tbuckley/cabot-search huggingface dataset:
HER2 as a prognostic factor in metastatic breast cancer treated with taxanes.
Authors: E. Parkes, S. M. McKenna, J. J. McAleer, J. Clarke, A. J. Clayton, C. R. James
Journal: Journal of Clinical Oncology (2010)

1150 Background: Metastatic breast cancer (MBC) is incurable. Palliative chemotherapy treatment prolongs survival and taxanes are among the most active agents used. HER2 overexpression is associated with poorer overall survival. The development of the HER2 targeted monoclonal antibody, trastuzumab, resulted in greatly improved outcome for patients with HER2 overexpressing MBC patients in clinical trials. We sought to evaluate outcomes of taxane chemotherapy in our patients and also the implication of HER2 overexpression. Methods: We carried out a retrospective analysis of patients who were referred to breast cancer specialist clinics within the Belfast City Hospital between January 2003 and December 2005. We identified all patients who received a taxane based regimen as palliative chemotherapy for MBC. Results: A total of 77 patients (7.3% of overall number) received taxane based palliative chemotherapy for MBC. Thirty-four (44.2%) were ER+/HER2, 24 (31.2%) were triple negative (TN) and 19 (24.7%) were HER2-positive (and so received docetaxel/trastuzumab). Median age was 48.3 years (range 29-68). Median times from original diagnosis of breast cancer to taxane treatment for MBC were similar in all 3 groups. Median overall survival from the start of taxane based treatment was 14.6 months for ER-positive/HER2-negative patients, 8.0months for TN patients and 36.8 months for HER2-positive patients (p=0.004). Median overall survival from time of diagnosis was 35 months (ER-positive), 27.5 months (TN) and 72.5 months (HER2-positive). Conclusions: Trastuzumab in combination with taxane-based chemotherapy has greatly improved clinical outcomes for patients with HER2 overexpressing metastatic breast cancer. However, it is recognized that these patients were treated before the use of adjuvant taxanes and trastuzumab became standard of care. In taxane- and trastuzumab-naïve patients who are fit enough for chemotherapy HER2 can be regarded as a good prognostic factor. No significant financial relationships to disclose.
A phase I/II study of OGX-011 and a gemcitabine (GEM)/platinum regimen as first-line therapy in 85 patients with advanced non-small cell lung cancer
Authors: J. J. Laskin, D. Hao, C. Canil, C. W. Lee, J. Stephenson, M. Vincent, B. Gitlitz, S. Cheng, N. R. Murray
Journal: Journal of Clinical Oncology (2007)

7596 Background: OGX-011 is a second-generation antisense oligonucleotide designed to knockdown expression of the cytoprotective chaperone, clusterin, thereby facilitating apoptosis and sensitization of many human cancer cell-lines to chemotherapy. Methods: Eligibility criteria: stage IIIB/IV NSCLC; no prior chemotherapy; =1 measurable lesion; ECOG =1; adequate organ function; no active CNS metastasis. Treatment: infusion of OGX-011 initial loading doses (3 in 1 week), followed by weekly OGX-011 with standard chemotherapy: GEM (1,250 mg/m 2 ) Days 1+8 and either cisplatin (75 mg/m 2 ) or carboplatin (AUC=5) Day 1 q21 days, (maximum 6 cycles). Results: 85 pts (phase I=10 and phase II=75) enrolled between Dec 04 and Nov 06. Based on phase I results, dose of OGX-011 was 640 mg. Data is available on the first 53 pts; all received =1 dose of OGX-011 and were considered evaluable for safety and efficacy. Demographics: female (47%); stage IV (87%); median age 61 (45–79) yrs; ECOG PS =1 (62%); median no. of cycles delivered was 4. Principal grade 3/4 toxicities were hematologic: neutropenia (32%) + thrombocytopenia (17%). Other common toxicities included fatigue, nausea, vomiting, fever, chills, constipation, + anorexia. Two serious adverse events previously reported as associated with GEM/platinum therapy were documented: acute cortical blindness with stroke + thrombotic thrombocytopenic purpura. Responses: 12 confirmed PR (ORR = 23%). Median PFS is 101 days (53–260+). Of the first 24 patients who have all been followed for =1 yr, median survival is 383 days (19–751+); 14/24 (58%) survived &gt;1 yr; 10/14 remain alive as of 12/13/06. Conclusions: 1-yr survival rate =50% may justify a phase III randomized trial. Survival data on 46 pts followed for =1 yr will be presented. OGX-011 is being developed by OncoGenex Technology Inc. + Isis Pharmaceuticals Inc. No significant financial relationships to disclose.
A phase I study of the addition of weekly oxaliplatin to weekly gemcitabine during radiotherapy for unresectable pancreatic or biliary malignancies
Authors: B. H. O’Neil, A. W. Blackstock, R. M. Goldberg, H. Shearer, H. K. Sanoff, M. Aklilu, S. Bernard, J. Martinie, H. J. Kim, J. E. Tepper
Journal: Journal of Clinical Oncology (2007)

