Ellen Chuang
Cornell University
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Featured researches published by Ellen Chuang.
Journal of Clinical Oncology | 2009
Linda T. Vahdat; Brian Pruitt; Carol J. Fabian; Ragene Rivera; David A. Smith; Elizabeth Tan-Chiu; Jonathan L. Wright; Antoinette R. Tan; Noshir Anthony Dacosta; Ellen Chuang; John W. Smith; Joyce O'Shaughnessy; Dale Shuster; Nicole Meneses; Kumari Chandrawansa; Fang Fang; Patricia E. Cole; Simon Ashworth; Joanne L. Blum
PURPOSE Eribulin mesylate (E7389), a nontaxane microtubule dynamics inhibitor, is a structurally simplified, synthetic analog of the marine natural product halichondrin B. This open-label, single-arm, phase II study evaluated efficacy and tolerability of eribulin in heavily pretreated patients with metastatic breast cancer (MBC). METHODS MBC patients who were previously treated with an anthracycline and a taxane received eribulin mesylate (1.4 mg/m(2)) as a 2- to 5-minute intravenous (IV) infusion on days 1, 8, and 15 of a 28-day cycle. Because of neutropenia (at day 15), an alternative regimen of eribulin on days 1 and 8 of a 21-day cycle was administered. The primary end point was overall response rate. RESULTS Of the 103 patients treated, the median number of prior chemotherapy regimens was four (range, one to 11 regimens). In the per-protocol population (n = 87), eribulin achieved an independently reviewed objective response rate (all partial responses [PRs]) of 11.5% (95% CI, 5.7 to 20.1) and a clinical benefit rate (PR plus stable disease > or = 6 months) of 17.2% (95% CI, 10.0 to 26.8). The median duration of response was 171 days (5.6 months; range, 44 to 363 days), the median progression-free survival was 79 days (2.6 months; range, 1 to 453 days), and the median overall survival was 275 days (9.0 months; range, 15 to 826 days). The most common drug-related grades 3 to 4 toxicities were as follows: neutropenia, 64%; leukopenia, 18%; fatigue, 5%; peripheral neuropathy, 5%; and febrile neutropenia, 4%. CONCLUSION Eribulin demonstrated activity with manageable tolerability (including infrequent grade 3 and no grade 4 neuropathy) in heavily pretreated patients with MBC when dosed as a short IV infusion on days 1 and 8 of a 21-day cycle.
Journal of Community Health | 2012
Victoria Blinder; Linda T. Vahdat; H. T. Gold; I. de Melo-Martin; Mary Katherine Hayes; Ronald J. Scheff; Ellen Chuang; Anne Moore; Madhu Mazumdar
Employment status is related to treatment recovery and quality of life in breast cancer survivors, yet little is known about return to work in immigrant and minority survivors. We conducted an exploratory qualitative study using ethnically cohesive focus groups of urban breast cancer survivors who were African-American, African-Caribbean, Chinese, Filipina, Latina, or non-Latina white. We audio- and video-recorded, transcribed, and thematically coded the focus group discussions and we analyzed the coded transcripts within and across ethnic groups. Seven major themes emerged related to the participants’ work experiences after diagnosis: normalcy, acceptance, identity, appearance, privacy, lack of flexibility at work, and employer support. Maintaining a sense of normalcy was cited as a benefit of working by survivors in each group. Acceptance of the cancer diagnosis was most common in the Chinese group and in participants who had a family history of breast cancer; those who described this attitude were likely to continue working throughout the treatment period. Appearance was important among all but the Chinese group and was related to privacy, which many thought was necessary to derive the benefit of normalcy at work. Employer support included schedule flexibility, medical confidentiality, and help maintaining a normal work environment, which was particularly important to our study sample. Overall, we found few differences between the different ethnic groups in our study. These results have important implications for the provision of support services to and clinical management of employed women with breast cancer, as well as for further large-scale research in disparities and employment outcomes.
