tbuckley/cabot-search huggingface dataset:
Phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients. Digestive Group of French Federation of Cancer Centers.
Authors: Y Bécouarn, M Ychou, M Ducreux, C Borel, F Bertheault-Cvitkovic, J F Seitz, S Nasca, T D Nguyen, B Paillot, J L Raoul, J Duffour, A Fandi, G Dupont-André, P Rougier
Journal: Journal of Clinical Oncology (1998)

PURPOSE To evaluate the objective tumor response rate and safety profile of oxaliplatin when administered to patients with previously untreated metastatic colorectal adenocarcinoma. PATIENTS AND METHODS A total of 39 patients were entered onto this phase II trial. One patient was excluded for having had a second cancer, so the study was based on 38 patients. Patients were treated with oxaliplatin 130 mg/m2 as a 2-hour infusion on day 1, every 21 days. Patients were assessed for response every three courses. All clinical and radiologic data were reviewed by an external panel of experts, with their assessment being considered definitive. RESULTS Nine partial responses (PRs) were observed (response rate, 24.3%; 95% confidence interval, 11.8% to 41.2%). The median duration of response was 216+ days. Fifteen patients (40.5%) had stable disease and 13 (35.2%) had progressive disease. The median progression-free survival time for all patients was 126+ days (range, 21 to 447+). The main toxicity was peripheral sensory neuropathy. Grade 3 neurotoxicity (National Cancer Institute common toxicity criteria [NCI-CTC]) was reported in 13%. Hematologic and gastrointestinal toxicities were mild. The incidence of grade 3 neutropenia was 5.2%, while that of grade 3 or 4 thrombopenia was 7.9%. Vomiting (grade 3 or 4) occurred in 7.9% of patients and grade 3 diarrhea in 2.6%. CONCLUSION This phase II study provides clear evidence of the safety and efficacy of oxaliplatin monotherapy at this dose and schedule in patients with previously untreated metastatic colorectal carcinoma.
Effect of oral aprepitant in management of delayed chemotherapy-induced nausea and vomiting (DCINV) after high-dose chemotherapy (HDC) and hematopoietic stem cell transplant (HCT)
Authors: L. M. Isola, G. Goldberg, G. Chandra
Journal: Journal of Clinical Oncology (2009)

e20548 Background: This study assessed the safety and efficacy of Aprepitant, a neurokinin 1 receptor antagonist, in the management of DCINV associated with HCT. Methods: Pilot phase I-II RCT, adult patients undergoing ablative HCT. Eligibility Criteria: Presence of DCINV (&gt;1 episode of vomiting/24 hrs or &gt;25 mm on nausea visual analogue scale (VAS) on day 2–14 post- HCT). Control arm: ondansetron + metoclopramide. Aprepitant arm: Same regimen + aprepitant 125 mg on d1 and 80 mg d2–3. Controls with DCINV persisting &gt;72 hours were crossed to treatment arm. Safety endpoints: Primary: myeloid engraftment (ANC&gt;500/μL by d15.) Secondary: platelet engraftment (plts &gt;20,000/μL by d21.) Efficacy endpoints: Primary: no episodes of emesis. Secondary: VAS reduction ≥ 25 mm Results: 12 pts, ages 23–62 yrs, were randomized, 9 to treatment arm. Two of 3 controls crossed over. The study was interrupted prior to completion of accrual to control arm. Results are summarized as median ± SD in the table below. Treatment arm showed no delay in granulocyte and platelet engraftment, less emesis, and little difference in VAS compared to control. No patients in either group developed unexpected grade III-IV toxicities, including VOD or IPS. Conclusions: The use of aprepitant for control of DCINV after myeloablative HCT decreased the frequency of DCINV and had no adverse effect on granulocyte and platelet engraftment. This pilot study supports the safety and efficacy of aprepitant for DCINV in the setting of HCT. [Table: see text] [Table: see text]
The influence of FDG-PET/CT on CT-based surgical management for patients with squamous-cell cancer at thoracic esophagus.
Authors: H. Guo, J. Yu, B. Zhang, H. Li, H. A. Wakelee
Journal: Journal of Clinical Oncology (2010)

