tbuckley/cabot-search huggingface dataset:
Management of pemetrexed toxicity in acute renal failure
Authors: J. Brandes, S. A. Grossman, H. Ahmad
Journal: Journal of Clinical Oncology (2005)

2121 Background: Pemetrexed is a multi-targeted antifolate approved by the FDA for patients (pts) with mesothelioma and non-small cell lung cancer. As this agent is almost exclusively cleared by renal excretion, trials leading to its approval were conducted in pts with normal renal function. However, this cycle active agent is often administered with cisplatin to pts with pleural effusions and ascites. As a result, the potential for drug accumulation in effusions and for accompanying renal insufficiency is real. Guidelines for the management of pemetrexed toxicity in the presence of renal failure have not been established Methods: A case of treatment related acute renal failure following chemotherapy with cisplatin and pemetrexed in a patient with advanced mesothelioma and ascites is presented. Pharmacologic studies in this patient were performed. Results: In pts with normal renal function, pemetrexed plasma concentrations peak early and become undetectable after about 48 hours. In the presented case, pemetrexed plasma levels six days after a dose of 500 mg/m2 were 100.2 mcg/l and 63.9 mcg/l after 8 days. The half-live of drug elimination was 65 hours, which is markedly prolonged. Pemetrexed also accumulated in the ascites of the patient. Drug levels in the ascites after 5 days were 257 mcg/l, suggesting that effusions might significantly alter the pharmacokinetics of pemetrexed. Treatment with leucovorin, folate, and continuous veno-venous hemodialysis was initiated. Dialysis was unsuccessful in removing pemetrexed. Thymidine and carboxypeptidase were not available. The patient developed severe myelosuppression and mucositis that resolved without serious complications. Conclusions: This case highlights challenges, available treatments, and the need for more data to optimally manage pts in renal failure who received pemetrexed. No significant financial relationships to disclose.
Concomitant accelerated hyper-fractionated radiotherapy and temozolomide in the treatment of high grade astrocytoma: Updated results
Authors: T. Hashem, H. Metwaly, M. Abouelfetouh
Journal: Journal of Clinical Oncology (2006)

11523 Background: The safety and efficacy of accelerated hyper-fractionated radiotherapy (RT) combined with temozolomide (TMZ) in patients with high grade astrocytoma have already been reported.Updated results on survival will be presented. Methods: Twenty-four patients with newly diagnosed and histologically proven high grade astrocytoma were enrolled onto this study. Treatment protocol included RT delivered in fractions of 150 cGy 3 times daily with at least 4-hour intervals between fractions to a total dose 4050 cGy. The target volume was the tumor plus the edema with a 2-cm margin. A boost of 1800 cGy was given to the tumor plus a 2-cm margin to a total dose of 5850 cGy delivered in 39 sessions over 2.5 weeks. TMZ dose was (150 g/m 2 /day 7 d/wk) given 2 hours prior to RT, throughout the course of RT. Results: Of the 24 patients included 5 (21%) developed G2 &amp; G3 neutropenia, and 4 patients (17%) developed G2 &amp; G3 thrombocytopenia. Non-hematologic toxicities were: G2 &amp; G3 vomiting in 8 (33%) patients, G2 &amp; G3 fatigue in 13 (54%) patients, G2 skin rash in 4 (17%), and G2 acute radiation reaction in 2 (8%) patients. The12 months and 18 months survival rates were 67% and 51.5% respectively. Patients aged &lt;45 years and those who underwent debulking surgery had better survival rates (69% &amp; 70%) in comparison to those aged ≥45 years and those who underwent biopsy only (27% &amp; 36%). Conclusions: The results achieved particularly with respect to survival are promising and should be confirmed. No significant financial relationships to disclose.
Safety, efficacy and pharmacokinetics of nimotuzumab, a humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody, as monotherapy in patients with locally advanced or metastatic pancreatic cancer (PC)
Authors: D. Strumberg, M. E. Scheulen, R. A. Hilger, J. Krauss, N. Marschner, F. Lordick, F. Bach, D. Reuter, L. Edler, K. Mross
Journal: Journal of Clinical Oncology (2006)

