tbuckley/cabot-search huggingface dataset:
Adjuvant chemotherapy with cisplatin and gemcitabine in resected non-small cell lung cancer: A single institutional experience.
Authors: Sergio Carrera, Itziar Rubio, Aintzane Sancho, Ines Marrodan, Alberto Muñoz, Estibaliz Iza, Eluska Iruarrizaga, Aitziber Buque, Begoña Calvo, Unai Aresti, Guillermo Lopez-Vivanco
Journal: Journal of Clinical Oncology (2012)

e17522 Background: Adjuvant chemotherapy in operable non small cell lung cancer (NSCLC) has been shown to improve overall survival in many meta-analysis. The use of cisplatin and gemcitabine combination is considered one of the standard regimens for first-line treatment of advanced NSCLC, with mild side effects. The aim of the study was to evaluate the clinical feasibility and toxicity of the cisplatin-gemcitabine combination in adjuvant setting. Methods: Resected NSCLC patients who met criteria for recommending adjuvant chemotherapy received treatment with cisplatin 75 mg/m 2 on day 1 and gemcitabine 1.200 mg/m 2 on days 1 and 8 of each 21 days cycle. A maximum of four cycles were delivered. Main objectives were clinical feasibility, drug delivery, and efficacy. Results: From November-2004 to July-2011 a total of 89 patients (73 male/16 female, median age 57) were included. Surgery: lobectomy 62.9%, pneumonectomy 29.2%, bilobectomy 5.6%, wedge resection 2.2%. Tumor stages: 19.1% IB, 55.1% II, 23.6% III, 2.2% IV; histology: 48.3% squamous, 43.8 % adenocarcinoma, 3.4 % large cell carcinoma and 4.5% NSCLC not otherwise specified. ECOG 0: 62.9%, ECOG 1: 37.1%. Toxicity: grade 3/4 neutropenia 19.1%/6.7 %; grade 3 febrile neutropenia 3.4%; grade 3/4 anaemia 6.7%/1.1%; grade 3/4 thrombocytopenia 6.7%/4.5%; grade 3 ototoxicity 1.1%; no grade 3/4 nephrotoxicity was reported. There was one toxic death. Compliance: 85.4% of the patients received 4 cycles of the combination chemotherapy. Cisplatin dose intensity was 24.6 mg/m 2 /wk and gemcitabine dose intensity was 773.6 mg/m 2 /wk. Median overall survival and progression free survival has not yet been reached. With a median follow up of 36 months, 77.5% of the patients are still alive and 61.8% without documented relapse. Reported 3 year overall survival in patients with ECOG 0 was 82%, and in patients with ECOG 1 54%, being this difference statistically significant. Conclusions: Combination chemotherapy with cisplatin and gemcitabine in adjuvant setting is safe and feasible with a good toxicity profile. Those patients with ECOG 0 benefit most. Our data are similar to those obtained in previously reported trials.
Serotonin Reuptake Inhibitor Use During Pregnancy—Reply
Authors: Alan S. Brown, Heli Malm, Andre Sourander
Journal: JAMA Psychiatry (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Clinical management and resolution of stomatitis in BOLERO-2.
