tbuckley/cabot-search huggingface dataset:
Systematic comparative analysis of efficacy of EGFR tyrosine kinase inhibitors (TKIs) in the frontline versus salvage therapy of NSCLC.
Authors: T. K. Owonikoko, M. Behera, H. N. Tran, Z. Chen, R. P. Chowdry, N. F. Saba, S. S. Ramalingam, F. R. Khuri
Journal: Journal of Clinical Oncology (2011)

7602 Background: Randomized trials showed equivalent overall survival outcome for patients treated with EGFR TKIs or standard cytotoxic chemotherapy in the frontline setting. The best sequence of administration of these agents has become uncertain. We conducted a systematic review of published clinical trials of EGFR TKI in the frontline setting versus later settings. Methods: Published trials of erlotinib or gefitinib therapy for NSCLC were identified by an electronic search of public databases (MEDLINE, EMBASE, Cochrane library). All prospective studies of single agent therapy with erlotinib or gefitinib were independently identified by two authors for inclusion in the analysis. Demographic data, treatment response, progression-free and overall survival (PFS; OS) were extracted for systematic analysis using Comprehensive Meta Analysis software (Version 2.0). Outcome data were pooled and reported as weighted means of median age, RR, PFS and OS. We compared the weighted means between 1st line and all other lines of therapy. In order to exclude the effect of patient selection bias and ethnicity, we compared within subgroups of studies with the following characteristics: randomized phase III trials (RCT), studies out of Asia (A) and studies outside Asia (N-A). Results: A total of 205 studies were reviewed and 57 studies enrolling 8,768 patients were eligible for this analysis. Weighted overall median age was 51.2 yrs (55.7 for 1st line vs. 49.1 for salvage); 55.2, 36.0 and 60.5 yrs for RCT, A and N-A populations respectively. Conclusions: Early use of EGFR TKIs in the frontline setting results in superior clinical outcome compared to delayed use in the salvage setting. However, there was no significant difference between early and delayed use in the non-Asian patient population. Supported by NIH P01 CA116676. TKO, FRK and SSR are Distinguished Cancer Scholars of the Georgia Cancer Coalition. Patient population RR (%) PFS (months) OS (months) 1st line Subsequent lines P value 1st line Subsequent lines 1st line Subsequent lines Overall 30.5 15.8 <0.0001 5.1 3.4 15.1 8.6 Asians 44.7 25.6 <0.0001 6.4 4.1 18.9 10.9 Non-Asian 10.6 10.5 0.94 3.2 2.8 18.8 10.9 RCT 47.2 9.9 <0.0001 6.8 2.2 20.5 7.0
Progression free survival in patients with metastatic and recurrent renal cancer treated with sorafenib—Single center experience
Authors: A. Kapoor, S. Chatterjee, J. H. Pinthus, S. J. Hotte, N. Kleinmann
Journal: Journal of Clinical Oncology (2008)

16141 Background: Treatment of metastatic renal cell carcinoma (RCC) with sorafenib was previously shown to prolong progression free survival (PFS) with a median of 5.5 months. One of the advantages of using sorafenib is a relatively tolerable side effect profile. We examined our own experience with sorafenib as first line treatment of metastatic RCC in a heterogonous patient population, including patients with brain and bone metastases. Methods: We analyzed PFS defined as increased in size of target lesion or appearance of new metastases. Twenty one patients with metastatic RCC were treated with oral sorafenib (400mg bid administered in 4- week cycles for the first 24 weeks and in 8- week cycles thereafter). Follow up consisted of four-weekly appointments with blood work and physical exams, quarterly or/as needed CT and bone scans, and ranged from 23–85 weeks (median 54 weeks). Soft tissue metastases were defined as within the lungs or liver (n=12). Two patients had brain metastases, five had bone metastases and two had local recurrence in the nephrectomy bed. Nine patients presented initially with metastatic tumor and 7 underwent cytoreductive nephrectomy. Eleven patients underwent therapeutic nephrectomy for localized disease. Results: The median PFS was 8.4 months (range 1.2–59 months). Four patients (19%) were progression free at last follow-up (median 12.75 months). Median PFS for patients with soft tissue metastases vs. patients with brain or bone metastases was 8.7 vs 6.1 months respectively, with no statistically significant difference. Median PFS for patients with solitary vs. multiple metastases was 12.25 vs. 8.75 months respectively. Durable PFS greater than 1 year was observed in 24% of patients. Stage, grade, age or gender did not predict PFS. During a follow-up period of up to 85 weeks, 7 (33%) death were recorded. All patients had some degree of side effects, most commonly gastro intestinal (81%), skin reaction (76%), fatigue (76%), and cardiovascular (57%). However, none of them had to stop therapy. Four patients who progressed were switched to sunitinib. Conclusions: Treatment of patients who have heterogonous and diverse metastatic RCC with sorafenib can achieve a median PFS of 8.4 months with frequent but tolerable side effects. No significant financial relationships to disclose.
Results and Cost Effectiveness of "on-Demand" Plerixafor Added to Chemotherapy and Granulocyte Colony-Stimulating Factor for Peripheral Blood Stem Cell Mobilization in Multiple Myeloma
Authors: Giuseppe Milone, Massimo Martino, Annalia Di Marco, Salvatore Leotta, Andrea Spadaro, Mara Morelli, Giuseppe Avola, Maria Grazia Camuglia, Alessandra Cupri, Valentina Zammit, Potito Rosario Scalzulli, Calafiore Valeria, Attilio Olivieri, Giovanni Tripepi
Journal: Blood (2015)
Prostate-specific membrane antigen (PSMA)–targeted imaging of metastatic prostate cancer (PCa) via small molecule inhibitors: Comparison to bone scan, CT/MRI, and<sup> 111</sup>In capromab.
Authors: R. E. Coleman, J. A. Barrett, A. Hussain, K. M. Slawin, T. Armor, N. D. LaFrance, J. W. Babich
Journal: Journal of Clinical Oncology (2011)