15008 Purpose: Locally advanced pancreatic cancer (LAPC) leads to a poor survival, and current therapies are inadequate. External beam radiotherapy (EBRT) has been used to obtain local control, but the most effective systemic agent, gemcitabine(gem), can be used only at low doses with standard RT. Oxaliplatin (ox) has activity in PC, and has been delivered safely at doses near full systemic doses with EBRT for rectal cancer. We set out to define the maximum tolerated dose (MTD) of ox in combination with gem + upper abdominal EBRT. Methods: Patients (pts) with LAPC or biliary ca were eligible. Prior systemic therapy was allowed. A 3 + 3 design was employed with 4 dose levels (table). Gem + ox was given once weekly. EBRT was given in 1.8 Gy fractions to 50.4 Gy using a multi-field technique. DLT was defined as any grade 4 tox or grade 3 tox resulting in treatment delay &gt; 1 wk. Results: 11 pts have completed therapy (Table). 10 pts had LAPC, 1 had ampullary ca. No pts in the first 2 cohorts had DLT. Pt #3 in cohort 3 had DLT (grade 3 elevated liver enzymes). Cohort 3 was expanded; patients 4 and 5 in the cohort have completed therapy without DLT; pt 6 is not yet evaluable. To date, 43 grade 3 toxic events have occurred in 11 evaluable patients. No grade 4 toxicities have occurred. The most common grade 3 tox are: nausea (63%), metabolic (54%), hyperglycemia (45%), neutropenia (36%), vomiting (27%). SD was best radiographic response in 8 of 8 evaluable pts. One patient with ampullary ca had regression of disease from vessels and was resected, but had positive retroperitoneal margin and died of a post-operative complication. Five pts have died (OS 2.6–12.2 mos). Median OS is currently 9 mos (95% CI 4.6, 12.3). Conclusions: Weekly oxaliplatin can be given safely with weekly gemcitabine (200 mg/m2) during EBRT for LAPC. The ox MTD in this combination is not yet defined, but is at least 30 mg/m2 weekly. Final dose results and updated efficacy results will be presented at the meeting. [Table: see text] [Table: see text]
Neoadjuvant gemcitabine/cisplatin for resectable adenocarcinoma of the pancreatic head—a prospective phase I trial
Authors: S. Heinrich, B. Pestalozzi, M. Schafer, T. Hany, P. Bauerfeind, A. Perren, A. Knuth, P. Clavien
Journal: Journal of Clinical Oncology (2007)

15095 Background: Pancreatoduodenectomy (PD) alone was considered a standard treatment for cancer of the pancreatic head for a long time before the recent advent of adjuvant chemotherapy (CTX). Since adjuvant chemotherapy cannot be applied to all patients (pts), and neoadjuvant chemoradiation is toxic, we initiated a prospective phase II trial in August 2001 to test the safety and outcome of neoadjuvant CTX without radiation for resectable pancreatic cancer. Methods: Pts with cytologically confirmed resectable ductal adenocarcinoma of the pancreatic head were eligible for this phase II trial. Staging and restaging examinations included chest and abdominal CT-scan, endoscopic ultrasound with cytology, PET/CT and diagnostic laparoscopy. CTX consisted of four treatments of gemcitabine (1000mg/m 2 ) and cisplatin (50mg/m 2 ) every two weeks, and PD was planned at week 8. CA 19–9, prealbumin serum levels, and quality of life (QLQ- 30) were also determined before and after CTX. The primary study end-point was resectability based on re-staging examinations. Follow-up CT- scans were performed every six months. Results: Thirty-one pts entered this trial. Of these, 27 completed CTX and restaging until analysis. At restaging two pts had peritoneal metastases resulting in a resectability rate of 93% (25/27). No grade IV, and 7 transient grade III toxicities occurred in five pts. Median progression-free and overall survival after diagnosis were 9.2 months (95% CI 7.7–10.8) and 26.5 months (95% CI 15.2–37.7), respectively, for resected pts. After CTX, CA 19–9 serum levels were decreased by 48% (p=0.01). Moreover, the overall quality of life was increased by 24% (p=0.02). Prealbumin serum levels were abnormal in 40% of the pts on study entry, and normal in all but 89% after CTX (p=0.02). Conclusions: Neoadjuvant gemcitabine/cisplatin over two months is well tolerated and does not jeopardize resectability of adenocarcinoma of the pancreatic head. It offers several advantages including patient selection for surgery, improvements in the nutritional status and quality of life. A randomized trial comparing adjuvant and neoadjuvant+adjuvant treatment is being planned. No significant financial relationships to disclose.
Phase II trial of thalidomide in combination with irinotecan in adults with recurrent glioblastoma multiforme
Authors: V. K. Puduvalli, P. Giglio, M. D. Groves, K. R. Hess, E. Jackson, S. Mahankali, M. Gilbert, V. A. Levin, C. Conrad, S. Hsu, W. K. A. Yung
Journal: Journal of Clinical Oncology (2005)

