tbuckley/cabot-search huggingface dataset:
Comparative study of six cycles versus twelve cycles of adjuvant temozolomide post concurrent chemoradiation in newly diagnosed glioblastoma.
Authors: Menal Bhandari, Ajeet K Gandhi, Pramod Kumar Julka, Chitra Sarkar, Dayanand Sharma, Goura Kishor Rath
Journal: Journal of Clinical Oncology (2013)

e13034 Background: This study assesses the impact of 6 cycles of adjuvant TMZ (conventional arm) versus 12 cycles (Extended arm) on Progression free survival (PFS), evaluate the toxicity and correlate the outcome with EGFR, P53 and MIB I labelling Index. Methods: Between December 2010 to October 2012, 36 post operative patients of Glioblastoma between age 18-65 years and Karnofsky Performance Score (KPS) ≥ 70 were included. Patients were randomized to receive Radiation with a dose of 60 Gray in 30 fractions over 6 weeks at 2 gray/fraction with concomitant TMZ (75 mg/m 2 /day) and Adjuvant therapy with either 6 or 12 cycles of TMZ(150 mg/m2 for 5 days, 28 days cycle). Patients were then assessed monthly clinically and imaged with MRI/CT every 3 monthly or when symptomatic. Toxicity was assessed using CTCAE version 3.0. Statistical Analysis was done using SPSS version 17.0.Kaplan Meier method was used for analysis of survival and log rank test was used for assessing the impact of variables on survival. Results: Of 36 patients, 18 patients were treated in each arm. Median age and KPS in both the arms was 47 years and 80 respectively. 44 % patients in the conventional arm and 50% patients in the Extended arm underwent complete surgical resection. 22% patients in the conventional arm and 28% in the extended arm did not complete their intended treatment. Grade ¾ Thrombocytopenia was seen in 16% in the extended arm and 0% in the conventional arm.EGFR, P 53 and MIB 1 &gt;20% was seen in 26%, 45% and 20% patients respectively, overall. Median follow up was 18 months for both the arms (Range 10-23 months).At last follow up,8 patients in each arm had progression. Median PFS was 10 months vs.18.4 months (p 0.47) in conventional and extended arm respectively. On Univariate analysis, patients with KPS ≤ 80 had poorer survival than those &gt;80 (Median PFS 9.5 Months vs. 16.9 Months; p 0.02).Age, extent of resection, EGFR, P53, MIB 1 did not significantly alter survival in the two treatment groups. Conclusions: Our study showed that schedule of extended Temozolomide is well tolerated by patients and tend to have better progression free survival. Further prospective randomized studies are needed to validate the findings of our study.
Seropositivity to tumour antigens as a potential new biomarker for melanoma relapse.
Authors: Lisa Louise Clark, Henry Hepburne-Scott, Mark R. Middleton, Christian H.H Ottensmeier, Kevin A Myers, Andrea Barbara Tarlton, Ann Petruckevitch, Oliver Bassett, Pheobe Bonner, Rohini Sharma, Paul D. Nathan
Journal: Journal of Clinical Oncology (2015)

e20049 Background: Current prognostic markers fail to identify many patients with stage II / III melanoma who go on to relapse. Immunity has been assumed to play a part in influencing risk of recurrence. We assessed whether seropositivity to a panel of tumour antigens was associated with relapse risk and also measured serum s100 levels and SAA. Methods: 43 melanoma patients with histologically proven, completely resected AJCC stage II n17 (40%), III n 19 (44%) and IV n 7 (16%) disease were recruited. Following informed consent, patients donated 1 serum sample per month for up to 13 months. Seropositivity to NYESO, gp100, Tyrosinase, Mart-1 and MAGE-3 tumour antigens was assessed by ELISA immunoassays (Serametrix). 