12504 Background: Nimotuzumab (OSAG101, Theraloc) is a humanized monoclonal antibody (mAb) that binds to the EGFR. In preclinical studies the antibody has shown potent antitumor activity. Based on phase I data, the recommended dose has been established at 200 mg weekly. A previous phase II study in children with high grade brain tumors showed activity of nimotuzumab as a monotherapeutic agent, even in prognostically very unfavorable pontine glioma. No drug related side effects were reported. The present ongoing phase II study was aimed at evaluating the safety and efficacy of nimotuzumab monotherapy in patients (pts) with locally advanced or metastatic PC. Methods: Pts who failed standard chemotherapy with gemcitabine or another first line regimen for advanced disease and had at least one measurable lesion were eligible for the study. Nimotuzumab was given iv as induction therapy at 200 mg once weekly for 6 weeks. Follow up by CT was performed after 8 weeks. Pts continued receiving treatment 3-weekly until disease progression or unacceptable toxicity occurred. Endpoints included tumor response (RECIST), time to disease progression, and safety. Blood samples were collected prior to first dose, at end of infusion, and 3h, 6h, 48h, as well as every time before subsequent nimotuzumab doses were administered. Nimotuzumab concentrations in serum were measured by cellular ELISA. Results: Enrollment is complete, with treatment ongoing. In total, 55 pts were treated (28 women/ 27 men; ECOG status of 1 [n= 41] or 0 [n=14], median age 63.6 yrs [range 46–83 yrs]). Pts evaluable for response: n= 36; CR:0; PR:0; SD:6 pts (median TTP 19.2 weeks; 14.1–26.1). The only reported treatment-related adverse event was rash grade 1 in 1 pt. After 200 mg single dose, the mean value of C max was calculated to 141 ± 33 μg/ml. The t 1/2 was calculated to 45 h, volume of distribution to 1.46 ± 0.3 l, respectively. The total clearance was determined to 23 ± 6 ml/h. The trough values after 168 h were 6.2 ± 6.3 μg/ml. Conclusions: These data confirm that nimotuzumab is safe and well tolerated. To improve efficacy, a combination trial with gemcitabine is planned. [Table: see text]
Abstract 18376: Angiographic Graft Patency After Multivessel Minimally Invasive Coronary Artery Bypass Grafting: MICS CABG Patency Study
Authors: Joseph T McGinn, Masood Shariff, Harry Lapierre, Benjamin Sohmer, Nikhil Goyal, Marc Ruel
Journal: Circulation (2012)

Objective: Previous publications from our institutions have shown that minimally invasive coronary artery bypass grafting (MICS CABG) is safe, widely applicable, and associated with fewer infections, less transfusions, and better recovery than standard CABG. However, graft patency rates are unknown. The MICS CABG Patency Study prospectively evaluated angiographic bypass graft patency at 6 months after MICS CABG. Methods: In this dual-center study, 61 patients were prospectively enrolled and underwent MICS CABG through a 4-7cm left thoracotomy approach, where the left internal thoracic artery (LITA), the ascending aorta for proximal anastomoses, and all distal coronary targets were accessed without endoscopic or robotic assistance. The primary outcome was graft patency at 6 months, using 64-slice CT angiography. Secondary outcomes included conversions to sternotomy and major adverse cardiovascular events (MACE). ( Clinical Trial Registration Unique identifier: NCT01334866 ) Results: Mean age was 64.1±8.1 years, the mean ejection fraction was 48.8±10.4%, and there were 8 females in the study (13.1%). Surgeries were performed off-pump in 52 patients (85.2%). Complete revascularization was achieved in all patients, and the median number of grafts was 3. There was no perioperative mortality, no conversion to sternotomy, and 1 reopening for bleeding. Transfusion occurred in 15 patients (24.6%).The median length of hospital stay was 4 days, and patients were followed-up to 6 months, with no mortality or MACE. At 6 months, overall CT angiographic graft patency was 91.2% for all grafts, and 100% for LITA grafts. Conclusions: MICS CABG is safe, feasible, and associated with excellent rates of graft patency at 6 months post-surgery.
Phase I dosing-escalating study of oxaliplatin in combination with oral tegafur-uracil/leucorvin in patients with advanced gastric cancer
Authors: J.-S. Chen, J.-S. Huang, T.-S. Yang, Y.-C. Lin, H.-M. Wang, C.-T. Liau, K.-M. Rau
Journal: Journal of Clinical Oncology (2004)

