tbuckley/cabot-search huggingface dataset:
Short induction docetaxel, doxorubicin, cisplatin and methotrexate followed by concurrent chemoradiation for nasopharyngeal carcinoma (NPC). A pilot study
Authors: J. Espinos Jimenez, J. M. Lopez-Picazo, M. Moreno Jimenez, A. Chopitea, J. de la Camara, S. de la Cruz, J. Garcia-Foncillas, S. Martin-Algarra, J. L. Perez Gracia, A. Gurpide Ayarra
Journal: Journal of Clinical Oncology (2005)

5590 Background: Neoadjuvant chemotherapy and concurrent chemoradiotherapy induces high response rate, increase local control and probably reduces the risk of distant metastases in NPC patients (pts). However the experience with modern drugs as docetaxel is small in this setting. Our purpose is to study the efficacy, tolerability and safety of a new combination therapy schedule in non-metastatic NPC pts Methods: From February 1998 until June 2004 eighteen pts with histologically proven stage I-IVb NPC were initially treated with docetaxel (80 mg/m2 on day 1), cisplatin (75 mg/m2 on day 1), doxorubicin (50 mg/m2 on day 1) and methotrexate (3 g/m2 with leucovorin rescue on day 14) every 3 weeks for two cycles followed by radiation (70 Gy, 35 fractions, 3D planning) with concurrent docetaxel (80 mg/m2) and cisplatin (75 mg/m2) on days 42, 63 and 84. Those pts with residual cervical disease after therapy had planned salvage surgery. Results: Patient characteristics were: 14 male (77.8%); median age 48 years (range 25–68); ECOG 0–1 (100%); stage was I 1 pt (5.6%), II-III 10 pts (55.6%), IVa-IVb 7 pts (38.8%). Median follow-up was 23.5 months (range 2–82). Toxicity: Neutropenia grade 3 and 4 4 pts (22.2%) and 8 pts (44.4%) respectively, mucositis grade 3 and 4 8 pts (44.4%) and 4 pts (22.2%) respectively and dermitis grade 3 2 pts (11.1%). Response to induction therapy was: CR 1pt (5.5%), PR 12 pts (66.6%). Response to whole program was: CR 12 pts (66.6%), PR 4 (22.2%). Median overall and disease-free survival have not been reached. Mean overall survival was 58.6 months (95%CI: 42.3–74.9) and mean disease-free survival was 52.1 months (95%CI: 35.4–68.8). Conclusions: The results of this small pilot study are very encouraging in terms of survival with an acceptable toxicity profile. No significant financial relationships to disclose.
Retrospective observational study: Bevacizumab (B) use and outcomes among metastatic colorectal cancer (mCRC) patients (pts) receiving care in the outpatient community in the United States.
Authors: Eric S. Nadler, Kavita Rohidas Sail, Lei Chen, Stephen F. Thompson, Michael A. Kolodziej
Journal: Journal of Clinical Oncology (2012)

547 Background: This study assessed utilization and outcomes of B use in mCRC pts receiving 1 st - (1L) and 2 nd -line (2L) treatment (Tx) in this setting. Methods: Data were abstracted primarily from US Oncology’s iKnowMed electronic medical record system. Multivariate Cox models were used for overall survival (OS) when testing differences between B and nonbiologic use. mCRC pts initiating 1L or 2L Tx from 1/1/07-6/30/09 were included. Cost of care was derived from outpatient claims data in US Oncology’s Claims Data Warehouse. Results: 1795 pts were identified in 1L setting, 615 in 2L, and 323 in both 1L and 2L; 90% of 1L and 87% of 2L pts received combination Tx. Most received biologics (73% 1L, 65% 2L); among these, most included B (1131/1179 [96%] 1L, 312/345 [90%] 2L). B was commonly combined with FOLFOX (665/1131 [59%]) in 1L and FOLFIRI (135/312 [43%]) in 2L. Results for B use are described as 1L and 2L, respectively. Mean (median) numbers of cycles were 9.1 (7.0) and 7.0 (5.0), and 23% (301/1321) and 34% (120/348) received ≤3 cycles. Mean (median) durations of use were 141 (113) and 108 (75.5) days; average doses across all cycles for B were 5.5 mg/kg and 5.7 mg/kg. Consistent with the literature, 1L B was associated with a 23% reduction in risk of mortality vs nonbiologics (HR=0.77; CI: 0.60-0.98; P=0.036); however, 2L B was not associated with risk of mortality reduction (HR=0.87; CI: 0.62-1.22; P=0.44). With 1L B-containing regimens, median OS was 546.5 days in pts who continued B in 2L (n=269), and 569 days (P=0.11) in pts who did not (n=28); median costs for 2L B vs non-B were $5155 vs $3867 (P=0.068). 