tbuckley/cabot-search huggingface dataset:
Phase II study of bavituximab plus paclitaxel and carboplatin in locally advanced or metastatic breast cancer: Interim results.
Authors: M. Jain, N. Raizada, R. Kuttan, J. Shan, R. Digumarti
Journal: Journal of Clinical Oncology (2010)

1062 Background: Bavituximab, a chimeric IgG1 monoclonal antibody against the membrane phospholipid, phosphatidylserine complexed with β2-glycoprotein I on tumor vasculature, was tested in combination with paclitaxel and carboplatin in a multicenter, open label, phase 2 trial in adults (n=46) with locally advanced or metastatic breast cancer. Methods: Subjects received intravenous administration of weekly doses of 3 mg/kg bavituximab until disease progression and up to 6 cycles of carboplatin at a dose of AUC=2 and paclitaxel 100 mg/m2 on days 1, 8, and 15 of a 28 day cycle for up to 6 cycles in a Simon 2-stage design. Tumor response was determined by use of the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Results: 46 Asian (India) female subjects median age 52 yrs (range 30-73 yrs) were treated. Prior treatment included surgery in 24 pts (52%), chemotherapy in 17 (37%), and radiation therapy in 12 pts (26%). Overall response rate (CR+PR) was 9/15 (60%, 95% CI, 32.3-83.7%) in the initial group of 15 subjects. To date, in the initial cohort, the median progression-free survival (PFS) is 5.6 mos. (95% CI, 5.5-10.8). Median duration of response and median overall survival are pending as follow-up is continuing. AEs have been reported by 43/46 (93.5%) treated patients which were mostly mild to moderate. The 6 most common AEs have been neutropenia (60.9%), leukopenia (43.5%), pain in extremity (34.8%), asthenia (32.6%), pyrexia (30.4%), anemia (28.3%). Safety analysis revealed 45 SAEs in16 subjects (incl grade 3 arterial thromboses in one subject). Conclusions: Bavituximab, a unique phosphatidylserine targeting monoclonal antibody which is capable of inducing immune enhancement (He, et al., Clin Cancer Res 2009) and immune cell-mediated destruction of tumor vasculature appears to be safe and well tolerated when given in combination with paclitaxel and carboplatin and has produced a promising 60% overall response rate in an initial group of subjects using RECIST criteria for locally advanced or metastatic breast cancer. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Peregrine Pharmaceuticals Peregrine Pharmaceuticals Peregrine Pharmaceuticals Peregrine Pharmaceuticals Peregrine Pharmaceuticals
Clinical experience with carboplatin (CBDCA) and oral vinorelbine (NVBO) in first-line advanced non-small cell lung cancer (NSCLC) treatment.
Authors: S. Garcia Adrian, J. Firvida, D. Marrupe, M. Salgado, E. Perez Lopez, F. J. Perez, M. Mendez
Journal: Journal of Clinical Oncology (2010)

e18143
Relationship between dialysis schedule and day-of-week association with mortality in the dialysis outcome and practice patterns study (DOPPS)
Authors: Hui Zhang, Douglas E. Schaubel, John D. Kalbfleisch, Jennifer L. Bragg-Gresham, Bruce Robinson, Ronald L. Pisoni, Bernard Canaud, Michel Jadoul, Takashi Akiba, Akira Saito, Rajiv Saran
Journal: Journal of the American Society of Nephrology (2008)
Phase II trial of neoadjuvant bevacizumab (BEV), capecitabine (CAP), and radiotherapy (XRT) for locally advanced rectal cancer
Authors: C. H. Crane, C. Eng, B. W. Feig, P. Das, J. M. Skibber, G. J. Chang, R. A. Wolff, S. Krishnan, D. M. Maru, L. M. Ellis, M. A. Rodriguez-Bigas
Journal: Journal of Clinical Oncology (2008)