Breast Journal | 2007
Kevin J. Cheung; Wayne Tam; Ellen Chuang; Michael P. Osborne
Abstract: Collision tumors are rare clinical entities in which two histologically distinct tumor types show involvement in the same site. The occurrence of these tumors in the breast is extremely rare. Here, we present a case of a patient with both invasive ductal carcinoma and chronic lymphocytic leukemia in the breast. Wide excision with sentinel lymph node biopsy revealed palpably abnormal lymph nodes negative for breast carcinoma on frozen section. Histopathological examination of these lymph nodes showed extensive involvement by lymphoma and review of the breast specimen demonstrated the same lymphoma at the periphery of the ductal carcinoma. We review the literature and discuss possible etiologies for the dual presentation of both cancers.
Annals of clinical and translational neurology | 2014
Gigi J. Ebenezer; Karen Carlson; Diana Donovan; Mv Cobham; Ellen Chuang; Anne Moore; Tessa Cigler; Maureen Ward; Maureen E. Lane; Anita Ramnarain; Linda T. Vahdat; Michael Polydefkis
We sought to define the clinical and ultrastructure effects of ixabepilone (Ix), a microtubule‐stabilizing chemotherapy agent on cutaneous sensory nerves and to investigate a potential mitochondrial toxicity mechanism.
Clinical Breast Cancer | 2015
Tessa Cigler; Devora Isseroff; Barbara Fiederlein; Sarah Schneider; Ellen Chuang; Linda T. Vahdat; Anne Moore
BACKGROUND Chemotherapy-induced alopecia (CIA) is a distressing adverse effect of many chemotherapy agents. The TC (docetaxel [Taxotere] and cyclophosphamide) chemotherapy regimen is typically associated with complete alopecia. Scalp cooling with cold caps has been reported to minimize or prevent CIA. We conducted a prospective study to assess efficacy of scalp cooling in preventing CIA among women receiving adjuvant TC chemotherapy for breast cancer. METHODS Women at the Weill Cornell Breast Center who independently elected to use scalp cooling with cold caps during adjuvant TC chemotherapy were asked to participate. Degree of hair loss was assessed by a single practitioner using Deans alopecia scale (grade 1/excellent [< 25% hair loss], grade 2/good [25%-50% hair loss], grade 3/moderate [50%-75% hair loss], grade 4/poor [> 75% hair loss]), by digital photographs, and by patient self-report of hair thinning or the need to wear a wig/head covering, or both. Assessments were made before each chemotherapy treatment and at follow-up visits between 3 weeks and 3 months after completion of chemotherapy. RESULTS Of 20 evaluable patients, 10% reported a need to wear a wig/head covering at the follow-up visit. Deans alopecia score was excellent for 65% of patients, good for 25% of patients, and moderate or poor for 10% of patients. The majority of patients reported hair thinning after every chemotherapy cycle. No patient discontinued therapy because of an intolerance to cold caps. CONCLUSION Scalp cooling with cold caps appears to be effective in preventing CIA among the majority of women undergoing treatment with TC chemotherapy.