1524 Background: Rationally designed combination chemotherapy can potentially improve the prognosis of patients with recurrent GBM. In this study, the efficacy of thalidomide and irinotecan against recurrent GBM was tested to assess if synergistic activity of cytotoxic and antiangiogenic agents could affect clinical outcome. Methods: In this ongoing phase II study, patients with recurrent GBM with a KPS≥70 and less than three relapses after radiation therapy and chemotherapies are eligible for entry; the total planned enrollment is 32 patients. Patients are placed on low dose daily warfarin (1 mg) for prevention of thrombosis. Non-enzyme-inducing anticonvulsants are mandated for those needing anti-seizure therapy. Irinotecan is administered at 125 mg/m2 weekly for 4 weeks followed by 2 weeks rest; thalidomide is initiated at 100 mg daily and escalated weekly up to 400 mg daily. Patients undergo clinical and radiologic evaluations every 6-weeks. The primary endpoint is progression free survival at 6 months (PFS-6). To determine possible radiologic correlates to treatment effects, DCE- MR perfusion-imaging studies are obtained at baseline and subsequent follow-up visits. Results: Of the 26 evaluable patients enrolled to date, 24 have adequate follow up, the majority of whom have failed temozolomide or nitrosourea therapy. Median age is 48 years and median KPS is 90. Five patients are alive and progression free at 6-months whereas 16 have progressed with a median TTP of 14 weeks (95% CI: 11, Not Reached). The PFS-6 is 28% (13%, 60%). The best response was a PR in one patient and stable disease in 15. No treatment related deaths have been noted. There have been 3 deaths among the 26 patients with a 6-month survival by Kaplan Meier analysis being 82% (66%, 100%]). Grade 3 and 4 toxicities included fatigue, constipation, diarrhea, leukopenia, and typhilitis requiring dose reductions. Imaging data (DCE-MRI) and their correlation to clinical response will be presented. Conclusions: The results of this ongoing study suggest that the combination of irinotecan and thalidomide has promising activity in patients with recurrent glioblastomas following alkylator therapy and may warrant further assessment in this population Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis, Schering-Plough EMD, Novartis, Pfizer, Schering-Plough Celgene, Genentech, Novartis, Pfizer, Pfizer Oncology (oringially Pharmacia), Schering-Plough
Male breast cancer in Chinese population
Authors: D. Suen, A. Kwong
Journal: Journal of Clinical Oncology (2008)

22167 Objective: Breast cancer is uncommon in men, occurring in 1% of the male population based on Western data. There is limited knowledge about the natural history and prognosis of male breast cancer in Chinese population. This study aims to perform a 10 year review of the clinical presentation and outcome of male breast patients in Hong Kong. Methods: A retrospective study of patients with male breast cancer treated in Hong Kong from January 1995 to December 2005 was performed. Results: A total of 54 male breast cancers were treated in eight hospitals during this 10 year study period. The mean age at diagnosis was 66.9 years old. Of those where family history was known, only 7.7% had a family history of breast cancer. 48 (88.9%) of these patients were known to have undergone a mastectomy (6 unknown) of which 31.3% also had axillary dissection performed. 85.4% of these were invasive carcinoma of which 1 was invasive lobular carcinoma, 2 were mucinous carcinoma, 5 were invasive papillary carcinoma and the rest were invasive ductal carcinoma. 14.6% were in-situ carcinomas, where 3 were intraductal papillary carcinoma and the rest were ductal carcinoma in-situ. Of the invasive tumors, 64.5% were classified as Grade II and above. 34.4% of these patients had nodal involvement and the most common stage of presentation were either Stage 1 (37.5%) or Stage 2 (41.7%). Majority of the tumors were oestrogen (91.8%) and progesterone (78%) receptor positive and 56% were cerbB2 positive. Where treatment data was available, all patients with ER positive tumors except for 1 patient received tamoxifen. 18.2% received adjuvant chemotherapy and 41.7% received radiation therapy. The mean follow up was 55.9 (2–178) months. The 2 year- vs. 5-year disease free and overall survival were 92.0% and 80.5% vs. 65.3% and 69.6% respectively. Interestingly 10 patients also had a second primary cancer not of breast origin. Conclusions: Male breast cancer in Chinese men is rare and present at an older age but at an early stage (Stage 1 and 2). Although a majority of our cohort did not have family history of breast cancer, there was a high incidence of second primary cancer not of breast origin. Further investigation with genetic study in this group of patients is likely to be of relevance. No significant financial relationships to disclose.
Final results of a phase I study of idelalisib (GSE1101) a selective inhibitor of PI3Kδ, in patients with relapsed or refractory CLL.
Authors: Jennifer R. Brown, Richard R. Furman, Ian Flinn, Steven E. Coutre, Nina D. Wagner-Johnston, Brad S. Kahl, Stephen Edward Forbes Spurgeon, Don M. Benson, Sissy Peterman, David Michael Johnson, Daniel Li, Roger D. Dansey, Thomas Michael Jahn, John C. Byrd
Journal: Journal of Clinical Oncology (2013)