1L OS observed in this study was less than 1L OS reported in the BRITE registry (660 days; 95% CI: 21.9-24.4 months [doi: 10.1634/theoncologist.2009-0071]). Conclusions: This study re-examines previously reported observations from the BRITE registry, but evaluates pts treated more recently and in both 1L and 2L settings. Our study did not show a significant survival advantage with prolonged use of B following progression. Further research is needed to confirm these findings. Research and editorial assistance was funded by sanofi-aventis U.S. LLC.
Subgroup analysis of crizotinib versus either pemetrexed (PEM) or docetaxel (DOC) in the phase III study (PROFILE 1007) of advanced <i>ALK</i>-positive non-small cell lung cancer (NSCLC).
Authors: Benjamin J. Solomon, Scott N. Gettinger, Gregory J. Riely, Shirish M. Gadgeel, Hiroshi Nokihara, Ji-Youn Han, Toyoaki Hida, Miyako Satouchi, Editta Baldini, Salvatore Siena, Nobuyuki Yamamoto, Leora Horn, Vanessa Roberts Tassell, Anna Polli, D. Ross Camidge
Journal: Journal of Clinical Oncology (2013)

8105 Background: PROFILE 1007 compared the efficacy and safety of crizotinib with that of standard-of-care chemotherapy in patients with ALK+ NSCLC. Although the study was not designed for formal assessment of patient outcomes on crizotinib vs. PEM or crizotinib vs. DOC, due to later interest, we performed retrospective efficacy and safety analyses of patient subgroups treated with crizotinib or each chemotherapy individually. Methods: Patients with stage IIIB/IV ALK+ NSCLC previously treated with 1 prior platinum-based regimen were randomized to receive crizotinib 250 mg PO BID or chemotherapy (PEM 500 mg/m 2 or DOC 75 mg/m 2 , IV q3 wk). Patients with progressive disease on chemotherapy were offered crizotinib treatment in a separate study. In these subgroup analyses, PFS and ORR based on independent radiologic review, and safety were evaluated. Results: Of 347 patients randomized, 172 received crizotinib, 99 PEM, 72 DOC, and 4 no treatment. At data cutoff (Mar 2012), 85 crizotinib patients, 21 PEM patients, and 7 DOC patients were receiving treatment. Median treatment duration was longer in the crizotinib arm (7.1 mo) than in either the PEM (4.1 mo) or DOC (2.1 mo) treatment subgroups. Median PFS was significantly longer on crizotinib (7.7 mo) than on either PEM (4.2 mo; HR, 0.59; P=0.0004) or DOC (2.6 mo; HR, 0.30; P&lt;0.0001). 1-year PFS rates were 31% on crizotinib, 16% on PEM, and 6% on DOC. The ORR on crizotinib (66%) was significantly higher than on either PEM (29%; risk ratio, 2.31; P&lt;0.0001) or DOC (7%; risk ratio, 9.65; P&lt;0.0001). The most common all-causality adverse events with crizotinib were diarrhea (60%), vision disorder (60%), and nausea (55%); with PEM, nausea (38%), fatigue (36%), and decreased appetite (26%); and with DOC, alopecia (47%), neutropenia (43%), and nausea (36%). Conclusions: Crizotinib’s superior efficacy over chemotherapy, with a distinct but generally tolerable and manageable side effect profile in patients with advanced ALK+ NSCLC, was also observed in separate comparisons with either PEM or DOC. In patients receiving chemotherapy, median PFS, 1-year PFS rates, and ORR were all numerically higher on PEM than on DOC. Clinical trial information: NCT00932893.
