tbuckley/cabot-search huggingface dataset:
A multicenter phase II study of volociximab in patients with relapsed metastatic melanoma
Authors: J. Barton
Journal: Journal of Clinical Oncology (2008)

9051 Background: Preclinical studies demonstrate that the α5β1 integrin antibody volociximab inhibits tumor angiogenesis by blocking binding of activated endothelial cells to fibronectin present in the extracellular matrix, thereby inducing apoptosis and inhibiting tumor growth. Methods: Nineteen eligible patients (median age 60 years; PS 0–1; 8 women, 11 men) with biopsy-accessible metastatic melanoma who had failed at least one prior systemic therapy were enrolled into a non-randomized, two-stage, phase 2 study. Eighteen patients had stage IV disease, 17 had prior chemotherapy (1–8 regimens) and 9 had prior biological therapy. Volociximab was administered at 15 mg/kg weekly until progression. The primary endpoint was progression free survival at week 8 assessed by RECIST criteria, and advancement to the second stage of the study required ≥9 of 15 patients to be progression free. Baseline and 4 wk post-treatment tumor biopsies were obtained and analyzed by immunohistochemistry and molecular profiling. Results: Among 19 evaluable patients, there was one confirmed partial response of 4 months duration, two subjects with stable disease (3 months and ongoing > 3 months) and 16 patients with progressive disease by week 8. Predominantly mild or moderate adverse events were observed in eighteen patients with the most common being gastrointestinal, mainly nausea/vomiting/diarrhea, in 13 subjects (68%) and fatigue in 10 (53%). Neutropenia was not observed. One serious adverse event of anemia and thrombocytopenia reported in a 56 year-old woman was deemed possibly related to treatment with volociximab. Analysis of 13 paired biopsies was consistent with localization of volociximab to tumor tissue. Association of tumor cell integrin expression with response is being investigated, along with histologic and molecular profiling studies of paired biopsies to define markers relevant to the biologic activity of volociximab. Conclusions: Weekly volociximab was well tolerated but demonstrated insufficient clinical activity to proceed to the second stage of the trial. Ongoing candidate and discovery-based biomarker studies provide an opportunity to identify molecular characteristics that may define a responsive patient subset. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration BioGen IDEC BioGen IDEC
Randomised, double blind, placebo-controlled, multi-centre, group-sequential trial of G17DT for patients with advanced pancreatic cancer unsuitable or unwilling to take chemotherapy
Authors: A. D. Gilliam, E. G. Topuzov, A. M. Garin, I. Pulay, P. Broome, S. A. Watson, B. Rowlands, A. Takhar, I. Beckingham
Journal: Journal of Clinical Oncology (2004)

2511 Background: Pancreatic adenocarcinomas express CCK-2 receptors and respond to amidated gastrins resulting in transcriptional activation of EGF receptor ligands, matrix metalloproteinases and anti-apoptotic factors which collectively increase tumorigenic potential. The gastrin gene may also be activated resulting in gly-gastrin secretion. G17DT, a gastrin immunogen, induces neutralising antibodies against amidated and glycine-extended gastrin-17. Methods: Randomised, double blind, placebo-controlled, multi-centre trial of patients with advanced pancreatic cancer unsuitable or unwilling to take chemotherapy, performed outside the US. Inclusion criteria were Karnofsky performance score (KPS) ≥60, life expectancy >2 months. Patients received G17DT or the vehicle only at weeks 0, 1, 3, 24 and 52. Primary endpoint was survival; secondary endpoints included tolerability, KPS, weight change, quality of life and tumour response. Results: 154 patients: 79 randomised to G17DT, 75 to placebo. Intention to Treat (ITT) analysis gave median survival of 151 vs 82 days, G17DT:placebo, (p=0.03, Log rank). Time to deterioration of Karnofsky index was longer in the G17DT group than placebo: median 138 (95% CI: 84–165) vs 78 days (95% CI: 56–97) (p=0.038, Wilcoxon). G17DT was well tolerated; 2/79 (2.5%) G17DT patients vs 0/74 (0%) placebo patients developed sterile abscess at the injection site. Conclusion: G17DT prolongs survival, maintains performance and provides a well tolerated new therapeutic option for advanced pancreatic cancer patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aphton Corp. Aphton Corp. Aphton Corporation
Tissue confirmation of disease recurrence in patients with breast cancer: Pooled analysis of two large prospective studies.
Authors: E. Amir, M. Clemons, O. C. Freedman, N. Miller, R. E. Coleman, C. Purdie, L. Jordan, P. Quinlan, A. M. Thompson
Journal: Journal of Clinical Oncology (2010)