4091 Background: Anti-VEGF therapy may lead to enhanced tumor response or increased toxicity in patients treated with neoadjuvant chemoradiation. We designed a phase II trial to assess the efficacy and safety of BEV with neoadjuvant CAP-based chemoradiation in locally advanced rectal cancer. Methods: Between April 2004 and December 2007, 25 patients EUS/CT staged T3/N1 (19) or T3 N0 (6) rectal cancer were treated with neoadjuvant XRT (50.4 Gy in 28 fractions over 5.5 weeks using a posterior 3-field technique), BEV intraveneously every 2 weeks (5 mg/kg for 3 doses), and CAP 900 mg/m2 PO twice daily only on days of radiation (Monday through Friday). Surgical resection followed a median of 7.3 weeks (range 5.9–11) after the completion of chemoradiation. Results: Eight of 25 patients (32%) had pathologic complete response (pCR), and 6/25 (24%) had <10% viable tumor cells in the specimen. Overall sphincter preservation (SP) rate was 18/25 (72%). Procedures included abdominoperineal resection (APR, 6), proctectomy with coloanal anastamosis (8), and low anterior resection (10). All patients with SP underwent initial diverting iliostomy. With a median FUof 22.1 months (range 3.3–30.5), all patients are alive, there has been one pelvic recurrence (2 yr actuarial rate 7%) and 3 distant recurrences. No patient had grade 3 HFS or gastrointestinal (GI) toxicity; CAP was held for greater than 2 days in 4 patients and the dose was reduced by 25% in 3 patients for grade 2 HFS, fatigue or GI toxicity. There was no significant hematologic toxicity, ATEs or DVTs. There were three wound complications that required surgical intervention (one coloanal anastamostic dehiscence requiring completion APR, and two perineal wound dehiscences after initial APR). Five minor complications that resolved without operative intervention (2 delayed perineal wound healing, 2 anastomotic leaks and a superficial wound infection). Conclusions: The addition of BEV to neoadjuvant chemoradiation resulted in encouraging pCR and local tumor control rates without an increase in acute toxicity. The risk of perineal wound complication due to concurrent BEV and the timing of surgery requires further study. Supported by Genentech, Inc. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech Genentech, Roche Genentech
A clinical study investigating MPC-6827 with carboplatin in the treatment of patients with relapsed glioblastoma multiforme.
Authors: K. F. Grossmann, J. H. Ward, W. L. Akerley, M. J. Glantz, J. F. De Groot, R. Aiken, J. J. Olson, Y. Matsuoka, M. K. Yu, R. L. Jensen
Journal: Journal of Clinical Oncology (2010)

2095 Background: MPC-6827 (Azixa; 4-arylaminoquinazoline) is a microtubule destabilizing agent that achieves high brain concentrations. MPC-6827 disrupts newly formed blood vessels in xenografts. We determined the safety and tolerability of MPC-6827 administered in combination with carboplatin. Methods: Three preselected doses of MPC-6827 were tested: 2.1, 2.7, and 3.3 mg/m2 in a standard “3 + 3” design. MPC-6827 was given as a 2-hr IV infusion every 2 of a 6 wk cycle in the 2.1 mg/m2 cohort or 3 wks of 4 in subsequent cohorts. Carboplatin was administered IV at AUC 4 every 2 wks for the cohort receiving 2.1 mg/m2 of MPC-6827 (n = 8) or on Day 1 of each 4 wk cycle for the 2.7 mg/m2 (n = 3) and 3.3 mg/m2 dose levels (n = 8). Patients were observed for acute DLTs during the first cycle. PK evaluations were performed. Results: As of December 7, 2009, 19 patients (median age, 51, range, 21-75; median number of prior therapies, 2, range 1-4) in first or second relapse were enrolled in the study. Fourteen patients (74%) had one lesion. Sixteen patients (95%) had a Karnofsky performance score greater than 70. All patients had previously received the Stupp regimen. Three patients (15.7%) experienced a grade 3 or greater MPC-6827 or carboplatin-related adverse event, including pyrexia (5.3%), transient ischemic attack (TIA) (5.3%), and thrombocytopenia (5.3%). The TIA occurred at the 3.3 mg/m2 dose level and was the only MPC-6827-related SAE and DLT at this dose level. The grade 4 thrombocytopenia occurred in a patient receiving carboplatin on the every 2 wk schedule. The median plasma half life of MPC-6827 was 3.22 hrs (range 2.04-9.03). Two subjects achieved a partial response in this study (duration 7.5 mos and at least 4.3 mos) by Macdonald criteria. Another 6 patients achieved stable disease (duration range 1–7 mos). The median progression-free survival time was 1.8 mos (95% CI: [1.3, 7.1]). Data collection is ongoing. Conclusions: The combination of MPC-6827 at 3.3 mg/m2 with carboplatin in patients with recurrent/refractory GBM is safe and well tolerated. In this patient population with a highly vascularized tumor, no incidence of cerebral hemorrhage has been reported. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Myriad Pharmaceuticals Myriad Pharmaceuticals Myriad Pharmaceuticals
Dasatinib (BMS354825), a dual Src-Abl inhibitor, is active in Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+CML) following treatment failure with imatinib mesylate and AMN107
Authors: Z. Estrov, S. O’Brien, F. Giles, G. Garcia-Manero, G. Borthakur, F. Ravandi, I. Sams, C. Nicaise, H. Kantarjian
Journal: Journal of Clinical Oncology (2006)