4266 Background: The aim of this dosing-finding study was to determine the maximum- tolerated dose (MTD), the dose-limiting toxicities (DLTs) and to define the recommended dose of biweekly oxaliplatin (OXA) (Oxalip®, TTY Biopharm Company, Taipei, Taiwan) with a fixed dose of oral tegafur-uracil (UFUR®, TTY Biopharm Company, Taipei, Taiwan) / leucvorin (LV) in patients with advanced gastric cancer (GA). Secondary objectives included evaluation of the safety and anti-tumor activity. Methods: Between Oct 2001 to Aug 2003, 28 chemo-naive patients with advanced GA were enrolled. OXA was administrated as 2-hour infusion (dose from 55 mg/m2, 70 mg/m2, 85 mg/m2, 100 mg/m2, and 115 mg/m2) on day 1 and 15 every 28 days with tegafur-uracil 300 mg/m2/day and LV 60 mg/day orally three times a day from day 1 to day 21, followed by one-week rest. DLTs were defined as grade IV hematologic toxicity or grade III non-hematologic toxicity in the first course of treatment. Safety and efficacy were evaluated throughout treatment. Dose escalation to the next cohort was based upon standard criteria for phase I trial. Results: There were 11 females (39.7%) and 18 males (60.7%) with a median age of 58.5 (32–72). The dose level of OXA 100 mg/m2 was found to be MTD. The most common DLT is diarrhea. Major grade III/IV toxicities of the 28 patients were: vomiting 4 (14.3%), diarrhea 4 (14.3%), renal 2(7.1%), leukopenia 1(3.6%), and thrombocytopenia 2 (7.1%). There were two treatment-related deaths due to neutropenia infection and upper gastrointestinal bleeding, respectively. The response among 28 patients were partial response 13 (46.4%, 95% CI 26.74% to 66.12%), stable disease 9 (32.1%), and 6 (21.5%) progressive disease, respectively. By the end of Nov. 2003, 14 patients were expired. The median time to treatment failure, time to progression and overall survival were 124 days, 107 days and 407 days, respectively. Conclusions: The recommended dose for phase II study is OXA 100 mg/m2 biweekly with fixed dose of oral tegafur-uracil 300 mg/m2/day and LV 60 mg/day three times a day for 21 days in cycle of 28 days. The most common DLT is diarrhea. The response was 46.4%. No significant financial relationships to disclose.
Is local lymph node involvement a prognostic factor in paediatric renal cell carcinoma?
Authors: P. Indolfi, G. Bisogno, G. Cecchetto, A. Ferrari, L. Piva, M. Carli, V. Donofrio, A. Schiavetti, G. De Salvo, A. Donfrancesco
Journal: Journal of Clinical Oncology (2007)

