tbuckley/cabot-search huggingface dataset:
Sorafenib plus cisplatin and gemcitabine in the treatment of advanced hepatocellular carcinoma (HCC): A phase II study by the Gruppo Oncologico dell'Italia Meridionale (prot. GOIM 2705).
Authors: F. Giuliani, A. Febbraro, R. Addeo, D. Rizzi, E. Maiello, S. Del Prete, S. Pisconti, G. Colucci
Journal: Journal of Clinical Oncology (2011)

225 Background: Sorafenib is the standard treatment in advanced HCC. The combination of cisplatin and gemcitabine demonstrated to be active and well tolerated in tumors with a similar poor outcome such as pancreatic and biliary-tract cancers. Considering these data, the GOIM started a phase II trial aiming to evaluate the activity and safety of the combination of sorafenib, gemcitabine and cisplatin in advanced HCC. Methods: Patients affected by advanced HCC, not suitable for surgery or locoregional procedures, with measurable disease (Recist criteria), age ≥ 18 years, clip-score ≤3, ECOG performance status ≥ 60 (K.fsky), adequate bone marrow reserve and renal and hepatic function and who signed written informed consent, were enrolled and received cisplatin 40 mg/mq iv plus gemcitabine 800 mg/mq iv bi-weekly, while sorafenib was orally administrated at the dosage of 400 mg bid continuously. A maximum of 6 cycles of chemotherapy was planned; a maintenance with sorafenib was permitted for not progressing patients. The evaluation of activity was performed every three cycles. A Simon's two stage, two steps study design was applied: at the first step, at least 3 OR had to be observed among the first 28 patients to continue the enrollment. Up to now, 23 patients have been enrolled. Their main characteristics were: sex (male/female) 19/4, median age: 70 yrs, median PS 80,main sites of disease liver 22, lymph nodes 4, lung 2, others 3. Results: Up to now 18 patients are evaluable for activity while 5 are too early. One CR, 3 PR, 6 SD and 8 PRO for an ORR of 4/18 (22%) and a tumor control of 10/18 (55%). Twenty-one patients are evaluable for safety. The main observed side effects (%G1-2/G3-4) (NCI criteria) were: hand-foot skin reaction (HFSR) 9/14, mucositis 9/4, diarrhea 23/4, nausea/vomiting 23/0, leucopenia 23/0, anemia 9/0, thrombocytopenia 19/4, asthenia 14/14, cardiovascular 0/4, others 9/4. Conclusions: Our preliminary data seems to demonstrate that the combination of cisplatin, gemcitabine, and sorafenib is active and well tolerated in advanced HCC patients. The accrual is ongoing. No significant financial relationships to disclose.
539 2-YEAR RESULTS OF TELBIVUDINE (LDT) ROADMAP STUDY VERIFY THE OPTIMAL EFFICACY AND SAFETY RESULTS IN HBEAG POSITIVE CHRONIC HEPATITIS B (CHB) PATIENTS
Authors: T. Piratvisuth, P. Komolmit, T. Tanwandee, W. Sukeepaisarnjaroen, H.L. Chan, M.G. Pessoa, E. Fassio, S. Ono-Nita, F. Bessone, J. Daruich, S. Zeuzem, H. Cheinquer, Y. Dong, A. Trylesinski
Journal: Journal of Hepatology (2012)
A modest proposal on gun control—and a real one
Authors: Douglas Kamerow
Journal: BMJ (2016)