The Diagnostic Value of CD1d Expression In Leukemic B-Chronic Lymphoproliferative Disorders (B-CLPDs)
Authors: Eleytherios Moustakidis, Emmanuil Spanoudakis, Irene Bouchliou, Evangelia Nakou, Paraskevi Miltiades, asiliki Kotoula, Dimitrios Margaritis, George Bourikas, Richard Szydlo, Anastasios Karadimitris, Konstantinos Tsatalas, Ioannis Kotsianidis
Journal: Blood (2010)
Appropriateness of testing for heparin-induced thrombocytopenia in hospitalized patients.
Authors: Azadeh Namakydoust, Debasmita Saha, Gresa Ajeti, Brandon Bair, Karen Hook, Enrique Ballesteros, Lisa Holle
Journal: Journal of Clinical Oncology (2016)

252 Background: Heparin induced thrombocytopenia (HIT) is a devastating thrombotic complication of heparin therapy and occurs in 0.2 to 5% of patients receiving heparin products and is a clinicopathologic diagnosis. The American Society of Hematology Guidelines, recommend the use of the “4Ts” scoring system to determine the pre-test probability of suspected cases. Also, a presumptive clinical diagnosis of HIT must be followed by immediate cessation of all forms of heparin and initiation of alternate anticoagulation. Proper diagnosis and treatment can be difficult for medical and surgical clinicians, with implications for morbidity, mortality, patient safety, and cost. The Objective of this study was to assess the incidence and appropriateness of HIT testing at our institution before and after an educational session for clinicians. We hypothesized that our intervention would provide better quality care of patients with suspected HIT. Methods: First, a retrospective chart review was conducted for a 3-month period, in which we collected baseline patient and HIT-testing data. Next, an “in-service” type lecture was delivered on seven occasions to various hospitalist groups. Follow-up data for an additional 3-month period was collected after these sessions. Results: See Table. Conclusions: In this single-center study, our educational interventions were successful in reducing inappropriate HIT testing, and encouraging consultation with hematology colleagues. Future studies are needed to evaluate the utility of online teaching modules, electronic order sets,and applicability to other medical centers. [Table: see text]
Bevacizumab (BEV) plus chemotherapy (CT) continued beyond first disease progression (PD) in patients with metastatic colorectal cancer (mCRC) previously treated with BEV-based therapy: Outcomes according to KRAS status and first-line CT backbone in the ML18147 study.
Authors: Stefan Kubicka, Richard Greil, Thierry André, Jaafar Bennouna, Javier Sastre, Eric Van Cutsem, Roger Von Moos, Pia J. Osterlund, Priti Hegde, Martina A. Sersch, Stuart Osborne, Frank Hermann, Dirk Arnold
Journal: Journal of Clinical Oncology (2014)

520 Background: ML18147 is the first randomized phase III study to show that continuing BEV + standard CT as second-line (2L) treatment significantly improves overall survival (OS) and progression-free survival (PFS) in patients with mCRC who progressed after receiving a standard first-line (1L) BEV-containing regimen. Here we report an exploratory analysis of outcomes based on CT backbone and KRAS status. Methods: Patients with unresectable, histologically confirmed mCRC who progressed ≤3 months after discontinuing 1L BEV were randomised to 2L CT (crossed over from oxaliplatin to irinotecan and vice versa) ± BEV. This post-hoc analysis evaluated OS, PFS, overall response rate (ORR) and disease control rate (DCR) according to 1L CT backbone (irinotecan- or oxaliplatin-based) and KRAS status (Scorpion ARMS test for KRAS codons 12 and 13). Results: In total, 616 patients (75% of the ITT population) were included in this analysis; 316 had wild-type (WT) and 300 had mutant-type (MT) KRAS status; 355 received 1L irinotecan and 261 received 1L oxaliplatin. BEV+CT beyond PD prolonged OS and PFS vs CT alone, regardless of whether oxaliplatin- or irinotecan-based CT was used in the 1L and whether patients had WT or MT KRAS (Table). Adverse events were not increased when continuing BEV+CT beyond PD and were consistent with previous findings. Conclusions: This post hoc analysis suggests that continuing BEV + 2L oxaliplatin or irinotecan-based CT (following crossover) leads to prolonged OS and PFS, regardless of KRAS status or if oxaliplatin or irinotecan-based CT was used in the 1L. Clinical trial information: NCT00700102. [Table: see text]
Antitumor effects of dual inhibition of the Src and insulin-like growth factor-1 receptor (IGF-1R) pathways in prostate cancer (PCa).
