tbuckley/cabot-search huggingface dataset:
Addition of DMXAA (ASA404) to docetaxel in patients with hormone-refractory metastatic prostate cancer (HRMPC): update from a randomized, phase II study
Authors: R. Pili, M. Rosenthal
Journal: Journal of Clinical Oncology (2008)

5007 Background: DMXAA (ASA404) is a novel tumor vascular disrupting agent. In animal models DMXAA has synergistic anti-tumor effects in combination with cytotoxics, including taxanes. A randomized study in non-small cell lung cancer reported a 5-month survival benefit when DMXAA was added to carboplatin+paclitaxel. This randomized phase II study examined the efficacy and safety of DMXAA in combination with docetaxel in HRMPC. We reported previously that the DMXAA-docetaxel combination was well-tolerated and increased PSA response rate compared with docetaxel alone (59 vs 37%). Data are now available on 3-month PSA reduction, tumor response rates and time to tumor progression (TTP). Methods: Patients had progressive metastatic, androgen-independent, histologically confirmed prostate adenocarcinoma, previously untreated with cytotoxics. Patients were randomized to receive docetaxel (75 mg/m2) ± DMXAA (1200 mg/m2) every 21 days for up to 10 cycles. Efficacy endpoints included prostate-specific antigen (PSA) response rate, objective response rate, time to tumor progression and median survival. Results: 33 patients received DMXAA plus docetaxel (DMXAA arm). 38 patients received docetaxel alone (control arm). Similar numbers of patients in each arm experienced serious adverse events (14 vs 13 in the DMXAA and control arms, respectively). 62.5% patients in the DMXAA arm had at least a 30% reduction in PSA during the first 3 months, compared with 47.4% patients in the control arm. Response rates by modified RECIST were 23.1% and 9.1% in the DMXAA and control arms (among 26 and 33 assessable patients), respectively. Investigator-determined time to tumor progression was 7.3 months in the DMXAA arm and 6.9 months in the control arm. Conclusions: Addition of DMXAA to a standard docetaxel regimen was generally well tolerated. Data on 3-month PSA reduction, tumor response rate and TTP support previous PSA response findings in suggesting improved efficacy with a DMXAA-docetaxel combination compared to docetaxel alone. Further evaluation of DMXAA in HRMPC is warranted. No significant financial relationships to disclose.
A Crossover Design for Comparative Efficacy
Authors: Henry E. Wiley, Darby J.S. Thompson, Clare Bailey, Emily Y. Chew, Catherine A. Cukras, Glenn J. Jaffe, Richard W.J. Lee, Erin K. Loken, Catherine B. Meyerle, Wai Wong, Frederick L. Ferris
Journal: Ophthalmology (2016)
P-181 Outcome Analysis of Upfront Definitive Chemoradiation for Unresectable Pancreatic Adenocarcinoma: A Single Center Experience for over 25 years
Authors: H.K. Koh, E.K. Chie, K. Kim, J.-Y. Jang, S.-W. Kim, S.-W. Han, D.-Y. Oh, S.-A. Im, T.Y. Kim, Y.-J. Gang, S.W. Ha
Journal: Annals of Oncology (2015)
Phase I trials of novel molecularly targeted therapies: Should we pay more attention to toxicities occurring after cycle 1?
Authors: S. Postel-Vinay, C. A. Gomez-Roca, L. R. Molife, B. Anghan, J. Soria, S. B. Kaye, X. Paoletti
Journal: Journal of Clinical Oncology (2010)

2515
Effects of chronic renal failure on enzymes of energy metabolism in individual human muscle fibers.
Authors: A Conjard, B Ferrier, M Martin, A Caillette, H Carrier, G Baverel
Journal: Journal of the American Society of Nephrology (1995)