Authors: Alejandra T. Perez, Hope S. Rugo, José Baselga, Lowell Hart, Kathleen I. Pritchard, Francis P. Arena, J F Eakle, M Geberth, Gabriel N. Hortobagyi, Tibor Csõszi, Michael Gnant, Edmond Emilien Chouinard, Shinzaburo Noguchi, Vichien Srimuninnimit, Puttisak Puttawibul, Daniel Yick Chin Heng, Ashok Panneerselvam, Tanya Taran, Tarek Sahmoud, Howard A. Burris
Journal: Journal of Clinical Oncology (2013)

558 Background: In BOLERO-2, adding everolimus (EVE) to exemestane (EXE) more than doubled progression-free survival without affecting quality of life vs EXE alone in postmenopausal women with hormone-receptor–positive advanced breast cancer who had recurrence or progression on/after nonsteroidal aromatase inhibitor therapy. Although mTOR inhibitors are generally well tolerated, stomatitis is one of their most clinically relevant and potentially dose-limiting toxicities (Sonis Cancer2010). The incidence, grade, and clinical course of stomatitis among patients (pts) participating in the BOLERO-2 study are described. Methods: Pts were randomized 2:1 to receive EVE+EXE or placebo (PBO)+EXE. Stomatitis incidence, severity, consequent dose interruptions/adjustments, study drug discontinuations, and time to resolution were recorded. Results: The median duration of EVE+EXE treatment exposure was 30 wk (range, 1-123 wk). Stomatitis (any grade) occurred more frequently with EVE+EXE than with PBO+EXE (59% vs 12%, respectively). Grade 3 stomatitis occurred in 8% vs 1% of pts receiving EVE+EXE vs PBO+EXE, respectively; no grade 4 was reported. Onset of grade ≥2 stomatitis after treatment initiation was earlier in the EVE+EXE arm vs the PBO+EXE arm: median time was 15d vs 24d, respectively. In the EVE+EXE arm, 97% of pts with grade 3 stomatitis (n=38) improved to ≤1 after a median of 13 d. Complete resolution was observed in 82% of these pts after a median of 38 d. In the PBO+EXE arm, all pts with grade 3 stomatitis (n=2) improved to ≤1 after a median of 18 d. Complete resolution was observed after a median of 29 d. Overall, 24% of pts in the EVE+EXE arm required dose interruptions/adjustments vs 1% of pts in the PBO+EXE arm, and 3% of pts (n=13) discontinued EVE+EXE vs &lt;1% of pts (n=1) discontinuing PBO+EXE, all related to stomatitis. Conclusions: The BOLERO-2 data foster a new era of combining targeted and endocrine therapies. In the study, treatment-emergent stomatitis was of mild to moderate intensity, occurred shortly after treatment initiation, and was generally reversible. Most incidents were successfully managed with palliative interventions and temporary dose modifications. Oral hygiene and other preventive measures are recommended. Clinical trial information: NCT00863655.
High dose chemotherapy (HDCT) and hematopoietic stem cell transplantation (HPSCT) with subsequent immunotherapy in metastatic breast cancer (MBC): Final results of a phase I stud
Authors: H. J. Stemmler, C. Salat, H. Lindhofer, M. Menzel, H. Sauer, M. Untch, G. Konecny, G. Ledderose, H. J. Kolb, V. Heinemann
Journal: Journal of Clinical Oncology (2004)

726 Introduction: This phase-I study prospectively analysed the efficacy and toxicity of HDCT, HPSCT and subsequent immunotherapy with T–cell reinfusion in chemotherapy-sensitive patients with MBC. Patients and methods: After leukapheresis and cryopreservation of T-cells, patients received 2 cycles of standard chemotherapy ET (epirubicin/paclitaxel) and 1 cycle of EI (epirubicin/ifosfamide) followed by G-CSF and stem cell harvest. After a third cycle of ET, responders (CR/PR) underwent HDCT (thiotepa 600 mg/m2/melphalan 140–180 mg/m2) and HPSCT. Once hematopoietic reconstitution was achieved, T-cells were reinfused followed by application of bispecific antibodies against HER-2/neu and EpCAM. Results: Thirty-three patients were recruited on study, and nineteen pts who had responded to initial standard chemotherapy (4 CR, 15 PR, OR = 58%) underwent HDCT and HPSCT. Subsequently, another 6 patients achieved a CR after HDCT resulting in an overall CR rate of 10/33 pts (30%). Two early deaths were observed (one toxic, one PD). T-cell reinfusion and bispecific antibodies were given to 17 patients. The main side effects during HDCT were severe (grade 3 / 4) hematotoxicity, mucositis, gastrointestinal toxicity. Elevated liver enzymes (grade 2 / 3) were seen in all patients. The intravenous application of bispecific antibodies resulted in intermittent fever and chills. Within a follow-up period of 54.7 to 79.1 months, all patients relapsed, and two patients are still alive. The median progression-free survival was 10.6 months (range: 2.1–31.2) and the median overall survival was 22.7 months (range: 1.8–79.1+). Conclusion: Despite a high complete remission rate and despite a novel immunotherapeutic approach including bispecific antibodies and T-cell reinfusion, HDCT and subsequent HPSCT failed to induce a major improvement of survival in chemosensitive patients with metastatic breast cancer. No significant financial relationships to disclose.
Similar exposure and pharmacokinetics of bevacizumab in pediatric and adult cancer patients: Analysis of individual data of 152 pediatric patients.
