2. Peripheral Neuropathy PN can be caused by many agents, common ones include alcohol, diabetes, chronic renal failure Infections such as varicella (shingles), HIV, occasionally EBV, CMV Also toxins such as heavy metals (lead, arsenic, mercury) Many chemotherapy drugs About 10% of people with myeloma have PN before any treatment

3. Peripheral Neuropathy Typical chemotherapy related neuropathy differs from that of other forms of PN Glove and stocking distribution Generally sensory, i.e. what a person feels, rather than motor, i.e. what a person can functionally do Estimates run that over 1/3 of chemotherapy drugs can cause PN Risk of PN often dose related, how much drug a pt. receives over time

4. In patients with myeloma, several drugs associated with PN: Thalidomide- PN related to both dose and time on continuous treatment Bortezomib-risks for PN development include –Intravenous administration –Twice weekly versus weekly –Combination with other drugs: egg doxorubicin, platinum, lenalidomide, thalidomide

5. vincristine: part of VAD regimen, used much less frequently now for myeloma; often improves with time Cisplatin-part of DT-PACE regimen-also associated with tinnitus

6. “coasting” can occur, i.e. signs and symptoms continue to develop after therapy stops (particularly true for bortezomib) Genetic predisposition may occur— estimated that 1% of myeloma patients are extremely susceptible to bortezomib related PN and may experience this after one dose

7. ASCO Guidelines for the Treatment of PN Examined 250 trials over twenty years; 42 high quality trials selected to see what drugs helped (or didn’t) (JCO 4/14/2014

8. Not recommended: Hershman et al JCO 32:1941-1967, 2014

9. Recommended: Duloxetine (Cymbalta) Tricyclic antidepressants-nortryptiline (pamelor), amitr1ptyline Gabapentin Topical gel-baclofen, amitriptyline, ketamine

10. Drug alternatives Data suggests acupuncture lowers nausea in pts undergoing chemotherapy Ask your provider for a referral Some insurance plans cover acupuncture Contact: National Certification Commission for Acupuncture and Oriental Medicine. The website is: www.nccaom.org.www.nccaom.org.

11. Steroid induced myopathy This is defined as weakness that develops in “large muscle groups” related to steroids First studied in 1959 Appears to be more common when fluorinated steroids used, DEXAMETHASONE! Any type of steroid can cause this (even inhalers)

13. Typically develops in weeks to months Acute form also exists (symptoms occur in matter of 5-7 days) Symptoms include increasing weakness of upper arms, thighs Difficulty rising from a chair, walking up stairs, lifting more than very light objects repetitively

14. Treatment Recovery is possible but takes weeks to months Reduce or discontinue steroids whenever possible Every other day dosing of steroid Change to less toxic form (e.g. dexamethasone to prednisone) Aerobic exercise, resistance training

15. No medicines appear to be useful Ineffective treatments include: –Potassium and phosphorus supplements –Dilantin (phenytoin) –High dose Vitamin E –Anabolic steroids (what body builders, athletes use)

16. SUPPLEMENTS IP-6

17. Copyright © 2014 American Medical Association. All rights reserved. From: Trends in Alternative Medicine Use in the United States, 1990-1997: Results of a Follow-up National Survey JAMA. 1998;280(18):1569-1575. doi:10.1001/jama.280.18.1569 Figure 2.—Estimated annual out-of-pocket expenditures for alternative therapies vs conventional medical services, United States, 1997. Data are from the Health Care Financing Administration, United States.RBRVS indicates Resource-Based Relative Value Scale. Figure Legend :

18. Use of alternative medications very common among pts receiving chemotherapy Richardson et al JCO 18:2505, 2000

19. Caveats: Some supplements may interfere with chemotherapy agents Blood 2009, 113: 5927

20. Diet: eating from the FDA guidelines Exercise: 20-30 minutes 3-5x weekly Meditation: appears to improve symptoms such as nausea, fatigue Other interventions: music, acupuncture, volunteer activities, sun exposure Ask your doctor their opinion regarding your supplements Make sure they know you are taking them

21. Thanks!