Gun violence has gotten out of hand here in the United States. It is not just last year’s high profile mass shootings in San Bernardino, Colorado Springs, Roseburg, Charleston, and Chattanooga. It is also the more than 3000 children (under 18) who were killed or injured here by guns in 2015. A smart legislator in the state of Missouri has come up with a good idea to protect the US from gun violence. Since much of the US has strict laws regulating (some would say restricting) abortions, presumably to protect the health of Americans, maybe we can learn something from them and apply the same principles to another perceived health risk—firearms. Representative Stacey Newman, a Democrat from the suburbs of St Louis, introduced House Bill 1397 to the 98th Missouri General Assembly last year. In it, she matched the conditions under which Missourians can purchase firearms to those required to obtain an abortion. Under Newman’s proposed … Language: en
Prognostic factors and long-term survivorship in patients with recurrent or metastatic head and neck cancer (HNC): An analysis of two Eastern Cooperative Oncology Group (ECOG) randomized trials
Authors: A. Argiris, Y. Li, A. Forastiere
Journal: Journal of Clinical Oncology (2004)

5514 Background: The ECOG conducted two successive phase III randomized trials comparing cisplatin-based doublets (E1393: cisplatin/paclitaxel, low dose vs. cisplatin/paclitaxel, high dose, and E1395: cisplatin/paclitaxel vs. cisplatin/5-FU) in patients (pts) with recurrent or metastatic HNC. These studies found no significant differences in antitumor efficacy between treatment arms. Methods: We analyzed prognostic factors for response and survival combining data from E1393 and E1395 using logistic regression and Cox regression models. Results: A total of 399 eligible pts were analyzed. Median follow-up was 4.75 years (ys). The 1-, 2-, 3- and 5-y overall survival (OS) rates for all pts were 32%, 12%, 7%, and 3.6%, respectively, the median OS 7.8 months, and the objective response rate 32%. On multivariate analysis, independent unfavorable predictors of objective response were weight loss, performance status (PS) of 1 (vs. 0), residual disease at the primary, site other than oropharyngeal, history of radiation therapy (RT) (P=0.06), and well/moderate tumor differentiation (TD) (P=0.07). Independent prognostic factors for OS were weight loss, PS 1 (vs. 0), poor TD (favorable), oral cavity (OC) or hypopharyngeal (HP) primary, and history of RT, and for time to progression (TTP): poor TD (favorable), OC or HP primary, and history of RT. Pts with 2 or less adverse prognostic factors had a median OS of 1 y, whereas pts with 3–5 had a median OS of 0.5 ys (P<0.0001). Response to chemotherapy could also be included in the prognostic models of OS and TTP as an independent predictor. 49 pts (12%) survived for 2 ys or longer and 6 pts were alive at 5 ys. 2-y survivors were more likely to have had a response to chemotherapy, poor TD, white race, PS of 0, and no prior RT. Two out of 49 pts surviving at least 2 ys developed a second primary tumor. Conclusions: Clinical parameters and TD are strong pretreatment predictors of outcome in HNC and should be considered in the design of future randomized trials. A small percentage of pts with recurrent or metastatic HNC achieves long-term survival. No significant financial relationships to disclose.
Decreased toxicity schedule of suitinib in renal cell cancer: 2 weeks on/1 week off
Authors: F. Gyergyay, K. Nagyványi, I. Bodrogi
Journal: Journal of Clinical Oncology (2009)