Authors: Kelong Han, Thomas Peyret, Nathalie H. Gosselin, Angelica Linnea Quartino, Sridharan Gururangan, Clinton F. Stewart, Fariba Navid, Mohamad-Samer Mouksassi, Jin Jin, David E. Allison
Journal: Journal of Clinical Oncology (2014)

10062 Background: Bevacizumab (BEV) is approved for various cancers. BEV pharmacokinetics (PK) is well established by a population PK (PPK) model in adults, but has not been comprehensively evaluated in children. Four pediatric studies have been conducted to assess BEV exposure (EXP) and PK in children, to explore the influence of patient variables on BEV PK and to compare BEV EXP and PK between pediatric and adult patients. Methods: BEV was administered at 5, 7.5, 10 or 15 mg/kg (Q2W or Q3W) with chemotherapy to children with primary CNS tumor (n=76), metastatic soft tissue sarcoma (n=39), osteosarcoma (n=27), or other refractory solid tumors (n=10). A nonlinear mixed effects PK model was fitted to BEV serum concentrations (Cs). Pediatric BEV EXP (trough Cs) were simulated by the pediatric PPK model under the same BSA-based or WT-based dose, and compared to adult EXP simulated by the adult PPK model. Results: Totally 1,464 BEV Cs from 152 patients between 6 months and 21 years old (median 10.8) were analyzed, with 9 patients under the age of 3 years. Body weight (WT) ranged from 5.9 to 125 kg (median 43.8 kg). Typical BEV clearance (CL), central volume of distribution (V1) and half life for a 75 kg individual are 9.47 mL/h, 2.98 L and 18 days in children (vs. 9.31 mL/h, 2.91 L and 20 days in adults based on the adult PPK model). In pediatric patients, CL and V1 increase with WT and are lower in females and primary CNS tumor, and CL decreases with albumin. Age is not correlated with WT-normalized CL or V1. BEV EXP in children decreases with decreasing WT given the same mg/kg dose. BEV EXP under BSA-based dose (mg/m2) and WT-based dose both generally fall within the 90% predictive interval of adult EXP across pediatric age and WT range. Conclusions: A robust BEV PPK model for children that can be used to perform simulations was developed based on this large pediatric population with a wide range of age (0.5~21 years) and WT (5.9~125 kg). BEV PK is similar across pediatric age range when corrected for WT. BEV PK and factors correlated with BEV PK are similar in pediatric and adult patients. Pediatric BEV EXP is similar to adult EXP across pediatric WT range. BSA-based dose offers no substantial advantage over WT-based dose.
Effect of interferon-α on redirected T-cell killing of pancreatic and gastric cancers.
Authors: David M. Goldenberg, Edmund A Rossi, Diane L Rossi, Thomas M. Cardillo, Maria Zalath, Chien-Hsing Chang
Journal: Journal of Clinical Oncology (2014)

3056 Background: Trop-2 is highly expressed in diverse epithelial cancers with limited presence on normal tissues. (E1)-3s is a T-cell redirecting trivalent bsAb, which comprises an anti-CD3 scFv covalently linked to a stabilized dimer of a Trop-2-targeting Fab (Rossi et al., mAbs, 2014; 6(2), in press). IFNα has demonstrated clinical efficacy in multiple solid cancers, and is approved for melanoma, Kaposi sarcoma and various hematologic cancers. We studied the effects of IFNα on (E1)-3s-mediated T-cell killing of gastric and pancreatic cancer cell lines. Methods: DOCK-AND-LOCK was used to link an anti-CD3 scFv to a stabilized Fab dimer of the humanized anti-Trop-2 mAb, hRS7. T-cell activation, cytokine induction and cytotoxicity were evaluated ex vivo using PBMCs or purified T cells with NCI-N87 gastric cancer as target cells. In vivo activity was assayed with NCI-N87 and Capan-1 (pancreatic) xenografts. Results: In presence of target cells and PBMCs, (E1)-3s did not cause excess cytokine production. When combined with (E1)-3s, peginterferonalfa-2a, which alone did not increase T-cell activation or raise cytokine levels over baseline, enhanced T-cell activation, but did not significantly increase cytokine induction. In vitro, (E1)-3s mediated a highly potent (IC50=0.37 pM) T-cell lysis of NCI-N87 target cells. Inclusion of peginterferonalfa-2a potentiated the activity of (E1)-3s, improving the IC50 (0.14 pM) by more than 2.5-fold (P=.0001). A more potent form of IFNα, 20*-2b, enhanced the potency of (E1)-3s by more than 7-fold (IC50=0.05 pM; P<.0001). In vivo, combining peginterferonalfa-2a with (E1)-3s delayed Capan-1 tumor out-growth longer than each single agent (P<0.0007, log-rank), with all animals cured in the combination group (MST>57 d), versus 18% and 14% in the (E1)-3s (MST=50 d) and peginterferonalfa-2a (MST=53 d) groups, respectively. Combination therapy delayed tumor out-growth of NCI-N87 compared to (E1)-3s or peginterferonalfa-2a single-treatment groups (MST>66 vs. 49 or 35 days, respectively; P<0.0094). Conclusions: T-cell-mediated killing of Trop-2-expressing pancreatic and gastric cancer was effectively induced by (E1)-3s and enhanced significantly with IFNα.