7003 Background: Signals through PI3K-delta regulate activation, proliferation and survival of B cells, critically influence homing and retention of B cells in lymphoid tissues, and are hyperactive in many BEcell malignancies. Idelalisib (GS-1101) is a first-in-class, selective, oral inhibitor of PI3Kδ that reduces proliferation, enhances apoptosis, and inhibits homing and retention of malignant B cells. Methods: Pts with relapsed/refractory CLL were treated continuously with single-agent oral idelalisib from 50E350 mg/dose (QD or BID). Response evaluated by investigators per Hallek (2008) and Cheson (2012). Results: 54 pts (9F/45M) median (range) age 63 (37E82) years enrolled with: bulky lymphadenopathy (80%), refractory disease (70%), extensive prior therapies (median: 5, range: 2E14), unmutated IgHV (91%), del17p and/or TP53 mutation (24%), del11q (28%), NOTCH1 mutation (17%). The median (range) exposure was 9 (0E41+) months. 25 (46%) pts completed the primary study, 23 (43%) enrolled into an extension study. ORR was 30/54 (56%, 2 CR, 28 PR). Of the 28 PR, 22 met Hallek (2008) and 6 met PR with lymphocytosis Cheson (2012). 44/54 (81%) showed a lymph node response (≥50% reduction in the nodal SPD). 21/54 were SD and 3/54 NE. The median (range) time to first response was 1.9 (0.9-12.9) months. Median PFS was 17 months and median DOR was 18 months. Idelalisib treatment resulted in resolution of splenomegaly (14/20, 70%) and normalization of cytopenias: anemia (17/25, 68%); thrombocytopenia (27/34 79%), neutropenia (15/15, 100%). Most common AEs independent of causality (any Grade/≥Gr 3) included fatigue (31%/2%), diarrhea (30%/6%), pyrexia (30%/4%), rash (22%/0%), upper respiratory tract infection (22%/0%), pneumonia (20%/19%). 2% of pts had ≥Gr 3 ALT/AST elevation. 15% of pts discontinued due to AEs, 7% potentially treatment-related. There were no dose-limiting toxicities. Conclusions: Idelalisib shows substantial clinical activity and a favorable safety profile in heavily pretreated, refractory and highErisk pts with CLL. Phase 3 trials with idelalisib in combination with rituximab or bendamustine/rituximab are ongoing. Clinical trial information: NCT01539512, NCT01569295.
A Randomized, Double-Blind, Placebo-Controlled Study With Pegylated Recombinant Human Megakaryocyte Growth and Development Factor (PEG-rHuMGDF) as an Adjunct to Chemotherapy for Adults With De Novo Acute Myeloid Leukemia
Authors: Eric Archimbaud, Oliver G. Ottmann, John A. Liu Yin, Klaus Lechner, Herve Dombret, Miguel A. Sanz, Gerhard Heil, Pierre Fenaux, Wolfram Brugger, Alan Barge, Caroline O’Brien-Ewen, James Matcham, Dieter Hoelzer
Journal: Blood (1999)
A phase II study of ABT-869 in hepatocellular carcinoma (HCC): Interim analysis
Authors: H. Toh, P. Chen, B. I. Carr, J. J. Knox, S. Gill, J. Steinberg, D. M. Carlson, J. Qian, Q. Qin, W. Yong
Journal: Journal of Clinical Oncology (2009)