Authors: F. Dayyani, N. Parikh, J. H. Song, J. C. Araujo, J. M. Carboni, M. M. Gottardis, G. C. Trudel, C. Logothetis, G. E. Gallick
Journal: Journal of Clinical Oncology (2011)

e15004 Background: The Src and IGF-1R axes are aberrantly activated in both PCa and the microenvironment of bone metastases. Dasatinib and BMS-754807 are clinically promising small molecule inhibitors with high potency against Src family kinases and IGF-1R, respectively. The aim of this study was to establish antitumor co-operativity by combining IGF-1R and Src blockade in a preclinical PCa model. Methods: LNCaP and PC3 cells were used as models for androgen-dependent and independent PCa, respectively. Inhibition of Src and IGF-1R pathways was accomplished by pharmacologic agents (dasatinib against Src and BMS-754807 against IGF-1R) as well as by shRNA. Serum IGF-1 levels were measured in patients (pts) with castration-resistant PCa (CRPC) treated with dasatinib and docetaxel in a phase II trial. Results: Src inhibition decreased proliferation of PCa cells, and migration in modified Boyden Chamber and wound assays. In contrast, IGF-1R blockade induced apoptosis (increased Sub-G1 fraction cells, Annexin-V(+) cells and PARP cleavage). Phosphorylation of Akt was partially inhibited by either drug alone and almost completely abrogated by the combination. Intraprostatic injection of shIGF-1R or shSrc PC3 cells in nude mice led to an 83% and 60% decrease in tumor size compared to control shRNA, respectively. In both cell lines, all observed antitumor effects were enhanced when dual blockade was used, relative to blocking the Src or IGF-1R pathway alone. In 9/19 (47%) pts with CRPC, treatment with dasatinib resulted in a compensatory increase of serum IGF-1 levels. Conclusions: Dual inhibition of Src and IGF-1R is effective and complementary in PCa, mediated, in part, through inhibition of the downstream target Akt. In about half of pts treated with dasatinib, an increase in soluble IGF-1 levels was observed, indicating there is a compensatory upregulation of survival pathways that might be abrogated by dual inhibition of Src and IGF-1R. The combination of dasatinib and BMS-754807 may be a rational therapeutic approach in PCa by blocking complementary processes of tumor growth and progression.
Comparison of definitive chemoradiotherapy and esophagectomy for stage I esophageal squamous cell carcinoma.