e13550 Background: This study is designed to investigate whether integrated FDG-PET/CT would influence the surgical management based on CT for potentially operable esophageal cancer. Methods: Between September 2003 and June 2007, a prospective study of 78 patients with newly-diagnosed thoracic esophageal cancer, who underwent PET/CT following conventional diagnostic work-up (including CT) before surgery, was performed. Surgical pathology or clinical evidence of tumor progression during a follow-up of at least six months was used as the gold standard. The value of the additional PET/CT scan was assessed. Results: Surgery was opted against after radiographic evaluation in 21 (27%) patients. A total of 1,040 lymph nodes at 386 stations were harvested during surgery; 31 patients (54.4%) were found to have metastatic lymph nodes, totaling 135 at 76 stations. The primary tumors of 77 (98.7%) patients displayed an increased FDG uptake at PET/CT with mean SUVmax of 12.2. The accuracy of PET/CT for defining T4 tumors (unresectable) was 68.8%, versus 71.6% when comparing with CT (Non-significant). However, the accuracy of PET/CT was higher than that of CT in defining stage IV disease (86% vs. 63%; p = 0 .003). In the 18 patients with discordant results, FDG-PET correctly upstaged 11 patients from M0 to M1 disease, and downstaged 3 patients from M1 to M0 disease. The transthoracic approach based on CT alone was altered in 13 patients (22.8%) because PET/CT detected more involved LN stations (mainly at upper right mediastinum), which resulted in additional removal of lymph nodes in 28 nodal groups. Conclusions: Integrated PET/CT is more accurate than CT in assessing resectability. This can potentially alter the transthoracic approach and, thus, lead to a change in CT-based surgical management. No significant financial relationships to disclose.
Tumor burden is not related to quality of life in patients with metastatic colorectal cancer
Authors: J. A. Sloan, A. Grothey, E. Green, X. Zhao, M. E. Campbell, D. W. Szydlo, D. J. Sargent, R. M. Goldberg
Journal: Journal of Clinical Oncology (2008)

4017 Background: The significance of tumor burden (TB), as both a prognostic and an outcome measure in colorectal cancer patients (pts) has recently come under scrutiny. Tumor response endpoints have been poor predictors of overall survival (OS). There has been mounting evidence that QOL has prognostic significance (Sloan, JCO, 1998). The purpose of this study was to describe the relationship between TB and QOL in pts with metastatic colorectal cancer (MCRC). Methods: 989 pts with MCRC participating in Intergroup study N9741 provided data at baseline (bl) and every 12 weeks (wk) on overall QOL and fatigue (single-item numerical analogues), and total symptom distress (McCorkle Symptom Distress Scale [SDS]). TB was represented by actual tumor measurements (TM) and as an ordinal tumor response. A 10-point change on a 0–100 point scale was defined a priori as clinically meaningful in QOL-related variables. The sample size provided over 90% power to detect all but the smallest effect size (<0.1 Standard Deviation) for all statistical procedures involved, so p-values alone are of limited relevance. Results: We observed weak correlations among TM at bl and QOL (-0.07), fatigue (-0.18), and symptom distress (-0.14), indicating lack of any strong relationship. Changes from bl scores to 12 wk in TM were not associated with changes in QOL, fatigue, or symptom distress (correlations of -0.003, 0.06, and 0.05 respectively). Correlation between QOL and bl TM remained consistently low across subsets based on patient performance status and age. Concordance between patients reporting a tumor response and a clinically meaningful improvement at 12 wk in QOL, fatigue, or symptom distress was only 12.9%, 9.6%, and 11.9% respectively. Similarly, only 67.7%, 57%, and 59.7% of the patients reporting a clinically significant improvement in QOL, fatigue, and symptom distress had a tumor response. Conclusions: There was little evident relationship between the QOL-related variables and TB in these patients, suggesting that changes in TB have little impact on how the patient feels. These data raise questions about the value of tumor response as an endpoint with immediate clinical relevance for patients with advanced colorectal cancer (ACRC). No significant financial relationships to disclose.
New perspectives on metastatic patterns in lung cancer: The M. D. Anderson thoracic medical oncology database
Authors: Y. Oh, J. J. Lee, J. M. Hanneken, S. Liu, M. C. Camarillo, S. H. Taylor, S. M. Lippman, W. K. Hong, D. J. Stewart, D. D. Karp
Journal: Journal of Clinical Oncology (2007)