e16113 Background: Sunitinib (SU) is an oral multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, FLT3, CSF-1R and RET approved for treatment of metastatic renal cell cancer (mRCC). Pharmacokinetics and pharmacodynamics suggest that dose reduction might decrease the plasma concentration of SU and its major metabolite to an ineffective level. Methods: Pts with mRCC, measurable disease, ECOG PS 0–2 received SU 50 mg po daily 4 weeks on/2 weeks off. Results: Of 36 pts, median age 59.5 yrs (range 42–83), M/F (26:10), ECOG: 0 (21); 1 (9); 2 (6); prior nephrectomy (35),prior radiation therapy (28), prior cytokine therapy: IFNα (25), IL-2+IFNα (9) none (2); pts with 1 metastatic organ (24); 2 metastatic sites (7); ≥ 3 sites (5); Sites of metastases: Lung (27), Bone (11), Liver (3); MSCC risk factors: 0 (20), 1–2 (14); ≥3 (2). Objective response occurred: PR (13) 42%; CR (2) 5%; SD (9) 25%. Number of cycles (6 weeks cycles) given was: 162 (2–15).Main side effects were: fatigue 42% (Gr≥3: 17%), diarrhoea 42% (Gr≥3: 25%), nausea 31% (Gr≥3: 6%), stomatitis 10%, anorexia 10%, weight-loss 20% (Gr≥3: 11%), hand-foot syndrome 39% (Gr≥3: 17%), hypertension 28%, anemia 25%, neutropenia 8%, thrombopenia 11%, hypothyroidism 11%. Five cases of dose reduction and two cases of treatment discontinuation occurred due to toxicity. During the second part of the study if serious toxicity had been reported, instead of dose reduction, two weeks on and one week off schedule (50mg daily) had been offered to pts. 14 pts (79 cycles) were treated according to the schedule. Short term side effects decreased significantly: fatigue 28%, diarrhea 14%, nausea 14%, stomatitis 7%, anorexia 7%, weight-loss 7%, hand-foot syndrome 14%, hypertension 7%, anemia 14%, hypothyroidism 11%. Conclusions: Further prospective studies are needed to confirm the better tolerance of the SU, without decreasing the dose intensity of the treatment. No significant financial relationships to disclose.
Reinduction with the same cytostatic treatment in patients with metastatic breast cancer: an Eastern Cooperative Oncology Group study.
Authors: G Falkson, R Gelman, J Glick, C I Falkson, J Harris
Journal: Journal of Clinical Oncology (1994)

PURPOSE To investigate the therapeutic value of reinduction with the same cytostatic treatment that had been used in induction treatment for women with metastatic breast cancer. MATERIALS AND METHODS One hundred six women with metastatic breast cancer were given dibromodulcitol (mitolactol), doxorubicin, vincristine, tamoxifen, and fluoxymesterone (DAVTH) for 6 months of induction treatment, then randomized to receive one of two chemotherapy regimens if they had obtained an induction partial response (PR) or no change (NC), or to receive observation versus chemotherapy if they had obtained an induction complete response (CR). Patients were then retreated with DAVTH reinduction after relapse. RESULTS Seventy-four patients were eligible or had minor reasons for ineligibility. Severe or life-threatening toxicity was documented in 46%, and lethal toxicity in 4%. Eighteen percent had a response on reinduction (zero of 16 induction nonresponders, 15% induction PR, 44% induction CR). The median time to treatment failure (TTF) from reinduction was 3 months, and the median survival duration from reinduction was 14 months. In a logistic model, factors associated with more reinduction responses were observation after induction CR (P = .002) and age greater than 55 years (P = .04). Time since induction was not significant. CONCLUSION Reinduction of response after treatment failure remains a therapeutic problem. The need for better salvage treatment underlines the importance of developing new regimens.
Phase II trial of sorafenib (S) and capecitabine (C) for hepatocellular carcinoma (HCC) in cirrhotic patients (pts).
Authors: Cristhiam Mauricio Rojas-Hernandez, Yehuda Z. Patt, M. Houman Fekrazad, Kim A. Steinberg, Mary Roach, Fa-Chyi Lee
Journal: Journal of Clinical Oncology (2013)