An exploratory study to investigate the immunomodulatory activity of radiation therapy in combination with pembrolizumab in patients with renal cell cancer.
Authors: Jianqing Lin, Jean H. Hoffman-Censits, William Kevin Kelly, Madalina Tuluc, Colette Shaw, Jennifer Louie, Larry Harshyne, Rhonda Kean, Voichita Bar-Ad, Robert B. Den, Mark Hurwitz, Jennifer Maria Johnson, Christine Hubert, Sherin Philipose, Benjamin E. Leiby, Sandeep P. Deshmukh, Adam Dicker, D. Craig Hooper, Bo Lu
Journal: Journal of Clinical Oncology (2017)

518 Background: Preclinical data suggest there are synergistic effects of radiation therapy (RT) and check point inhibitors in anticancer immunity. The primary objective of this study was to explore the immunomodulatory activity of RT alone or in combination with Pembrolizumab (pembro) in solid tumors including renal cell cancer (RCC) patients (pts). Methods: RCC pts who progressed after at least one front-line therapy were eligible. Pts were treated with either RT (8Gy x 1 or 4Gy x 5) followed by (f/b) pembro or 1 dose pembro f/b RT f/b pembro. Pre- and post RT tumor biopsy was obtained to evaluate PD-L1 expression (assay by QualTeck). Immune markers from peripheral blood before, during, and after treatment were analyzed using flow cytometry. Treatment response was measured based on modified RECIST criteria. Results: 12 RCC patients were enrolled including 2 with non-clear cell subtype. One pt was not evaluable since pt quickly deteriorated and was taken off study. As of September 30, 2016, 5 pts were still on study with 3 pts having partial response (27.2%, responders) and were on study for at least 9.8 months. 2 responders were treated with 8 Gy f/b pembro while 1 was treated with pembro f/b RT f/b pembro. Six pts (54.5%, non-responders) had PFS between 2 – 4 m and were off study. For adverse events, 1 pt developed grade 4 pneumonitis after 10 cycles of pembro (RT to adrenal mets). Grade 3 AEs include fatigue, nausea, hyperglycemia, lymphopenia, thrombocytopenia, and AST elevation (post RT for liver mets). PDL1 expression and tumor infiltrating lymphocytes presence after RT showed various patterns. Preliminary flow cytometry showed persistent higher numbers of monocytes in non-responders compared with responders. CD4+, CD8+, and NK cells and other markers are under-analyzed and the results will be presented. Conclusions: The combination of RT (8Gy or 20Gy) with pembro is feasible and tolerated, and demonstrates clinical activity. The AE profile is similar to single agent pembro. Monocytes, T, and NK cell kinetics are being examined. Clinical trial information: NCT02318771.
Liver regenerative nodular hyperplasia consecutive to preoperative chemotherapy: Impact on outcome of liver surgery for colorectal metastases
Authors: D. A. Wicherts, R. J. de Haas, M. Sebagh, O. Ciacio, F. Lévi, B. Paule, D. Azoulay, H. Bismuth, D. Castaing, R. Adam
Journal: Journal of Clinical Oncology (2009)

4097 Background: Regenerative nodular hyperplasia (RNH) represents the worst evolutive stage of vascular lesions induced by prolonged chemotherapy on the liver. Its incidence and impact on the outcome of resection for colorectal liver metastases (CLM) are however unknown. We evaluated the effect of RNH on postoperative morbidity and assessed its evolution in time at repeat hepatectomy. Methods: All patients that underwent hepatectomy for CLM between January 1990 and November 2006 after 1 line of chemotherapy of more than 6 cycles were included. Detailed histopathologic analysis of the nontumoral liver was performed at first and repeat hepatectomies according to a standard format. Results: Of 146 included patients, 24 (16%) received 5- fluorouracil (5-FU) and leucovorin (LV) alone, 92 (63%) had 5-FU, LV and oxaliplatin, 18 (12%) had 5-FU, LV and irinotecan, and 12 (8%) were treated by 5-FU, LV, oxaliplatin and irinotecan. Overall, RNH occurred in 22 of 146 patients (15%). Patients treated by oxaliplatin more often had RNH compared to oxaliplatin-naïve patients (22% vs 4%) (P=0.003). The presence of RNH was associated with increased postoperative hepatic morbidity (23% vs 11%) (P=0.05). None of the RNH patients died within 60 days postoperatively. A preoperative gamma-glutamyltransferase level &gt;80 U/L and a total bilirubin level &gt;15 μmol/L were independent predictive factors of RNH at first hepatectomy. Two of 22 patients with RNH underwent repeat hepatectomy. RNH disappeared at second hepatectomy in both patients following prolonged treatment with irinotecan. Conclusions: Patients with CLM that receive prolonged courses of preoperative oxaliplatin have an increased risk of RNH and associated postoperative hepatic morbidity. Upfront treatment with short courses of highly effective regimens may therefore be most appropriate. In addition, the continuation of oxaliplatin should be discouraged in case of RNH to avoid its negative effects on further surgery. No significant financial relationships to disclose.