7630 Background: We previously reported a retrospective study suggesting that sites of metastatic disease characterize distinct prognostic groups with non-small cell lung cancer (NSCLC) (ASCO 2005 Abstract No: 7197). To confirm these observations, we prospectively evaluated pts with newly diagnosed NSCLC to correlate extent of disease with survival. Methods: We developed a prospective comprehensive database of 2,487 pts registered in the Thoracic Medical Oncology Department from 9/1/2004 - 8/31/2006, with up to 845 days follow-up. 694 were untreated stage IV NSCLC pts with data for ECOG performance status (PS), TNM staging, histology, identification of all metastatic sites, and survival. Results: Bone was the most common metastatic site, affecting 280 pts, 114 having bone only metastases (280/114). Similarly, the following results were found for lung (261/137), brain (143/46), adrenal (112/36), and liver (98/31). PS = 0 (101), PS = 1 (329), PS = 2 (103), PS = 3 (74), PS = 4 (10), PS = unknown (77). As of January 2007, median survival for the group was 8 months. By the Cox regression model, statistically significant effects on overall survival were seen for gender, smoking status, age, performance status, and number of metastases. The following hazard ratios [with 95% CI] of death were seen for males vs. females 1.41 ([1.13, 1.75], p = 0.0025), former smokers vs. non-smokers 1.66 ([1.18, 2.31], p = 0.0032), active smokers vs. non-smokers 1.79 ([1.21, 2.64], p = 0.0036), for one year increase in age 1.02 ([1.00, 1.03], p = 0.0046), for one unit increase in performance status 1.63 ([1.45, 1.82], p &lt; 0.0001) and for one unit increase in number of metastases 1.48 ([1.32, 1.66], p &lt; 0.0001). Pts with one metastatic site had superior survival over pts with more sites. Six of 10 metastatic sites were found to have significant independent effects on overall survival, based on log-rank test. Conclusions: Number and sites of metastases were strong independent determinants of survival in NSCLC. Furthermore, our work suggests marked heterogeneity of metastatic patterns at presentation. Pts with fewer metastatic sites demonstrate better survival. Future targeted therapy protocols should stratify according to metastatic sites to better analyze patterns of failure and outcomes. No significant financial relationships to disclose.
Impact of prognostic markers on outcomes in patients with advanced chronic lymphocytic leukemia treated with the regimen of fludarabine/rituximab plus oblimersen (Bcl-2 Antisense)
Authors: B. Mavromatis, K. Rai, P. K. Wallace, C. Soho, B. Landrigan, P. Meyn, T. Wei, K. K. Chan, A. Chanan-Khan
Journal: Journal of Clinical Oncology (2006)