4581 Background: ABT-869 is a novel orally active, potent and selective inhibitor of the vascular endothelial growth factor and platelet derived growth factor families of receptor tyrosine kinases. Results of an interim analysis of a phase 2 trial of ABT-869 in HCC are presented. Methods: An open-label, multicenter phase II trial (M06–879) of oral ABT-869 at 0.25 mg/kg daily in Child-Pugh A (C-PA) or QOD in Child-Pugh B (C-PB) patients (pts) until progressive disease (PD) or intolerable toxicity, is ongoing. Key eligibility criteria included unresectable or metastatic HCC; up to one prior line of systemic treatment; and at least one measurable lesion by computed tomography (CT) scan. The primary endpoint was the progression free (PF) rate at 16 weeks. Secondary endpoints included objective response rate (ORR), time to progression (TTP), progression free survival (PFS) and overall survival (OS). CT scans were assessed centrally and by the investigators; presented results are from central assessment. Results: 44 pts were enrolled from 09/07 to 08/08 at 6 centers internationally, with interim data available for 34 pts. There were 28 C-PA pts (median age, 63.5 y [range, 20- 81]) and 6 C-PB pts (median age, 64.5 y [range, 36–69]) and 73.5% received no prior systemic therapy. For the 19 evaluable C-PA pts included in the per-protocol interim analysis, 8 (42.1%) were progression free at 16 weeks [95% CI 20.3, 66.5]. The estimated ORR was 8.7% [95% CI, 1.1, 28] for the 23 C-PA pts and 0% for the 2 C-PB pts who had at least one post-baseline CT scan reviewed by central imaging. For all 34 pts, median TTP was 112 d [95% CI, 110, -], median PFS was 112 d [95% CI, 61, 168] and median OS was 295 d [95% CI, 182, 333]. The most common adverse events (AEs) for all pts were hypertension (41%), fatigue (47%), diarrhea (38%), rash (35%), proteinuria (24%), vomiting (24%), cough (24%) and oedema peripheral (24%). The most common grade 3/4 AEs for all pts were hypertension (20.6%) and fatigue (11.8%). Most AEs were mild/moderate and reversible with interruption/dose reductions/or discontinuation of ABT-869. Conclusions: ABT-869 appears to benefit HCC patients, with an estimated TTP of 112 days and an acceptable safety profile. Updated results from this ongoing study will be presented. [Table: see text]
Unexpected dermatologic toxicities from anticancer therapies: Survivors’ perspectives
Authors: M. Gandhi, C. Calahan, K. Oishi, M. Lacouture
Journal: Journal of Clinical Oncology (2009)

e20673 Background: As oncologic therapies have shown improved survival, there is a growing attention to other aspects of the cancer experience from the survivors’ perspectives. Gastrointestinal, constitutional, and dermatologic toxicities are frequently experienced and further study of their impact is important to prevent inconsistent antineoplastic drug administration. This study is aimed to evaluate survivors’ perceptions of unexpected toxicities. Methods: CancerCare, a national nonprofit organization, mailed 1,369 surveys to cancer survivors completing their treatment. The survey divided into two sections asked patients to rate their concern about dermatologic, gastrointestinal, and constitutional toxicities prior to and after therapy completion. Toxicities were also rated on a 1 to 10 scale based on their negative impact. Results: 379 survivors responded to the survey, yielding a 28% response. Of those 379, 250 (66%) were diagnosed with breast cancer. The remaining 127 (33%) had ovarian, lung, colorectal, prostate, bladder, kidney, or other malignancy. Prior treatments included: chemotherapy, radiation, surgery, targeted therapies, or any combination of the preceding. The most frequently unanticipated events carrying a negative impact were dermatologic: dry skin and skin irritation. Following were constitutional (insomnia and fatigue) and gastrointestinal toxicities (diarrhea and constipation). Before undergoing treatment, skin irritation was concerning to 40%. After treatment, 80% reported concern and 47% were negatively impacted. Dry skin prior to treatment was concerning to 34%, and 79% were concerned after having undergone therapy. In retrospect, 44% reported that having dry skin caused a negative impact. Gastrointestinal and constitutional toxicities were also examined, and overall, respondents’ level of concern remained largely unchanged pre and post treatment. Conclusions: Dermatologic toxicities are least anticipated by the cancer patients prior to their treatments, when compared to gastrointestinal and constitutional events. Since dermatologic toxicities have a negative impact on survivors’ lives, pre-therapy counseling and effective interventions are crucial, in order to maximize quality of life. [Table: see text]