6530 Background: Dasatinib is a dual Src-Abl kinase inhibitor which is 300 fold more potent than imatinib and 20-fold more potent than AMN107 (a selective potent Bcr-Abl kinase inhibitor). Dasatinib also inhibits Src which may overcome CML resistance. Methods: Study Aims: To report the experience with dasatinib in patients who develop CML failure post AMN107. Patients and Methods: All patients on the ongoing dasatinib studies at our institution were reviewed for prior therapy/response to AMN107 and outcome on imatinib. Results: 16 patients with Ph+CML following treatment failure with AMN107 received dasatinib. All patients had previously shown hematologic resistance to imatinib. AMN107 failure was due to hematologic resistance in all 16 pts. Median age was 60 years (range 22 to 76 years); median follow-up on dasatinib is 3 months (range &lt;1 to 9 months). CML phase was chronic in 2, accelerated in 6, blastic in 6, and second chronic/accelerated in 2. Abl mutations were found in 7/16 patients before dasatinib therapy: G250E+F359L, G250E, Y253F, Y253H, H396R (1 patient each), T315I (2 patients). All patients received dasatinib 70 mg orally BID (n = 10), 140 mg single daily dose (n = 5), or 120 mg orally BID (n = 1). Responses were observed in 5 of 7 patients with mutations including 4/4 with P loop mutations and 1/2 with other mutations; the 2 patients with T315I had resistant disease. Conclusions: Dasatinib is active in patients with CML resistant to both imatinib and AMN107. [Table: see text] [Table: see text]
Altered gene expression of IL-6 and rennin in colonic biopsies from collagenous colitis and ulcerative colitis compared to healthy controls
Authors: H. Strid, Ashok Kumar Kumawat, Curt Tysk, Elisabet Hultgren Hörnquist, J. Bohr
Journal: Gut (2011)

Altered gene expression of IL-6 and rennin in colonic biopsies from collagenous colitis and ulcerative colitis compared to healthy controls
Short- and long-term safety with sunitinib in an expanded access trial in metastatic renal cell carcinoma (mRCC)
Authors: C. Porta, C. Szczylik, S. Bracarda, R. Hawkins, G. A. Bjarnason, S. Oudard, S. Lee, G. Carteni, S. Hariharan, M. E. Gore
Journal: Journal of Clinical Oncology (2008)

