Author
Mihaela C. Cristea
Bio: Mihaela C. Cristea is an academic researcher from City of Hope National Medical Center. The author has contributed to research in topics: Ovarian cancer & Cancer. The author has an hindex of 24, co-authored 103 publications receiving 1824 citations.
Topics: Ovarian cancer, Cancer, Medicine, Lung cancer, Gemcitabine
Papers
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University of Oklahoma1, Duke University2, University of Minnesota3, University of Texas Southwestern Medical Center4, Texas Oncology5, University of Chicago6, Mayo Clinic7, Yale University8, Princess Margaret Cancer Centre9, City of Hope National Medical Center10, Stanford University11, Sutter Health12, Cedars-Sinai Medical Center13, Northwestern University14, Harvard University15, University of Arizona16
TL;DR: The data support expansion of the treatment indication for poly(ADP-ribose) polymerase inhibitors to include patients with HRD-positive ovarian cancer beyond those with BRCA mutations and clinically relevant activity of niraparib among women with heavily pretreated ovarian cancer.
Abstract: Summary Background Late-line treatment options for patients with ovarian cancer are few, with the proportion of patients achieving an overall response typically less than 10%, and median overall survival after third-line therapy of 5–9 months. In this study (QUADRA), we investigated the activity of niraparib monotherapy as the fourth or later line of therapy. Methods QUADRA was a multicentre, open-label, single-arm, phase 2 study that evaluated the safety and activity of niraparib in adult patients (≥18 years) with relapsed, high-grade serous (grade 2 or 3) epithelial ovarian, fallopian tube, or primary peritoneal cancer who had been treated with three or more previous chemotherapy regimens. The study was done in the USA and Canada, and 56 sites screened patients (50 sites treated at least one patient). Patients received oral niraparib 300 mg once daily continuously, beginning on day 1 and every cycle (28 days) thereafter until disease progression. The primary objective was the proportion of patients achieving an investigator-assessed confirmed overall response in patients with homologous recombination deficiency (HRD)-positive tumours (including patients with BRCA and without BRCA mutations) sensitive to their last platinum-based therapy who had received three or four previous anticancer therapy regimens (primary efficacy population). Efficacy analyses were additionally done in all dosed patients with measurable disease at baseline. Findings Between April 1, 2015 and Nov 1, 2017, we screened 729 patients for eligibility and enrolled 463 patients, who were initiated on niraparib therapy. At the time of database lock (April 11, 2018), enrolment had closed and the study was ongoing, with 21 patients still on treatment. Patients had received a median of four (IQR 3–5) previous lines of therapy, and the median follow-up for overall survival was 12·2 months (IQR 3·7–22·1). 151 (33%) of 463 patients were resistant and 161 (35%) of 463 patients were refractory to the last administered platinum therapy. 13 (28%) of 47 patients in the primary efficacy population achieved an overall response according to RECIST (95% CI 15·6–42·6; one-sided p=0·00053). The most common drug-related grade 3 or worse treatment-emergent adverse events were anaemia (113 [24%] of 463 patients) and thrombocytopenia (95 [21%] of 463 patients). The most common treatment-emergent serious adverse events were small intestinal obstruction (34 [7%] of 463 patients), thrombocytopenia (34 [7%] of 463 patients), and vomiting (27 [6%] of 463 patients). One death due to gastric haemorrhage was considered treatment related. Interpretation We observed clinically relevant activity of niraparib among women with heavily pretreated ovarian cancer, especially in patients with HRD-positive platinum-sensitive disease, which includes not only patients with a BRCA mutation but also a population with BRCA wild-type disease. We identified no new safety signals. Our data support expansion of the treatment indication for poly(ADP-ribose) polymerase inhibitors to include patients with HRD-positive ovarian cancer beyond those with BRCA mutations. Funding Tesaro.
312 citations
Johns Hopkins University1, Vanderbilt University2, Mayo Clinic3, University of Wisconsin-Madison4, University of Colorado Boulder5, Duke University6, University of California, San Francisco7, City of Hope National Medical Center8, Harvard University9, University of Texas at Austin10, Fred Hutchinson Cancer Research Center11, Memorial Sloan Kettering Cancer Center12, University of South Florida13, Fox Chase Cancer Center14, Stanford University15, University of California, Los Angeles16, Brigham and Women's Hospital17, Case Western Reserve University18, University of Pennsylvania19, Northwestern University20, University of California, San Diego21, University of Michigan22, University of Texas Southwestern Medical Center23, Ohio State University24, Yale University25, University of Nebraska Medical Center26, University of Utah27, Roswell Park Cancer Institute28, National Comprehensive Cancer Network29
254 citations
Johns Hopkins University1, Vanderbilt University2, Mayo Clinic3, University of Wisconsin-Madison4, University of Colorado Boulder5, Duke University6, Stanford University7, University of California, San Francisco8, City of Hope National Medical Center9, University of Tennessee Health Science Center10, University of Texas MD Anderson Cancer Center11, University of Washington12, Moffitt Cancer Center13, Fox Chase Cancer Center14, University of Alabama at Birmingham15, Brigham and Women's Hospital16, University Hospitals of Cleveland17, Northwestern University18, University of California, San Diego19, University of Michigan20, Ohio State University21, Harvard University22, Yale Cancer Center23, Memorial Sloan Kettering Cancer Center24, University of Utah25, Roswell Park Cancer Institute26, National Comprehensive Cancer Network27
TL;DR: Recent updates to neoadjuvant chemotherapy recommendations, including the addition of hyperthermic intraperitoneal chemotherapy, and the role of PARP inhibitors and bevacizumab as maintenance therapy options in select patients who have completed primary chemotherapy are focused on.