1007 Background: Decisions about systemic treatment of recurrent breast cancer are usually based on the estrogen (ER), progesterone (PgR), and HER2 receptor status of the primary tumor. Two recent prospective studies have investigated discordance in receptor status between the primary tumor and recurrent disease and assessed the impact of this on patient management. Methods: Individual patient data from the UK BRITS and Canadian DESTINY studies were pooled. In both these studies, biopsies of recurrent lesions were prospectively obtained from consenting patients and analyzed for ER, PgR by immunohistochemistry and HER2 by immunhistochemistry and FISH. Receptor status of recurrent disease was compared to the primary tumor. Recruiting clinicians assessed whether or not receptor discordance affected subsequent systemic treatment. Results: 258 patients underwent biopsy. The mean age was 60.1 years (range 27-87). Recurrent biopsy specimens were obtained from locoregional recurrence in 54% and from distant metastases in 46%. The most common sites of distant recurrence biopsy were bone (25%), liver (24%), skin (15%), bone marrow (11%), paracentesis (9%), soft tissue (6%), lung (6%), and other (4%). Discordance in ER, PgR, or HER2 between the primary and recurrent disease were 13%, 28%, and 5% respectively. Gain or loss of receptor expression was equally prevalent for ER and HER2, but for PgR loss of receptor was more common than gain (76% vs. 8%). There was no receptor discordance among triple negative primary tumors. Biopsy results altered management in 15.9% of patients (95% CI 11.7-20.9%, p=<0.0001). The duration between primary and recurrent disease, number of prior lines of therapy, and site of recurrence did not affect discordance rates. Conclusions: This is the largest prospective analysis of ER, PgR, and HER2 in matched primary and recurrent breast cancer and demonstrates substantial discordance in receptor status. The number needed to biopsy to alter immediate patient management was 6.3. Patients with recurrent breast cancer should have tissue confirmation of receptor status of recurrent disease. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca
Efficacy and safety of FOLFIRINOX in patients with metastatic pancreatic cancer.
Authors: Jean Philippe Metges, Jean François Ramée, Jean-Yves Douillard, Eveline Boucher, Roger Faroux, Veronique Guerin-Meyer, Isabelle Cumin, Laurent Miglianico, Catherine Le Roux, Olivier Dupuis, Marc Porneuf, You Heng Lam, Nacredine Achour, Pierre-Luc Etienne, Oana Cojocarasu, Stephane Corbinais, Philippe Deguiral, Guillaume Geslin, Loic Campion, Francoise Grude
Journal: Journal of Clinical Oncology (2014)