e15136 Background: S is the currently approved treatment for HCC. C has antitumor activity in HCC and biliary tree cancers. The combination of the two, if tolerated, could possibly improve antitumor response, and patient-overall survival (OS). Methods: This phase II trial of S and C accrued unresectable HCC pts. with histologically confirmed disease or radiological characteristics of HCC in cirrhotics with an elevated AFP of &gt; 400 ng/mL. Eligibility criteria were: ECOG Performance status of ≤ 2, Child-Pugh (CP) class A or B-7 cirrhosis, hemoglobin ≥ 8.5 g/dL, platelets ≥ 50,000/µL, ANC ≥ 1500 cells/µL, and a serum creatinine of ≤ 2.0 mg/dL (creatinine clearance &gt; 30 mL/minute). HIV+ patients were excluded. All subjects received a combination of S and C, on a 14-day treatment schedule. S dose was started at 400 mg BID daily with dose adjustments for hand foot syndrome. Starting C dose was 850 mg/m 2 BID for 7 days and a 7-day break; doses were adjusted as tolerated. The primary end point was assessment of safety and tolerability. OS and disease control rate (DCR) were also estimated. Results: 15/47 assessed pts. met inclusion criteria. One patient was never treated and excluded from analysis. Response data were available on 13 and safety data on all 14. Median pts.’ age was 64 years (56-79), and 75 % were male. Etiologies included viral hepatitis (64%), or viral hepatitis and alcohol in another 29%; 50% of pts. had CP class A (5-6) and 50% B-7 cirrhosis. With a median follow up of 12 months (M), median OS (mOS) was 11.3 (95% CI, 2.7-21.3) M. DCR was 54% (CR 8%, PR 15% and SD 31%). Grade 3-4 adverse events included: thrombocytopenia 9(64%), neutropenia 1(7%), anemia 2(14%); electrolyte imbalance, hypophosphatemia 3(21%), hypomagnesemia 2(14%), hypocalcaemia 1 and hyponatremia 1 (7%) each. Liver abnormalities included; hyperbilirubinemia 3(21%), increased AST 2(14%). Skin and mucosal abnormalities included hand-foot syndrome 3(21%), mucositis 1, alopecia 1 and skin rash 1 each. DVT occurred in 3 (21%). Conclusions: At tolerable doses, S and C seem active and safe palliative treatment for HCC in CP A &amp; B-7 cirrhotics. It was associated with a DCR of 54% and mOS of 11.3 M. The small sample size does not allow comparison with single agent S. Clinical trial information: NCT01032850.
Genomic change index (GCI) and liquid biopsies in predicting and monitoring response to therapy in advanced pancreatic ductal adenocarcinoma (PDAC).
Authors: Madappa N. Kundranda, Julia Beck, Donald Peter Braun, Howard B. Urnovitz, William Marvin Mitchell, Ekkehard Schütz
Journal: Journal of Clinical Oncology (2015)

309 Background: Advanced PDAC is a lethal disease with dismal 5 year survival. The current modalities for monitoring therapy response using serum (CA) 19-9 levels have poor specificity and radiological responses have long lag times. Tests for rapid and accurate clinical assessment are needed for early decision making. Methods: 5 patients (pts) with locally advanced unresectable or metastatic PDAC were treated with gemcitabine and nab-Paclitaxel on a bi-weekly schedule. Tumor tissue was collected at baseline and plasma was collected at each cycle (3 time points). Tumor tissue and leukocyte DNA was used to prepare shotgun sequencing libraries and PCR-based enrichment of 124 genes for paired-end high-throughput sequencing. Copy-number variations were called by comparing tumor vs. leukocytes read counts in genomic windows. Algorithms were used to quantify a Genomic Change Index (GCI) from selected variations of the cancer genome. Somatic mutations were quantified in cell-free plasma DNA (cfDNA) of 3 pts using droplet digital PCR (ddPCR) as a function of treatment. Results: Of the 5 pts evaluated, the lowest GCI’s (&lt;10) was present in a non-responding (NR) pt receiving chemotherapy. 4 pts with varying degrees of clinical, biochemical and radiological (ranging from partial (PR) to stable disease (SD) to complete (CR)] responses, showed elevated GCIs (≥15). Detected tumor mutations were followed by liquid biopsies. In a patient with SD, mutKRAS and mutTP53 cfDNA copies of 20-80 per mL plasma (cp/mL) did not significantly change over time. In a patient with CR and &gt;70% decrease in CA19-9; no copies of mutKRAS and 4-10 cp/mL mutTP53 were detected at the 3 time points measured. In a pt with PR and rising CA19-9, there was also an increase in mutKRAS and mutTP53 cp/mL. Conclusions: 1.) Our pilot study indicates that GCI may be similarly predictive of PDAC response to therapy as we have previously reported with head/neck and colorectal carcinomas. 2.) ddPCR has sufficient sensitivity to monitor tumor mutations in the plasma of PDAC pts and could provide a specific biomarker to monitor response. Both tests are currently being validated with longer follow up and larger number of patients.
Application of Evolutionary Principles to Cancer Therapy
Authors: Pedro M. Enriquez-Navas, Jonathan W. Wojtkowiak, Robert A. Gatenby
Journal: Cancer Research (2015)

