutropenia, all in the combination arm (5%) and 9 episodes of G3-4 thrombocytopenia. As of January 14, 2013, 47 pts have continued on to Part 2. Data for bev beyond progression is not yet available. Conclusions: In this study of patients with recurrent GBM, the addition of carboplatin to bev did not result in additional clinical benefit compared to bev monotherapy. This large multicentre population-based study demonstrated that clinical outcomes in patients with recurrent GBM treated with bev were inferior to previously reported studies. Ongoing follow-up of patients on bev beyond progression, and novel secondary and exploratory endpoints continues. Clinical trial information: ACTRN12610000915055.
A phase II Study of FOLFOX versus POF (paclitaxel plus FOLFOX) versus IP PAC (intraperitoneal paclitaxel) plus FOLFOX as a first-line treatment in advanced gastric cancer (AGC): A feasibility analysis.
Authors: Rongbo Lin, Shen Zhao, Hui Li, Jie Liu, Nanfeng Fan
Journal: Journal of Clinical Oncology (2017)

56 Background: Double regimens are commonly accepted for AGC in East Asia. However, triple regimens are recommended in west countries. POF regimen (a modified DCF reported in 2007, 2008, 2009, 2010 ASCO) appeared to be of good efficacy and was well tolerated in patients with AGC. Intraperitoneal paclitaxel showed high local concentration in abdominal cavity and low systemic toxicity. The aims of this study were to find out if the triplet POF was more effective with manageable side effects and IP PAC in combination with FOLFOX had higher local control rate and manageable systemic toxicity than doublet FOLFOX in AGC. Methods: The patients with AGC were randomized to three group. The FOLFOX regimen consisted of oxaliplatin 85 mg/m 2 , levoleucovorin 200 mg/m 2 , and 5-FU 400 mg/m 2 bolus on day 1, then 5-FU 2400 mg/m 2 continuous infusion over 46 hours. The POF regimen consisted of a 3-hour infusion of paclitaxel 135 mg/m 2 , followed by FOLFOX omitted 5-FU bolus. The IP PAC plus FOLFOX regimen consisted of paclitaxel 80 mg/m 2 intraperitoneally plus FOLFOX. Every 14 days repeated for all three regimens. Up to 9 cycles of treatment were administered, followed by S-1 until disease progression Results: From 4 th November 2015 to 10 th June 2016, 21 patients with ECOG PS 0-1 were assigned for the study. Grade ¾ toxicities, in the FOLFOX group (n = 7), neutropenia and nausea was one respectively; in the POF group (n = 9); neutropenia were two, stomatitis, nausea, vomiting, and fatigue was one respectively; in the IP PAC plus FOLFOX group (n = 5), neutropenia and fatigue was one respectively. No treatment-related death occurred. Median progression free survival and overall survival were 68 days and 194 days in FOLFOX group, 128 days and 282 days in POF group, 89 days and 178 days in IP PAC plus FOLFOX group. Conclusions: This pilot analysis showed three regimens including IP PAC plus FOLFOX had good safety profits. The POF group seemed to have better PFS and OS than the other two groups. This ongoing phase II study is feasible. Clinical trial information: NCT02845908.
A phase II study of gemcitabine, erlotinib, and S-1 in patients with advanced pancreatic cancer.
Authors: Boram Han, Hyeong Su Kim, Dae Ro Choi, Byoungyong Shim, Kyung Hee Lee, Jin Won Kim, Jung Han Kim, Jung Hoon Kim, Hunho Song, Choong Kee Park, Sung Hoon Moon, Jong Hyeok Kim, Jang Yong Jeon, Jung Woo Lee, Dae Young Zang
Journal: Journal of Clinical Oncology (2017)