Clinical Cancer Research | 2017
Nancy Chan; Amy Willis; Naomi Kornhauser; Maureen Ward; Sharrell Lee; Eleni Nackos; Bo Ri Seo; Ellen Chuang; Tessa Cigler; Anne Moore; Diana Donovan; Mv Cobham; Veronica Fitzpatrick; Sarah Schneider; Alysia Wiener; Jessica Guillaume-Abraham; Elnaz Aljom; Richard Zelkowitz; J. David Warren; Maureen E. Lane; Claudia Fischbach; Vivek Mittal; Linda T. Vahdat
Purpose: Bone marrow–derived progenitor cells, including VEGFR2+ endothelial progenitor cells (EPCs) and copper-dependent pathways, model the tumor microenvironment. We hypothesized that copper depletion using tetrathiomolybdate would reduce EPCs in high risk for patients with breast cancer who have relapsed. We investigated the effect of tetrathiomolybdate on the tumor microenvironment in preclinical models. Experimental Design: Patients with stage II triple-negative breast cancer (TNBC), stage III and stage IV without any evidence of disease (NED), received oral tetrathiomolybdate to maintain ceruloplasmin (Cp) between 8 and 17 mg/dL for 2 years or until relapse. Endpoints were effect on EPCs and other biomarkers, safety, event-free (EFS), and overall survival (OS). For laboratory studies, MDA-LM2-luciferase cells were implanted into CB17-SCID mice and treated with tetrathiomolybdate or water. Tumor progression was quantified by bioluminescence imaging (BLI), copper depletion status by Cp oxidase levels, lysyl oxidase (LOX) activity by ELISA, and collagen deposition. Results: Seventy-five patients enrolled; 51 patients completed 2 years (1,396 cycles). Most common grade 3/4 toxicity was neutropenia (3.7%). Lower Cp levels correlated with reduced EPCs (P = 0.002) and LOXL-2 (P < 0.001). Two-year EFS for patients with stage II–III and stage IV NED was 91% and 67%, respectively. For patients with TNBC, EFS was 90% (adjuvant patients) and 50% (stage IV NED patients) at a median follow-up of 6.3 years, respectively. In preclinical models, tetrathiomolybdate decreased metastases to lungs (P = 0.04), LOX activity (P = 0.03), and collagen crosslinking (P = 0.012). Conclusions: Tetrathiomolybdate is safe, well tolerated, and affects copper-dependent components of the tumor microenvironment. Biomarker-driven clinical trials in high risk for patients with recurrent breast cancer are warranted. Clin Cancer Res; 23(3); 666–76. ©2016 AACR.
Cancer Research | 2014
Alexander Starodub; Allyson J. Ocean; Manish A. Shah; Linda T. Vahdat; Ellen Chuang; Michael J. Guarino; Vincent J. Picozzi; Sajeve Samuel Thomas; Pius Maliakal; Serengulam V. Govindan; William A. Wegener; Robert M. Sharkey; David M. Goldenberg
IMMU-132 is an ADC of the active metabolite of CPT-11, SN-38, conjugated by a pH-sensitive linker (average drug-antibody ratio = 7.6) to the humanized anti-Trop-2 antibody, hRS7, exhibiting rapid internalization after binding to Trop-2. Trop-2 is a type I transmembrane protein expressed at high prevalence (∼1 x 10*5) and specificity by many carcinomas. We report the results of a Phase I clinical trial of 25 patients with different metastatic cancers (pancreatic, 7; triple-negative breast [TNBC], 4; colorectal [CRC], 3; gastric, 2; small-cell lung [SCLC], 2; esophageal, prostatic, ovarian, non-small-cell lung, renal, tonsillar, urinary bladder, 1 each) after failing a median of 3 prior treatments (some including topoisomerase-I and -II inhibiting drugs). IMMU-132 was administered in repeated 21-day cycles, with each treatment given on days 1 and 8. Dosing started at 8 mg/kg/dose (i.e., 16 mg/kg/cycle), and escalated to 18 mg/kg before encountering dose-limiting neutropenia, in a 3+3 trial design. Fatigue, alopecia, and occasional mild to moderate diarrhea were some of the more common non-hematological toxicities, with 2 patients also reporting a rash. Over 80% of 24 assessable patients had stable disease or tumor shrinkage (17/24 SD; 3/24 PR) among the various metastatic cancers as best response by CT. Three patients (CRC, TNBC, SCLC) have PRs by RECIST; median TTP for all patients, excluding those with pancreatic cancer, is >18 weeks. Neutropenia has been controlled