In order to improve knowledge about the mechanisms underlying the alterations of energy metabolism recently observed in the skeletal muscle of patients suffering from chronic renal failure, this study was designed to test (1) whether changes in the activity of key enzymes of energy metabolism occur in the muscle of these patients, and if so (2) whether the different muscle fiber types are equally altered in their metabolic machinery. For this, the maximum activities of 14 enzymes were measured in individual muscle fibers microdissected from biopsies of rectus abdominis muscle obtained from seven normal subjects and seven patients with end-stage renal failure before renal replacement therapy. A large decrease in the activities of beta-hydroxyacyl-coenzyme A dehydrogenase, a key enzyme of the beta-oxidation pathway, of citrate synthase, which initiates the tricarboxylic acid cycle, and of fructose-1,6-bisphosphatase, which contributes to the synthesis of glycogen from lactate, was observed in the three fiber types (slow-twitch oxidative, fast-twitch oxidative-glycolytic, and fast-twitch glycolytic). A smaller reduction of the activities of phosphofructokinase and/or pyruvate kinase, two key enzymes of glycolysis, was also observed in slow-twitch oxidative and/or fast-twitch oxidative-glycolytic fibers. These results demonstrate that the abnormalities of muscle energy metabolism observed in patients with chronic renal failure are due, at least in part, to intrinsic changes in the key enzymes of major energy-providing pathways; they also offer a satisfactory explanation for the defect of oxidative metabolism recently demonstrated in the muscle of these patients.
Ipilimumab plus temozolomide in metastatic melanoma.
Authors: S. P. Patel, A. Y. Bedikian, N. E. Papadopoulos, W. Hwu, K. B. Kim, J. Homsi, M. A. Davies, S. E. Woodman, L. G. Radvanyi, K. Woodard, S. Mahoney, P. Hwu
Journal: Journal of Clinical Oncology (2011)

8579 Background: Ipilimumab (Ipi), an antibody which releases T-cell suppression and enhances immune response, has shown an overall survival benefit in a Phase III trial of previously treated patients (pts) with metastatic melanoma (MM). To evaluate the benefit of adding cytotoxic chemotherapy to Ipi, we performed a clinical study of Ipi plus temozolomide (Tem) in pts with MM. Methods: Pts between the ages of 18 and 75 with unresectable Stage III or Stage IV MM and an ECOG Performance Status of 0-1 were enrolled in a Phase II trial of Ipi plus Tem. Pts who received previous systemic therapy or those with brain metastases were excluded. Induction phase consisted of Ipi 10mg/kg intravenous on Day 1 and oral Tem 200 mg/m2 on Days 1 – 4 every 3 weeks for 4 courses. Maintenance consisted of Ipi 10 mg/kg intravenous on Day 1 repeated every 12 weeks and oral Tem 200 mg/m2 on Days 1 – 5 repeated every 4 weeks until disease progression or unacceptable toxicity (tox) occurred. Accrual was planned in 2 stages with a need for a minimum of 7 pts to reach at least 6 months of progression-free survival (PFS) in the first stage. The primary endpoint was 6-month PFS rate. Results: To date, data are available on response for 27 pts, 6-month PFS for 15 pts, and tox for 28 pts. Using immune-related response criteria, a modification of WHO criteria, there were 6 (22%) confirmed partial responses and 12 (44%) pts experienced stable disease for an overall disease control rate of 67%. At the present time, there are 7 pts with a minimum 6 months of PFS. With regard to adverse events, there was no Grade 4 non-hematologic tox. The most commonly observed tox was pruritis (61%) followed by skin rash (54%), headache (46%), and constipation (46%). Grade 3 events seen in more than one patient were fatigue (7%) and diarrhea (7%). The only Grade 4 hematological tox was one episode of Grade 4 neutropenia while anemia was the most common hematologic tox overall at 36%. Conclusions: The combination of Ipi plus Tem is safe and well-tolerated in pts with MM. Clinical activity appears superior to Ipi or Tem alone. Based on the current number of pts reaching 6 months of PFS, the trial has met criteria for continuation and will run to full accrual. Updated data on median overall survival as well as 6-month PFS rates will be available at the time of the meeting.
Explained and Unexplained Ischemic Heart Disease Risk after Renal Transplantation
Authors: Bertram L. Kasiske, Harini A. Chakkera, Joseph Roel
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Whether the high incidence of ischemic heart disease (IHD) among renal transplant patients can be attributed to the same risk factors that have been identified in the general population is unclear. The risk for major IHD events occurring &gt;1 yr after transplantation among 1124 transplant recipients was estimated by using the risk calculated from the Framingham Heart Study (FHS). The FHS risk predicted IHD (relative risk, 1.28; 95% confidence interval, 1.20 to 1.40; P &lt; 0.001); however, the FHS risk tended to underestimate the risk of IHD for renal transplant recipients. This was largely attributable to increased risks associated with diabetes mellitus and, to a lesser extent, age and cigarette smoking for renal transplant recipients. For men, the relative risks for diabetes mellitus were 2.78 (1.73 to 4.49) and 1.53 for the transplant recipient and FHS populations, respectively; the relative risks for age (in years) were 1.06 (1.04 to 1.08) and 1.05, respectively, and those for smoking were 1.95 (1.20 to 3.19) and 1.69, respectively. For women, the relative risks for diabetes mellitus were 5.40 (2.73 to 10.66) and 1.82, respectively. There was a tendency for the risk associated with cholesterol levels to be higher for transplant recipients, compared with the FHS population, but the risks associated with high-density lipoprotein cholesterol levels and BP appeared to be comparable. Independent of these and other risk factors, the adjusted risk of IHD for the transplant recipient population has decreased. Compared with the era before 1986, transplantation between 1986 and 1992 was associated with a lower relative risk of 0.60 (0.39 to 0.92); transplantation after 1992 was associated with an even lower relative risk of 0.27 (0.11 to 0.63) for IHD. Of concern was the fact that dihydropyridine calcium channel antagonists were associated with an increased risk for IHD (relative risk, 2.26; 95% confidence interval, 1.24 to 4.12; P = 0.008), and this association was independent of other antihypertensive agents and risk factors. Therefore, although the FHS risk predicts IHD after renal transplantation, it tends to underestimate the risks, especially the risk associated with diabetes mellitus. The unexpected finding that dihydropyridine calcium channel antagonists were associated with an increased IHD risk merits further evaluation.
Final analysis of MM-014: Single-agent lenalidomide in patients with relapsed and refractory multiple myeloma
Authors: M. A. Hussein, P. G. Richardson, S. Jagannath, S. Singhal, W. Bensinger, R. Knight, J. B. Zeldis, Z. Yu, M. Olesnyckyj, K. C. Anderson
Journal: Journal of Clinical Oncology (2008)