1stquartile ranges were calculated per antigen. Patients with serum antibody levels > 2 x this value were determined seropositive as previously described (Gnjatic et al. 2009). SAA and s100 levels were measured with Hu SAA specific (Invitrogen) and S100 specific (Roche diagnostics) ELISA. The relationship between biomarkers and 1) relapse on or after study 2) relapse on study and 3) survival was assessed using cox proportional hazards regression analysis. Random effect logistic regression models were used to examine whether a linear trend existed over time for each patient that had biomarkers measured at monthly intervals. Patient outcome at time of last follow up in 2014 included 20 (46%) alive, 21 (49%) deceased and 2 (5%) with unknown outcome status. Results: Patients seropositive to 1 or more tumour antigens were 79% less likely to relapse on or after study than those with no immunity at any time point (HR 0.212 95% CI 0.050 – 0.898, p = 0.035). Relapsers on study (within 12 months) were seronegative to all tumour antigens tested, each with an immune score of 0. As expected, rising s100 levels were associated with relapse. For each increase in mean log e S100 value the risk of relapse on or after study increased by a factor of 11 (HR 11.47 95% CI 1.263-104.132 p0.030). Raised mean log e SAA values were not correlated with time to relapse on or after study, or patient survival. Conclusions: Seronegativity may identify a group of patients at particularly high risk of relapse and may have implication for which patients benefit from adjuvant immunotherapy.
Clinical activity of LY2835219, a novel cell cycle inhibitor selective for CDK4 and CDK6, in patients with non-small cell lung cancer.
Authors: Jonathan Wade Goldman, Leena Gandhi, Amita Patnaik, Lee S. Rosen, John Frederick Hilton, Kyriakos P. Papadopoulos, Sara M. Tolaney, Muralidhar Beeram, Drew Warren Rasco, Scott P. Myrand, Richard P Beckmann, Palaniappan Kulanthaivel, Martin Frenzel, Damien Cronier, Edward M. Chan, Keith Flaherty, Patrick Y. Wen, Anthony W. Tolcher, Geoffrey Shapiro
Journal: Journal of Clinical Oncology (2014)

8026 Background: LY2835219, a novel cell cycle inhibitor selective for the cyclin-dependent kinases CDK4 and CDK6 (CDK4/6), has shown antitumor activity in human NSCLC xenograft models. Importantly, KRAS mutant xenografts exhibit greater sensitivity to LY2835219 compared to KRAS wildtype xenografts. To evaluate the safety and clinical activity of LY2835219, we conducted a Phase I study with cohorts for multiple cancers. Here, we report results for a cohort of 49 NSCLC patients: 19 KRAS wildtype, 26 KRAS mutant, and 4 with unknown KRAS status. Methods: Patients with advanced NSCLC that progressed or relapsed after standard treatments received continuous therapy with LY2835219 orally every 12 hours (Q12H) on Days 1-28 of a 28-day cycle. RECIST v1.1 was used to assess tumor response. Progression-free survival (PFS) was described using the Kaplan-Meier method. Results: In the NSCLC cohort, 49 patients with a median of 4 prior systemic therapies received single-agent LY2835219 either at the maximum tolerated dose of 200 mg Q12H (n=25) or, to gain additional safety and efficacy data, at 150 mg Q12H (n=24). The most common possibly related treatment-emergent adverse events across all grades were diarrhea (including 2% G3), nausea (4% G3), fatigue (2% G3), vomiting (2% G3), and anemia (2% G3); there were no Grade 4 events. The disease control rate (DCR = complete response [CR] + partial response [PR] + stable disease [SD]) was 51% with 1 confirmed PR. The median duration of SD was 5.6 months and the median PFS (n=49) was 2.1 months. Among the 49 NSCLC patients, 20 (41%) reached at least 4 cycles and 13 reached at least 6 cycles, with 5 of these 13 patients still receiving LY2835219 therapy (range: 7-12 cycles). Consistent with NSCLC xenograft studies, the DCR in this clinical trial was 37% for KRAS wildtype (n=19) and 54% for KRAS mutant (n=26) NSCLC. Conclusions: In a cohort of patients with advanced NSCLC and a median of 4 prior systemic therapies, single-agent LY2835219 demonstrated acceptable safety and achieved an overall DCR of 51%, reflecting in part the higher DCR of 54% for KRAS mutant NSCLC. Thus, LY2835219 merits further clinical investigation for NSCLC, including KRAS mutant disease. Clinical trial information: NCT01394016.
