The Heart of the Matter: Issues in Cardio-Oncology Research

Transcription

1 The Heart of the Matter: Issues in Cardio-Oncology Research Edith Pituskin RN MN Nurse Practitioner, Radiation Oncology, Cross Cancer Institute PhD (c), Faculty of Rehabilitation Medicine, University of Alberta Assistant Clinical Professor, Faculty of Medicine & Dentistry

2 Objectives To describe the development of one NP s program of research To discuss issues and opportunities related to NP research

3 Oncology RN x 25 years NP in Radiation Oncology x 4 years Previous experience

4 Research Work Rapid Access Palliative Radiotherapy Program Multidisciplinary team working Pituskin E, Fairchild A, Driga A, Dutka J, Gagnon L, Tachynski P, Borschneck J,& Ghosh S. Multidisciplinary Team Contributions Within a Dedicated Outpatient Palliative Radiotherapy Clinic: a Prospective Descriptive Study. International Journal of Radiation Oncology, Biology & Physics Volume 78, Issue 2, Pages , 1 October 2010.

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7 Research Work Rapid Access Palliative Radiotherapy Program Multidisciplinary team working TKIs and palliative RT Pituskin E, Fairchild A, Chow E, Wu J, Presutti R, Gaudreault M, DeAngelis C, North S, Kerba M, & Venner P. Concurrent Tyrosine Kinase Inhibitors and Palliative Radiotherapy in the Treatment of Metastatic Renal Cell Carcinoma: A Retrospective Database Review. International Journal of Radiation Oncology * Biology * Physics Vol.78, Issue 3, Supplement, Page S586.

8 Site Concurrent TKI ± 14 days of RT Single Fraction Multi-fraction Brain Cervical spine Thoracic spine Lung, hilar, mediastinum Lumbo-sacral spine Pelvis, hip, SI Femora Ribs, sternum, clavicles, humeri, scapulae Total Pain Relief BPI current pain and ESAS pain scores were compared from available baseline and best follow-up response. Baseline pain improved from 4.57/10 to 1.56/10 in follow-up in patients receiving TKI in n = 10 who could be reached by telephone.

9 Research Work PhD program Faculty of Rehabilitation Medicine, U of A Cardiotoxicity of novel cancer therapies Alberta Cancer Research Institute (ACRI) Graduate Studentship, September

10 What is cardiotoxicity? Cardiomyopathy Series of negative changes to LV declining pump performance Other effects Vasculature Pericarditis, pericardial thickening arrhythmias

11 Why is it important? The majority of anticancer agents have negative effect on CV system Aging population Increased survivorship

12 Albertan Survivors of Adult Cancer, at least 1 year Post-Diagnosis (March, 2009 data) Sites total > 80,000 Cardiotoxic Treatments Breast 19,945 anthracyclines, trastuzumab, AI, steroids, VEGF-I, RT Prostate 16,399 mitoxantrone, steroids Colon 6,033 fluorouracil Melanoma 5,291 Endometrium 4,104 progestational agents Thyroid 2,884 Lymphoma 2,851 anthracyclines, cardiac radiation, steroids Rectum 2, 496 fluorouracil Kidney 2,486 VEGF-I Cervix 2,039 cisplatin Bladder 1,834 cisplatin Testis 1,612 cisplatin, steroids Lung 1,598 cisplatin, VEGF-I, cardiac radiation Ovarian 1,416 carboplatin Leukemia 1,412 anthracyclines, steroids Slide courtesy JR Mackey

13 Preclinical CVD Often asymptomatic Poor exercise tolerance Frequently, normal ejection fraction

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15 With standard anti-cancer therapies.. Multiple hits to cardiovascular system increased risk of death from cardiovascular disease vs cancer

16 Jones, L.W. JACC, 50(15)

17 Clinical detection

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20 N = 26, mean 20 months post-chemo Compared to controls: 46% vs 0% low cardio-respiratory fitness Overweight/obese 72% vs 50% Resting sinus tachycardia 50% vs 0%

21 Pharmaceutical Percentage of Responders According to the Time Elapsed From AC Administration and Start of HF Therapy AC = anthracyclines; HF = heart failure. (Cardinale JACC 2010)

