tbuckley/cabot-search huggingface dataset:
Shifting of patient characteristics enrolled on phase I clinical trials
Authors: M. Kundranda, P. Fu, L. Patrick, S. Manda, J. Gibbons, A. Dowlati
Journal: Journal of Clinical Oncology (2008)

13507 Background: Phase I trials serve an important first step in anticancer drug development. In most studies eligibility includes patients with advanced refractory solid tumors and good performance status (PS) ECOG 0, 1, 2. However, in the past few years a number of new therapies for a variety of solid tumors have been approved. We hypothesized that this has resulted in a changing of the characteristics of those patients enrolled on phase I trials. Methods: We reviewed 191 phase I trials published in the Journal of Clinical Oncology between 1998 and 2006. We reviewed each trial and determined the following patient characteristics: number of patients, gender, median age, race, type of malignancy, and number of prior therapies. Results: Of the trials we reviewed, 136 were in patients with advanced solid tumors. Median age (58 years) of patients did not change over the studied period nor did proportion of female patients (45%). African Americans are significantly underrepresented in phase I trials (8.4% of all patients). For other characteristics, we then compared the first half of the studied period to the 2nd half and found a statistically significant decline in the proportion of PS 2 patients enrolled (10% vs 6.5%, p=0.01). There was no change in the proportion of patients with colorectal cancer (mean 26% of patients), but a significant decline (∼50% drop) in the number of lung cancer patients was observed (14% vs 7% of all patients). Breast cancer patients only comprise a very small portion of phase I patients (5.7%) and this has not changed over time. No change in proportion of renal (6% of patients) or head/neck cancer patients (4%) was seen. There were a decrease in patients with no prior therapy over time (14% vs 6.9%) and an increase in patients with greater or equal than 3 prior therapies (21% vs 36%). Conclusions: The increase in availability of anticancer therapies for solid tumors has a led to a decrease in number of a patients with no prior therapies and patients with lung cancer enrolled on phase I studies. Changing demographics of patients needs to be considered in the design of future phase I trials. (Supported by grants U01 CA62502 and K23 CA109348–01). No significant financial relationships to disclose.
Differences in epidemiology, histology and survival between smokers and never-smokers with non-small cell lung cancer treated with platinum-based chemotherapy
Authors: K. Khodadad, S. Haghighi, S. Otukesh, Z. Esfahanimonfared, M. R. Masjedi, S. Karimi, A. Zakeriabeiazni, M. Mojtahedzadeh, E. Maraghi
Journal: Journal of Clinical Oncology (2008)

22093 Background: There are basic differences in characteristics and survival between smokers and never-smokers with non-small cell lung cancer (NSCLC). We aim to study the impact of smoking status on the behavior of the disease, and to identify differences in outcomes between these two groups. Methods: An analytical cross sectional study using a existing database of patients with NSCLC over a 9-year period. Clinical and histologic characteristics, response to treatment and survival outcome were reviewed and compared between smoker and never-smoker populations. Results: There were 510 patients; 281 patients (55.1%) were smokers and 208 patients (40.8%) were never-smokers and 21 patients (4.1%) had no smoking data. In never-smokers and smokers the most common pathology were adenocarcinoma (67.8%) and squamous cell carcinoma (45.6%), respectively (P<0.001). Female/male ratio was 74.7% (89/119) and 5.6% (15/266) in never-smokers and smokers, respectively. The never-smokers were almost 5 years younger than smokers (57.5 vs 62.3 year, respectively). Median overall survival among smokers (167 pts.) and never-smokers (140 pts.) with advanced NSCLC treated by platinum-based chemotherapy (± radiotherapy) in our department was not statistically significant (9.5 m and 10.3 m, respectively) (P=0.5). Response rate in never-smokers was 25% (37/148) compare to 32.4% (56/173) in smokers (P=0.17). Stage distribution was not similar between the two groups (P=0.001)(stages IIIB/IIIBE/IV were 15.5/31.8/52.7% and 33.5/23.7/42.8% in never-smokers and smokers, respectively). In treated patients with advanced NSCLC, multivariate analysis did not demonstrate smoking history as a prognostic factor on survival and response outcomes. Conclusions: Although in our study there are significant differences in the gender, mean age, stage and histologic characteristics between smokers and never-smokers with NSCLC, but no differences in terms of response to chemotherapy and survival outcome were observed in patients with advanced disease treated with platinum-based chemotherapy. This could imply that this disease in advanced stages is equally aggressive in both groups. No significant financial relationships to disclose.
Use of wild-type (wt) KRAS, BRAF, and PIK3CA, combined with KRAS mutations (mut) in codon 13 and RNA expression level of amphiregulin (AREG) and epiregulin (EREG), to predict cetuximab (CE) response with high accuracy in colorectal cancer of all four Dukes' stages.
Authors: Paulina Pechanska, Tobias Mayr, Bernd Hinzmann, Irina Klaman, Suzette Daniel Abd el Messih, Michael Becker, Jens Hoffmann, Andre Rosenthal
Journal: Journal of Clinical Oncology (2012)