8524 Background: Lenalidomide (Len) in combination with high-dose dexamethasone (Dex) is approved for previously treated patients (pts) with multiple myeloma (MM). This study determined the efficacy and safety of Len monotherapy in pts with relapsed/refractory MM. Methods: Len monotherapy (30 mg qd) was given to pts with relapsed/refractory MM in a single-arm, open-label multi-center study. Len was administered daily on days 1–21 every 28 days. Concomitant Dex was not permitted. No anticoagulation prophylaxis was recommended. Treatment was continued as tolerated until disease progression. Response was assessed every month using modified EBMT criteria and toxicity using NCI-CTCv3. Results: All 222 enrolled pts had received ≥2 prior anti-MM therapies, including bortezomib (43%), thalidomide (80%), and SCT (45%); 46% had ≥4 prior therapies with a mean time from diagnosis of 4 years. At database lock, 64 pts (29%) had received treatment for >9 months. For the intention-to-treat population (n=222), the overall response (OR: CR+PR) was 26%. An additional 66% of the pts experienced stable disease (SD). OR for the efficacy-evaluable population (n=184) was 32% and 68% experienced SD. By study completion, 151 pts (69%) had progressed with a median time-to-progression (TTP) of 5.4 months. Median progression-free survival (PFS) was 4.7 months, and median overall survival (OS) was 1.9 years with 41% of pts alive after 3 years. Median duration of response was 13 months (median FU: 14 months). The most common grade 3/4 lab toxicities were neutropenia (60%), thrombocytopenia (39%) and anemia (20%). Only 4% of pts developed febrile neutropenia and DVT; no grade 3/4 peripheral neuropathy was seen. Conclusions: The encouraging OR, duration of response, TTP, PFS, and OS seen in this study demonstrate that Len monotherapy at a dose of 30 mg once daily (3 wks on, 1 wk off) is effective, durable, and well tolerated steroid-sparing therapy for heavily pretreated pts with relapsed/refractory MM. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Celgene Celgene, Millennium Celgene Celgene, Millennium Celgene
Treatment of postural obstructive sleep apnoea by a new vibrating postural device. A preliminary study
Authors: Joaquin Durán-Cantolla, Ferrán Barbé, Jordi Rigau, Daniel Oreja, Manuel Sanchez De La Torre, Antoni Picó, Naiara Pedraza, Cristina Martínez-Null, Jose Luís Manjón, Joaquín Durán Carro, Carlos Javier Egea Santaolalla
Journal: European Respiratory Journal (2013)