Efficacy and safety of ramucirumab (RAM) for metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma across age subgroups in two global phase 3 trials.
Authors: Kei Muro, Jae Yong Cho, Gyorgy Bodoky, Chanchal Goswami, Yee Chao, Lucas Vieira dos Santos, Yasuhiro Shimada, Eldar Topuzov, Eric Van Cutsem, Josep Tabernero, John Raymond Zalcberg, Ian Chau, Rebecca Cheng, Yanzhi Hsu, Michael Emig, Mauro Orlando, Hansjochen Wilke, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2017)

3 Background: REGARD and RAINBOW are two phase 3 studies which demonstrated significant survival benefits and manageable toxicity in patients with advanced gastric cancer (GC) randomized in the second-line setting to receive RAM or placebo. We examined outcomes by age (≤45, 45-70, ≥70, ≥75 years). Methods: Patients were randomized 2:1 to receive RAM 8 mg/kg + best-supportive care (BSC) or placebo (PL) + BSC (REGARD); or 1:1 RAM 8 mg/kg + paclitaxel (PTX) or PL + PTX (RAINBOW). Kaplan-Meier analysis and Cox proportional hazards regression were performed for overall survival (OS) and progression-free survival (PFS). Subpopulation treatment effect pattern plot (STEPP) assessed efficacy and the incidence of adverse events (AEs) across age subgroups. Results: Baseline characteristics were generally well balanced between arms amongst the age subgroups. Efficacy outcomes are summarized in the Table. STEPP analysis revealed no obvious patterns for differential risks in terms of efficacy and AEs (any grade or grade ≥3) according to age. Conclusions: Compared with PL, the efficacy of RAM was maintained in all age groups, with similar rates of toxicity. Despite some limitations regarding patient numbers in some age subgroups, this exploratory subgroup analysis supports the use of RAM for the treatment of GC, irrespective of age. Clinical trial information: NCT00917384 and NCT01170663. [Table: see text]
Cisplatin-based neoadjuvant chemotherapy (NAC) in bladder cancer patients (Pts) with borderline renal function: Implications for clinical practice.
Authors: Vadim S. Koshkin, Pedro C. Barata, Haris Zahoor, Lisa A. Rybicki, Hamid Emamekhoo, Nima Almassi, Katherine Tullio, Alicia M Redden, Amr Farouk Fergany, Jihad Kaouk, Georges-Pascal Haber, Jennifer Beach, Allison Martin, Kimberly D Allman, Jorge A. Garcia, Timothy D. Gilligan, Brian I. Rini, Petros Grivas
Journal: Journal of Clinical Oncology (2017)

390 Background: Cisplatin-based NAC prior to cystectomy is a standard of care in muscle-invasive bladder cancer (MIBC). There are limited data for pts with borderline glomerular filtration rate (GFR) who get cisplatin-based NAC. Methods: A retrospective review of pts who received cisplatin-based NAC at Cleveland Clinic (2005-2016) was done. Pts with pre-NAC GFR of 40-59 mL/min by either CG or MDRD formula (low GFR group; n = 17) were compared to pts with GFR ≥ 60 (nl GFR group; n = 74) for treatment-related toxicities and outcomes, such as pathologic complete (pCR, pT0N0) and partial response (pPR, &lt; pT2N0), overall survival (OS) and recurrence-free survival (RFS). Comparisons were made using Fisher’s exact, Wilcoxon, or log-rank tests. Results: Pts with low GFR were older (median age 69 vs 64, p = .02) with worse PS (44% vs 20% ECOG &gt; 0, p &lt; .05). Gender, race, hydronephrosis rates and TURBT features (stage, grade, LVI, CIS) did not differ. For NAC, 64 pts got Gem/Cis (49 normal GFR, 15 low GFR), 23 got MVAC (22 normal GFR, 1 low GFR), 4 got other. Low GFR pts were less likely to get MVAC (6% vs 30%, p = .08) and more likely to get split-dose cisplatin (38% vs 18%, p = .10) and have NAC modified (delayed, dose reduced or stopped) (69% vs 36%, p = .02). 