5114 Background: Sunitinib malate is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs and PDGFRs that has demonstrated substantial antitumor activity in the first- and second-line mRCC settings (JAMA 2006;295:2516; NEJM 2007;356:115). Here, we present an analysis of safety for patients (pts) with < 6 months (“short term”) and ≥ 6 months (“long term”) of sunitinib use in an ongoing, international, open-label expanded access trial in first- and second-line mRCC. Methods: The purpose of this trial was to provide sunitinib prior to regulatory approval to mRCC pts without access to study drug due to trial ineligibility or other reasons; thus, eligibility criteria were minimized to broaden enrollment. Pts ≥18 yrs with histologically-confirmed mRCC received sunitinib 50 mg orally, once-daily in 6-wk cycles (4 wks on treatment, 2 wks off). Results: As of December 2007, 4,616 pts had been enrolled, with data available for 3,997 pts. Of those pts with data, 1,913 (48%) were short-term and 2,084 (52%) were long-term, with 1,880 pts (47%) having discontinued. Of 2,117 pts who remained on study, 25% of short-term pts had treatment-related adverse events (AEs), compared with 69% of long-term pts; while 12% and 39%, respectively, had grade 3 or 4 treatment- related AEs. 13% of short-term pts discontinued due to AEs compared with 8% of long-term pts, suggesting a lack of cumulative serious toxicity. For ongoing pts on sunitinib, selected grade 3 or 4 treatment-related AEs included nausea (in <1% and 1% of short- and long-term pts, respectively), mucosal inflammation (<1% and 2%), diarrhea (1% and 4%), and fatigue (2% and 6%). Transient laboratory grade 3 or 4 AEs, such as thrombocytopenia (2% and 6%) and neutropenia (<1% and 5%), may have contributed most to the overall increased incidence of grade 3 or 4 AEs in long-term pts. Of note, the incidence of grade 3 or 4 cardiac disorders remained the same (≤1%) regardless of treatment duration or trial status. Conclusions: As expected, advanced RCC pts on sunitinib for a longer duration experienced a comparative increased frequency in overall incidence of AEs. However, serious toxicity was not cumulative, nor was there an apparent increase in grade 3 or 4 cardiac disorders. No new or unexpected long-term toxicities were identified. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Inc Bayer, GlaxoSmithKline, Pfizer, Pfizer Inc, Roche, Schering-Plough, Wyeth Pfizer Inc Pfizer, Pfizer Inc Bayer, Pfizer Pfizer
A phase I, pharmacokinetic (PK), and pharmacodynamic (PD) study of the farnesyl transferase inhibitor (FTI) R115777 in combination with weekly paclitaxel in patients (pts) with advanced solid cancers
Authors: A. Patnaik, A. C. Mita, E. Izbicka, G. Carrizales, A. Howes, M. Troenaru, A. W. Tolcher, S. Zhang, K. Berg, E. K. Rowinsky
Journal: Journal of Clinical Oncology (2004)