6609 Background: Bcl-2, an anti-apoptotic protein is associated with treatment resistance and poor prognosis in pts with chronic lymphocytic leukemia (CLL). Preclinical studies have shown that oblimersen (Obl) enhances apoptosis induced by fludarabine (Flu) and rituximab (Rit). Increased CR and nPR in a phase 3 study confirmed the clinical benefit of combining Obl with a standard Flu+cyclophosphamide regimen in relapsed or refractory CLL pts. Similarly, in a phase 2 study, we found encouraging clinical activity when Obl was added to Flu/Rit. Here we report on outcomes related to baseline prognostic markers. Methods: All patients received Flu+Rit+Obl. Pts received Obl 1.5mg/kg/d, d1–7 by continuous IV, Rit (125 mg/m 2 on d4, 250 mg/m 2 on d6), and Flu 25mg/m 2 /d, d6–8 in the 1st cycle, and Obl 3mg/kg/d and Rit 375mg/m 2 on d5 only, plus Flu on d5–7 in later q28 d cycles. Baseline data were collected on baseline cytogenetics and expression of Zap-70 and CD38 expression. Results: In the initial cohort, 24 pts (19 PT, 5 UT) were treated. CD 38 over-expression, Zap-70 expression, and abnormal cytogenetics were common; normal karyotypes (NK) were observed in only 5 (3 UT, 2 PT) pts. Median number of Flu+Rit+Obl cycles was 6. Overall, 5/5 UT and 12/19 PT pts responded. Two molecular CRs were noted (by flow and IgV h gene analysis), including 1 UT (CD38+, NK) and 1 PT (13q deletion) that had been refractory to Flu+Rit+Obl. Three nPRs were noted (2 UT [both CD38 and Zap-70+; 1 trisomy 12; 1 NK], and 1 PT [13q deletion]). Two PRs were observed in pts refractory to Flu and Flu+Rit, respectively. Two PRs were observed in 2 pts with poor risk (11q-) cytogenetics. Overall, 8/10 CD38+ pts and 5/11 Zap-70+ pts responded. Conclusions: Flu+Rit+Obl is an active and tolerable regimen in CLL. Major responses were noted in Flu- and/or Rit-refractory pts. Activity is noted despite poor prognostic markers. Accrual is ongoing. Efficacy, safety, and Bcl-2 regulation data will be presented. [Table: see text] [Table: see text]
ARQ 197-215: A randomized, placebo-controlled phase II clinical trial evaluating the c-Met inhibitor, ARQ 197, in patients (pts) with hepatocellular carcinoma (HCC).
Authors: I. Borbath, A. Santoro, J. Van Laethem, B. Daniele, L. Cicalese, S. Zeuzem, P. Buggish, L. Bolondi, J. R. Strosberg, G. Abbadessa
Journal: Journal of Clinical Oncology (2010)

TPS215 Background: ARQ 197 is a selective, non-ATP competitive inhibitor of c-Met, the exclusive tyrosine kinase receptor for hepatocyte growth factor (HGF) implicated in tumor cell migration, invasion, proliferation, and angiogenesis. Overexpression of c-Met and HGF is associated with poor prognosis in patients with HCC. A previously reported phase I study (ASCO 2009 abstract 3523) demonstrated the safety, MTD, and PK of ARQ 197 monotherapy and this drug has now been evaluated as both monotherapy and in combination with other anti-cancer agents in over 300 cancer pts. A phase 1b study evaluating use of ARQ 197 in pts with HCC and cirrhosis revealed no worsening of liver function and preliminary evidence of both safety and efficacy. Methods: Pts are currently being enrolled into this global, randomized, double blind, placebo-controlled phase II clinical trial. Eligible pts must present with ECOG performance score <2, and have progressed to or not tolerated one prior line of systemic chemotherapy. Pts cannot present with Child-Pugh B-C cirrhotic status. Pts are being randomized in a 2:1 fashion to receive either 360 mg. oral ARQ 197 twice daily (bid) (A) or placebo (P) and are evaluated by CT or MRI scan at regular six-week intervals. Pts randomized to P are eligible for crossover to open label A following radiographic progression of disease (PD). The primary endpoint is time-to-tumor progression (TTP). Secondary objectives (or endpoints) include comparisons of the study arms for median progression-free survival (PFS), overall survival (OS), biomarker analyses, pharmacokinetics, and safety. Treatment continues until confirmed PD or unacceptable toxicity. As of 31 December 2009, 8 out of 99 required pts were enrolled and treated. Participating centers are located in Italy (8), Germany (5), Spain (5), Belgium (3), Canada (2) and the United States (2). This trial is expected to complete enrollment by the fall of 2010. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ArQule
Quality of life and exercise capacity in lung transplant recipients with and without sleep-disordered breathing
Authors: Frederike Kruse, Bjoern E. Kleibrink, Thomas Rabis, Yi Wang, Gerhard Weinreich, Markus Kamler, Helmut Teschler, Urte Sommerwerck
Journal: European Respiratory Journal (2014)

