Amit M Oza

University Health Network, Toronto, Ontario, Canada

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Publications (184)1468.71 Total impact

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    ABSTRACT: Background: Eribulin mesylate is a synthetic microtubule inhibitor that showed cytotoxic synergy in combination with gemcitabine preclinically. This combination was assessed in a Phase I dose-finding trial in patients diagnosed with advanced solid tumours who had received up to two prior chemotherapy regimens for metastatic disease (CP cohort). Methods: Dose escalation was performed in a 3+3 design to identify the recommended phase II dose (RP2D). Two additional expansion cohorts in women with gynaecologic cancers at the RP2D (G), and further dose escalation of metastatic chemotherapy-naive patients (CN), were evaluated. Results: 45 patients were treated: 21 (CP), 10 (G) and 14 (CN). The initial combination of eribulin and gemcitabine was administered on days 1, 8, and 15 of a 28-day cycle; however, due to 2 out of 6 dose-limiting haematological toxicities at the first dose level, a reduced dose-intense schedule was assessed. The RP2D was defined at 1.0 mg m(-2) eribulin and 1000 mg m(-2) gemcitabine day 1 and 8 q3 weeks. No other significant toxicities were observed in the G expansion cohort. Neutropenia prevented further dose escalation in the CN cohort. Objective responses were seen in all three cohorts - 2/21 (CP), 1/10 (G) and 2/14 (CN). Conclusions: The combination of eribulin and gemcitabine was well tolerated at the RP2D.British Journal of Cancer advance online publication, 10 November 2015; doi:10.1038/bjc.2015.343
    British Journal of Cancer 11/2015; DOI:10.1038/bjc.2015.343 · 4.84 Impact Factor
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    ABSTRACT: Purpose: Given the implications for clinical care and prevention in identifying a BRCA1/2 mutation, the objective of this study was to determine current BRCA1/2 testing practices in ovarian cancer and to identify future directions. Methods: Two parallel complementary web-based surveys were sent by email to representatives of Gynecologic Cancer InterGroup (GCIG) and to referral centers in countries with and without GCIG membership. Questions posed addressed indications of BRCA1/2 testing for ovarian cancer; the implication of genetic counseling; and prevention strategies employed. Results: Among the GCIG, 22 collaborative groups from 19 countries answered the survey. For the complementary survey, 22 referral centers replied. Findings show criteria to offer germline BRCA1/2 testing are mixed; 55% of GCIG members based testing decisions on histology and, among all respondents the main testing criterion remains family history. Typically, genetic counseling is scheduled prior to the genetic testing; however, if negative, results may not be communicated by the genetic counselor. Time between testing and communicating results varies widely between the groups. Lastly, recommendations to relatives regarding risk reduction surgery are inconsistent. Conclusion: Our study highlights the need for collaborative efforts to devise international guidelines around BRCA1/2 testing in ovarian cancer to ensure consistent BRCA1/2 screening practices are adopted. Clinical practice is evolving rapidly and as BRCA1/2 testing is expected to become more widespread, new approaches are required. Coordinating BRCA1/2 testing practices is crucial in terms of care for the patient diagnosed with ovarian cancer but also towards cancer prevention for affected family members.
    Gynecologic Oncology 10/2015; DOI:10.1016/j.ygyno.2015.10.010 · 3.77 Impact Factor

  • The Lancet Oncology 10/2015; 16(13):e478-e479. DOI:10.1016/S1470-2045(15)00311-3 · 24.69 Impact Factor

  • AACR Ovarian Cancer Meeting, Florida; 10/2015
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    ABSTRACT: Purpose: Preclinical studies have shown that angiogenesis inhibition can improve response to radiation therapy (RT). The purpose of this phase 1 study was to examine the angiogenesis inhibitor sorafenib in patients with cervical cancer receiving radical RT and concurrent cisplatin (RTCT). Methods and materials: Thirteen patients with stage IB to IIIB cervical cancer participated. Sorafenib was administered daily for 7 days before the start of standard RTCT in patients with early-stage, low-risk disease and also during RTCT in patients with high-risk disease. Biomarkers of tumor vascularity, perfusion, and hypoxia were measured at baseline and again after 7 days of sorafenib alone before the start of RTCT. The median follow-up time was 4.5 years. Results: Initial complete response was seen in 12 patients. One patient died without achieving disease control, and 4 experienced recurrent disease. One patient with an extensive, infiltrative tumor experienced pelvic fistulas during treatment. The 4-year actuarial survival was 85%. Late grade 3 gastrointestinal toxicity developed in 4 patients. Sorafenib alone produced a reduction in tumor perfusion/permeability and an increase in hypoxia, which resulted in early closure of the study. Conclusions: Sorafenib increased tumor hypoxia, raising concern that it might impair rather than improve disease control when added to RTCT.
    International journal of radiation oncology, biology, physics 09/2015; DOI:10.1016/j.ijrobp.2015.09.009 · 4.26 Impact Factor