305 Background: FOLFIRINOX, one of the gold standard in metastatic pancreatic cancer as first-line therapy for patients under 76 years with PS 0-1, good haematological and renal function and a subnormal bilirubin level (Prodige 4 criteria), was analysed in Brittany (B) and Pays de la Loire (PL) in routine clinical practice. Methods: Our aim is to evaluate the use of Folfirinox between July 2010 and December 2012 in B/PL. Results: Data of 340 patients have been studied (198 men, median age 63 years [29-81]). 208 patients were metastatic at diagnosis (liver 67%). 62 primary tumors were resected and 51 patients had received previous adjuvant chemotherapy (gemcitabine, n=48). The median progression free survival PFS and overall survival OS were respectively 6.80 months IC95% [6.18-7.43] and 10.97 months IC 95% [9.56-11.83]. Patients could be divided into 4 groups : Group 1 composed of patients treated according to Prodige 4 trial (n=242), Group 2 1 st line metastatic patients with at least one Prodige 4 non-eligibility criterion (n=25), Group 3 locally advanced patients (n=59) and Group 4 by Folfirinox in 2 nd line (n=14). The median number of cycles was 9 [1-27] in Group 1 and 6 [1-12] in Group 2. Clinical benefit was 65% (group 1) vs 56% (group 2). During treatment, 81% of patients had a dose adjustment (Group 1) vs 72% (Group 2) and 32% vs 40% presented grade III/IV toxicity (mostly neuro- or haematotoxicity). Median PFS were respectively in Group 1 vs Group 2 : 6.54 months IC95% [5.98-7.29] vs 4.14 [1.68-6.21] (p=0.0107) and median OS :10.91 months IC 95% [8.94-12.02] vs 7.0 IC95% [4.01-11.20] (p=0.0166). For Group 3 and 4, median OS were respectively 11.24 months [10.0-15.01] vs 11.50 [4.83-14.09]. Others results will be shown at the meeting. For Group 1, stopping treatment before progression induced significatively better median PFS and OS than going on treatment until progression : PFS : 8.25 IC95[7.52-8.74] vs 3.48. IC95 [3.09-4.44] (p&lt;0.0001) and OS : 12.78 months IC95 [11.60-15.54] vs 7.62 IC95 [6.44-9.49] (p&lt;0.0001). Conclusions: Our results for Group 1 are relatively consistent with those of Prodige 4: objective response rate (39% vs 32%), PFS (6.5 vs 6.4 months) and OS (10.9 vs 11.1 months). Non eligibity for Prodige 4’s criteria decreases PFS and OS significantly.
Telomere length in pleural fluid is not different between malignant and benign effusions
Authors: K. B. Sriram, Relan, B. E. Clarke, E. E. Duhig, M. N. Windsor, K. S. Matar, R. Naidoo, L. Passmore, E. McCaul, D. Courtney, I. A. Yang, R. Bowman, K. M. Fong
Journal: Journal of Thoracic Oncology (2012)
A phase II trial of a biweekly schedule of capecitabine (X) plus irinotecan (I) as first-line treatment in patients (pts) with metastatic colorectal cancer (MCRC)
Authors: P. Garcia-Alfonso, G. Perez-Manga, M. C. Gonzalez, P. Lopez, E. Gonzalez, J. Belon, M. Molina, V. Pachon, L. Iglesias, I. Siso
Journal: Journal of Clinical Oncology (2005)

3540 Background: Standard 3-weekly X+I (XELIRI regimen) has been shown to be highly active and well tolerated as first-line therapy in MCRC. We conducted a phase II study to evaluate the efficacy and safety of a novel biweekly XI regimen in previously untreated pts with MCRC. Methods: Eligible pts had histologically confirmed, measurable locally advanced or MCRC, measurable disease, ECOG PS ≤2 and adequate bone marrow, renal and hepatic functions. Previous adjuvant chemotherapy was allowed if completed ≥6 months before study enrollment. Pts received irinotecan 175mg/m2 d1 as a 90-min i.v. infusion and X 1000mg/m2 bid orally d2–8. For pts >65 years, doses were reduced to 140mg/m2 and 750mg/m2 bid, respectively. Cycles were repeated every 2 wks until progressive disease, unacceptable toxicity or withdrawal of consent. Results: : 45 pts were enrolled: M/F (78%/22%); median age 67 years (range 42–80). 25 pts (56%) were >65 years. ECOG PS 0–1 (93%). Primary tumor sites were colon (51%), rectum (47%) or both (2%). Median number of metastatic lesions was 2 (29% with ≥2 sites), with the most common sites being the liver (56%), and lung (23%). Previous treatment included surgery (73%), adjuvant chemotherapy (44%) and radiotherapy (20%). To date, 408 cycles (median 10, range 2–12) have been administered. Median relative dose intensity was 94% for capecitabine and 99.5% for irinotecan. All pts were evaluable for safety (see table). 38 pts are evaluable for efficacy: ORR was 50% (95% CI, 33–67%) and tumor growth control (RR + SD) was seen in 87% of pts (95% CI, 72–96%). Conclusions: The biweekly X+I schedule is a highly active first-line treatment for locally advanced or MCRC with a manageable toxicity profile in both pts ≤65 and >65 years of age. No significant financial relationships to disclose.
Cytokine expression profiles of patients with acute myelogenous leukemia (AML) and non-Hodgkin lymphoma (NHL) detected by multiplex assay
Authors: V. B. Reddy, D. K. Oelschlager, J. S. Nolan, K. L. Taylor, J. Post, W. E. Grizzle, U. Manne
Journal: Journal of Clinical Oncology (2007)

