Issues in Cancer Survivorship Larissa A. Korde, MD, MPH June 26, 2010
Estimated US Cancer Cases in Women: 2006-2008 CA Cancer J Clin 2006; 56:106-130; CA Cancer J Clin 2008;58:71 96.
Relative Survival* (%) By Cancer Site US, 1975-2003 Site 1975-1977 1984-1986 1996-2003 All sites 50 54 66 Breast (female) 75 79 89 Colon 51 59 65 Leukemia 35 42 50 Lung and bronchus 13 13 16 Melanoma of the skin 82 87 92 Non-Hodgkin lymphoma 48 53 64 Ovary 37 40 45 Pancreas 2 3 5 Prostate 69 76 99 *5-year relative survival rates based on follow up of patients through 2004. Source: Surveillance, Epidemiology, and End Results Program, 1975-20041, Division of Cancer Control and Population Sciences, National Cancer Institute, 2007.
Overview Menopausal symptoms Chemotherapy induced menopause Hormonal therapy side effects Hot flashes Musculoskeletal pain (aromatase inhibitors) Bone health
Managing Menopausal Symptoms
Hot Flashes a feeling of intense heat with sweating and rapid heartbeat, may typically last from two to thirty minutes for each occurrence Affect ~65% of women with breast cancer Therapeutic options Pharmacologic SSRIs/SNRIs: venlafaxine Centrally active agents: clonidine, gapapentin Non Pharmacologic Mind-body approaches Lifestyle modification
Hot Flash Management: Pharmacologic SSRI/SNRI Numerous agents evaluated in RCTs Venlafaxine 37.5 75 150 mg qd Sertraline 50 mg qd Caution: Cyp2D6 interaction in women on tamoxifen Centrally active agents Clonidine 0.1 mg qd As effective as venlafaxine in recent trial Gabapentin 300 900 mg qd Lancet. 2000 Dec 16;356(9247):2059-63 Breast J. 2006 Mar-Apr;12(2):114-22 Breast Cancer Res Treat. 2008 Aug 1. [Epub ahead of print]
SSRIs and Tamoxifen Metabolism Jin, Y. et al. J. Natl. Cancer Inst. 2005 97:30-39
Hot Flash Management: Non- Pharmacologic Mind-body approaches Hypnosis (JCO published online September 22, 2008) Acupuncture (J Clin Oncol. 2007 Dec 10;25(35):5584-90) Yoga Promising results Lack of placebo control in many trials Supplements Vitamin E Black cohosh Soy products
Hot Flash Management: Lifestyle Modification Hot flash diary: identify triggers Keep body temperature cool: dress in layers use a fan choose cold food and drinks sleep in cool room Regular exercise Avoidance of smoking Avoidance of dietary triggers spicy/hot foods, Caffeine alcohol
AI Related Musculoskeletal Complaints Aromatase inhibitors are considered optimal treatment for postmenopausal women with HR+ disease Musculoskeletal symptoms are common in women taking aromatase inhibitors ~30% report myalgias/arthralgias/arthritis Increased risk of carpal tunnel syndrome Associated with obesity, chemotherapy use, prior HRT use Significant number discontinue therapy (~5%) Sestak, SABCS 2008 Abst 2071;Dent SABCS 2008, Abst 2079
AI Related Musculoskeletal Complaints Class effect? Comparable rates on different AIs Substantial number of women experience joint/muscle pain on one AI but not another Recommended management Symptomatic/supportive: Tylenol, NSAIDs Drug holiday to document relationship of drug to symptoms Switch from one AI to another? Switch to tamoxifen Renshaw, SABCS 2008, Abst 2072
Pilot Study of Acupuncture for AI Related Joint Symptoms 21 participants randomized to immediate or delayed acupuncture Significant reduction in pain scores with acupuncture Crew et al, J Cancer Surviv. 2007 Dec;1(4):283-91
Cancer Therapy Induced Bone Loss Chemotherapy Aromatase inhibitors Oophorectomy Goserelin Estrogen depletion Bioavailable estradiol BMD
Estrogen levels 200 Bioavailable E2, pmol/m 2 160 120 80 40 0 Premenopausal women Postmenopausal women Normal men Androgen deprivation therapy Khosla S, et al. J Clin Endocrinol Metab. 2001;86:3555-3561
Bone Loss and Fracture Risk 16X Gradient risk for fragility fracture 8X 4X 0.5X 2X 1X Normal Osteopenia Osteoporosis +1.0T 0-1.0T -2.0T -3.0T -4.0T
Bone Loss and AIs No patient with normal bone at baseline became osteoporotic after 5 years' treatment with anastrozole Status at baseline Status at 5 years Anastrozole (n=81) Tamoxife n (n=86) Normal bone Normal bone Osteopenic Osteoporotic Not recorded 12 (15%) 14 (17%) 0 6 (7%) 16 (19%) 3 (3%) 0 13 (15%) Osteopenic Normal bone Osteopenic Osteoporotic Not recorded 1 (1%) 21 (26%) 4 (5%) 21 (26%) Annual 3 rates 4 (5%) (%)* 2.5 21 (24%) 1 (1%) 2 22 (26%) 1.5 1 0.5 No. at risk Years Anastrozole Tamoxifen 0 0 0 3092 3094 Anastrozole Tamoxifen 1 2 3 4 5 6 Time since randomization (years) 1 2923 2932 2 2724 2741 3 2553 2579 4 2393 2401 5 2070 2100 6 845 846 *Calculated using Kaplan-Meier estimates
ABSCG-12 Accrual 1999-2006 1803 premenopausal breast cancer patients Endocrine-responsive (ER and/or PgR positive) Stage I and II, < 10 positive nodes No chemotherapy except neoadjuvant Treatment duration: 3 yrs Tamoxifen 20 mg/day Tamoxifen 20 mg/day + Zoledronic acid 4 mg Q6Mos Anastrozole 1 mg/day Surgery (+RT) Goserelin 3.6 mg Q28D Anastrozole 1 mg/day + Zoledronic acid 4 mg Q6Mos Gnant M, et al. ASCO 2008. Abstract LBA4.
Disease-Free Survival: ZA Vs No ZA 100 90 80 70 60 50 40 No. of Events Hazard ratio (95% CI) events vs no ZA, P Value 30 ZA 54 0.643 (0.46 to 0.91), P =.011 20 No ZA 83 10 0 0 12 24 36 48 60 72 84 Time since randomization, mos Number at risk No ZA 904 838 735 565 441 265 161 60 ZA 899 851 744 573 434 270 131 59 Disease-free survival, % Gnant M, et al. ASCO 2008. Abstract LBA4.
Summary/Conclusions Hot flashes Related to early menopause Treatable with both pharmacologic and lifestyle interventions AI related musculoskeletal symptoms Change in AI Alternative approaches Bone loss Bisphosphonates Possible favorable effects on disease recurrence