  • Cancer Research 08/2015; 75(15 Supplement):4670-4670. DOI:10.1158/1538-7445.AM2015-4670 · 9.33 Impact Factor

  • Cancer Research 08/2015; 75(15 Supplement):LB-307-LB-307. DOI:10.1158/1538-7445.AM2015-LB-307 · 9.33 Impact Factor
  • S Lheureux · K Karakasis · A M Oza ·

    07/2015; 39(5). DOI:10.1016/j.canep.2015.07.002
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    ABSTRACT: The ICON7 trial previously reported improved progression-free survival in women with ovarian cancer with the addition of bevacizumab to standard chemotherapy, with the greatest effect in patients at high risk of disease progression. We report the final overall survival results of the trial. ICON7 was an international, phase 3, open-label, randomised trial undertaken at 263 centres in 11 countries across Europe, Canada, Australia and New Zealand. Eligible adult women with newly diagnosed ovarian cancer that was either high-risk early-stage disease (International Federation of Gynecology and Obstetrics [FIGO] stage I-IIa, grade 3 or clear cell histology) or more advanced disease (FIGO stage IIb-IV), with an Eastern Cooperative Oncology Group performance status of 0-2, were enrolled and randomly assigned in a 1:1 ratio to standard chemotherapy (six 3-weekly cycles of intravenous carboplatin [AUC 5 or 6] and paclitaxel 175 mg/m(2) of body surface area) or the same chemotherapy regimen plus bevacizumab 7·5 mg per kg bodyweight intravenously every 3 weeks, given concurrently and continued with up to 12 further 3-weekly cycles of maintenance therapy. Randomisation was done by a minimisation algorithm stratified by FIGO stage, residual disease, interval between surgery and chemotherapy, and Gynecologic Cancer InterGroup group. The primary endpoint was progression-free survival; the study was also powered to detect a difference in overall survival. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN91273375. Between Dec 18, 2006, and Feb 16, 2009, 1528 women were enrolled and randomly assigned to receive chemotherapy (n=764) or chemotherapy plus bevacizumab (n=764). Median follow-up at the end of the trial on March 31, 2013, was 48·9 months (IQR 26·6-56·2), at which point 714 patients had died (352 in the chemotherapy group and 362 in the bevacizumab group). Our results showed evidence of non-proportional hazards, so we used the difference in restricted mean survival time as the primary estimate of effect. No overall survival benefit of bevacizumab was recorded (restricted mean survival time 44·6 months [95% CI 43·2-45·9] in the standard chemotherapy group vs 45·5 months [44·2-46·7] in the bevacizumab group; log-rank p=0·85). In an exploratory analysis of a predefined subgroup of 502 patients with poor prognosis disease, 332 (66%) died (174 in the standard chemotherapy group and 158 in the bevacizumab group), and a significant difference in overall survival was noted between women who received bevacizumab plus chemotherapy and those who received chemotherapy alone (restricted mean survival time 34·5 months [95% CI 32·0-37·0] with standard chemotherapy vs 39·3 months [37·0-41·7] with bevacizumab; log-rank p=0·03). However, in non-high-risk patients, the restricted mean survival time did not differ significantly between the two treatment groups (49·7 months [95% CI 48·3-51·1]) in the standard chemotherapy group vs 48·4 months [47·0-49·9] in the bevacizumab group; p=0·20). An updated analysis of progression-free survival showed no difference between treatment groups. During extended follow-up, one further treatment-related grade 3 event (gastrointestinal fistula in a bevacizumab-treated patient), three grade 2 treatment-related events (cardiac failure, sarcoidosis, and foot fracture, all in bevacizumab-treated patients), and one grade 1 treatment-related event (vaginal haemorrhage, in a patient treated with standard chemotherapy) were reported. Bevacizumab, added to platinum-based chemotherapy, did not increase overall survival in the study population as a whole. However, an overall survival benefit was recorded in poor-prognosis patients, which is concordant with the progression-free survival results from ICON7 and GOG-218, and provides further evidence towards the optimum use of bevacizumab in the treatment of ovarian cancer. The National Institute for Health Research through the UK National Cancer Research Network, the Medical Research Council, and Roche. Copyright © 2015 Oza et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.
    The Lancet Oncology 06/2015; 15(8). DOI:10.1016/S1470-2045(15)00086-8 · 24.69 Impact Factor