3136 Background: R115777 (tipifarnib, ZARNESTRA), an oral methyl quinolinone selectively inhibits farnesyl transferase, a critical enzyme in several cell signal transduction pathways. The preclinical synergism of FTIs with taxanes and the antitumor activity of R115777 in breast cancer provided the rationale for evaluating this regimen. Methods: Pts received escalating doses of weekly paclitaxel (1 hr on days 1, 8 & 15 every 4 weeks) and a fixed dose of R115777 (200 mg po BID) administered for 21 days followed by 7 days rest. This study also sought to evaluate whether inhibition of protein farnesylation could be detected using the chaperone protein HDJ2 as a PD surrogate of effect in peripheral blood mononuclear cells (PBMCs). Results: Thus far, 15 pts stratified by prior myelotoxic therapy into heavily (HP) and lightly pretreated (LP) cohorts (median age 57 [range 32–77], males/females-5/10) have received a total of 75 courses [range 1–14 per pt] at dosages of 60, 75, 80 and 90 mg/m2 of paclitaxel. At 90 mg/m2 of paclitaxel DLTs occurred in 2 HP pts (febrile neutropenia, grade 3 diarrhea/fatigue) and in 1 LP pt (febrile neutropenia). Non-dose-limiting neutropenia (grade 3), stomatitis, fatigue, diarrhea, and rash, have also been observed. Preliminary PK analysis of paclitaxel (with/without R115777) in 8 pts at 60 and 75 mg/m2 shows no significant difference in Cmax or AUC, when performing a paired analysis of individual pt parameters. The mean trough R115777 concentration following repeated doses was 211 ng/mL. The proportion of unfarnesylated HDJ2 increased with treatment in 5/5 evaluable pts at 75 and 90 mg/m2 of paclitaxel. Two HP pts (1 with breast, 1 with squamous cell skin cancer) remain on study with stable disease (SD) at 14 and 8 courses, respectively. Further treatment of HP/LP pts continues at 80 mg/m2 and 90 mg/m2of paclitaxel, respectively. Conclusions: The combination of R115777 and paclitaxel appears safe and feasible, with biologically relevant concentrations of R115777 and evidence of consistent inhibition of protein farnesylation in PBMCs. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Johnson and Johnson Pharmaceutical Research and Development Johnson and Johnson Pharmaceutical Research and Development Johnson and Johnson Pharmaceutical Research and Development Johnson and Johnson Pharmaceutical Research and Development
The value of multi-marker reverse transcriptase-polymerase chain reaction (MM RT-PCR) assay in lymphatic drainage (LY) and peripheral blood (BL) for molecular staging of melanoma patients (pts) after lymph node dissection (LND)
Authors: W. Ruka, Z. I. Nowecki, P. Rutkowski, J. Kulik, E. Lorenc, A. Nasierowska-Guttmejer, Z. Zurawski, M. Zdzienicki, J. A. Siedlecki
Journal: Journal of Clinical Oncology (2006)

8053 Background: We assessed the presence of melanoma cells in LY and BL in melanoma pts after LND with MM RT-PCR assay for the evaluation of disease outcomes. Methods: Between 05/2002 and 06/2005 we collected 24-hr LY in 207 stage III melanoma patients after radical LND (91 - completion LND after positive sentinel node biopsy - CLND and 116 - therapeutic LND for clinically/cytologically detected regional lymph node (LN) metastases - TLND). In 101 pts (since 02/2004) we have simultaneously collected a 5 ml sample of BL. In order to detect melanoma cells, RT-PCR assays with primers specific for tyrosinase, MART1 (MelanA) and uMAGE mRNA were applied. The drain fluid or BL sample was assumed to be positive if the presence of at least 1 marker was detected in the assay. Median follow-up time for survivors was 13 months (range: 4 - 39 months). Results: The LY MM RT-PCR assay results were positive in 57/207 pts (27.5%) - in 13 for tyrosinase only, in 17 for MART1 only, in 10 for uMAGE only, in 13 for a combination of the two markers and in 4 simultaneously for all three markers. We observed a significantly higher rate of recurrences in pts with positive LY MM RT-PCR results (44/57 cases; 77%) than in those with negative results (72/150 cases; 48%; p=0.0004). Positive results of the LY MM RT-PCR correlated with established predictive factors: the number of involved lymph nodes (p=0.03), extracapsular extension of LN metastases (p=0.004) and type of LND (CLND vs. TLND; p = 0.0004). We observed a significant relationship between positive LY MM RT-PCR results and shorter overall (OS) and disease free survival (DFS), both in univariate and multivariate analyses. In 107 pts, in whom the LY and BL MM RT-PCR assays were analyzed concurrently, we found positive results of the LY RT-PCR assay in 33 cases (32.7%) and the BL RT-PCR assay in 24 cases (23.7%) (17 of these positive results were detected in both tests), but longer follow-up time is necessary to perform a survival analysis in this group. Conclusions: We observed positive results of MM RT-PCR assay for melanoma cells in approximately 28% of LY after LND, which correlated significantly with early melanoma recurrences and shorter survival. No significant financial relationships to disclose.
Depression, anxiety and world assumptions amongst cancer patients
Authors: L. Pishniak, A. Ashkenazi, D. Sadeh-Tassa, Y. Yagil, A. Figer
Journal: Journal of Clinical Oncology (2004)