Background   The prevalence of sleep disordered breathing (SDB) is high in patients after lung transplantation (LTX). It is well-established that SDB is associated with decreased health related quality of life (HRQL). In contrast, findings of SDB impact on exercise capacity (EC) are conflicting. This study therefore aimed to compare HRQL and EC in LTX patients with and without SDB.   Methods   Full in-lab polysomnography (PSG) was performed in 53 stable LTX recipients (≥6 months after LTX) according to AASM standards. We compared the non-SDB group (apnea-hypopnea index(AHI)   Results   There was a negative correlation between AHI and sleep efficiency (r=-0.23, p=0.02). No significant correlation was found between the AHI and sleep efficiency and the 6MWT. In CPE Pmax predicted correlated inversely with the AHI (r=-0.2, p=0.04). Peak O2 uptake predicted correlated inversely with the AHI (r=-0.3, p=0.03) and positively with sleep efficiency (r=0.2, p=0.08). In general, SF36 domains did not differ between SDB and non-SDB patients.   Conclusion   SDB in LTX recipients is associated with a diminished maximal EC. In patients with and without SDB we found no meaningful difference in HRQL measures.
A phase II study of bevacizumab, docetaxel and oxaliplatin in gastric and gastroesophageal junction (GEJ) cancer
Authors: B. F. El-Rayes, N. Hammad, P. A. Philip, A. F. Shields, L. K. Heilbrun
Journal: Journal of Clinical Oncology (2008)

15608 Background: VEGF (vascular endothelial growth factor) has a central role in angiogenesis, tumor growth, and metastasis. VEGF expression is increased in gastric cancer. Inhibition of VEGF results in impaired growth and metastasis of gastric cancer in preclinical models. Bevacizumab, an anti-VEGF monoclonal antibody, has demonstrated anti-tumor activity in multiple diseases. This phase II study was undertaken to determine the effects of adding bevacizumab to a regimen of docetaxel and oxaliplatin. Methods: The primary endpoint was time to progression (TTP) in patients with locally advanced or metastatic adenocarcinoma of the stomach or GEJ treated with docetaxel, oxaliplatin and bevacizumab. Previously untreated patients with a performance status (PS) of 0–1 were eligible for this study. Patients received bevacizumab 7.5 mg/kg, docetaxel 70 mg/m2, and oxaliplatin 75 mg/m2 administered on day 1 of a 21 day cycle. Results: A total of 8 patients (median age 44, males 75%, gastric 50%) were enrolled on the study. Median PS was 1. Partial responses were documented in 4 patients and stable disease in 4. No treatment related deaths were observed. The most commonly reported grade 3–4 toxicities were neutropenia (38%), fever (13%), acute neuropathy (13%), and hypertension (13%). One hospitalization was for neutropenic fever. Gastrointestinal (GI) perforation occurred in 2 patients after the second cycle. Perforation was not found at the tumor site in the patient who required surgery. The site of perforation could not be ascertained in the second patient who was managed medically. Both patients had had no prior surgical resection of the primary tumor. For now the study is accruing one patient at a time until a total of 10 to ensure patient safety. Conclusions: The regimen of docetaxel, oxaliplatin and bevacizumab appears to be very active. The development of GI perforations in 2 patients was of concern. At this time, bevacizumab should not be used in gastric or GEJ cancers outside of a clinical trial until its safety is well established. No significant financial relationships to disclose.
Radiation morbidity and micronuclei in lymphocytes of prostate cancer patients
Authors: T. Lee, R. R. Allison, K. F. O’Brien, A. L. Wiley, R. M. Johnke, W. Wang
Journal: Journal of Clinical Oncology (2007)