517 Background: wt KRAS and wt BRAF are established clinical markers to predict response to CE in patients (pts) with mCRC. Some pts with KRAS mut in codon 13 respond to CE, while the majority of them do not. Recently, it was shown that pts with CRC of Duke C and wt KRAS and wt BRAF do not benefit from CE added to FOLFOX (ASCO 2011 abstr 3607). In addition, data indicated that AREG and EREG RNA expression is also correlated with CE response. We established a panel of 133 xenograft models from primary tumor tissue of pts with CRC of all four Dukes stages and conducted a therapy experiment with CE (AACR '11, LB9086). Methods: mut status of KRAS (G12, G13, A146T); BRAF (V600E) and PIK3CA (E542K, E545K, H1047R) was assessed in all xenografts by allele-specific RT-PCR. KRAS codon 61 was sequenced. AREG and EREG expression levels were analyzed by RT-PCR expression assays. Results: We observed response to CE (treated to control ratio &lt; 20%) in 18/67 (27%) of the treated xenografts. The distribution of responder (R) to non-responder (NR) is: Duke A: n=8; 2R / 6NR; B: n= 22; 8R / 14NR; C: n=28; 4R / 24 NR; D: n= 9; 4R / 5NR. Retrospective classification based on KRAS mut status identified R with a sensitivity (S + ) of 83%, and NR with a specificity (S - ) of 61%. If mut status in BRAF and PIK3CA were added the classifier showed S + of 83% / S - of 78%. If any mut except in KRAS codon 13 were considered, the classifier reached S + of 94% / S - of 69%. We improved S - of the classifiers to 86%; 90%, and 86%, respectively by adding AREG and EREG RNA expression data. The most accurate classifier combined wt KRAS, wt BRAF, wt PIK3CA with mut in codon 13 and RNA expression of AREG and EREG and reached S + of 94% / S - of 86%. Classification in corresponding primary tumors showed similar accuracy. Conclusions: We developed a powerful classifier for all Dukes stages to predict response to CE with S + of 94% and S - of 86%. In adjuvant setting the mut based classifier reaches S + of 100% and S - of 68%; S - can be improved to 79% by adding AREG/EREG. This novel classifier has the potential to be used in the adjuvant and metastatic setting to improve pts selection for CE therapy.
Palliative care interventions and end-of-life care outcomes for hepatocellular patients (pts) at two Veterans Affairs (VA) medical centers.
Authors: Zhen Wang, Sarah Lee, Sejal Kothadia, Yucai Wang, Victor Tsu-Shih Chang, Yeun-Hee Anna Park, Ellen Olson, David Klein, Fengming Zhong
Journal: Journal of Clinical Oncology (2016)