  • Cancer 06/2015; 121(18). DOI:10.1002/cncr.29484 · 4.89 Impact Factor
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    ABSTRACT: The prognosis for women with recurrent and metastatic endometrial cancer is poor, and improved therapies are needed. The mammalian target of rapamycin (mTOR) pathway is an important target, and mTOR inhibitors show clinical activity in endometrial cancer. An open-label, multicenter, randomized, phase II trial of oral ridaforolimus compared with progestin or investigator choice chemotherapy (comparator) was undertaken in women with metastatic or recurrent endometrial cancer who had progressive disease following one or two lines of chemotherapy and no hormonal therapy. The primary end point was progression-free survival (PFS) assessed by independent radiologic review. One hundred thirty patients were enrolled (64 received ridaforolimus and 66 received the comparator), and median age was 66 years. Treatment discontinuation as a result of adverse events was 33% with ridaforolimus versus 6% with the comparator, with common (> 10%) grade 3 toxicities being hyperglycemia, anemia, and diarrhea. Thirty-eight percent (ridaforolimus) versus 71% (comparator) of patients discontinued treatment as a result of disease progression. Median PFS at the protocol prespecified interim analysis with 58 PFS events (primary end point) was 3.6 months (95% CI, 2.7 to 7.3 months) for ridaforolimus and 1.9 months (95% CI, 1.9 to 2.3 months) for the comparator (hazard ratio, 0.53; 95% CI, 0.31 to 0.90; P = .008). PFS rate for ridaforolimus versus comparator was 48% versus 18% at 16 weeks and 38% versus 15% at 24 weeks. Objective response rate for ridaforolimus versus comparator was 0% versus 4% (P = .925), and stable disease was achieved in 35% versus 17% of patients (P = .021). Oral ridaforolimus shows encouraging activity in advanced endometrial cancer but is associated with significant toxicity. Inhibition of the PI3K/Akt/mTOR pathway may be a viable therapeutic target. © 2015 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 06/2015; DOI:10.1200/JCO.2014.58.8871 · 18.43 Impact Factor