15540 Background: Since formation of micronuclei (MN) in interphase cells is a reflection of DNA damage, it has been postulated that enhanced peripheral blood lymphocytes (PBL) radiosensitivity might correlate with the development of radiation morbidity. Methods: We conducted the cytokinesis-block (CB) MN assay of PBL in 54 prostate cancer (PC) patients ( mean age ± SEM: 68 ± 1.6 yrs) who had no previous exposure to cytotoxic agents. Patients received standardized pelvic radiotherapy (RT) (41.4 -50.4 Gy) with mean follow-up of 29.1± 3.3 mos. Blood samples were drawn before RT and at designated intervals after RT initiation. Gastrointestinal (GI) and genitourinary (GU) morbidity were determined using RTOG criteria. Results: Average reactors (AR, n = 14) were defined as patients who did not develop morbidity. Grade 1 (G1R, n = 19) and Grade 2 reactors (G2R, n = 21) were defined as those who developed Grade 1 or Grade 2 GI or GU morbidity, respectively. Results of the MN yield in PBL before RT indicated that (1) at baseline level (0 Gy), differences in MN yield for AR, G1R, and G2R patients were insignificant; (2) after ex vivo irradiation (1 - 4 Gy), MN yield followed a linear-quadratic polynomial trend in AR, G1R, and G2R patients; and (3) differences in MN yield in AR vs. G1R or AR vs. G2R patients were significant (P = 0.0001). After the initiation of RT, MN yields in PBL at 24 h, one week, and six weeks, the ratio of relative increment (RI) of RT-induced MN yield, i.e. MN RI = MN (RT-induced) - MN (pre-RT)/ MN (pre-RT) in both G1R and G2R patients was significantly higher than that in AR patients. Our results suggest that prediction of GI or GU morbidity in patients is potentially possible through the evaluation of both ex vivo radiation dose-response relationship of MN in PBL before the initiation of RT and the in vivo MN RI after RT. No significant financial relationships to disclose.
Evaluating 2-chlorodeoxycytidine for its novel mechanism as a DNA methylation inhibitor
Authors: M. K. Yu, M. Wade, F. A. Fitzpatrick
Journal: Journal of Clinical Oncology (2004)

3125 Background: Many tumor suppressor genes are silenced by epigenetic alterations of CpG islands in the promoter regions. A clinical example of this is seen in colorectal cancer. Although the adenomatous polyposis coli gene is frequently somatically mutated in colon carcinoma, methylation of the adenomatous polyposis coli gene is seen in early colon adenomas. Thus, epigenetic silencing of tumor suppressor genes may play a role in the progression of colon polyps to carcinomas. Further, reactivation of critical tumor suppressor genes in carcinomas may decrease chemotherapy resistance. 5'-aza-deoxycytidine is a DNA methyltransferase inhibitor. This drug has problems of DNA mutagenesis. We are evaluating 2-chlorodeoxycytidine for its inhibitory properties of s-adenosylhomocysteine hydrolase. Since s-adenosylmethionine is the only source of methyl donor for all mammalian methyltransferases, we can indirectly inhibit DNA methylation by depleting s-adenosylmethionine. Methods: A growth inhibition experiment is done comparing HT-29 cells treated with 2-chlorodeoxycytidine and cells treated with vehicle. This time point is then used for future experiments. Genomic DNA is isolated and digested with a methylation sensitive restriction enzyme. Methylation sensitive endonuclease digested DNA will be amplified by real time polymerase chain reaction to assess for promoter methylation. We will next evaluate global methylation level of the genome using HPLC. We have also performed microarray on vehicle and treated samples. The effect of 2-chlorodeoxycytidine compared to 5'-aza-deoxycytidine on gene expression is evaluated. Results: 300 nM 2-chlorodeoxycytidine inhibits cell proliferation within 48 hours. Many known genes silenced by methylation, including genes in the interferon pathway, were upregulated by at least 2 fold after 48 hours of 2-chlorodeoxycytidine. Conclusion: 2-chlorodeoxycytidine, a known adenosine deaminase inhibitor, also may indirectly inhibit DNA methylation, reactivating critical tumor suppressor genes in various malignancies. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration US NIH (grant# R01 NS044417–01)