164 Background: Palliative care interventions and their effect on EOL outcomes for liver cancer pts have not been described. We investigated the association between palliative care intervention and EOL care outcomes. Methods: We reviewed the charts of pts with hepatocellular carcinoma and who were seen by palliative care at 2 VA medical centers from 2006 to 2012. We investigated the association between EOL outcomes (number of ER visits, ICU visits, chemotherapy, place of death, number of hospitalizations during their last 30 days), and interventions such as early referral (within 30 days of diagnosis), defined goals of care, holding a family meeting, and symptom assessment and management. The protocol was reviewed by the IRB of both VAs and analyses were done with SAS Studio v3.4. Results: 82 charts were reviewed (30 from EOVA and 52 from BVA). All Pts were men; 30 (39%) were white and 47(61%) African American. Interval from diagnosis to palliative care consult was 68 days (median). 72 (90%) pts were not aware of their diagnosis. 48 (65%) were not aware of prognosis. 65 (88%) had decision making capacity. 32 (39%) pts were DNR/DNI. 60 (86%) pts chose symptom management and 10 (14%) life prolongation. 47 pts (50%) had family meeting. In the last month, 35 pts (48%) had ER visit. 9 pts (12%) had ICU visits, 4 pts (5%) had chemotherapy and 48 pts (71%) had at least 1 hospitalization. 68 (85%) underwent symptom assessment. Most frequently treated symptoms were pain (78%), nausea (27%), constipation (46%), dyspnea (34%). Significant associations were found for early referral and ER admissions (OR = 3.2, p = 0.0178), family meeting and site of death (OR = 0.136 p = 0.0037), family meeting and number of hospitalizations (OR = 0.2652, p = 0.0169). Pts choosing symptom management and who had family meetings associated with hospice/home as place of death (chisq = 5.7368, p = 0.016). Knowledge of prognosis was not associated with site of death. Conclusions: In this population, many palliative care interventions were performed. Early referral, family meetings were significantly associated with site of death, ER admissions, and number of hospitalizations. These results should be replicated in larger studies.
First-in-human dose-escalation safety and PK trial of a novel humanized monoclonal CovX body dual inhibitor of angiopoietin 2 and vascular endothelial growth factor.
Authors: D. S. Mendelson, L. S. Rosen, M. S. Gordon, J. W. Goldman, A. J. Olszanski, H. Dai, R. Perea, A. Gollerkeri
Journal: Journal of Clinical Oncology (2011)

3055 Background: CVX-241 is a fusion protein comprised of a recombinant humanized IgG1 scaffold designed to specifically and selectively fuse, via a chemical linker, to two engineered angiopoietin-2 (Ang2) binding and two vascular growth factor (VEGF) binding peptides. In preclinical studies, CVX-241 is antiangiogenic and decreases tumor proliferation. Methods: In stage 1, pts with solid tumors received escalating doses of CVX-241 in cohorts of 3-6 pts at the following doses: 0.3, 1, 3, 6, 12, 15 or 18 mg/kg. An additional 18 pts are planned to be treated at the maximum tolerated dose (MTD) in stage 2. CVX-241 was given once weekly in 4 week cycles as a 90 min IV infusion, decreased to 30 min as tolerated. DLTs were defined as ≥ Gr 3 AEs unrelated to tumor progression in cycle 1. Serum PK was assessed by ELISA. DCE-MRI were conducted pre-dose, Day 4, and Day 28, in pts at 3 mg/kg and higher. Results: Data is available on 17 pts enrolled in stage 1 at doses 0.3 to 12 mg/kg. Among the 17 pts (10F/7M), the median age was 62 years (42-77), ECOG performance status 0-1. Drug exposure in pts ranged from 15-113 days (median 49 days). No DLTs were observed. The most common AEs were fatigue (29%), decreased appetite (23%), back pain (18%), and dyspnea (18%). There were no pts with proteinuria or hemorrhage. Gr 2 hypertension was observed in 1 pt (6%) at 12 mg/kg. Gr 3 toxicities included cholecystitis, clostridium difficile, colitis and diarrhea which occurred in 1 pt and which were considered unrelated to CVX-241. Total serum Ang2 (bound plus free) increased by approximately up to 90 fold and total plasma VEGF (bound plus free) increased by 2-3 fold with escalating doses (up to 3 mg/kg). Low titer anti-drug antibodies have been observed in some patients without clear effects on PK or safety. The best overall response available to-date in 13 pts is SD in 7 pts. Conclusions: CVX-241 is a novel dual inhibitor which to-date is well-tolerated in pts with advanced malignancies. Updated safety, efficacy and PK/PD data will be reported at the meeting.
Efficacy and Safety of Recombinant Human Soluble Thrombomodulin (ART-123) in Disseminated Intravascular Coagulation (DIC): Results of Phase III Randomized, Double-Blind, Clinical Trial.
Authors: Hidehiko Saito, Ikuro Maruyama, Shuji Shimazaki, Yasuhiro Yamamoto, Naoki Aikawa, Ryuzo Ohno, Akio Hirayama, Tamotsu Matsuda, Hidesaku Asakura, Mitsuyoshi Nakashima, Nobuo Aoki
Journal: Blood (2006)
Laparoscopic gastrectomy for gastric adenocarcinoma: A single institution’s experience and oncologic outcomes of 65 consecutive patients.
Authors: Amanda Kathleen Arrington, Joyce Ho, Joseph Kim, Vijay Trisal, Joshua D. I. Ellenhorn
Journal: Journal of Clinical Oncology (2012)