Abstract The dynamic cancer ecosystem, with its rich temporal and spatial diversity in environmental conditions and heritable cell phenotypes, is remarkably robust to therapeutic perturbations. Even when response to therapy is clinically complete, adaptive tumor strategies almost inevitably emerge and the tumor returns. Although evolution of resistance remains the proximate cause of death in most cancer patients, a recent analysis found that evolutionary terms were included in less than 1% of articles on the cancer treatment outcomes, and this has not changed in 30 years. Here, we review treatment methods that attempt to understand and exploit intratumoral evolution to prolong response to therapy. In general, we find that treating metastatic (i.e., noncurable) cancers using the traditional strategy aimed at killing the maximum number of tumor cells is evolutionarily unsound because, by eliminating all treatment-sensitive cells, it enables rapid proliferation of resistant populations—a well-known evolutionary phenomenon termed “competitive release.” Alternative strategies, such as adaptive therapy, “ersatzdroges,” and double-bind treatments, shift focus from eliminating tumor cells to evolution-based methods that suppress growth of resistant populations to maintain long-term control. Cancer Res; 75(22); 4675–80. ©2015 AACR.
Innovations in Health Care Delivery and the Future of Medicine
Authors: Howard Bauchner, Donald Berwick, Phil B. Fontanarosa
Journal: JAMA (2016)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Phase II study of neoadjuvant and adjuvant gefitinib (G) with neoadjuvant chemoradiotherapy (CRT) in operable esophageal adenocarcinoma (EAC).
Authors: R. A. Juergens, M. K. Gibson, S. C. Yang, M. Brock, R. Heitmiller, N. Tsottles, M. A. Rudek, M. Canto, L. Kleinberg, A. A. Forastiere
Journal: Journal of Clinical Oncology (2010)

e14532 Background: Esophageal cancer offers an intriguing and accessible model for studying novel inhibitors of cancer-related pathways. EGFR is expressed in 30%-70% of EAC. Given the need in EAC for improved therapies and better predictors of outcome, we proposed to study the effectiveness of EGFR targeted therapy in EAC. Methods: Patients (pts) included PS 0-1 adults with untreated, resectable stage II-IVa EAC and with normal organ function. A Simon 2 stage design used a power of 90% and 2-sided alpha of 5%. The null was a pathologic complete response rate (pCR) = 25% and the alternative was a pCR = 45%. Stage 1 had 17 pts with expansion to 36 pts if > 4 had pCR. Pts were treated with a 2 week run-in of G at 250 mg daily. Paclitaxel (50 mg/m2) and cisplatin (30 mg/m2) were given IV wkly × 5 doses along with 4,500 cGy of XRT. G continued daily until 1 week prior to surgery. Surgery was performed wks 9 or 10 from CRT start date. Adjuvant G began 2-8 wks post-op and continued 1 year. Specimens were collected for pharmacokinetic (PK) and pharmacodynamic (PD) analyses. Results: 17 pts were treated. Demographics include: mean age (range)-57 (38-73); M:F-9:1; 95% White, 5% Hispanic; Stages: 3 IIA; 2 IIB; 10 III; 2 IVa. 90% of pts received all the CRT. 10% missed 1 or 2 doses of CT due to myelosuppresion or renal insufficiency. All pts completed > 90% of pre-operative G. Side effects of the G included grade 1 rash and diarrhea. All 17 pts had surgery. 1 pt died during surgery. Pathologic response was: 3 pts pCR (18%); 1 stage 0 (Tis); 2 stage I; 2 IIA; 4 IIB; 4 III; 1 IVa; 1 undetermined. 11 total pts downstaged; 4 pts were unchanged; 1 pt upstaged; 1 was undetermined. 13 pts started the adjuvant G. Of these, 5 completed 1 year. 1 stopped for knee surgery. 1 stopped due to a heart attack. 6 stopped due to progression. Median TTP was 15.7 mos. Median OS for the 17 pts was 31.5 mos. Median follow-up was 30 months. PK and PD studies are being analyzed. Conclusions: The addition of G to standard neoadjuvant CRT is feasible but does not improve the pCR rate. Exploratory analyses are being done to see if a subset of pts may benefit from EGFR therapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
Hemodynamic Ramp Tests in Patients With Left Ventricular Assist Devices
Authors: Nir Uriel, Gabriel Sayer, Karima Addetia, Savitri Fedson, Gene H. Kim, Daniel Rodgers, Eric Kruse, Keith Collins, Sirtaz Adatya, Nitasha Sarswat, Ulrich P. Jorde, Colleen Juricek, Takeyoshi Ota, Valluvan Jeevanandam, Daniel Burkhoff, Roberto M. Lang
Journal: JACC Heart Failure (2015)
Unconjugated anti-CD20 IgG combined with radioconjugated anti-CD22 IgG improves treatment responses in a nude mouse B-cell lymphoma xenograft model
Authors: M. Mattes, R. Sharkey, H. Karacay, D. Goldenberg
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