476 Background: Gemcitabine-based chemotherapy is considered as a standard front-line treatment for patients with advanced pancreatic cancer. Although addition of erlotinib or S-1 to gemcitabine has yielded better outcomes, it has showed just modest improvement in survival. To overcome this limitation, we evaluated the efficacy and safety of the combination of gemcitabine, erlotinib, and S-1 for the treatment of advanced pancreatic cancer. Methods: Chemotherapy-naïve patients with pathologically proven locally advanced, recurrent or metastatic pancreatic adenocarcinoma were assessed for eligibility. Gemcitabine at 1,000 mg/m 2 was administered intravenously on day 1, and 8, erlotinib at 100 mg/day was administered on day 1-21, and S-1 at 60 mg/m2 was administered on days 1-14 every 21 days and continued to maximum of 8 cycles of treatment. Dose escalation of S-1 to 80 mg/m2 was permitted from second cycle for pre-defined tolerable patients. Results: Thirty-seven patients (median age 61.5 years) were enrolled. A total of 140 cycles of chemotherapy were administered (median of 3.8; range 1–8 cycles). Toxicities were evaluated in 36 patients, and the responses were evaluated in 31 patients. Major grade 3/4 toxicities included neutropenia (25%), febrile neutropenia (2.8%), fatigue (22.2%), infection (8.3%), vomiting (5.6%), and mucositis (5.6%). The overall response rate was 12.9% [95% confidence interval (CI), 5.1-28.9%] and disease control rate was 74.2% (95% CI, 56.8-86.3%). The median progression-free survival and overall survival were 3.4 months (95 % CI, 2.3-4.5 months) and 5.7 months (95 % CI, 3.9-7.6 months), respectively. Conclusions: The combination of gemcitabine, erlotinib, and S-1 provided an acceptable toxicity profile and modest clinical benefits in patients with advanced pancreatic cancer. Clinical trial information: NCT01693419.
Temporal trends in healthcare utilization following primary melanoma diagnosis among Medicare beneficiaries
Authors: J.P. Lott, Q. Wang, L.J. Titus, T. Onega, H.D. Nelson, M.A. Weinstock, J.G. Elmore, A.N.A. Tosteson
Journal: British Journal of Dermatology (2017)

Little is known about the impact of primary melanoma diagnosis on healthcare utilization and changes in utilization over time. To evaluate population-based temporal trends in healthcare utilization following primary melanoma diagnosis. We conducted a before-and-after multiple time series study of Medicare beneficiaries aged ≥ 66 years with primary melanoma diagnoses between 2000 and 2009 using the Surveillance, Epidemiology, and End Results Medicare database. Primary exposure was time from primary melanoma diagnosis at 3-6 months and 6-24 months postdiagnosis. Covariates included tumour-, patient- and geographical-level characteristics and healthcare utilization in the 6 months before diagnosis. Poisson regression was used to estimate population-based risk-adjusted utilization rates for skin biopsies, benign skin excisions, internal medicine office visits and dermatology office visits. The study population included 56 254 patients with first diagnoses of primary melanoma. Most patients were ≥ 75 years old (56·8%), male (62·1%), and had in situ melanoma (42·4%) or localized invasive melanoma (45·9%). From 2000 to 2009, risk-adjusted skin biopsy rates 24 months postdiagnosis increased from 358·3 to 541·3 per 1000 person-years (P < 0·001), and dermatology visits increased from 989·0 to 1535·6 per 1000 person-years (P < 0·001). Benign excisions and internal medicine visits remained stable. In 2000, risk-adjusted skin biopsy rates 6 months postdiagnosis increased by 208·5 relative to the 6 months before diagnosis (148·7 vs. 357·2) compared with an observed absolute increase of 272·5 (290·9 vs. 563·1) in 2009. Trends in dermatology visits were similar. Utilization of skin biopsies and dermatology office visits following primary melanoma diagnosis has increased substantially over time. These results may inform optimization of care delivery for melanoma within the Medicare population.
Concomitant Medications and Gastrointestinal Events in Thalassemia and MDS Patients Receiving Deferasirox for Transfusional Iron Overload: Data From the EPIC Study
Authors: M Domenica Cappellini, Amal El-Beshlawy, John B Porter, Antonis Kattamis, Kerry Taylor, Christian Rose, Vernon J Louw, Ali El-Ali, Nicolas Martin, Norbert Gattermann
Journal: Blood (2012)