  • Gynecologic Oncology 06/2015; 138(2). DOI:10.1016/j.ygyno.2015.06.014 · 3.77 Impact Factor
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    ABSTRACT: The diagnosis, investigation, and management of ovarian cancer are in a state of flux-balancing ever rapid advances in our understanding of its biology with 3 decades of clinical trials. Clinical trials that started with empirically driven selections have evolved in an evidence-informed manner to gradually improve outcome. Has this improved understanding of the biology and associated calls to action led to appropriate changes in therapy? In this review, the authors discuss incorporating emerging data on biology, combinations, dose, and scheduling of new and existing agents with patient preferences in the management of women with ovarian cancer. Cancer 2015. © 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2015 The Authors. American Cancer Society.
    Cancer 06/2015; 121(18). DOI:10.1002/cncr.29481 · 4.89 Impact Factor
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    ABSTRACT: Introduction: Olaparib (Lynparza®) is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor that has become the first 'personalized' therapy available for patients with BRCA mutation-positive ovarian cancer (OC). A capsule formulation of the drug has recently received approval for use in this population for platinum-sensitive recurrent disease for maintenance therapy following platinum-based chemotherapy in Europe and as third- or fourth-line platinum-sensitive therapy in the USA. Areas covered: This article reviews the development of olaparib in OC with a focus on safety evaluation. Data are based on published literature and reports available from the olaparib development program database. Expert opinion: Oral olaparib 400 mg twice daily has acceptable tolerability when administered as maintenance monochemotherapy in women with relapsed OC. The common toxicities - nausea/vomiting, fatigue and anemia - are mild or moderate in severity and appear consistent across subgroups (BRCA carriers/wild-type). Though the risk is low, long-term monitoring of patients is warranted to determine the potential risk for hematological complications such as anemia, myelodysplastic syndrome or acute myeloid leukemia.
    Expert Opinion on Drug Safety 06/2015; 14(8):1-12. DOI:10.1517/14740338.2015.1045875 · 2.91 Impact Factor
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    ABSTRACT: Optimal management of women with early stage GCT presents a management conundrum - they have excellent prognosis but a third will relapse. Advances uncovering the molecular characteristics of GCTs have not been matched by improvements in our understanding and treatment. Stage I GCT patients referred to Auckland City Hospital (1955-2012) and Princess Margaret Cancer Centre (1992-2012) were identified. Baseline characteristics, histopathology and outcomes were recorded retrospectively. One hundred and sixty stage I GCT patients were identified with median age of 49 years. Median follow-up was 7.0 years (range 0.1-44.2 years). Fifty-one patients (32%) relapsed with a median time to relapse (TTR) of 12.0 years (1.3-17.7 years) - 20 initial relapses occurred 10 years post-diagnosis. Higher relapse rates (43% vs. 24% p=0.02) and shorter TTR (10.2 vs. 16.2 years p=0.007) were seen with stage Ic versus stage Ia disease. Cyst rupture was associated with increased relapse (p=0.03). Surgery was the main therapeutic modality at relapse. Eighty six percent of patients received non-surgical management at least once post-relapse. Clinical benefit rate was 43% with chemotherapy, 61% with hormonal therapy and 86% with radiation. Five- and 10-year overall survival (OS) were 98.5 and 91.6%, respectively. Median OS was similar in patients with (24.3 years) and without relapse (22.3 years). Surgery remains fundamental at diagnosis and relapse. Caution should be exercised in recommending adjuvant chemotherapy at initial diagnosis given OS was greater than 20 years even with relapse. Hormonal therapy at relapse appears encouraging but needs further assessment. Novel treatment strategies need exploration with international collaboration essential for this. Copyright © 2015. Published by Elsevier Inc.
    Gynecologic Oncology 05/2015; 138(2). DOI:10.1016/j.ygyno.2015.05.011 · 3.77 Impact Factor
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    ABSTRACT: DepoVax is an innovative and strongly immunogenic vaccine platform. Survivin is highly expressed in many tumor types and has reported prognostic value. To generate tumor-specific immune response, a novel cancer vaccine was formulated in DepoVax platform (DPX-Survivac) using survivin HLA class I peptides. Safety and immune potency of DPX-Survivac was tested in combination with immune-modulator metronomic cyclophosphamide in ovarian cancer patients. Almost all the patients receiving the therapy produced antigen-specific immune responses; higher dose vaccine and cyclophosphamide treatment generating significantly higher magnitude responses. Strong T cell responses were associated with differentiation of naïve T cells into central/effector memory and late differentiated polyfunctional antigen-specific CD4+ and CD8+ T cells. This approach enabled rapid de novo activation/expansion of vaccine antigen-specific CD8+ T cells and provided a strong rationale for further testing to determine clinical benefits associated with this immune activation. These data represent vaccine induced T cell activation in a clinical setting to a self tumor antigen previously described only in animal models.
    OncoImmunology 05/2015; 4(8):00-00. DOI:10.1080/2162402X.2015.1026529 · 6.27 Impact Factor
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    ABSTRACT: Background: Low-grade serous (LGS) carcinomas of the ovary, fallopian tube and primary peritoneum are a unique subset of serous carcinomas for which current therapies (chemotherapy, hormonal) have demonstrated limited efficacy. KRAS or BRAF mutations, which activate the RAS/RAF/MEK/ERK signaling pathway, are present in many LGS carcinomas. Binimetinib is a potent inhibitor of MEK1/2, a key component of the RAS/RAF/MEK/ERK pathway, and has demonstrated activity in other disease settings where dysregulation of this pathway is present. Methods: This is a 2-arm, open-label, 2:1 randomized Phase 3 study of binimetinib vs physician’s choice chemotherapy (pegylated liposomal doxorubicin, paclitaxel or topotecan) in patients with LGS carcinomas. Eligible patients must have LGS carcinoma that is recurrent or persistent following at least 1 prior platinum-based chemotherapy and no more than 3 prior lines of chemotherapy, and must have RECIST v1.1-defined measurable disease confirmed by blinded independent central review (BICR). Prior to randomization, confirmation of LGS diagnosis is required. Patients are eligible regardless of RAS/RAF mutational status; however, tumor tissue will be retrospectively analyzed for mutations in RAS/RAF and other genes. Prior treatment with a MEK inhibitor or BRAF inhibitor is prohibited. Randomization is stratified by last platinum-free interval and number of prior systemic therapy regimens. The primary endpoint is progression-free survival as determined by the BICR; secondary endpoints include overall survival, overall response, duration of response, disease control rate, safety, quality of life and pharmacokinetics of binimetinib. Binimetinib is administered 45 mg BID orally. Patients receive therapy until disease progression or unacceptable toxicity. Crossover is permitted from physician’s choice chemotherapy to binimetinib upon BICR-confirmed progression. This study will enroll 300 patients worldwide (NCT01849874). Clinical trial information: NCT01849874
    Journal of Clinical Oncology 05/2015; 33. · 18.43 Impact Factor