20014 Background: RCC in childhood is rare. Children with RCC tend to have a similar overall prognosis when compared with adults, where prognosis worsens with increasing stage, although direct comparisons of adult and paediatric data isn’t easy. The aim of our study is to identify the prognostic significance of local lymph node involvement in children with Renal Cell Carcinoma (RCC). Methods: On the basis of a retrospective study, the recently founded Italian Association for Paediatric Hematology and Oncology-Rare Tumors Paediatric Age (AIEOP-TREP) identified 16 patients (9 females) with RCC and local lymph node involvement at 10 of these centers. The cases were observed among 59 paediatric RCC, corresponding to 27.1% of RCC presenting in Italy from January 1973 to May 2006. Results: Overall, 9 patients were alive and disease free at last follow-up: eight patients had regional lymph node dissection (RLND) from the diaphragm at the aortic bifurcation, and one had the para-aortic lymph nodes removal. Six patients died: one had RLND (died from progression of disease), three had the renal hilum lymph nodes removal, and two the para-aortic lymph nodes dissection. One patient was lost to follow-up after relapse: this patient had para-aortic lymph node removal at diagnosis. Estimated 25-year DFS and OS rates for all patients were 64.2% and 50.5%, respectively. Given the small number of patients, little can be said about the value, if any, of adjuvant immunotherapy in this group of RCC. Conclusions: Children with lymph node positive RCC had a relatively unfavourable long- term prognosis. In our experience the RLND improves the prognosis. Further investigation of the biologic differences is warranted. Because of the very low incidence of paediatric RCC, an international clinical trial will be required to establish optimal therapy for children with RCC. No significant financial relationships to disclose.
Four year follow-up of infliximab in rheumatoid arthritis patients refractory to multiple dmard treatment: Attrition and long-term clinical effect
Authors: B. Vander Cruyssen, Patrick Durez, Rene Westhovens, F. Van den Bosch, H. Mielants, L. De Clerck, A. Peretz, Michel Malaise, L. Verbruggen, N. Vastesaegere, A. Geldhof, F. De Keyser
Journal: Annals of the Rheumatic Diseases (2006)
Effect of YM155, a potent survivin suppressant, on the antitumor effect of rituximab in diffuse large B-cell lymphoma (DLBCL) xenograft models: FLT-/FDG-PET imaging studies.
Authors: K. Mitsuoka, S. Miyoshi, A. Kita, K. Yamanaka, M. Nakata, Y. Murakami, A. Noda, M. Jitsuoka, H. Fushiki, S. Nishimura
Journal: Journal of Clinical Oncology (2010)

8087 Background: YM155 is a novel small-molecule survivin suppressant, and is currently under development for the treatment of non- Hodgkin's lymphoma in a phase II clinical trial. Therapy monitoring by non-invasive PET (positron emission tomography) imaging study allow a straightforward translation from preclinical to clinical research. The aim of this study was to evaluate the utility of the PET tracers, FLT(3'-deoxy-3'-[18F]fluorothymidine) and FDG(2-[18F]fluoro-2-deoxy-D-glucose) to monitor tumor response to YM155 in combination with rituximab (RTX) treatment in diffuse large B cell lymphoma (DLBCL) xenograft model. Methods: YM155 (0.5 mg/kg/day) was administered on day 0 (D0) as a 7-day continuous subcutaneous infusion, and RTX (50 mg/kg/day) was administered by intravenous bolus injection on D0 and D+2 in mice (N=4) with the human derived DLBCL xenograft, WSU-DLCL- 2. FLT/FDG uptake was evaluated using a small-animal PET scan, Inveon (Siemens), on D0 (before treatment), D+3, +7, and +14 / on D0 and D+3 after treatment, respectively. At each time point, excised tumors from other mice (N=4) were evaluated for histopathology with proliferative activity (Ki-67 index). Results: YM155 in combination with RTX (combo) resulted in significant (P <.05) regression of tumor size compared to the RTX monotherapy group without loss of body weight. PET imaging data showed tumor uptake of FLT/FDG significantly decreased in the YM155 alone (-17%/-18%) and combo (-50%/-42%) groups on D+3 compared to baseline (D0) in contrast to the RTX alone (+72%/+12%) or saline (+126%/+48%) groups where uptake increased, respectively. In addition, significant (P <.05) decrease of the Ki-67 positive cells in the tumor compared to the RTX alone group could be observed on D+3. Conclusions: YM155 may increase anti-tumor activity of RTX for the treatment of DLBCL. FLT-PET as a cell proliferation imaging, FDG-PET imaging reflecting glucose metabolism and Ki-67 index, respectively may be a useful biomarker of this combination therapy. No significant financial relationships to disclose.
The risk of nodal metastasis and survival of various cell types of uterine cancer: A study of 16,640 patients
Authors: K. Y. Yang, D. S. Kapp, J. M. Hu, J. Y. Shin, K. Osann, C. B. Powell, L. Chen, J. K. Chan
Journal: Journal of Clinical Oncology (2008)