Safety, immunogenicity, and clinical activity of the immunotherapeutic vaccine, DPX-Survivac, in a Phase 1/1b trial of women with ovarian, fallopian tube, or peritoneal cancer.
Authors: Jeannine A. Villella, Michelle K. Wilson, Neil Lorne Berinstein, Jennifer Brown, Stephanie Lheureux, Marcus O. Butler, Janelle Ramsahai, Kunle Odunsi, Mohan Karkada, John J. Nemunaitis, Michael Morse, Tanja Pejovic, James Bentley, Genevieve Weir, Lisa MacDonald, Marianne Stanford, Tomasz Burzykowski, Rita Nigam, Marc Mansour, Amit M. Oza
Journal: Journal of Clinical Oncology (2015)

3072 Background: Survivin is important in apoptosis, proliferation, and angiogenesis. High expression has been linked to progression and drug resistance. DPX-Survivac vaccine (DPX) contains a mix of survivin HLA class I peptides designed to evoke a cytotoxic T cell response against survivin. This trial reports the safety and immune response profiles of DPX in combination with metronomic low dose oral cyclophosphamide (CPA) in ovarian cancer (OC). Methods: 40 Stage IIc-IV OC patients with no evidence of disease progression post-platinum chemotherapy were enrolled. Adverse events and dose limiting toxicities (DLT) were defined by CTCAE v4.03. Immune correlates (MDSCs; T regs; B cells) and vaccine induced T cell immunity (ELISpot; tetramer analysis) was assessed in purified PBMC and blood. Clinical response was assessed by CT and CA125. Results: 34/40 pts had an HLA match with the vaccine. Local injection site reactions (ISR) were the main DLT with 2 grade 3 skin ulcerations in cohort C. One hematological grade 3 DLT was seen in cohort 2. Immune response increased with dose (B vs C p = 0.01) and use of CPA (A vs C p = 0.02). Subsequent cohorts (Table) were de-escalated to find a dose with similar immunogenicity and reduced ISR. Skin ulcerations were not seen in Cohort 3, with a slightly lower immune response (non-significant). CD4 T cell immune responses were also seen in HLA unmatched pts. A radiological and biochemical response was confirmed in 1 pt with residual disease post-platinum therapy and correlated to a robust immune response. Conclusions: DPX-Survivac is well tolerated with proven immunogenicity and preliminary evidence of clinical activity. The recommended phase 2 dose is based on tolerance for localized ISR and immune response. A randomized phase 2 in consolidation/maintenance OC and open label studies in recurrent DLBCL and OC are planned. Clinical trial information: NCT01416038. Ph Cohort Pts (n) CPA Priming DPX Boost DPX (0.1mL) Skin ulceration Grade (n) Immune ELISpot Response 256 to > 4000 SFU/106 PBMC n (%) Dose (ml) n Freq wks n Freq wks I A 7 N 0.5 3 3 0 0 2 (1) 3 (43) B 6 Y 0.1 3 3 0 0 3 (1) 3 (50) C 6 Y 0.5 3 3 0 0 2 (1), 3 (2) 5 (83) Ib 1 6 Y 0.25 2 3 4 8 2 (2), 3 (1) 6 (100) 2 9 Y 0.25 2 3 4 8 3 (1) 4 (44) 3 6 Y 0.25 3 8 0 0 0 4 (67)