Abstract: Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years from diagnosis. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. The best outcomes are observed in patients whose primary treatment includes complete resection of all visible disease plus combination platinum-based chemotherapy. Research efforts are focused on primary neoadjuvant treatments that may improve resectability, as well as systemic therapies providing improved long-term survival. These NCCN Guidelines Insights focus on recent updates to neoadjuvant chemotherapy recommendations, including the addition of hyperthermic intraperitoneal chemotherapy, and the role of PARP inhibitors and bevacizumab as maintenance therapy options in select patients who have completed primary chemotherapy.
164 citations
TL;DR: Although the use of IP/IV chemotherapy increased significantly at National Comprehensive Cancer Network centers between 2003 and 2012, fewer than 50% of eligible patients received it.
Abstract: PurposeA 2006 randomized trial demonstrated a 16-month survival benefit with intraperitoneal and intravenous (IP/IV) chemotherapy administered to patients who had ovarian cancer, compared with IV chemotherapy alone, but more treatment-related toxicities. The objective of this study was to examine the use and effectiveness of IP/IV chemotherapy in clinical practice.Patients and MethodsProspective cohort study of 823 women with stage III, optimally cytoreduced ovarian cancer diagnosed at six National Comprehensive Cancer Network institutions. We examined IP/IV chemotherapy use in all patients diagnosed between 2003 and 2012 (N = 823), and overall survival and treatment-related toxicities with Cox regression and logistic regression, respectively, in a propensity score–matched sample (n = 402) of patients diagnosed from 2006 to 2012, excluding trial participants, to minimize selection bias.ResultsUse of IP/IV chemotherapy increased from 0% to 33% between 2003 and 2006, increased to 50% from 2007 to 2008, and ...
152 citations
TL;DR: Interdisciplinary palliative care in the ambulatory care setting resulted in significant improvements in QOL, symptoms, and distress for NSCLC patients.
144 citations
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01 Jan 2014
TL;DR: Lymphedema is a common complication after treatment for breast cancer and factors associated with increased risk of lymphedEMA include extent of axillary surgery, axillary radiation, infection, and patient obesity.
1,988 citations
01 Aug 2016
TL;DR: Trimetazidine is indicated in adults as add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled by or intolerant to first-line antianginal therapies.
Abstract: 4 CLINICAL PARTICULARS 4.1 Therapeutic Indications Trimetazidine is indicated in adults as add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled by or intolerant to first-line antianginal therapies. 4.2 Posology and method of administration Oral administration. Posology The dose is one tablet of 35mg of trimetazidine twice daily during meals. Special populations Renal impairment In patients with moderate renal impairment (creatinine clearance [30-60] ml/min) (see sections 4.4 and 5.2), the recommended dose is 1 tablet of 35mg in the morning during breakfast. Elderly Elderly patients may have increased trimetazidine exposure due to age-related decrease in renal function (see section 5.2). In patients with moderate renal impairment (creatinine clearance [30-60] ml/min), the recommended dose is 1 tablet of 35mg in the morning during breakfast. Dose titration in elderly patients should be exercised with caution (see section 4.4). Health Products Regulatory Authority
1,677 citations
TL;DR: The principles behind targeted delivery approaches are reviewed to determine potential reasons for their limited clinical translation and success and criteria and considerations that must be taken into account for the development of novel actively targeted NCs are proposed.
Abstract: Targeted delivery approaches for cancer therapeutics have shown a steep rise over the past few decades. However, compared to the plethora of successful pre-clinical studies, only 15 passively targeted nanocarriers (NCs) have been approved for clinical use and none of the actively targeted NCs have advanced past clinical trials. Herein, we review the principles behind targeted delivery approaches to determine potential reasons for their limited clinical translation and success. We propose criteria and considerations that must be taken into account for the development of novel actively targeted NCs. We also highlight the possible directions for the development of successful tumor targeting strategies.
1,335 citations
City of Hope National Medical Center1, Harvard University2, American Society of Clinical Oncology3, Virginia Commonwealth University4, University of North Carolina at Chapel Hill5, University of Michigan6, Northwestern University7, National Coalition for Cancer Survivorship8, Princess Margaret Cancer Centre9, Johns Hopkins University10
TL;DR: The guideline update reflects changes in evidence since the previous guideline and inpatients and outpatients with advanced cancer should receive dedicated palliative care services, early in the disease course, concurrent with active treatment.
Abstract: Purpose To provide evidence-based recommendations to oncology clinicians, patients, family and friend caregivers, and palliative care specialists to update the 2012 American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) on the integration of palliative care into standard oncology care for all patients diagnosed with cancer. Methods ASCO convened an Expert Panel of members of the ASCO Ad Hoc Palliative Care Expert Panel to develop an update. The 2012 PCO was based on a review of a randomized controlled trial (RCT) by the National Cancer Institute Physicians Data Query and additional trials. The panel conducted an updated systematic review seeking randomized clinical trials, systematic reviews, and meta-analyses, as well as secondary analyses of RCTs in the 2012 PCO, published from March 2010 to January 2016. Results The guideline update reflects changes in evidence since the previous guideline. Nine RCTs, one quasiexperimental trial, and five secondary analyses from RCTs in the 2012 PCO on providing palliative care services to patients with cancer and/or their caregivers, including family caregivers, were found to inform the update. Recommendations Inpatients and outpatients with advanced cancer should receive dedicated palliative care services, early in the disease course, concurrent with active treatment. Referral of patients to interdisciplinary palliative care teams is optimal, and services may complement existing programs. Providers may refer family and friend caregivers of patients with early or advanced cancer to palliative care services.
1,283 citations