8197 Background: The term ‘World assumptions’ (WA) refers to beliefs by which one defines his/her own identity and coping strategies. Psychologists have been interested in the association between depression, anxiety and WA. It was even suggested that anxiety and depression can be treated by mainly focusing on altering dysfunctional beliefs. The aim of the current study was to investigate which beliefs are associated with anxiety and depression amongst cancer patients. Methods: We conducted a convenience sampling with 69 female breast cancer patients, and 68 colorectal cancer patients (33 males, 35 females), aged 35–85, treated in 3 urban medical centers in Israel. Measurements were made using the world assumptions scale and the brief symptoms index. Results: In our sample, anxiety and depression were both found to be significantly more severe among breast cancer patients than in colorectal patients. Breast cancer patients also reported more dysfunctional world assumptions. A Pearson correlation procedure showed a significant association between some of the world assumptions and anxiety and depression. Conclusions: Since we conducted an uncontrolled field study, our findings can be explained in several ways. For examle, participants in our study were treated in distinct medical settings. This can account for at least some of the differences we found. Still, our results indicate that breast cancer patients are more prone to suffer from psychological distress, in addition or as a result of their disease. We also found that negative or rigid world assumptions, expressed by cancer patients in a regular medical examination, need to be perceived by health professionals as a possible indication for an underlying psychological distress. Finally, since some of the WA were associated with depression and anxiety, brief cognitive psychotherapy can be tested for achieving rapid psychological relief. No significant financial relationships to disclose.
Evaluation of the protective effects of zoledronic acid on bone mass in premenopausal women undergoing adjuvant chemotherapy following treatment discontinuation
Authors: D. L. Hershman, D. McMahon, K. D. Crew, T. Shao, S. Cremers, L. Brafman, D. Awad, E. Shane
Journal: Journal of Clinical Oncology (2009)

562 Background: Adjuvant chemotherapy is associated with a significant reduction in bone mineral density (BMD) in premenopausal women with breast cancer (BC). We previously showed that this loss of BMD can be prevented with zoledronic acid (ZA) every 3 months for a year. Since bone loss in women with osteoporosis is prevented with annual ZA, we examined whether protection from bone loss by ZA in women with BC persists following discontinuation of ZA. Methods: A randomized, double-blind, multicenter, phase III trial comparing ZA (4 mg every 3 months) versus placebo for 1 year in premenopausal women with BC undergoing adjuvant chemotherapy was conducted. Patients had serial BMD measurement at 0 (after surgery and before chemotherapy), 6, 12 and 24 months. Demographic, clinical, and tumor characteristics were collected. Serum was stored at -70°C and analyzed in batches. The secondary outcome of percent change in BMD at 24 months, one year following the last ZA/placebo, is presented. Intention-to-treat analyses with linear mixed models were performed using SAS version 9. Results: Of 101 patients randomized, 85 completed 12 month, and 62 completed 24 month evaluations; mean age 41 (SD 5.2). Demographic and baseline characteristics were similar between treatment groups. By 24 months, 38 (61%) had not regained their menses; 22 patients were on tamoxifen, 25 were on an aromatase inhibitor. Chemotherapy without ZA was associated with a significant decline from baseline in lumbar spine (LS) BMD after both 12 (-5.4%) and 24 (-6.3%) months. Similarly total hip (TH) and femoral neck (FN) BMD declined by 2.6% and 2.4% by 24 months, respectively. In contrast, BMD remained stable in ZA-treated patients (p &lt; 0.0001 vs placebo). Patients who received ZA had stable BMD at 24 months (LS -0.58%, TH 0.83%, FN 0.04%). Analysis of bone turnover markers is ongoing. Conclusions: Premenopausal women receiving adjuvant chemotherapy for BC had significant bone loss in the first year that persisted in the second year. ZA every 3 months for a year effectively prevented bone loss during the first year and 1 year after completion of ZA treatment. One year of ZA maintains BMD in premenopausal BC patients for an additional year after discontinuation of ZA. [Table: see text]