18530 Background: To determine the cytokine expression profiles of patients with AML and NHL using a sensitive bead-based Luminex multiplex assay in a routine clinical diagnostic setting. Methods: Blood (plasma/serum) samples were collected from ten AML and five NHL patients. Six control samples from patients diagnosed as non-neoplastic/non-autoimmune/non-inflammatory were also analyzed for comparison. All samples were frozen prior to analysis. Using a bead-based Luminex assay (Human Cytokine 8-Plex Assay, Bio- Rad, Hercules, CA) we analyzed these samples for a panel of cytokines (IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma, and TNF-alpha). This assay uses polystyrene microspheres, which provides simultaneous quantitation of these cytokines in a single sample. The expression levels were presented in picograms/mL. Average values for each of these markers were obtained for each group of patients (AML versus NHL versus Controls), and their expression levels were compared using χ2 analysis. Results: Overall, there was a significant difference in the expression profiles of all these cytokines among three patients groups (χ2, P &lt; 0.001). All cytokines were consistently expressed at low levels in NHL patients as compared to control group. However, the levels of IL-6 and IL-8 were increased by 2.7 and 5.8 times, respectively in AML patients as compared to controls. Conclusions: The low levels of cytokines in NHL and AML patients suggest suppressed immune system in these two disease conditions; however, these findings warrant further studies to explore the underlying mechanisms for the increased levels of IL-6 and IL-8 in AML patients. Currently, studies are in progress to compare the levels of cytokines measured by Luminiex assay in different stages of leukemias and lymphomas (initial, post treatment and recovery phase etc.). These studies are partially funded by grants from the National Institute of Health/National Cancer Institute (RO1-CA98932–01 and U24-CA086359). No significant financial relationships to disclose.
Early and late complications among long-term colorectal cancer survivors with and without ostomy
Authors: L. J. Herrinton, L. Liu, M. C. Hornbrook, M. Grant, C. S. Wendel, S. J. Coons, M. J. Mohler, C. M. Baldwin, E. Z. Matayoshi, S. B. Green, R. S. Krouse
Journal: Journal of Clinical Oncology (2008)

15012 Background: Most colorectal cancers are treated with major surgical procedures, often requiring a permanent intestinal stoma. The differences in long-term complications are not known based on the procedure required. We compared the risk of early and late complications among long-term survivors of colorectal cancer (CRC) with and without a permanent ostomy. Methods: The analysis included members of Kaiser Permanente Northern California who survived 5 years or longer following their cancer diagnosis in 1976–1999. Ostomy patients were compared to controls who had comparable surgical treatment without ostomy. Cases and controls were matched on cancer site (rectum, rectosigmoid junction, colon), time since diagnosis, age, and sex. Current health-plan members in 2002–2005 who participated in a survey during this time were eligible. Complications selected a priori were ascertained from computerized clinical data using ICD-9 codes for the immediate post-operative period (30 days post surgery) and longer. The hazard ratio (HR) and 95% confidence interval (CI) for the risk of complication comparing ostomates to controls was estimated using Cox proportional hazards modeling. Results: Ostomates (n=207) and controls (n=252) were included, half of whom were followed for 10 years or longer. Complications directly related to stomas were 5.3% during the immediate post-operative period and 18.4% longer term. Significant differences between groups for the risk of long-term complications included anorectal abscess (HR 2.8, CI 1.1–6.8), enterocutaneous fistula (HR 1.9, CI 1.0–3.5), intestinal obstruction (HR 1.5, CI 1.1–2.0), urinary retention (HR 1.4, CI 1.0–2.2), impotence (HR 1.5, CI 1.0–2.3), and ureteral obstruction (HR 9.1, CI 2.2- 37.1). Conclusions: Treatment-related complications are significantly greater in CRC survivors who have intestinal stomas. Our results demonstrate the importance of peri-operative discussions, post-operative planning, and long-term follow-up of this population. No significant financial relationships to disclose.
A phase I study of bevacizumab (B) with fluorouracil (F) and hydroxyurea (H) with concomitant radiotherapy (X) (B-FHX) for poor prognosis head and neck cancer (HNC)
Authors: T. Y. Seiwert, D. J. Haraf, E. E. Cohen, K. Stenson, A. M. Mauer, A. Dekker, C. Bajda, R. R. Weichselbaum, H. X. Chen, E. E. Vokes
Journal: Journal of Clinical Oncology (2006)