by dose reduction to 8-10 mg/kg/dose (16-20 mg/kg/cycle), which is the Phase II dose. Immunohistochemistry showed strong expression of Trop-2 in most archived patient tumors, but is not detected in serum. Corresponding reductions in blood tumor marker titers (e.g., CEA, CA19-9) reflected tumor responses. No anti-antibody or anti-SN-38 antibodies have been detected despite repeated dosing. Peak and trough assessments of IMMU-132 concentrations in the serum show that the conjugate clears completely within 7 days, an expected finding based on in vitro studies showing 50% of the SN-38 is released in the serum every day. These results indicate that this novel ADC, given in doses ranging from 16-24 mg/kg per cycle, is active in diverse metastatic solid cancers. A Phase II study is ongoing to determine response rates in CRC, TNBC, and SCLC, while also evaluating its potency in other tumor types. Citation Format: Alexander N. Starodub, Allyson J. Ocean, Manish A. Shah, Linda T. Vahdat, Ellen Chuang, Michael J. Guarino, Vincent J. Picozzi, Sajeve S. Thomas, Pius P. Maliakal, Serengulam V. Govindan, William A. Wegener, Robert M. Sharkey, David M. Goldenberg. SN-38 antibody-drug conjugate (ADC) targeting Trop-2, IMMU-132, as a novel platform for the therapy of diverse metastatic solid cancers: Initial clinical results. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT206. doi:10.1158/1538-7445.AM2014-CT206
Cancer Research | 2009
Bhuvaneswari Ramaswamy; Kapil N. Bhalla; B Cohen; C Pellegrino; Dawn L. Hershman; Ellen Chuang; George Somlo; Matthew P. Goetz; R Swaby; U Hopkins; Paul J. Christos; I Espinoza-Delgado; Joseph A. Sparano
Abstract #404 Background: The oral HDACi vorinostat (V) sensitizes breast cancer cells to tubulin polymerizing agents and anti-VEGF directed therapies in vitro. We sought to determine the safety and efficacy of V plus paclitaxel (P) and bevacizumab (B) as first-line therapy for MBC. Methods : Eligible patients (pts) with measurable disease, ECOG PS 0 or 1, and no prior chemotherapy for MBC, received P (90mg/m2) on days 1, 8, 15 and B (10mg/kg) on days 1,15 every 28 days, plus V 200 mg (N=3) or 300 mg (N=28) BID orally for 3 days given the day before, day of, and day after each P dose. Response was assessed after every 3 cycles (RECIST). The trial was designed to distinguish between a response rate of 60% (alpha=0.10, beta=0.10) using Simon9s optimal 2-stage design. At least 12 responses were required in the first 28 evaluable pts in the 1 st stage and 21 of 41 in the 2 nd stage. Results : There were no dose-limiting toxicities among the first 6 pts treated at the 1 st (200 mg BID; N=3) and 2 nd (300 mg BID; N=3) dose levels. Among the 26 evaluable pts treated at the recommended phase II dose of 300mg bid in the 1 st stage, 14 patients had a partial response (PR-54%; 90% confidence interval [C.I.] 36%-71%), 6 had stable disease (SD) at 3 months and remain on treatment, 2 had SD as the best response with progressive disease (PD) at 11.8 and 15 months, and 4 had PD as their best response. Additionally, 2 of 3 pts treated at the first V dose level had a PR, indicating PR in 16 of 29 overall (55%, 90% C.I 38%-71%). Only 11 of 29 evaluable pts (38%) have progressed after a median followup of 10.5 months (R-2.3-14.9). Two pts had tumor biopsies and peripheral blood mononuclear cells (PBMC) collected before and 4 hours after the 3 rd V dose (300 mg BID) which showed increased acetylation of K69 lysine residue of the chaperone protein Hsp 90, upregulation of Hsp70, and downregulation of AKT by Western Blot, providing evidence of Hsp90 inhibition in tumor and PBMC. Gr 3-4 toxicities included neutropenia (26%), neuropathy (23%), fatigue (16%), thrombosis (10%), vomiting (6%), hypertension (3%), and diarrhea (3%). Conclusions : Our preliminary findings indicate that the HDACi V inhibits Hsp90 and downregulates AKT in breast cancer in vivo, and enhances the effectiveness of P plus B in MBC. Accrual is nearly complete and the final efficacy analysis will be presented. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 404.