4658 Background: Accurate and sensitive visualization of metastatic PCa remains a clinical challenge. 123I-MIP-1072 is a radiolabeled small molecule that selectively binds the extracellular enzymatic region of PSMA and is internalized and retained in viable PCa cells. In contrast, the antibody, 111In capromab pendetide, targets the intracellular domain of PSMA. This investigation studied administered dose, imaging time and the comparison of 123I-MIP-1072 imaging to current standard of care for visualizing PCa (bone scan, CT/MRI and 111In capromab) in patients (Pts) with radiographic evidence of metastatic PCa (mets). Methods: Eligible Pts with biopsy confirmed PCa and radiographic evidence of mets received either 10 or 5 mCi of 123I-MIP-1072 and 5 mCi of 111In capromab within 30 days of each other. With 123I-MIP-1072, serial whole body planar images were collected over 1 day with SPECT/CT imaging at 4 and 24 hr post injection (PI). 111In capromab SPECT/CT imaging occurred 3-5 days PI with blood pool imaging as needed. Results: 12 Pts in each cohort (57-83 years) received 123I-MIP-1072 and 111In capromab. After IV injection, 123I-MIP-1072 rapidly localized in both soft tissue and bone lesions, as visualized on planar imaging. At 4hr PI using SPECT/CT, 123I-MIP-1072 detected (known) lesions in the prostate, lymph nodes and bone at both doses tested with signal to noise (SNR) of >5:1. High SNR persisted through 24 hr PI. In contrast, due to prolonged blood clearance, 111In capromab at 3-5 days PI detected lesions in the prostate but infrequently detect lesions in the bone and required additional blood pool imaging to confirm lesions in lymph nodes. 123I-MIP-1072 detected more lesions with a higher SNR than 111In capromab when compared to CT/MRI and bone scan (standard of care) and was able to detect disease prior to CT/MRI and/or bone scan becoming positive, based on 12 week follow up imaging. Conclusions: 123I-MIP-1072 SPECT/CT detected prostate cancer localized in the prostate bed, soft tissues and bone within 4 hr PI. 123I-MIP-1072 alone shows concordance with multiple modalities currently used as standard of care in the detection and staging of PCa.
The effect of NK cell immunotherapy on cancer prognosis through its booster role on cellular (Th1) immunity and its compensator role to maintain the CD4 T-cell subset.
Authors: S. So, B. Zhao
Journal: Journal of Clinical Oncology (2011)

e13051 Background: With the exact progression of cell Immunotherapy, nowadays, more and more evidence shows that the Immunotherapy brings significant prognosis on patients with cancer. We observed immune cell subsets’ changing at the initial, progressing, and the terminal stage of cancer patients and measured cancer volume before and after NK cell Therapy on an untreated breast cancer patient. Through this study, we will like to prove that patients’ self-immunity plays an important role on their prognosis. Methods: We have analyzed leukocyte demarcation and lymphocyte subpopulations between healthy elderly and patients with cancer. We cultured healthy people autologous NK cells, infusing into the bodies, investigating the change of the subpopulation of immune cells in human bodies. The investigation in healthy people after several times of NK cell infusion was done as well. Results: After one round of NK cell infusion, we observed the increase of NK cells and the enhancement of cellular Th1 cell differentiation in vivo. After several rounds for a long time, the significance of CD4 T cells in maintaining the balance of healthy immune system was manifest. We suggest a new clinical reference system in maintaining the healthy immune system. So by autologous NK cells, Immunotherapy may act (1) as killer cells that kill cancer cells separately, (2) as the booster role that strengthen cellular Th1immunity to get rid cancer burden synthetically, (3) as the compensator that maintains CD4 lymphocytes number. Conclusions: The low immunity connects to cancer metastasis and progression. We do not only expect the killer effect of NK cell Immunotherapy, but also for its reinforcement on the immune system. Immunotherapy will be one more choice besides traditional cancer treatments as the 4th cancer therapy. The positive treatment can be combined with other treatments or adopted alone, especially for the “cancer refugees” who cannot be treated with other therapies or are not affected by them.
ERCC1 and RRM1 expression patterns in synchronous primary and metastatic urothelial cancer lesions.
Authors: L. C. Harshman, S. Manda, D. E. Hansel, J. McKenney, V. Oliveira, N. Simon, R. Dreicer, S. Srinivas, G. Bepler
Journal: Journal of Clinical Oncology (2011)

e15035 Background: ERCC1 (E1), the excision repair cross-complementation group 1 gene, and RRM1 (R1), the regulatory subunit of ribonucleotide reductase are DNA repair enzymes that are being investigated as potential predictive and prognostic biomarkers in urothelial carcinoma (UC). E1 is essential for nucleotide excision repair, and its expression has been linked to cisplatin sensitivity in multiple cancers. R1 is important in regulation of metastatic progression and gemcitabine efficacy. We undertook this analysis to assess for differences in gene expression between primary bladder tumors and nodal metastasis and whether heterogeneity portended an increased recurrence rate. Methods: From 1994-2008, 59 patients (pts) who received adjuvant platinum or gemcitabine chemotherapy for muscle invasive UC were identified. The medical records of these pts were retrospectively reviewed. Radical cystectomy (RC) and synchronous nodal specimens on existing and newly formed tissue microarrays were analyzed for tumoral E1 and R1 expression using AQUA. Results: Of these pts, 37 had paired samples of synchronous RC and nodal specimens (35 for E1, 29 for R1). Median age was 65 yrs. 51% were pT3 and 30% pT4. 95% had nodal involvement. More than half have recurred (57%). Median OS was 1.7 yrs (0.2-7.2). Mean E1 and R1 expression was 55.97 and 100.58 for the primary tumors and 52.05 and 111.94 for the nodal metastasis. Mean E1 and R1 expression did not significantly differ between the paired primary and nodal metastasis (R1, p=0.36, E1 p=0.38); nor did maximum expression. When evaluating the primary tumors of all 59 pts, no significant differences in E1/R1 expression were observed between the node negative and node positive pts (R1, p=0.37; E1, p=0.61). Conclusions: A paucity of data exists on E1 and R1 expression in UC. No differences in E1/R1 gene expression between synchronous primary tumors and nodal metastasis were observed in this small, advanced stage, but multi-institutional cohort. Data on intra-tumoral heterogeneity and impact on outcome will be presented. Further study of E1/R1 gene expression and correlation with outcome relative to adjuvant platinum- and gemcitabine-based therapies is planned in a larger cohort.
Risk of proteinuria with the new angiogenesis inhibitor axitinib in patients with cancer.
Authors: Andrew Kuei, Xiaolei Zhu, Shenhong Wu
Journal: Journal of Clinical Oncology (2013)

e20602 Background: The use of axitinib, a potent inhibitor of vascular endothelial growth factor receptor (VEGFR), is associated with proteinuria, which may cause morbidity and treatment interruptions in cancer patients. We performed a systematic review and meta-analysis of published clinical trials to assess the overall risk of proteinuria with axitinib. Methods: Potentially relevant studies were identified by searching databases including Pubmed and abstracts presented at the American Society of Clinical Oncology annual meetings until June, 2012. Eligible studies included prospective clinical trials in cancer patients treated with axitinib containing data on proteinuria. Summary incidence, relative risk (RR), and 95% confidence interval (CI) were calculated using the fixed- or random-effects models. Results: A total of 1,671 patients with advanced renal cell carcinoma (RCC) and other solid tumors from 9 studies were included for analysis. The overall incidences of all-grade and high-grade (grade 3 or 4) proteinuria with axitinib were 22.7% (95% CI: 10.4-42.6%) and 3.8% (95% CI: 2.6-5.7%) respectively. The risk did not vary significantly with tumor types (P=0.13). There was no significant difference between RCC and non-RCC patients (P=0.45), although the incidence in RCC patients was higher (30.0%, 95% CI: 8.4-66.7 versus 17.5%, 95% CI: 7.4-36.3%). In comparison with a control (gemcitabine), axitinib significantly increased the incidence of high-grade proteinuria (3.3%, 95% CI: 1.6-6.5% versus 0.1%, 95% CI: 0-2.3%; P=0.031). When compared to another angiogenesis inhibitor sorafenib, axitinib did not have a significantly higher risk of all-grade (RR=1.48, 95% CI: 0.92-2.38, P=0.10) and high-grade proteinuria (RR=1.81, 95% CI: 0.68-4.85, P=0.24). Conclusions: There was a significant risk of proteinuria associated with the use of axitinib in cancer patients.
Phase Ib study of ipilimumab alone or in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene (vaccine) in pancreatic cancer.
Authors: Dung Thi Le, Eric Lutz, Lanqing Huang, Beth Onners, Jennifer Uram, Sara Solt, Elizabeth Sugar, Lei Zheng, Elizabeth M. Jaffee, Dan Laheru
Journal: Journal of Clinical Oncology (2012)

211 Background: Ipilimumab (IPI) at 3mg/kg has been tested in pancreatic ductal adenocarcinoma (PDA) with a low but detectable response rate. This supports a role for immunotherapy in PDA. Melanoma (MEL) studies demonstrate a dose-response relationship with IPI. Preclinical studies show synergy between anti-CTLA-4 antibodies and GM-CSF cell-based vaccines. This study evaluated IPI 10mg/kg alone (Arm 1) versus IPI 10mg/kg + vaccine (Arm 2) in PDA. Methods: 30 subjects with previously treated, locally advanced or metastatic PDA were randomized (1:1) to Arm 1 or 2. Induction treatments were administered every 3 weeks (wk) X 4 doses. Subjects with stable disease (SD) or better between wk 14 and 22 were eligible for maintenance doses every 12 wks. Activity was assessed by response and overall survival (OS). IFN-g Elispots and ELISAs were used to detect induction of mesothelin-specific T cells and galectin-3 antibodies (Abs), respectively. Results: Baseline characteristics were similar (87% metastatic, 100% gemcitabine-treated) with the exception that Arm 1 had a lower % of subjects with &gt; 1 prior therapies (60 vs 100%). Arm 1 had 2 SD (7 and 22 wks). Arm 2 had 3 SD (1 delayed regression starting at wk 14 and maintained until wk 31, 1 delayed stabilization starting at wk 22 and ongoing at wk 57, 1 SD ongoing at wk 64). Transient CA19-9 declines were seen only in Arm 2 (7/15). Median OS was 3.3 vs 5.5 months in Arm 1 vs Arm 2 (p=0.12) with a 12 month OS of 7 vs 27%. 73% (Arm 1) and 80% (Arm 2) of subjects experienced immune related adverse events (IRAE). 20% of subjects on both arms had Grade 3-4 IRAEs including rash (1), colitis (2), Guillain-Barre (1), nephritis (1), and pneumonitis (1). Rash was less frequent in Arm 1 (53 vs 73%). IRAEs (p=0.037), mesothelin T cell responses (p=0.012), and enhancement of the T cell repertoire (p=0.026) were associated with OS in both arms. Galectin-3 Ab responses were associated with OS in Arm 2 (p=0.002). Conclusions: Immunotherapy has potential even in advanced PDA. IRAEs in PDA are similar to IRAEs in MEL. Delayed responses suggest that standard RECIST criteria will underestimate activity and targeting a population with a longer life expectancy may improve efficacy.
Bidirectional consultative process as a novel methodology to develop a pan-Canadian cancer quality initiative.
Authors: Gunita Mitera, Mary Agent-Katwala, Geoffrey A. Porter, Heather E. Bryant, Terrence Sullivan
Journal: Journal of Clinical Oncology (2013)

80 Background: To foster pan-Canadian quality improvement strategies in cancer diagnosis and treatment, a new publically funded opportunity was launched though a Request for Proposals (RFP). Methods to develop RFPs in the public health care sector are variable. To generate enthusiasm and ensure appropriateness and relevance of the RFP, a novel methodology was developed to refine and validate the focus of the RFP. Methods: An extensive multi-pronged bi-directional consultative process helped identify and engage with clinical experts, senior administrators, and other relevant stakeholders. In-person discussions with relevant stakeholders, an electronic stakeholder engagement survey, and two interactive electronic information sessions (Webinars) were included. The intent of the eBlast was to seek survey responses and also to build awareness of the upcoming opportunity. An eBlast engaged stakeholders and stakeholder networks for the electronic component of the bi-directional process. Secondary distribution encouraged wide-spread dissemination. The survey and recorded Webinar were publically posted online. Results: Approximately 30 in-person consultations occurred and the electronic survey and Webinar details were sent to approximate 1,000 individuals and external networks. 80 responses were received along with 76 Webinar attendees. Feedback was received from a representative cross-section of the Canadian quality community as measured by geographical distribution and discipline. There was general pan-Canadian agreement that the quality topic chosen was relevant and appropriate. Through this methodology refinements were made to finalize the organization and content of the RFP. Conclusions: When developing a national call for a publicly-funded quality improvement opportunity, it is imperative to ensure the topic considered is relevant, appropriate, and there is interest from stakeholders to apply. A bi-directional consultative process is a novel and economical method to ensure wide reaching engagement from relevant pan-Canadian stakeholders. This methodology can also be leveraged to refine and validate the final quality topic considered.
Generation of HM1.24-Specific Cytotoxic T Lymphocytes from Peripheral Blood Stem Cell Harvests of Patients with Multiple Myeloma.
Authors: Ali Jalili, Shuji Ozaki, Tomoko Hara, Etsuko Sekimoto, Yoichi Tanaka, Takashi Ohshima, Hironobu Shibata, Toshihiro Hashimoto, Masahiro Abe, Yasuhiko Nishioka, Toshio Matsumoto
Journal: Blood (2004)
Prospective observational trial of re-antiestrogen therapy after becoming resistant to ethinylestradiol treatment in hormone-dependent metastatic breast cancer.
Authors: Hirotaka Iwase, Yutaka Yamamoto, Mutsuko Ibusuki, Kei-ichi Murakami, Touko Inao, Yasuhiro Okumura, Yoko Omoto
Journal: Journal of Clinical Oncology (2013)

161 Background: After heavily treated estrogen deprivation therapy by aromatase inhibitors (AIs), an additional estrogen therapy may be useful in a certain condition. Furthermore, the estrogen therapy might sensitize a subsequent anti-estrogen therapy after the acquired resistance to estrogen. Methods: In the patients who obtained disease control (SD or more) by ethinylestradiol (EE2) therapy (1.5-3mg TID), the efficacy of anti-estrogen therapy using AI or fulvestrant was examined as a subsequent endocrine therapy. Primary endpoint was clinical benefit rate (CBR), and secondary endpoints were response rate (RR) and time to treatment failure (TTF). (Registration; UMIN000002831, prospective observational trial, sub-protocol analysis) Results: EE2 therapy was performed in 22 of postmenopausal breast cancer patients with ER-positive HER2-negative in primary or recurrent tumor, who had heavily pre-treated by endocrine therapies, including chemotherapies. At the median observation period of 13.6 months, RR of 41% (9/22) and CBR of 50% (11/22) were obtained (CR; 0, PR; 9, long SD; 2, SD; 4, PD; 3) and 4 patients withdrew this trial due to adverse events of early endocrine related symptoms and cerebral infarction. Although two patients were still ongoing, the median of duration of disease-control was 46 weeks (range; 23-62+). In thirteen patients who obtained disease control (SD or more) by EE2 therapy, fulvestrant for 6 patients or AI for 7 patients was used as a subsequent therapy. Fifty percent of fulvestrant group (3/6) and 43% of AI group (3/7) showed clinical benefit (PR or long SD). TTF of fulvestrant group was 15 weeks (median; range; 5-55+) and that of AI group was 19 weeks (median; range 5-33+). Furthermore, two patients who were responders to previous AI, got long SD to the subsequent EE2 re-treatment. Conclusions: EE2 therapy after resistance to estrogen deprivation therapy could be very useful, and a subsequent anti-estrogen therapy by AI or fulvestrant could be also effective in a certain condition. Thus, the changes of the endocrine environment by EE2 may induce the sensitization to hormone dependency in acquired hormone-resistant tumors. Clinical trial information: 000002831.