79 Background: The application of laparoscopy in the surgical treatment of gastric cancer has become more commonly utilized in recent years. Most of the published series are from Asia and few report on survival. Our objective was to elucidate the safety, efficacy, and oncologic outcomes of laparoscopic gastrectomy in patients with gastric adenocarcinoma. Methods: The medical records of all patients who underwent laparoscopic gastrectomy at City of Hope National Medical Center between 6/2005 and 8/2011 were retrospectively reviewed. Relevant data analyzed included patient demographics, operative parameters, complications, recurrence, and survival. Results: A total of 65 consecutive patients were identified. Of all laparoscopic procedures, 5 were proximal, 41 were distal, and 19 were total gastrectomies. Median age was 67 years (35-96). Median operative time was 370 min (228-583). Median EBL was 200 ml (10-900). Twenty-eight of the 65 laparoscopic gastrectomy cases employed robotic assistance in lymph node dissection. The median number of lymph nodes retrieved was 26. Forty-seven cases included D2 lymph node dissections, 16 cases were D1 dissections, and 2 cases involved D0 dissections. All intended D2 dissections had greater than 15 nodes retrieved. Median hospital stay was 7 days (3-39). Morbidity and mortality rates were 33% and 3%, respectively. Histological staging revealed most patients with Stage I or II disease. Median follow-up was 15 months (0.5 to 58). Cancer has recurred in 4 patients (6%). The 3-year overall survival for stage I disease (N=38) is 92%, stage II disease (N=17) is 71%, and for stage III (N=7) is 51%. Conclusions: The long-term oncologic outcomes and overall survival are comparable to that of open technique seen in other series. Our large institutional series shows that laparoscopic gastrectomy for gastric adenocarcinoma is feasible and safe and can be performed in patients with gastric cancer with excellent surgical and oncologic outcomes.
Treatment outcome with mTOR inhibitors for 65 cases of non-clear cell renal cell carcinoma: Association of long-term responses and oncogenomic events.
Authors: Martin Henner Voss, Diogo Assed Bastos, Christoph Karlo, Sujata Patil, Albulena Ajeti, A. Ari Hakimi, Darren Richard Feldman, Ana M. Molina, Michael F. Berger, James Hsieh, Robert John Motzer
Journal: Journal of Clinical Oncology (2013)

391 Background: Temsirolimus and everolimus are standard agents in the management of advanced renal cell carcinoma, but the registration trials primarily enrolled patients with clear cell histology. We assessed outcome in patients with non-clear cell RCC (ncRCC) treated with mTOR inhibitors at our center. Methods: Clinical features and histologic subtypes were characterized for ncRCC patients treated with single-agent temsirolimus or everolimus. Outcome was analyzed using the Kaplan-Meier method to determine progression free survival (PFS) and overall survival (OS). Genomic analysis of outliers with either durable or poor response was done by next-generation sequence analysis of tumor tissue and germline DNA. Results: 65 patients received temsirolimus (n = 46) or everolimus (n = 19). Histologic subtypes included papillary (n = 16), chromophobe (n = 9), collecting duct (n = 6), translocation-associated (n = 3), and unclassified (n = 31) RCC. Median follow-up for survivors is 29 mos. Median treatment duration for 52 patients, who continue therapy or stopped due to progression or death, is 2 mos. 8 patients (12.3%) were treated for ≥ 1 year (max. 37 mos), including papillary (n = 3), chromophobe (n = 2) and unclassified (n = 3) RCC. Tumor analysis identified genomic determinants of long term response in 2 unclassified RCC (complete functional loss of TSC1 and TSC2, respectively). No such changes were seen in 2 patients with chromophobe RCC and rapid progression on therapy. Conclusions: A subset of ncRCC patients derives benefit from mTOR inhibitors, but most have poor outcome. Durable responses can be linked to oncogenomic alterations within the mTOR pathway, and future goals should include the identification and characterization of such predictive tissue biomarkers. [Table: see text]
A rapid rituximab infusion schedule, safety, and tolerability: A local experience.
Authors: A. a. Abdulmasood, B. J. Al Bahrani, I. Mehdi, A. M. M. Nada
Journal: Journal of Clinical Oncology (2011)