4/17 pts (24%) with low GFR and 9/73 (12%) with normal GFR did not complete all planned NAC cycles (p = .26). Hematologic toxicity caused most dose delays but renal toxicity was the most common cause of NAC stoppage (4/9 normal GFR, 3/4 low GFR). NAC cycles completed (median 3 / group) and G-CSF use (31/61 normal GFR, 3/9 low GFR) were comparable. No difference was noted in time to cystectomy (mean 107 days for normal vs 103 days for low GFR from NAC start), surgical complications, length of stay, and either post-NAC or post-cystectomy GFR decline from baseline. Combined pathologic response (pCR/pPR) was higher in normal GFR pts (50% vs 18%, p = .02). OS and RFS at 2 years were 89% and 79% for normal GFR and 78% and 58% for low GFR. Conclusions: Low GFR pts were older with worse PS, had more NAC modifications, lower pCR/pPR and trend for shorter OS &amp; RFS, but most completed planned NAC cycles. For very carefully selected pts with GFR 40-59, cisplatin-based NAC is a treatment option.
Infectious complications in reduced intensity conditioning (RIC) allogeneic stem cell transplantation with antilymphocyte antibodies
Authors: R. Lamba, G. Carrum, R. Krance, H. Heslop, M. Brenner, U. Popat
Journal: Journal of Clinical Oncology (2004)

6627 Background: Infection is a frequent cause of morbidity and mortality following allogeneic stem cell transplantation. It is still not clear whether RIC regimens have an impact on incidence and severity of infections. Methods: We analyzed infectious complications and outcome in 53 patients with median age of 55 years (range, 16–75 years) who underwent allogeneic stem cell transplantation with a RIC regimen consisting of Fludarabine, total body irradiation, antithymocyte globulin or Campath with or without CD45 monoclonal antibodies. Sixty eight percent (36/53) of patients received Campath based regimen. Donors were HLA identical (24 related and 17 unrelated) or one antigen mismatched (3 related, 9 unrelated). Infectious prophylaxis was Levofloxacin, fluconazole, Ganciclovir and Bactrim. Results: There were 122 episodes of fever or other clinical infections, 54 were before day +30, 46 between day +30 and day +100, and 22 after day +100. Bacteria were isolated in 42% (5 gram negative, 46 gram positive), fungi in 6% (1 invasive aspergillosis, 6 yeast) and viruses in 9% (3 adeno, 6 herpes simplex, 1 parainfluenza, 1 CMV). Cultures were negative in 43% of episodes. CMV reactivation occurred in 21% (11/53), only one had CMV disease. Non relapse mortality was 11% (6/53), severe infections 4 (staph aureus 1, pseudomonas 1, adenovirus 1, yeast and VRE 1), GVHD (1) and idiopathic pneumonia syndrome (1). Thirty two percent (17/53) of patients died of disease progression and 57% (30/53) are alive at a median follow up of 15 months. Only donor CMV +/recipient CMV+ status was significantly associated with CMV reactivation, (P= .01). Conditioning regimen with Campath, acute or chronic GVHD, treatment with steroids or tacrolimus or donor type did not influence the risk of CMV reactivation, bacterial, viral or fungal infections. Conclusions: RIC stem cell transplantation using antilymphocyte antibodies is associated with low incidence of life threatening infections and non-relapse mortality. No significant financial relationships to disclose.