Authors: S. Yamamoto, R. Ishihara, M. Motoori, Y. Kawaguchi, Y. Takeuchi, K. Higashino, N. Uedou, M. Yano, S. Nakamura, H. Iishi
Journal: Journal of Clinical Oncology (2011)

67 Background: Chemoradiotherapy (CRT) of esophageal cancer has been proposed as an alternative to esophagectomy given the favourable survival rate and mild toxicity. However, no comparative study is reported between esophagectomy and CRT in stage I esophageal squamous cell carcinoma. Methods: A total of 54 patients treated by definitive CRT and 116 patients treated by esophagectomy at out institution between February 1995 and August 2008 were included in the analysis. Overall survival and recurrence rates were evaluated. Results: Of 170 patients who had clinical stage I esophageal squamous cell carcinoma and treated by definitive CRT or esophagectomy, 169 patients (99%) were completely followed up. CRT mainly consisted of two cycles of cisplatin and fluorouracil with concurrent radiotherapy of 60 Gy in 30 fractions. Median (range) observation period was 67 (10–171) months in SURG group and 30 (4–77) months in CRT group. In CRT group grade 3 or grade 4 hematological or non-hematological adverse effects were seen in 24 (44.4%) patients. 1-year and 3-year overall survival rates were 97.4% and 85.5% in the SURG group and 98.1% and 88.7% in the CRT group (P = 0.78). By using Cox proportional hazards modelling, overall survival was comparable between the 2 groups after adjusting for age, sex, and size of cancer. Hazard ratio of CRT for overall survival was 0.95 (95% CI: 0.37-2.47). The incidence or local recurrence including metachronous esophageal cancer was significantly higher in the CRT group than the SURG group (P &lt; 0.0001). All recurrences were intramucosal carcinomas and all of them were cured after the salvage treatment mainly using endoscopy. Conclusions: Overall survival rate of CRT was comparable with esophagectomy despite high local recurrence rate. Local recurrent carcinoma is endoscopically treatable in all patients without influence on overall survival. CRT appears to be a reasonable alternative to esophagectomy in patients with stage I esophageal cancer. No significant financial relationships to disclose.
Association between anti-cholinergic burden and delirium among patients with advanced cancer referred to a palliative care consult service.
Authors: Maxine Grace Jaucian De La Cruz, Joseph Baidoo, Vishidha Reddy Balankari, Jessica Marie Waletich-Flemming, Marvin Delgado-Guay, Jimin Wu, Diane D Liu, Eduardo Bruera
Journal: Journal of Clinical Oncology (2016)

213 Background: Delirium occurs in about 45-60% hospitalized patients and 80-85% at the end of life. Predisposing factors include anti-cholinergic medications as is often cited in the geriatric literature. Our study aimed to demonstrate the association of anti-cholinergic burden and delirium in patients with advanced cancer. Methods: Retrospective review of 775 consecutive patients seen by the palliative care inpatient consult team. Demographic data, MDAS, ECOG, and anti-cholinergic drugs were determined. Anticholinergic burden was measured using the anticholinergic drug scale (ADS), anticholinergic risk scale (ARS), and anticholinergic burden scale (ACB). Patients with delirium and those who did not develop delirium were compared. Association between delirium and anticholinergic use were analyzed using Chi-squared test, univariate and multivariate logistic regression models. Results: 270/775 (35%) had delirium at the time of consult. Median age was 58 years. The median total of anticholinergic drugs in both groups was 6. Anticholinergic burden using the ADS (median 2 vs. 3; p = 0.09) and ARS (median 0 vs. 1; p = 0.75) was not different in both groups. ACB score were significantly different in both groups (median 1 vs 2; p = 0.0006). Univariate analysis showed hematologic malignancy (OR = 1.85, 95%CI: (1.23, 2.77), p 0.0030, poor ECOG, age (OR = 1.03, 95%CI: (1.02, 1.04), p &lt; 0.0001) and ACB score (OR = 1.11, 95%CI: (1.03, 1.21), p 0.0069 to be associated with delirium. In our multivariate model ECOG (OR = 0.25, 95% CI: (0.17, 0.36), p &lt; 0.0001), and age (OR = 1.03, 95% CI: (1.01, 1.04), p &lt; 0.0001) are the only independent covariates significantly associated with the presence of delirium at admission. Conclusions: Our study found that in this younger population with cancer, the total number of anticholinergic drugs and the anticholinergic burden using 3 different scales were not associated with delirium suggesting a different mechanism. Further studies are needed to confirm these findings.
Cancer, depression, and health care coverage in the state of Nevada: A retrospective cross-sectional study.