e18546 Background: The use of rituximab is ever increasing in terms of labelled indications, off label usage, and increasing number of eligible patients. Its administration can cause hypersensitivity, angioedema, pulmonary infiltrates, cardiac events or respiratory distress syndrome. A usual recommended schedule and regular administration over 3- 4 hours require considerable healthcare resources and is inconvenient for patients. There are initial published reports in literature that indicated the safety and feasibility of a rapid infusion. We, in this study explored the feasibility, safety and tolerability of rapid rituximab infusion over a shorter abbreviated infusion time. Methods: A total of 24 patients diagnosed as CD20+ Non Hodgkin’s lymphoma were planned to receive rituximab at a dose of 375mg/m2 in combination with standard chemotherapy regimens, were included in the study from January 2009-December 2009. The administration of first rituximab dose was unaltered and given as per standard practice of 3-4 hours infusion. The second and subsequent doses were delivered over a total infusion time of 90 minutes only (20% of dose in the first 30 minutes, remaining 80% over next 60 minutes). Results: These patients, aged between 13 and 79 years, received a total of 153 rituximab infusions (chemotherapy events) with an average of 6 infusions per patient. The shorter infusions were well tolerated subjectively by all the patients. Grade 1 infusion related toxicity was reported in 5 infusion events (3.2%), and there were no acute reactions or G3/4 toxicity in any infusion episode. Conclusions: A rapid abbreviated infusion of rituximab is well tolerated subjectively, feasible and safe; when administered as second and subsequent infusions in the course of chemotherapy for those who tolerated first dose without significant infusion related toxicity. This shortened infusion schedule has resulted in a substantial reduction in resource utilization, is cost effective and patient compliant. It has an evidence based potential to be adopted as standard of care and practice. The patient selection and monitoring is however emphasized. Our institution has now adopted this as a routine day care practice.
Pelvic radiotherapy and urine substance P levels
Authors: A. F. Korcum, M. G. Aksu, O. Akdeniz, M. Sarigul, N. Erin
Journal: Journal of Clinical Oncology (2008)

9607 Background: Pelvic radiotherapy is widely used for the treatment of malignancies localized in the pelvis. Urinary complications are the major side effects of pelvic radiation. Etiopathogenesis of the radiation-induced bladder toxicity is not known. Substance P (SP) which is found in sensory neurons is important in both motor functions and local regulation of immune response in the urinary bladder. There are no clinical studies examining the effects of pelvic radiotherapy on urine SP levels. Hence, the goal of this study was to determine the acute and sub acute effects of RT on SP levels in the urine. Methods: Sixty-three patients were enrolled in the study. Out of 63 patients 15 of them had endometrial, 12 of them had cervical, 12 of them had prostate and 24 of them had rectal carcinoma. Each patient received 2 Gy daily fractions and urine samples were obtained before first fraction, one hour after first, eighth and twenty-fifth fraction and twelve weeks after the completion of RT. Each patient was evaluated for urinary side effects weekly, according to RTOG toxicity criteria. SP levels were determined directly form urine samples by enzyme immune assay. Results: Urinary side effects were reported in 36 % of patients after eighth fraction while most patients developed side effects after 25th fraction. Specifically all the prostate patients had grade one or 2 toxicity while only 66% of the patients with endometrial carcinoma developed toxicity. 93% and 84 % of patients with cervical and rectal carcinoma respectively had toxicity. Radiotherapy altered SP levels in the urine in patients with urinary toxicity. SP levels were decreased in most patients. Specifically SP levels decreased markedly (> 70 %) in 14 %, 24 % and 17 %, and intermediately (50–70 %) in 22 %, 14 % and 19 % of patients after first, eighth and twenty-fifth fractions respectively. In a group of patients, SP levels were increased after RT. SP levels increased markedly (> 90 %) in 6 %, 18 % and 15 % after first, eighth and twenty-fifth fractions respectively. Intermediate increase (50–90 %) was observed in 4 %, 4 % and 6 % of patients after first, eighth and twenty-fifth fractions respectively. Conclusions: These results demonstrate that RT affects peptidergic neurons in the bladder and altered Substance P levels could be responsible from acute and late toxicities of RT. No significant financial relationships to disclose.