Can pregabalin prevent paclitaxel-associated neuropathy?: A pilot trial.
Authors: Shivani S. Shinde, Drew K. Seisler, Gamini S. Soori, Pamela J. Atherton, Deirdre R. Pachman, Jacqueline M. Lafky, Kathryn Jean Ruddy, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2015)

9595 Background: Paclitaxel, a commonly used chemotherapeutic drug, can cause an acute pain syndrome (P-APS), considered to be an acute form of neuropathy, and chronic chemotherapy-induced peripheral neuropathy (CIPN). There are no good means to prevent and/or treat these prominent clinical problems. The purpose of this randomized, placebo-controlled, double-blinded pilot study was to obtain pilot data to support or refute the utility of pregabalin for the prevention of P-APS and CIPN, based on anecdotal reports suggesting that gabapentinoids were helpful in this setting. Methods: Patients scheduled to receive adjuvant weekly paclitaxel (80 mg/m2/dose) were randomized to receive pregabalin 75mg or a placebo, twice daily, starting on the first night of chemotherapy and continuing during the 12 weeks of chemotherapy. Patients completed the EORTC QLQ-CIPN20 questionnaire at baseline, prior to each dose of paclitaxel, and monthly for 6 months post treatment. Patients completed an acute pain syndrome questionnaire daily, for 6 days after each dose of paclitaxel. The primary endpoint was to determine the effect of pregabalin on the maximum of the worst acute pain scores for the week following paclitaxel administration for cycle 1. Secondary endpoints included the effect of pregabalin on paclitaxel-induced peripheral neuropathy and pregabalin-associated toxicities. Results: 46 patients were randomized; data regarding the acute pain syndrome and CIPN are presented in the Table. There were no differences in pain score or evidence of toxicity differences between the two study arms. Conclusions: The results of this pilot trial do not support that pregabalin is helpful for preventing P-APS or paclitaxel CIPN. Clinical trial information: NCT01637077. P-APS (Pain score over 6 days following initiation of paclitaxel; higher scores are worse) Placebo (N = 22) Pregabalin (N = 19) p-value Worse pain: Mean (SD) 3.2 (3) 2.6 (2.5) 0.56 Average pain: Mean (SD) 2.2 (2.6) 2.6 (2.2) 0.48 EORTC CIPN20 Sensory Neuropathy (higher scores represent fewer symptoms) Placebo (N = 22) Pregabalin (N = 19) p-value Mean (SD) 84.5 (16.7) 88.4 (12.5) 0.46 Median (Range) 90.7 (36.5-100) 91.9 (56.5-100)
Impact of oral mucositis on outcomes of multiple myeloma patients treated with high-dose melphalan conditioning and autologous stem cell transplantation (ASCT).
Authors: Graziella Chagas Jaguar, Gustavo Henrique Rodrigues, Andre Guollo, Vanessa Oliveira Camandoni, Leila Maria Magalhães Pessoa Melo, Fabio Abreu Alves, Vladmir Claudio Cordeiro Lima
Journal: Journal of Clinical Oncology (2013)

7037 Background: High-dose melphalan is the standard conditioning regimen for patients with multiple myeloma (MM) undergoing ASCT. However, this therapy is commonly associated with severe oral mucositis (OM). Low-level laser therapy (LLLT) has been reported as an effective method in preventing this complication. The aim of this study was to define the potential impact of OM on outcomes in patients with MM undergoing ASCT and receiving preventive LLLT. Methods: We describe a retrospective cohort of 79 consecutive patients with MM who received high-dose melphalan conditioning. All patients received prophylactic LLLT application performed daily from the beginning of the conditioning regimen up to day +2. The patients continued receiving LLLT in case of OM grade ≥ 2 until complete remission of the lesions. OM severity was assessed daily using WHO scale from the beginning of conditioning until hospital discharge. We examined the relationship between worst OM grade and clinical outcomes, including days with oral pain, days of total parenteral nutrition, days of LLLT and days with neutropenic fever. Results: Of 79 patients, 55 (69.62%) experienced OM grade 0-1, 16 (20.25%) experienced OM grade 2, 7 (8.86%) grade 3 and 1 (1.26%) grade 4. Patients with OM grade 0-2 had statistically fewer days of oral pain compared with grade 3-4 (0.88 and 6.25 days, respectively, p = 0.0001). The worst OM grade was also significantly (p &lt; 0.05) associated with days of narcotic therapy and length of LLLT. Severe OM was not associated with febrile days or the use of parenteral nutrition. Conclusions: Severe OM is associated with worse clinical outcomes. In this transplantation setting, severe OM was not common as previously reported in literature, probably due to LLLT. Controlled randomized trials should be performed to confirm the real benefit of LLLT in this scenario as well as the pharmacogenomics and pharmacokinetic studies to better understand interpatient variability of melphalan exposure and toxicity.