16589 Background: To investigate the risk of nodal metastasis in various histologic cell types of uterine cancer. Methods: Demographic and clinico-pathologic information were obtained from the Surveillance, Epidemiology, and End Results Program between 1988 and 2001. Data were analyzed using Chi-square tests, Kaplan-Meier analysis with log-rank tests, and Cox proportional hazards model. Results: 16,640 women underwent surgical staging for uterine cancer. The median age was 64 years (range 1–99). 85.4%, 6.8%, and 5.6% were Whites, Blacks, and Asians. Stage I, II, III, and IV diseases were found in 68.4%, 10%, 11.2%, and 10.5% of patients, respectively. Grade 1, 2, and 3 cancers were found in 24.4%, 34.8%, and 31.7% of tumors. 80% of the patients had endometrioid, 8.8% papillary serous (UPSC), 2.3% clear cell, and 8.9% sarcoma. In the overall study group, the risk of nodal metastasis was three-fold higher with UPSC compared to endometrioid (29.8% vs. 10.2%; p<0.001). Of stage I-III patients, the risk of nodal metastases was 5.6%, 15.8%, 12.6%, and 8.6% with endometrioid, UPSC, clear cell, and sarcoma, respectively (p<0.001). Of patients with nodal metastases, the proportion of patients with extensive nodal involvement (more than 5 positive nodes) was 11.8% in endometrioid, 22.7% in UPSC, 12.2% in clear cell, and 14.8% in sarcoma subtypes. The 5-year disease-specific survival of stage IIIC patients with endometrioid, UPSC, clear cell, and sarcoma cancers was 70.6%, 44.8%, 64.9%, and 48.4%, respectively (p<0.001). On multivariate analysis, age, stage, grade, and histology remained significant prognostic factors for survival. Conclusions: Papillary serous, sarcoma, and clear cell uterine cancers have a higher risk for nodal metastasis compared to endometrioid cancers. Uterine cancer patients, in particular those with high-risk cell types, should undergo comprehensive staging with nodal assessment. No significant financial relationships to disclose.
A phase II trial of arc-based hypofractionated IMRT in localized prostate cancer.
Authors: L. Best, M. Lock, E. Wong, G. Bauman, D. D'Souza, V. Venkatesan, T. Sexton, B. Ahmad, G. Rodrigues
Journal: Journal of Clinical Oncology (2010)

e15016 Background: To evaluate acute and late genitourinary (GU) and gastrointestinal (GI) toxicity and biochemical control of hypofractionated, image guided (fiducial markers and/or ultrasound guidance), simplified intensity modulated arc therapy (SIMAT) for localized prostate cancer. Methods: This phase II prospective clinical trial for T1a-2cNXM0 prostate cancer enrolled 66 patients who received 63.2Gy in 20 fractions over four weeks. Fiducial markers were used for image guidance in 30 patients and daily ultrasound (SonArray or ReStitu) for the remainder. Toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Results: Median follow-up was 36 months. Acute phase grade 2 toxicity was 34% and 25% for GU and GI symptoms, respectively. Acute grade 3 toxicity was 9% and 10% for GU and GI symptoms respectively. One patient with unrecognized Crohn's disease developed an acute grade 4 acute GI toxicity. Late grade 2 GU and GI toxicity was 14% and 25% respectively. Late grade 3 GU and GI toxicity was observed in 5% and 3% respectively. One late GI grade 4 toxicity was observed in a patient with significant comorbidities (anticoagulation, vascular disease). Acute GI toxicity > grade 2 was shown to be a predictor for late GI toxicity grade > 2 (p < 0.001). This trend was not seen for GU toxicity. The biochemical disease-free survival at three years was 95%. Conclusions: Hypofractionated SIMAT radiotherapy given as 63.2 Gy in 20 fractions is feasible with promising biochemical control rates. However, ongoing randomized controlled trials will ultimately clarify issues regarding patient selection and the true rate of severe toxicity that can be directly attributed to hypofractionated radiotherapy. No significant financial relationships to disclose.
MRI/US fusion-guided biopsy to detect clinically significant prostate cancer in the central gland correlating with index lesion.
Authors: Michele Fascelli, Thomas P Frye, Arvin Koruthu George, Steven Abboud, Raju Chelluri, Richard Ho, Sandeep Sankineni, Maria J Merino, Baris Turkbey, Peter L. Choyke, Bradford J. Wood, Peter A. Pinto
Journal: Journal of Clinical Oncology (2015)