Over 50% of obstructive sleep apnoea (OSA) patients met criteria for postural OSA. This is defined by an apnoea-hypopnea index (AHI) doubling in supine position vs. not supine. Our group in collaboration with SIBEL SA, have developed a patented postural device (PCT/ES2010707108 and P26018USPC). Is a vibrating device of 4 X 4 cm, weight of about 50 gr integrating an accelerometer, vibrator and other sensors. It is placed on the forehead and when detects that the patient is in the supine position for 30 s or more, starts a vibration, with increasing intensity, which ceases when the patient moves to lateral.Theses are results of a pilot study in patients with postural OSA. All patients were studied by standard polysomnography (PSG) three times; at baseline, and at 1 and 4 weeks of using the device. The aim was to demonstrate a significant reduction in the AHI and that this reduction was maintained over time. We also want to assess the quality and quantity of sleep using the device.We studied 12 patients (75% male), body mass index of 25.7 Kg/m2 (SD 3.3). The baseline AHI was 33.5 (SD14.7) and was reduced after 1 and 4 weeks using the device to 22.8 (SD 10.6; p = 0.004) and 19.7 (SD 7.4; p =0.002), respectively. The percentage of total sleep time (TST) in supine changed from 51.5% (SD 14.8%) at baseline to 16.4% (SD 16.0%; p = 0.002) and 25.2% (SD 21.0%; p = 0.005) at 1 and 4 weeks of using the device, respectively. The device did not significantly modify the TST and significantly reduced the arousal Index.The results suggest that this device is safe and could be useful as a treatment for postural OSA in a significant number of patients and its effect is maintained over time.
Impact of intensive stem cell mobilization therapy on outcomes following autologous stem cell transplantation (ASCT) for non- Hodgkin lymphoma (NHL)
Authors: L. E. Damon, L. Damon, L. Kaplan, T. Martin, C. A. Linker
Journal: Journal of Clinical Oncology (2007)

8119 Background: We retrospectively evaluated the impact of intense [I] stem cell mobilization therapy on event-free survival [EFS] and overall survival [OS] following ASCT for NHL. Methods: 80 patients (pt) were studied (2 Burkitt, 3 primary CNS, 3 follicular, 2 intravascular, 43 large cell, 12 mantle cell, 9 transformed, and 6 peripheral T-cell). Patients with very-high risk features (LDH &gt; 500 IU/L, first remissions &lt; 1 year, 2 or more extra-nodal sites, and/or primary CNS/intravascular/mantle cell/peripheral T-cell histology) were prospectively allocated to I stem cell mobilization (requiring hospitalization) with either cyclophosphamide [C] (6 g/m 2 ) + etoposide [E] (2g/m 2 ) + filgrastim [G-CSF] (±rituximab [R]) (n=5) or with cytarabine [A] (2 g/m 2 bid for 8 doses) + E (40 mg/kg) + G- CSF (±R) (n=45). 30 pt were mobilized (outpatient) with C 4g/m 2 + G-CSF ±R (non-intense [NI] mobilization). 76 pt received ASCT conditioning with carmustine [B] + E and C (CBV) and 2 with B + E + A and melphalan (BEAM); 2 pt did not undergo ASCT. Results: The median age was 54 (21–69 years [yr]) and 57% had an elevated LDH at presentation. 39 pt (49%) were primary induction failures (PIF). At NHL presentation, 38% were IPI high-intermediate or high risk. There were 3 non-relapse mortalities (4%): (2) B pneumonitis and (1) multi-organ failure (all following ASCT). With a median follow-up of 1.8 yr (0.1–6.4), the overall median EFS is 3 yr (48% [34–62] at 4 yr) and the median OS is 4.7 yr (59% [43–72] at 4 yr). Patients receiving I mobilization were similar to those receiving NI mobilization in terms of the # of prior therapies (median 2, each), the presenting IPI risk score, and the percent PIF (57% vs 41%; p=0.17). There were trends favoring I mobilization for both 4 yr EFS (58% [41–75] vs 35% [13–57]) and OS (66% [48–84] vs 52% [32–72]), neither statistically significant. In the sub-group of large B-cell NHL, 4 yr EFS was the same in pt receiving I mobilization (81% [63–98] vs 73% [50–96]; p=0.33) but OS was better (91% [79–100] vs 58% [35–82]; p=0.02). Conclusions: I stem cell mobilization therapy, compared to NI mobilization therapy, may improve outcomes for NHL pt with very-high risk features and may overcome the anticipated poor prognosis of these pt. No significant financial relationships to disclose.
Bone-targeted therapy for AIPCa
Authors: J. Brown, H. Sarao, R. J. Amato
Journal: Journal of Clinical Oncology (2004)