Charge convertibility and near infrared photon co-enhanced cisplatin chemotherapy based on upconversion nanoplatform
Authors: Jiating Xu, Ye Kuang, Ruichan Lv, Piaoping Yang, Chunxia Li, Huiting Bi, Bin Liu, Dan Yang, Yunlu Dai, Shili Gai, Fei He, Bengang Xing, Jun Lin
Journal: Biomaterials (2017)
Common polymorphisms in the estrogen receptor-1 may determine risk of hot flashes in early breast cancer patients using tamoxifen.
Authors: Vincent O. Dezentje, Henk-jan Guchelaar, Ron H. N. van Schaik, Judith M. Vletter - Bogaartz, Tahar van der Straaten, Judith A.M. Wessels, Elma Meershoek – Klein Kranenbarg, Elysee T.M. Hille, Els M. Berns, Caroline M. Seynaeve, Hein Putter, Cornelis J. H. Van De Velde, J. W. R. Nortier, Hans Gelderblom
Journal: Journal of Clinical Oncology (2012)

526 Background: In breast cancer patients the occurrence of hot flashes as common side effect of tamoxifen therapy may be associated with effective estrogen receptor antagonism dependent on genetic variations of metabolic enzymes and the estrogen receptor. Methods: 742 early breast cancer patients who were randomized to receive tamoxifen, followed by exemestane after 2.5 to 3 years within the Tamoxifen Exemestane Adjuvant Multinational (TEAM) Trial were genotyped for 30 germ line genetic variants of 11 enzymes that are involved in the tamoxifen metabolism and the estrogen receptor 1 (ESR1). These genetic variants were related to the occurrence of hot flashes during the first year of tamoxifen use (primary aim) and during the complete tamoxifen treatment period (secondary aim). A multivariable logistic regression was used to adjust for age and adjuvant chemotherapy. Results: No genetic variant was associated with the occurrence of hot flashes during the first year. Higher age was related to a lower incidence of hot flashes in the first year (adjusted odds ratio 0.94, 95% CI 0.92-0.96; p&lt;0.001). The ESR1 PvuII XbaI CG haplotype (CG/CG vs CG/other + other/other: adjusted odds ratio 0.44, 95% CI 0.21-0.92; p=0.03), ESR1 PvuII XbaI TA haplotype (TA/TA + TA/other vs other/other: adjusted odds ratio 1.86, 95% CI 1.09-3.14; p=0.02) and age (adjusted odds ratio 0.94, 95% CI 0.92-0.97; p&lt;0.001) were associated with the occurrence of hot flashes during the total tamoxifen treatment period. No association was found between the CYP2D6 predicted phenotype and hot flashes. Conclusions: Common polymorphisms in the estrogen receptor-1 might help to predict the occurrence of hot flashes in breast cancer patients treated with adjuvant tamoxifen. If replicated, this may provide clinicians with a tool to offer more personalized hormonal therapy.