Authors: Pannaga G. Malalur, Manas Agastya, Yaser Dawod, Linha Phan, Mohammad talha Farooqui, Ji won Yoo
Journal: Journal of Clinical Oncology (2016)

42 Background: The prevalence of depressive disorders in patients with malignancies is estimated at 20-50%, significantly greater than the general population. Existing literature reports a negative impact of depression on both the patient and their families. There is limited information regarding the impact of healthcare coverage on the prevalence of depression in such patients both in the state of Nevada and nationwide. Methods: A retrospective cross-sectional study was performed using the Behavioral Risk Surveillance System (BRFSS) database from 2010 to 2014. All adult subjects with a history of malignancy were included. Demographic factors and health care coverage were reviewed. Individuals with skin cancer as well as those with missing data were excluded. Patients were assigned to two groups based on their insurance coverage status. Study population was further stratified into Nevada and non-Nevada residents and analyzed. Association between depression and health care coverage across the study groups were assessed using Pearson chi-square test and regression models. Results: 183,530 subjects nationwide met our inclusion criteria. The Nevada population represented 1% (1676) of the total study sample. In Nevada, the prevalence of cancer patients without healthcare coverage was 7.5% (N = 126) compared to individuals with coverage 92% (N = 1550). This is significantly higher when compared to the national average of 4.9 % without coverage (p = 0.001). Overall, the rate of depression in cancer patients with no healthcare coverage nationally was notably higher compared to those with coverage (37.5% vs 22.7%, p = 0.001). Similarly, statistically higher rates of depression were noted in non-insured Nevada patients compared to those insured [49 (38.8%) vs. 357 (23%), p 0.001)]. Conclusions: This study demonstrates significant association between depression and lack of insurance coverage; both nationwide as well as in the state of Nevada. The proportion of uninsured Nevada residents with malignancies were higher compared to the national average. Improved and early screening for depression is crucial in mitigating the potential complications and morbidity associated with depression in patients with cancer.
A phase I study of S-1 in combination with sorafenib in metastatic renal cell carcinoma (mRCC).
Authors: Seiichiro Ozono, Tatsuya Takayama, Masato Fujisawa, Hideaki Miyake, Katsuyoshi Hashine, Iku Ninomiya, Katsunori Tatsugami, Hideki Sakai, Kojiro Ohba, Hideyuki Akaza, Taiji Tsukamoto, Seiji Naito
Journal: Journal of Clinical Oncology (2012)

447 Background: S-1 is an oral anticancer agent combining tegafur, a prodrug of 5-fluorouracil, with 5-chloro-2,4-dihydroxypyridine and potassium oxonate. The purpose of this study was to confirm the recommended dose (RD) and maximum tolerated dose (MTD) of S-1 in combination with sorafenib, a small molecular inhibitor of several tyrosine protein kinase, in Japanese patients with mRCC. We assessed dose-limiting toxicities (DLTs) and pharmacokinetic interactions during the first cycle of treatment. Methods: Eligible patients had a histologically confirmed diagnosis of clear cell or papillary mRCC, measurable lesions, a history of no previous treatment or not more than 1 regimen of cytokine treatment, an ECOG performance status of 0 or 1, prior nephrectomy, and adequate organ functions. In this study, four dose levels were prepared, and the starting dose was set at Level 1B. S-1 was administered on days 1 to 28, and sorafenib was given on days 1 to 42 as one cycle. The MTD was assessed using a “3 + 3” dose escalation design and was defined as the highest dose level for which the incidence of DLTs was less than 33%. Results: Between August 2009 and March 2010, 9 patients were enrolled. Two DLTs occurred in patients assigned to level 2, which was the full therapeutic dose of each agent. Therefore, the MTD was not confirmed, but the RD was determined to be level 2. Although renal clearance affected the pharmacokinetics of S-1, there were no obvious drug interactions between S-1 and sorafenib. Details are shown in the Table. Conclusions: This combination therapy can be administered with acceptable tolerability, no overlapping toxicity, and no drug interactions. The RD for phase II studies was fixed at level 2, and a phase II study is ongoing. [Table: see text]