22 Targeted agents New treatment paradigm in cancer New types of toxicities off-target effects

23 Trastuzumab Blocks HER2 signaling in tumor cells over-expressing HER2 receptors

24 Trastuzumab meta-analysis Overall Survival Viani et al BMC Cancer 200

25 Trastuzumab Blocks HER2 signaling in tumor cells over-expressing HER2 receptors Blocks HER2/neuregulin signaling in the heart HER2 protective in stress response pathways of heart Induction of these pathways loss of survival cues loss of cardiomyocytes

26 NYHA Class 3 or 4 HF Viani et al BMC Cancer 2007

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29 Trastuzumab-related cardiotoxicity Thought to be reversible Not so Currently no proven pharmacologic or non-pharmacologic approaches Wadhwa D, et al Trastuzumab mediated cardiotoxicity in the setting of adjuvant chemotherapy for breast cancer: a retrospective study. Breast Cancer Res Treat. 2009;117(2): McArthur HL, Chia S. Cardiotoxicity of trastuzumab in clinical practice. N Engl J Med. 2007;357(1):94-95.

30 MANTICORE Multidisciplinary Approach to Novel Therapies In Cardiology Oncology REsearch 101 (Breast)

31 MANTICORE Primary Objective: Determine if conventional heart failure pharmacotherapy can prevent trastuzumab mediated LV remodeling among women with HER2+ early breast cancer.

32 perindopril R bisoprolol placebo

33 MANTICORE Overview assessment* MRI biomarkers Randomization Bisoprolol** medication titration 2.5mg 5 10 assessment* MRI biomarkers assessment* MRI biomarkers assessment* MRI biomarkers Perindopril** 2mg 4 8 telephone follow up telephone follow up telephone follow up 0 7d 14d 21d mos trastuzumab *assessment = history, physical, labs ** or placebo

34 Recruitment to date N = 28 screened 4 = ultimately no herceptin (declined chemo, comorbidities) 5 on ACEI/BB/ARB 5 = debilitating stress/family issues 3 = geography 1 = language 1 = too ill/hospitalized 1 = worried about extra drugs/aes 1 = declined, no reason provided 7 consented September 22, January 31, 2011

35 Challenges.

36 1. Geography

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38 Amendment Remote monitoring Local accredited laboratory Portable BP cuff Patient confidence, proficiency

39 2. Stress too stressed, too much going on

40 existential plight? Timing of recruitment women s second shift? career, family/childcare, home, extended family

41 Clinical trial participation, by gender Lung cancer trials men twice as likely to enroll Colorectal cancer men 30% more likely to enroll Cancer Jan 15;106(2):420-5., Predictors of enrollment in lung cancer clinical trials., Du W, Gadgeel SM, Simon MS. JAMA Jun 9;291(22): Participation in cancer clinical trials: race-, sex-, and age-based disparities.murthy VH, Krumholz HM, Gross CP.

42 3. Single site Proximity of research MRI to cancer center

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44 Single site Proximity of research MRI to cancer center Oncology, cardiology specialties Research infrastructure

45 4. Referrals CCI new patient review

46 5. Investigator-initiated Infrastructure University research Personnel

47 Future work REB submission: patient outcomes in NP independent practise comparison of CCI experience vs literature GU Breast

48 Future work Prospective Study of Acute Cardiovascular Effects of First-line Sunitinib in Renal Cell Carcinoma Patients (SUnitinib Prospective CardiovasculaR Effect) (SUPER)

49 Cardio-Oncology REsearch (CORE) Team Collaboration of oncology, cardiology, basic research, biomedical engineering, rehabilitation medicine to provide rapid access for cancer patients to a specialized multidisciplinary cardiology team with expertise in prevention, diagnosis and treatment of heart failure; to develop effective prevention and treatment strategies of cardiotoxicity among cancer patients; to foster research collaborations between cardiology and oncology specialties.

50 Discussion (1) Recruitment issues

51 Discussion (2) Opportunities and/or barriers to NP research

52 Thanks! References available on request