2138 

Radioconjugated anti-CD20 antibodies have been used successfully in treating non-Hodgkin’s lymphoma, with a higher objective response rate than their unconjugated anti-CD20 IgG counterparts. The radioconjugate treatments include a large dose (~400 mg) of unconjugated anti-CD20 IgG, primarily to reduce uptake in the large normal B-cell sink to allow for better tumor uptake, but the combination might also evoke additional mechanisms of action that amplify the anti-tumor response. Other radioconjugates, such as radiolabeled anti-CD22 IgG, have also been effective clinically, and because a different antigen is targeted, this treatment might also benefit from a combination with an unconjugated anti-CD20 IgG. We have examined the combination of a 90Y-labeled humanized anti-CD22 IgG (epratuzumab, Immunomedics, Inc.) with an unconjugated humanized anti-CD20 IgG (veltuzumab, Immunomedics, Inc.) to determine if the combination could improve treatment responses. Nude mice bearing established s.c. Ramos human B-cell lymphoma xenografts (>0.1 cm3) were given a maximum tolerated dose of 90Y-epratuzumab (0.175 mCi) alone or pre-dosed one day earlier with the unconjugated anti-CD20 IgG, and then followed with 3 additional weekly injections of the unconjugated IgG. Tumors responded initially to the 90Y-epratuzumab alone, but after a few weeks regrew. Unconjugated anti-CD20 IgG given over 4 weeks at a total dose of 2.5 mg had no significant anti-tumor effect. However, approximately 85% of tumors in animals given the combination of a single dose of 90Y-epratuzumab with the 4 weekly injections of CD20 regressed completely with no evidence of regrowth over a period of 5 months week. This combination effect was observed with a little as 0.25 mg total dose of the unconjugated anti-CD20 IgG given over 4 weeks. The effect of the radioconjugated Ab was antigen-specific, since a non-reactive Ab labeled in the same way, and used together with the unconjugated anti-CD20, had no therapeutic effect. All animals tolerated the combination as well as they did the 90Y-eptratuzumab alone, indicating that the unconjugated antibody did not increase toxicity. The addition of anti-CD20 to radiolabeled epratuzumab did not alter epratuzumab’s tissue distribution or tumor uptake. The mechanism of action of this effect is currently under investigation. Thus, the combination of an unconjugated anti-CD20 with 90Y-epratuzumab improves anti-tumor responses and may represent an important new treatment strategy for NHL. (Supported in part from USPHS grant P01-CA103985.)