4729 Background: Prostate carcinoma is linked to osteoblastic metastasis. We investigated the value of bone-targeted therapy in selected pts with AIPCa. Eligibility included progressive AIPCa affecting bone, presence of worsening cancer-related symptoms, increasing prostate-specific antigen (PSA) values on 2 occasions at least 2 weeks apart, castrate serum testosterone concentrations of < 50 ug/L, disease progression after antiandrogen withdrawal, life expectancy > 3 three months, Zubrod performance status of ≤ 2, and normal organ/marrow function. Methods: Each pt received strontium-89 at 4 mCi on week 1, day 1. Each course of chemotherapy lasted for 8 weeks. Pts were treated in weeks 1, 3, and 5 with doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on the 1st first day of every week) in combination with ketaconazole (400 mg orally 3 times a day daily for 7 days). In weeks 2, 4, and 6, treatment consisted of paclitaxel (100 mg/m2 intravenously on the first day of every week) in combination with estramustine (280 mg orally 3 times a day for 7 days). After completion of 2 courses of chemotherapy, patients with stable or responding disease completed 2 further courses. Pts were then placed on maintenance ketaconazole until their disease progressed. Results: 19 pts have enrolled. 13 pt have completed strontium-89 and 4 courses of chemotherapy. 6 pts are too early for evaluation. Based on a reduction in PSA concentrations of at least 50% from baseline maintained for at least 8 weeks, 9 pts responded to treatment. 1 pt had at least an 80% reduction in PSA concentrations. All pts with symptomatic bone pain reported that the pain improved during treatment. Toxic effects were assessed and included: 3 pts who developed deep venous thrombosis. 8 pts had grade 4 neutropenia. Severe thrombocytopenia grade ≥ 3 occurred in 6 pts.Other common side effects were; edema, fatigue, pain flare, nausea, vomiting, raised transaminases, and skin reaction. Conclusions: Bone-targeted therapy consisting of one dose of strontium-89 plus alternating chemotherapy demonstrated promising activity in pts with AIPCa with an acceptable tolerability. This program continues to enroll pts. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amersham
Bronchogenic carcinoma following cardiac transplantation
Authors: J. F. Klamerus, E. Burke, C. V. Leier, G. A. Otterson
Journal: Journal of Clinical Oncology (2005)

7292 Background: For decades, elevated risk of certain de novo malignancies following solid-organ transplantation have been reported. In the last several years increased incidence of bronchogenic carcinoma has been variably (1.56 - 4.1% incidence) described as a common non-cutaneous malignancy among heart transplant recipients. Our objective was to systematically review cases of lung cancer following cardiac transplantation at our center. Patients and Methods: 267 patients underwent orthotopic cardiac transplantation at the Ohio State University between 1986 and 2004. Transplant records among the cohort of patients surviving greater than one month (n = 237) were reviewed. Nine patients with bronchogenic carcinoma were identified and their clinical charts reviewed. Results: 3.78% of heart transplant recipients at our center developed bronchogenic carcinoma, the most common non-cutaneous malignancy. Indications for transplant included: ischemic (6), dilated (1), viral (1), and idiopathic (1) cardiomyopathies. All patients were male with a mean age of 64 ± 3.9 years at diagnosis. Most had significant smoking histories (mean 44 pack years), and only one never smoked. The mean time from transplant to diagnosis of bronchogenic carcinoma was 96.7 ± 54.6 months (range, 28–198). All tumors were non-small cell in origin: squamous cell (5), adenocarcinoma (2), and poorly differentiated (2). The majority of patients (six) presented with advanced disease, TNM stage III or IV. Patients were treated with surgery, chemotherapy, chemoradiation or best supportive care. Four patients remain alive; 5 died within a mean of 8.9 months. Conclusion: An increased incidence of bronchogenic carcinoma was demonstrated in our cohort when compared to the general population (0.07%). Mean age at diagnosis and time from transplant to cancer diagnosis was greater in our sample than previously reported. The trends of male predominance, significant smoking histories, and poor survival with advanced stage were further strengthened by our review. Since surveillance CT scans identified early disease in two of our patients, regular screening for lung cancer may be indicated in heart transplant patients with significant smoking histories. No significant financial relationships to disclose.