Cancer Research | 2015
Aditya Bardia; Alexander Starodub; Rebecca Moroose; Ingrid A. Mayer; Jennifer R. Diamond; Ellen Chuang; Serengulam V. Govindan; Robert M. Sharkey; Pius Maliakal; William A. Wegener; Steven A. Hamburger; Allyson J. Ocean; David M. Goldenberg; Linda T. Vahdat
Background: TNBC, comprising 15-20% of all invasive breast cancers, represents an aggressive phenotype with high risk of recurrence and mortality. Trop-2 is a cell-surface glycoprotein expressed on many human carcinomas, including TNBC. High Trop-2 expression is associated with more aggressive disease and poor prognosis in several cancers, including breast cancer. We report interim results from a Phase I/II trial evaluating a novel ADC, IMMU-132 (isactuzumab govitecan), comprising a humanized anti-Trop-2 antibody conjugated to the topoisomerase I inhibitor, SN-38 (active metabolite of irinotecan). The drug:antibody ratio of 7.6 facilitates the delivery of high-dose chemotherapy preferentially to the tumor cells. Methods: Patients (pts) with relapsed/refractory metastatic epithelial tumors were enrolled at escalating IMMU-132 doses (8 to 18 mg/kg), given on days 1 and 8 of a 21-day cycle. The Phase II dose at this schedule was 10 mg/kg. CT scans were performed every 6-8 weeks to assess response using RECIST 1.1. During the dose-escalation portion, evidence of antitumor activity, including 3 partial responses (TNBC, small-cell lung cancer and colorectal cancer) and many with durable stable disease (SD), was observed, leading to Phase II expansion. Results: As of Sept. 25, 2014, a total of 132 pts have been enrolled, including 30 with advanced/metastatic TNBC. Currently evaluable TNBC pts (N=17) had a median age of 50 (33-77), with a median of 4 prior drug regimens (range 1-8), and 67% having received prior platinum-containing regimens. In this heavily pre-treated population, there were 4 PRs (25%) and 9 SDs (56.3%) per RECIST v1.1, representing a disease control (PR+SD g 4 mos) of 53% among evaluable pts with adequate follow-up. A maximum shrinkage of target lesions of 33%, 44%, 51%, and 60% for pts with PRs, and 14%, 19%, and 27% for 3 pts with SD, was determined. Biomarker CA15.3 directional changes correlated with RECIST. All but one pathology specimen were Trop-2+ by immunohistochemistry. HPLC analysis of serum samples found l5% unbound SN-38. The half-life of IMMU-132 was 23 h, which is similar to the predicted half-life from in vitro serum stability studies. Grade 3/4 toxicities were: neutropenia (G3, 4 pts, 23.5%) with 1 febrile neutropenia (5.9%), and lymphocytopenia (1 Gr 3, 1 pt, 5.9%). Grade 1/2 events were fatigue (35.3%), diarrhea (41.2%), and alopecia (29.4%). No pt discontinued therapy due to toxicity. Conclusions: Based on laboratory and initial clinical results, IMMU-132 is an ADC that selectively delivers a topoisomerase I inhibitor to cancer cells without the need for enrichment by a companion diagnostic. It is safe, well-tolerated, with preliminary evidence of encouraging efficacy in heavily-pretreated pts with relapsed/refractory metastatic TNBC. Randomized Phase III and combination trials are being planned. Citation Format: Aditya Bardia, Alexander Starodub, Rebecca L Moroose, Ingrid A Mayer, Jennifer R Diamond, Ellen Chuang, Serengulam V Govindan, Robert M Sharkey, Pius Maliakal, William A Wegener, Steven A Hamburger, Allyson J Ocean, David M Goldenberg, Linda T Vahdat. IMMU-132, a new antibody-drug conjugate (ADC) against Trop-2, as a novel therapeutic for patients with relapsed/refractory, metastatic, triple-negative breast cancer (TNBC): Results from Phase I/II clinical trial (NCT01631552) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-19-27.