44 Background: Central gland (CG) prostate cancers (CaP) are reported with lesser incidence and smaller tumor volume compared to the peripheral zone (PZ). Index tumor lesions defined by highest grade may be missed when in the CG. MRI/US fusion-guided biopsy allows targeting of lesions, potentially identifying cancer outside the traditional TRUS biopsy template. Methods: Retrospective review of 1,003 patients who underwent multiparametric MRI (mpMRI) found 2,119 suspicious lesions. Targets were biopsied and stratified by zonal distribution, CG or PZ. Cancer detection rates (CDR) were tabulated by location and correlated with PSA, Gleason score, prostate volume and MRI suspicion. Results: Fusion-guided biopsy targeted lesions in the central (711, 34%) or peripheral (1408, 66%) prostatic zones. CDR was similar between zones: 35.2% CG compared to 33.6% PZ (Table). CDR of clinically significant disease (Gleason &gt;4+3) was similar in the CG and PZ despite higher prostate volume in those with CG lesions. In contrast to TRUS biopsy, upgrading occurred in 18.5% of CG patients versus 13.3% PZ (p=0.024). 36.6% (77/210) of CG lesions represented the highest risk lesion on MRI, translating to 13% (77/592) of the biopsy-proven CaP cohort. Conclusions: CG cancers occur at a similar frequency as PZ CaP. CG lesions were more likely to be upgraded from TRUS biopsy, frequently representing the index lesion. In upgraded patients, CG targets constituted the index lesion in a third of all males. MRI/US fusion-guided biopsy identifies clinically significant disease of the CG not captured on traditional biopsy. [Table: see text]
Outcomes of first-line chemotherapy for advanced breast cancer in women with good versus poor quality of life at baseline
Authors: C. Lee, M. Stockler, V. Gebski, A. Coates, R. J. Simes
Journal: Journal of Clinical Oncology (2009)

1036 Background: Health-related quality of life (QL) is an established predictor of outcome in advanced breast cancer. The benefits and harms of chemotherapy in women with poor QL are unclear. Methods: We used data from 378 women receiving classical CMF in the control arms of 3 randomized trials. QL was rated at baseline by patients with linear analogue self-assessment scales (LASA) for physical well-being (PWB), mood, appetite, pain, nausea/vomiting, and overall QL; and by physicians with Spitzer's Quality-Of-Life Index (QL-I). Patients were divided into 3 groups according to their baseline QL scores: good (LASA 0–25, QL-I 5–7), intermediate (LASA 26–65, QL-I 8–10) or poor (LASA 66–100, QL-I 11–15). The main outcomes were overall survival (OS), progression-free survival (PFS), objective tumor response (OTR = CR or PR), weight loss, and grade 3 or 4 adverse events (AE). Results: All aspects of QL, except nausea/vomiting, were significant univariable predictors of OS and PFS. PWB, mood, appetite and QL-I were independently significant predictors of OS in a multivariable model with biomedical factors. Only patient's self-rated poor QL had lower rates of OTR, and higher rates of nonhematological AE than those with good QL (see Table), but rates of hematological AE were similar. Weight loss occurred more frequently in those with poor appetite (OR 5.8, p=0.05) or poor PWB (OR 4.9, p=0.05). Conclusions: Less than 25% of women with poor baseline QL responded to first line CMF but over 25% had severe non-hematological toxicity. Baseline QL predicts these outcomes beyond biomedical factors. [Table: see text] No significant financial relationships to disclose.