  • Gynecologic Oncology 05/2015; 138. DOI:10.1016/j.ygyno.2015.04.024 · 3.77 Impact Factor
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    ABSTRACT: Cediranib is a potent multitargeted inhibitor of vascular endothelial growth factor receptor (VEGFR) 1, 2 and 3. The study was initiated to evaluate the activity of cediranib in patients (pts) with recurrent ovarian, peritoneal or fallopian tube cancer (OC). Eligible pts had persistent/recurrent OC following one prior platinum-based chemotherapy with measurable disease or progression based on Gynecologic Cancer Inter Group CA-125 criteria. Because of toxicities observed in the first 23 pts, the initial starting dose of oral daily (od) cediranib was reduced from 45 mg to 30 mg. The primary endpoint was objective response rate at 16 weeks. This study was stratified into two arms: platinum-sensitive (PL-S) and platinum-resistant (PL-R). 74 pts were enrolled; 39 were PL-S and 35 PL-R, with a median age of 58 years [31-87]. In PL-S group, 10 partial responses (PR) and stable disease (SD) in 20 (51%) were confirmed while in the PL-R arm there were no confirmed PR and 23 pts (66%) had SD. The main grade 3/4 toxicities were hypertension (24%), fatigue (17%) and diarrhea (9%). The median progression-free survival for all patients was 4.9 months [3.9-7.0], 7.2 months [4.3-9] for PL-S and 3.7 months [2.6-4.5] for PL-R group. The median overall survival was 18.9 months (95% CI: 13.5-31.5); 27.7 months [17.8-43.3] for PL-S and 11.9 months [8.1-18.9] for PL-R group. Cediranib shows significant activity in recurrent platinum sensitive OC. The toxicities were expected and manageable at the dose of 30 mg od. Copyright © 2015. Published by Elsevier Inc.
    Gynecologic Oncology 04/2015; 138(1). DOI:10.1016/j.ygyno.2015.04.009 · 3.77 Impact Factor
  • Stephanie Lheureux · Amit M Oza ·

    The Lancet Oncology 04/2015; 16(5). DOI:10.1016/S1470-2045(15)70157-9 · 24.69 Impact Factor

Publication Stats

6k Citations
1,468.71 Total Impact Points


  • 2003-2015
    • University Health Network
      Toronto, Ontario, Canada
  • 1997-2015
    • University of Toronto
      • • Department of Medicine
      • • Department of Radiation Oncology
      Toronto, Ontario, Canada
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
  • 2011
    • St. James University
      Сент-Джеймс, New York, United States
    • Cedars-Sinai Medical Center
      • Cedars Sinai Medical Center
      Los Ángeles, California, United States
  • 2010
    • National Institutes of Health
      베서스다, Maryland, United States
  • 2008
    • University of California, Davis
      Davis, California, United States
  • 2002
    • Ottawa Regional Cancer Foundation
      Ottawa, Ontario, Canada