Cancer Research | 2015
David M. Goldenberg; Linda T. Vahdat; Alexander Starodub; Aditya Bardia; Ellen Chuang; Rebecca L Moroose; Jennifer R Diamond; Robert M. Sharkey; Pius Maliakal; Steven A. Hamburger; Allyson J. Ocean
Despite major advances in breast cancer treatment, TNBC, which comprises approximately 15% of all breast cancer cases, continues to have a poor prognosis, with an increased risk of recurrence and mortality. IMMU-132 is a new ADC targeting Trop-2, an antigen found in high prevalence in many epithelial cancers, including TNBC, and conjugated to SN-38, a topoisomerase inhibitor and active metabolite of irinotecan, at a high drug:antibody ratio (7.6:1). Studies in mice bearing human pancreatic tumor xenografts (Capan-1) have shown IMMU-132 remains intact in the serum until internalized within the tumor cell where SN-38 is released (pH dependent), resulting in selective cancer cell death. IMMU-132 was found to deliver >120-fold higher amount of SN-38 to xenografted tumors than irinotecan. In animals bearing established MDA-MB-468 TNBC xenografts, IMMU-132 at well-tolerated doses improved responses (more robust regression and delayed progression), compared to irinotecan at a maximum therapeutic dose regimen or to an irrelevant antibody conjugate control. Animals that progressed after receiving the control responded to IMMU-132 therapy, even after those tumors had more than doubled from their initial size. These encouraging pre-clinical data led to the development of the ongoing phase I/II clinical trial in patients (pts) with diverse relapsed/refractory epithelial cancers, including TNBC (NCT01631552). In dose escalation (8 to 18 mg/kg given on days 1 and 8 of a 3-week treatment regimen), dosing was limited primarily by neutropenia, with IMMU-132 being tolerated best for multiple cycles at 8 to 10 mg/kg. Since most (26/30) archival tumors from pts with TNBC expressed Trop-2 (30% ≥2+) and many cancer cell lines express abundant (i.e., >100,000) copies of Trop-2, no enrichment strategies for TNBC were employed to treat TNBC pts with IMMU-132. As of June 1, 2014, 10 pts with TNBC have completed their first response assessment by CT, with 6 having disease shrinkage as their best response; 2 pts had a partial response (-32 and -51% shrinkage of target lesions, with time to progression of 18+ and 30 wks, respectively), and 4 had stable disease (-3, -14 and -19 and -27% shrinkage for 18+, 14, 45, and 24 wks, respectively), according to RECIST. For all pts with diverse cancers treated to date at the phase II dose levels of 8 and 10 mg/kg, 6/25 (24%) had G3 neutropenia; G4 febrile neutropenia occurred in 1 pt. Alopecia, diarrhea, fatigue, nausea, and vomiting are the more common related non-hematological toxicities, but most occur at Grade ≤2. There has been no evidence of immunogenicity to the antibody or the drug, even over multiple cycles of treatment. These promising results in pts who failed multiple prior therapies (median, 4; range, 1-8) suggest IMMU-132 is a safe and potentially effective drug for pts with TNBC, justifying continued evaluation of IMMU-132 in less refractory pts and also in combination with other agents. Citation Format: David M Goldenberg, Linda T Vahdat, Alexander N Starodub, Aditya Bardia, Ellen Chuang, Rebecca L Moroose, Jennifer R Diamond, Robert M Sharkey, Pius P Maliakal, Steven A Hamburger, Allyson J Ocean. IMMU-132, a potential new antibody-drug conjugate (ADC) for the treatment of triple-negative breast cancer (TNBC): Preclinical and initial clinical results [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-19-08.