5530 Background: Increased VEGF levels are found in HNC. Preclinical data suggest synergistic antitumor activity of B with radiation and chemotherapy. We conducted a Phase I dose escalation study to determine the maximum tolerated dose and dose limiting toxicity (DLT) of B, when added to infusional 5-FU, Hydroxyurea (HU), and daily radiotherapy administered every other week in patients (pts) with poor prognosis HNC. Methods: Eligible pts had recurrent, or newly diagnosed HNC with high risk of recurrence, ± metastatic disease requiring local control, ECOG PS ≤2, and life expectancy &gt;12 weeks. Two week cycles were repeated 6–7 times (see table ). Results: 43 pts were treated (34 completed). DLT was reached at level 3 with 2 pts having gr 3 transaminase elevations and one pt gr 4 neutropenia. Treatment of 7 (6 evaluable) pts on level 4 resulted in one DLT (SMV thrombosis) and this dose level was chosen for expanded evaluation. In all level 4 pts (N = 27) gr 3 mucositis occured in 73.1% and gr 3 hand-foot syndrome in 15.4%. Additional gr 3 or worse toxicities in the expanded level 4 included: esophageal bleed (tumor bed, grade 5), stroke (grade 4), carotid rupture (3 wks post RT, grade 5), and neck ulceration with need for carotid stent (3 months post RT, grade 4). One sudden death of unclear etiology occurred. Median overall survival is 389 days. One/two year survival is 52.1/26%. Median survival for patients treated with re-irradiation for recurrent, non-metastatic HNC is 314 days; one/two year survival is 45.9/17.2%. With a median follow-up of 317 days 13 patients are still alive (12 are cancer free). Conclusions: B can be integrated with FHX chemoradiotherapy at a dose of 10 mg/m 2 every 2 weeks. While B related toxicities are seen, there appears to be no major synergistic toxicity. Long term activity is observed in this very high risk patient population. A randomized phase II trial of FHX with or without B in a lower risk population is ongoing. [Table: see text] No significant financial relationships to disclose.
Phase I pharmacokinetic and safety analysis of epothilone folate (BMS-753493): First-in-human clinical experience of a folate receptor-targeted chemotherapeutic agent administered on days 1, 4, 8, and 11 of a 21-day cycle.
Authors: M. J. De Jonge, S. Sleijfer, L. P. Martin, J. Marshall, J. F. Deeken, L. A. Konner, C. Aghajanian
Journal: Journal of Clinical Oncology (2010)

2607 Background: The high-affinity folate receptor alpha is selectively overexpressed in some epithelial tumors, including ovarian, endometrial, renal, and breast carcinomas, and in a few nonepithelial neoplasms. BMS-753493, a folate conjugate of epothilone analog BMS-748285, was designed to target folate receptor-expressing tumor cells. Methods: BMS-753493 was investigated in two parallel first-in-human phase I/II studies in subjects with advanced solid cancers. These studies differed only in dosing schedule. Both studies dosed 4 times every 21 days and followed a 3+3 open-label dose escalation scheme during phase I. CA190-001, discussed here, dosed once daily on days 1, 4, 8, and 11, while CA190-002 (companion abstract) dosed once daily on days 1-4. Results: Phase I escalated 5 cohorts to 33 mg. At 33 mg, three dose-limiting toxicities (DLTs) were observed, one each in 3 of 4 patients treated. The first DLT consisted of grade 2 ALT elevation resulting in omission of two doses. The second DLT consisted of grade 3 diarrhea. The third DLT consisted of grade 3 esophagitis. The 26 mg cohort was expanded to confirm the maximum tolerated dose, and one DLT (skipping day 4 and 11 doses due to Grade 2 AST elevation) was observed among 7 subjects treated as of December 2009. The most common related AEs were fatigue, diarrhea, nausea, vomiting, anorexia, and ALT/AST elevations. Although no complete or partial responses occurred, target lesion shrinkage up to 18% from baseline was observed. Plasma exposures (Cmax and AUC) of BMS-753493 and BMS-748285 on Day 1 and Day 4 increased in a dose-related manner in the dose range of 5 to 33 mg. All data are preliminary. Conclusions: At the doses and schedules tested, BMS-753493 demonstrated at best moderate activity with manageable toxicity. Pharmacokinetic data: BMS-753493, day 4 Dose (mg) N Cmax (ng/mL)GeoMean (CV%) AUC(0-T) (ng*h/mL) GeoMean (CV%) 5 3 583 (23) 232.3 (14) 10 4 1,343 (32) 642.4 (38) 17 6 2,427 (30) 1,409.3 (32) 26 3 3,892 (27) 2,467.5 (46) 33 3 3,914 (23) 2,919.9 (4) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb