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Jason konner

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https://www.readbyqxmd.com/read/28843653/characterization-of-folate-receptor-alpha-fr%C3%AE-expression-in-archival-tumor-and-biopsy-samples-from-relapsed-epithelial-ovarian-cancer-patients-a-phase-i-expansion-study-of-the-fr%C3%AE-targeting-antibody-drug-conjugate-mirvetuximab-soravtansine
#1
Lainie P Martin, Jason A Konner, Kathleen N Moore, Shelly M Seward, Ursula A Matulonis, Raymond P Perez, Ying Su, Anna Berkenblit, Rodrigo Ruiz-Soto, Michael J Birrer
PURPOSE: To characterize folate receptor alpha (FRα) expression in archival and fresh biopsy tumor samples from relapsed ovarian cancer patients. METHODS: Patients with ovarian tumors amenable to biopsy were eligible to enroll. Eligibility included a minimum requirement of FRα positivity in archival tumor samples (≥25% of cells with ≥2+ staining intensity). Patients received mirvetuximab soravtansine at 6mg/kg once every 3weeks. Core needle biopsies were collected before and after treatment and FRα levels assessed by immunohistochemistry...
August 24, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28841418/heterogeneous-tumor-immune-microenvironments-among-differentially-growing-metastases-in-an-ovarian-cancer-patient
#2
Alejandro Jiménez-Sánchez, Danish Memon, Stephane Pourpe, Harini Veeraraghavan, Yanyun Li, Hebert Alberto Vargas, Michael B Gill, Kay J Park, Oliver Zivanovic, Jason Konner, Jacob Ricca, Dmitriy Zamarin, Tyler Walther, Carol Aghajanian, Jedd D Wolchok, Evis Sala, Taha Merghoub, Alexandra Snyder, Martin L Miller
We present an exceptional case of a patient with high-grade serous ovarian cancer, treated with multiple chemotherapy regimens, who exhibited regression of some metastatic lesions with concomitant progression of other lesions during a treatment-free period. Using immunogenomic approaches, we found that progressing metastases were characterized by immune cell exclusion, whereas regressing and stable metastases were infiltrated by CD8(+) and CD4(+) T cells and exhibited oligoclonal expansion of specific T cell subsets...
August 24, 2017: Cell
https://www.readbyqxmd.com/read/28765325/diverse-brca1-and-brca2-reversion-mutations-in-circulating-cell-free-dna-of-therapy-resistant-breast-or-ovarian-cancer
#3
Britta Weigelt, Iñaki Comino-Méndez, Ino de Bruijn, Lei Tian, Jane L Meisel, Isaac Garcia-Murillas, Charlotte Fribbens, Ros Cutts, Luciano G Martelotto, Charlotte K Y Ng, Raymond S Lim, Pier Selenica, Salvatore Piscuoglio, Carol Aghajanian, Larry Norton, Rajmohan Murali, David M Hyman, Laetitia Borsu, Maria E Arcila, Jason Konner, Jorge S Reis-Filho, Roger A Greenberg, Mark Robson, Nicholas C Turner
PURPOSE: Resistance to platinum-based chemotherapy or PARP inhibition in germline BRCA1 or BRCA2 mutation carriers may occur through somatic reversion mutations or intragenic deletions that restore BRCA1 or BRCA2 function. We assessed whether BRCA1/2 reversion mutations could be identified in circulating cell-free DNA (cfDNA) of ovarian or breast cancer patients previously treated with platinum and/or PARP inhibitors. EXPERIMENTAL DESIGN: cfDNA from 24 prospectively accrued BRCA1 or BRCA2-germline mutant patients, including 19 platinum-resistant/refractory ovarian cancer and five platinum and/or PARP inhibitor pre-treated metastatic breast cancer patients, was subjected to massively parallel sequencing targeting all exons of 141 genes and all exons and introns of BRCA1 and BRCA2...
August 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28314788/the-parp-inhibitor-veliparib-can-be-safely-added-to-bendamustine-and-rituximab-and-has-preliminary-evidence-of-activity-in-b-cell-lymphoma
#4
Jacob D Soumerai, Andrew D Zelenetz, Craig H Moskowitz, M Lia Palomba, Paul A Hamlin, Ariela Noy, David J Straus, Alison J Moskowitz, Anas Younes, Matthew J Matasar, Steven M Horwitz, Carol S Portlock, Jason A Konner, Mrinal M Gounder, David M Hyman, Martin H Voss, Matthew G Fury, Devika Gajria, Richard D Carvajal, Alan L Ho, Jan H Beumer, Brian Kiesel, Zhigang Zhang, Alice Chen, Richard F Little, Christine Jarjies, Thu O Dang, Fallon France, Nishant Mishra, John F Gerecitano
Purpose: The PARP inhibitor veliparib enhances the cytotoxicity of alkylating agents. This phase I study evaluated veliparib with the bifunctional alkylator bendamustine (VB) in patients with relapsed/refractory lymphoma, multiple myeloma, and solid malignancies, with a cohort expansion of VB with rituximab (VBR) in patients with B-cell lymphomas.Experimental Design: This dose-escalation study evaluated safety, pharmacokinetics, and preliminary efficacy of veliparib (20-400 mg twice a day, days 1-7 of 28-day cycle) and bendamustine (70 and 90 mg/m(2) intravenously, days 1 and 2)...
August 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28029313/safety-and-activity-of-mirvetuximab-soravtansine-imgn853-a-folate-receptor-alpha-targeting-antibody-drug-conjugate-in-platinum-resistant-ovarian-fallopian-tube-or-primary-peritoneal-cancer-a-phase-i-expansion-study
#5
Kathleen N Moore, Lainie P Martin, David M O'Malley, Ursula A Matulonis, Jason A Konner, Raymond P Perez, Todd M Bauer, Rodrigo Ruiz-Soto, Michael J Birrer
Purpose This phase I expansion cohort study evaluated the safety and clinical activity of mirvetuximab soravtansine (IMGN853), an antibody-drug conjugate consisting of a humanized anti-folate receptor alpha (FRα) monoclonal antibody linked to the tubulin-disrupting maytansinoid DM4, in a population of patients with FRα-positive and platinum-resistant ovarian cancer. Patients and Methods Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer received IMGN853 at 6...
April 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27367496/uterine-cancer-after-risk-reducing-salpingo-oophorectomy-without-hysterectomy-in-women-with-brca-mutations
#6
MULTICENTER STUDY
Catherine A Shu, Malcolm C Pike, Anjali R Jotwani, Tara M Friebel, Robert A Soslow, Douglas A Levine, Katherine L Nathanson, Jason A Konner, Angela G Arnold, Faina Bogomolniy, Fanny Dao, Narciso Olvera, Elizabeth K Bancroft, Deborah J Goldfrank, Zsofia K Stadler, Mark E Robson, Carol L Brown, Mario M Leitao, Nadeem R Abu-Rustum, Carol A Aghajanian, Joanne L Blum, Susan L Neuhausen, Judy E Garber, Mary B Daly, Claudine Isaacs, Rosalind A Eeles, Patricia A Ganz, Richard R Barakat, Kenneth Offit, Susan M Domchek, Timothy R Rebbeck, Noah D Kauff
Importance: The link between BRCA mutations and uterine cancer is unclear. Therefore, although risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations (BRCA+ women), the role of concomitant hysterectomy is controversial. Objective: To determine the risk for uterine cancer and distribution of specific histologic subtypes in BRCA+ women after RRSO without hysterectomy. Design, Setting, and Participants: This multicenter prospective cohort study included 1083 women with a deleterious BRCA1 or BRCA2 mutation identified from January 1, 1995, to December 31, 2011, at 9 academic medical centers in the United States and the United Kingdom who underwent RRSO without a prior or concomitant hysterectomy...
November 1, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/26745694/a-phase-2-single-arm-study-of-iniparib-in-patients-with-brca1-or-brca2-associated-advanced-epithelial-ovarian-fallopian-tube-or-primary-peritoneal-cancer
#7
Katherine M Bell-McGuinn, Jason A Konner, William P Tew, Martee L Hensley, Alexia Iasonos, Eric Charpentier, Svetlana Mironov, Paul Sabbatini, Carol Aghajanian
OBJECTIVE: The aim of the study was to evaluate the activity and tolerability of iniparib monotherapy in women with BRCA1 or BRCA2-associated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer. METHODS AND MATERIALS: Eligible patients had advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer, germline BRCA1 or BRCA2 mutation, measurable disease, and at least 1 previous treatment regimen of platinum/taxane chemotherapy. Patients received iniparib 8 mg/kg intravenously on days 1 and 4 weekly, with imaging every 8 weeks...
February 2016: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/26404183/ovarian-clear-cell-carcinoma-outcomes-by-stage-the-msk-experience
#8
Catherine A Shu, Qin Zhou, Anjali R Jotwani, Alexia Iasonos, Mario M Leitao, Jason A Konner, Carol A Aghajanian
OBJECTIVE: Ovarian clear cell carcinomas (OCCCs) are rare, and uncertainty exists as to the optimal treatment paradigm and validity of the FIGO staging system, especially in early-stage disease. METHODS: We performed a retrospective cohort study of all OCCC patients diagnosed and treated at Memorial Sloan Kettering Cancer Center between January 1996 and December 2013. Progression-free survival (PFS) and overall survival (OS) were calculated by stage and race, and comparisons were made using the log-rank test...
November 2015: Gynecologic Oncology
https://www.readbyqxmd.com/read/25672916/parallel-phase-ib-studies-of-two-schedules-of-buparlisib-bkm120-plus-carboplatin-and-paclitaxel-q21-days-or-q28-days-for-patients-with-advanced-solid-tumors
#9
David M Hyman, Alexandra E Snyder, Richard D Carvajal, John F Gerecitano, Martin H Voss, Alan L Ho, Jason Konner, Jennifer L Winkelmann, Megan A Stasi, Kelsey R Monson, Alexia Iasonos, David R Spriggs, Philip Bialer, Mario E Lacouture, Jerrold B Teitcher, Nora Katabi, Matthew G Fury
PURPOSE: Phosphatidylinositol-3-kinase I (PI3K) inhibition sensitizes a wide range of cancer cell lines to platinum/taxane-based chemotherapy. This phase I study combines buparlisib, a pan-class 1A PI3K inhibitor, with two schedules of carboplatin and paclitaxel for patients with advanced solid tumors (ClinicalTrials.gov, NCT01297452). METHODS: There were two regimens: Group 1 received carboplatin AUC 5 and paclitaxel 175 mg/m(2), on day 1 of a 21-day cycle with pegfilgrastim support; Group 2 received carboplatin AUC 5 (day 1) and paclitaxel 80 mg/m(2) (days 1, 8, and 15) on a 28-day cycle without growth factor support...
April 2015: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/25601962/breaking-down-the-evidence-for-bevacizumab-in-ovarian-cancer
#10
EDITORIAL
Catherine A Shu, Jason A Konner
No abstract text is available yet for this article.
February 2015: Oncologist
https://www.readbyqxmd.com/read/23698798/feasibility-of-adjuvant-chemotherapy-after-pelvic-exenteration-for-gynecologic-malignancies
#11
Vaagn Andikyan, Fady Khoury-Collado, Samith Sandadi, William P Tew, Roisin E O'Cearbhaill, Jason A Konner, Yukio Sonoda, Richard R Barakat, Dennis S Chi, Nadeem R Abu-Rustum
OBJECTIVE: It is well documented that recurrence after pelvic exenteration remains high (up to 50%), and patients may require a prolonged period of recuperation following this aggressive surgery. We conducted a retrospective review to evaluate the feasibility of administering adjuvant chemotherapy after pelvic exenteration for gynecologic malignancies. METHODS: We reviewed the medical records of patients with any gynecologic cancer who underwent exenterative surgery between January 2005 and February 2011 at our institution...
June 2013: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/23032745/phase-i-trial-of-overlapping-long-peptides-from-a-tumor-self-antigen-and-poly-iclc-shows-rapid-induction-of-integrated-immune-response-in-ovarian-cancer-patients
#12
Paul Sabbatini, Takemasa Tsuji, Luis Ferran, Erika Ritter, Christine Sedrak, Kevin Tuballes, Achim A Jungbluth, Gerd Ritter, Carol Aghajanian, Katherine Bell-McGuinn, Martee L Hensley, Jason Konner, William Tew, David R Spriggs, Eric W Hoffman, Ralph Venhaus, Linda Pan, Andres M Salazar, Catherine Magid Diefenbach, Lloyd J Old, Sacha Gnjatic
PURPOSE: Long peptides are efficiently presented to both CD4(+) and CD8(+) T cells after intracellular processing by antigen-presenting cells. To investigate the safety and in vivo immunogenicity of synthetic overlapping long peptides (OLP) from a human tumor self-antigen, we conducted a phase I clinical trial with OLP from cancer-testis antigen NY-ESO-1 in various adjuvant combinations. EXPERIMENTAL DESIGN: Twenty-eight patients with advanced ovarian cancer in second or third remission were enrolled sequentially in three cohorts and received at least one vaccination...
December 1, 2012: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/22635030/gemcitabine-for-advanced-endometrial-cancer-a-retrospective-study-of-the-memorial-sloan-kettering-cancer-center-experience
#13
Rachel Nicole Grisham, Christina Adaniel, David M Hyman, Weining Ma, Alexia Iasonos, Carol Aghajanian, Jason Konner
BACKGROUND: Gemcitabine is active in several gynecologic malignancies including ovarian cancer, cervical cancer, and uterine leiomyosarcoma. It has been used in an off-label setting for the treatment of advanced endometrial cancer, despite lack of published data showing efficacy. We performed a retrospective study to determine the progression-free survival and response rate of endometrial cancer patients treated with gemcitabine at Memorial Sloan-Kettering Cancer Center. METHODS: Eligible patients had histologically confirmed advanced (stage IV or recurrent) endometrial cancer that was treated with single-agent gemcitabine at Memorial Sloan-Kettering Cancer Center between 1999 and 2009...
June 2012: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/22446622/progression-free-and-overall-survival-of-a-modified-outpatient-regimen-of-primary-intravenous-intraperitoneal-paclitaxel-and-intraperitoneal-cisplatin-in-ovarian-fallopian-tube-and-primary-peritoneal-cancer
#14
Joyce N Barlin, Fanny Dao, Nadim Bou Zgheib, Sarah E Ferguson, Paul J Sabbatini, Martee L Hensley, Katherine M Bell-McGuinn, Jason Konner, William P Tew, Carol Aghajanian, Dennis S Chi
OBJECTIVE: GOG study 172 demonstrated improved progression-free (PFS) and overall (OS) survival for patients with stage III optimally debulked ovarian and peritoneal carcinoma treated with IV/IP paclitaxel and IP cisplatin compared to standard IV therapy. The inpatient administration, toxicity profile, and limited completion rate have been blamed for the lack of acceptance and widespread use of this regimen. We sought to evaluate the PFS, OS, toxicity, and completion rate of a modified outpatient IP regimen...
June 2012: Gynecologic Oncology
https://www.readbyqxmd.com/read/22437824/clinical-and-histopathologic-characteristics-of-rash-in-cancer-patients-treated-with-mammalian-target-of-rapamycin-inhibitors
#15
Yevgeniy Balagula, Alyx Rosen, Belinda H Tan, Klaus J Busam, Melissa P Pulitzer, Robert J Motzer, Darren R Feldman, Jason A Konner, Diane Reidy-Lagunes, Patricia L Myskowski, Mario E Lacouture
BACKGROUND: Dermatologic adverse events stemming from anticancer therapies have become an increasingly frequent clinical problem. Inhibitors of mammalian target of rapamycin (mTOR), such as temsirolimus and everolimus, have been associated with a high rate of skin eruptions, but their clinical and histopathologic characteristics have not been explored. METHODS: A retrospective analysis of patients who were referred to the Dermatology Service for diagnosis and management of rash in the setting of therapy with the mTOR inhibitors everolimus and temsirolimus was performed...
October 15, 2012: Cancer
https://www.readbyqxmd.com/read/22072399/phase-i-clinical-pharmacokinetic-and-pharmacodynamic-study-of-kos-862-epothilone-d-in-patients-with-advanced-solid-tumors-and-lymphoma
#16
Jason Konner, Rachel N Grisham, Jae Park, Owen A O'Connor, Gillian Cropp, Robert Johnson, Alison L Hannah, Martee L Hensley, Paul Sabbatini, Svetlana Mironov, Svetlana Miranov, Samuel Danishefsky, David Hyman, David R Spriggs, Jakob Dupont, Carol Aghajanian
PURPOSE: To determine the maximum tolerated dose and safety of the epothilone, KOS-862, in patients with advanced solid tumors or lymphoma. PATIENTS AND METHODS: Patients were treated weekly for 3 out of 4 weeks (Schedule A) or 2 out of 3 weeks (Schedule B) with KOS-862 (16-120 mg/m(2)). Pharmacokinetic (PK) sampling was performed during cycles 1 and 2; pharmacodynamic (PD) assessment for microtubule bundle formation (MTBF) was performed after the 1st dose, only at or above 100 mg/m(2)...
December 2012: Investigational New Drugs
https://www.readbyqxmd.com/read/22067389/phase-ii-study-of-intraperitoneal-paclitaxel-plus-cisplatin-and-intravenous-paclitaxel-plus-bevacizumab-as-adjuvant-treatment-of-optimal-stage-ii-iii-epithelial-ovarian-cancer
#17
Jason A Konner, Diana M Grabon, Scott R Gerst, Alexia Iasonos, Howard Thaler, Sandra D Pezzulli, Paul J Sabbatini, Katherine M Bell-McGuinn, William P Tew, Martee L Hensley, David R Spriggs, Carol A Aghajanian
PURPOSE: Intraperitoneal (IP) cisplatin and intravenous (IV) or IP paclitaxel constitute a standard therapy for optimally debulked ovarian cancer. Bevacizumab prolongs progression-free survival (PFS) when included in first-line IV chemotherapy. In this study, the safety and feasibility of adding bevacizumab to a first-line IP regimen were assessed. PATIENTS AND METHODS: Treatment was as follows: paclitaxel 135 mg/m(2) IV over 3 hours day 1, cisplatin 75 mg/m(2) IP day 2, and paclitaxel 60 mg/m(2) IP day 8...
December 10, 2011: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/21982046/patterns-of-first-recurrence-following-adjuvant-intraperitoneal-chemotherapy-for-stage-iiic-ovarian-cancer
#18
Edward J Tanner, Destin R Black, Oliver Zivanovic, Siobhan M Kehoe, Fanny Dao, Jason A Konner, Richard R Barakat, Stuart M Lichtman, Douglas A Levine
OBJECTIVE: Adjuvant intraperitoneal (IP) platinum-based chemotherapy has been shown to improve outcome for patients with advanced ovarian cancer. We hypothesize that patients who have received adjuvant IP chemotherapy more commonly recur first at extraperitoneal sites than patients who have received adjuvant intravenous (IV) chemotherapy. METHODS: Patients with newly diagnosed stage IIIC optimally debulked serous ovarian cancer were identified from institutional databases...
January 2012: Gynecologic Oncology
https://www.readbyqxmd.com/read/20855460/farletuzumab-a-humanized-monoclonal-antibody-against-folate-receptor-alpha-in-epithelial-ovarian-cancer-a-phase-i-study
#19
Jason A Konner, Katherine M Bell-McGuinn, Paul Sabbatini, Martee L Hensley, William P Tew, Neeta Pandit-Taskar, Nicholas Vander Els, Martin D Phillips, Charles Schweizer, Susan C Weil, Steven M Larson, Lloyd J Old
PURPOSE: Folate receptor α expression is highly restricted in normal adult tissues but upregulated in a wide range of human cancer types, including epithelial ovarian cancer. Farletuzumab, a humanized monoclonal antibody against folate receptor α, has shown antitumor activity and favorable toxicity in preclinical evaluation. This phase I, dose-escalation study was conducted to determine the safety of weekly i.v. farletuzumab and establish the maximum tolerated dose (MTD). EXPERIMENTAL DESIGN: Patients with platinum-refractory or platinum-resistant epithelial ovarian cancer received farletuzumab (12...
November 1, 2010: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/20004956/incidence-and-management-of-bevacizumab-associated-gastrointestinal-perforations-in-patients-with-recurrent-ovarian-carcinoma
#20
John P Diaz, William P Tew, Oliver Zivanovic, Jason Konner, Paul J Sabbatini, Lisa A dos Santos, Nadeem R Abu-Rustum, Dennis S Chi, Carol Aghajanian, Richard R Barakat
OBJECTIVE: The objective of this study was to examine the incidence and management of bevacizumab-associated gastrointestinal (GI) perforations in patients with recurrent ovarian carcinoma. METHODS: We identified all patients who received bevacizumab off protocol from August 2004-August 2008. We examined their medical records for reports of confirmed GI perforation, associated clinicopathological factors, treatment, and outcomes. RESULTS: Six (4%) of 160 patients with ovarian carcinoma who had been treated with bevacizumab developed GI perforations, with a median of 4 (range, 2-8) previous cytotoxic regimens...
March 2010: Gynecologic Oncology
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