Ototoxicity Monitoring: The M. D. Anderson Experience. James H. Hall, Jr., M.A., CCC-A Hilary H. Arnaud, Au.D., CCC-A

Transcription

1 Ototoxicity Monitoring: The M. D. Anderson Experience James H. Hall, Jr., M.A., CCC-A Hilary H. Arnaud, Au.D., CCC-A

2 Objectives Overview and presentation of cancer in adult and pediatric patients Discuss ototoxicity and its implications for patients with cancer Identify ototoxic agents Understand the rationale for monitoring ototoxic changes Describe the protocol for monitoring ototoxicity Provide case study examples of ototoxicity Facilitating referrals in your practice

3 Cancer Basics Cancer A class of diseases in which a group of cell display uncontrolled growth, invasion, and, sometimes metastasis Approximately 1,450,000 new cancer diagnosis were made in the US in 2008 Approximately 22,000 children are diagnosed with cancer each year Approximately 295,000 cancer deaths occurred in the US in 2008 Approximately 4,000 children die from cancer each year Cancer is the #2 cause of death in the US (behind heart disease)

4 Introduction At M.D.Anderson, in the Head and Neck Clinic, we have approximately 94,000 patient visits per year. In the Audiology Clinic, we have approximately 3900 patient visits per Of those, approximately 200 patients are receiving potentially ototoxic treatment and are actively being monitored

5 Ototoxicity: Definition Ototoxicity - Damage to the ear, specifically the cochlea or auditory nerve, and sometimes the vestibular system, by a toxin. Ototoxic agents Agents, such as aminoglycoside antibiotics and certain chemotherapies, that have the potential to cause insult or damage to the auditory systems

6 Ototoxic Agents Over 200 potentially ototoxic agents have been identified Those of greatest concern for permanent hearing loss are: Aminoglycoside antibiotics Antineoplastic (chemotherapeutic) agents

7 Ototoxic Aminoglycoside Antibiotics Amikacin Gentamicin Neomycin Kanamycin Netilmicin Streptomycin Tobramycin Vancomycin

8 Incidence of Ototoxicity from Aminogylcoside Antibiotics All aminoglycosides are potentially ototoxic Range: 0% - 63% Kanamycin, streptomycin and gentamicin are considered to produce a rate of about 45% ototoxicity, with tobramycin, netilmicin and neomycin each being slightly less ototoxic

9 Ototoxic Chemotherapeutic Agents Difluoromethylornithine (DFMO) Vincristine Carboplatin (Paraplatin) Cisplatin (Platinol)

10 Ototoxic Chemotherapeutic Agents Difluoromethylornithine (DFMO) Liver cancer, melanoma, and some brain cancers Being investigated as a preventative agent for colon cancer Hearing loss typically occurs within 3-4 weeks following administration, with or without tinnitus Hearing loss is typically reversible following completion of treatment, within 3-4 weeks

11 Ototoxic Chemotherapeutic Vincristine Agents Used with lymphomas and leukemia Potentially ototoxic Occurrence is rare Case studies have reported hearing loss in both younger and older patients Generally irreversible

12 Ototoxic Chemotherapeutic Agents Platinum Compounds Cisplatin (Platinol) Approved by the FDA, December, 1978 Typically causes permanent hearing loss Carboplatin (Paraplatin) Second generation platinum compound Considered to be somewhat less ototoxic than cisplatin Approved by the FDA, March, 1989

13 Cisplatin / Carboplatin: Pediatric Patients Central Nervous System Tumors Brain Tumors Germ Cell tumors Tumors of the reproductive system Hepatoblastoma Liver tumor Neuroblastoma Solid tumors arising from any neural crest of the sympathetic nervous system Osteosarcoma Bone Cancer

14 Cisplatin / Carboplatin: Adult Patients Head and Neck Cancers Lung Cancers Gynecological Cancers Ovarian cancers Cervical cancers Genitourinary Cancers Bladder cancers Testicular cancers

15 Cisplatin / Carboplatin Ototoxicity: Pediatric patients Patient Risk Factors Hearing loss can be more pronounced with pediatric patients Elderly patients General overall poorer physical condition Renal failure Inability to clear cisplatin from the system

16 Tinnitus Cisplatin / Carboplatin Ototoxicity: Symptoms May be permanent or transient Minimal information in the literature regarding tinnitus Hearing loss Typically permanent, high and ultra high frequencies Typically bilateral, but may be unilateral

17 Cisplatin / Carboplatin Ototoxicity: Dosage Treatment Risk Factors Lower dosages result in less incidence hearing loss Higher dosages results in higher incidence of hearing loss Frequency of administration More frequent administration, with lower dosages has been shown to be less ototoxic More frequent administration, with high dosages has been shown to be more ototoxic

18 Cisplatin / Carboplatin Ototoxicity: Treatment Risk Factors Method of administration Intravenous Intra-arterial Hyperthermic intraperitoneal perfusion No information in the literature regarding this method of administration at this time Concurrent treatment with radiation therapy

19 Incidence of Cisplatin- and Carboplatin- Induced Ototoxicity Cisplatin Range: 11 91% Carboplatin Range: 12-82% The wide discrepancy is due to variable study methodologies: All of the listed risk factors Population Pediatric and elderly patients have high incidence of hearing loss Testing Procedures Testing procedures may vary significantly Higher incidence of hearing loss is noted when ultra high frequency testing is completed (i.e. testing above 8000 Hz)

20 Rationale for Monitoring Early detection of hearing loss --> Potential Treatment modification --> Prevention of further loss Limit the dose of the drug Change to an alternative drug Alter treatment regimen Improves counseling Provides realistic expectations Allows appropriate treatment planning Facilitates early introduction of hearing assistance Pre- and post treatment counseling offers the patient important information for post treatment planning in order to ensure an acceptable quality of life

21 Monitoring Procedures: A pre-treatment baseline audiogram is essential Chemotherapy treatment planning During and post-treatment comparison Testing should be completed prior to initial chemotherapy dosing Especially important with Cisplatin, which can cause hearing loss within 24 hours

22 MDACC Ototoxicity Monitoring Protocol Basic audiometry testing Tympanometry Acoustic reflexes testing Speech Reception Threshold testing Word Recognition testing Pure tone testing via air and bone conduction Distortion Product Otoacoustic Emissions DPOAEs have been shown to detect hearing loss prior to pure tone audiometry

23 Patient Issues with Testing Fatigue General acute illness Travel issues Priority issues

24 Monitoring Procedures: Aminoglycosides Baseline testing should be completed prior to administration While it is desirable to test prior to initial dosing with aminoglycosides, typically testing can be completed with 72 hours of administration Subsequent testing should be based on drug administration Typically 1-2 times per week, during administration

25 Monitoring Schedule: Cisplatin Schedule for monitoring Baseline within 1 week prior to beginning of treatment, or within 24 hours of administration 24 hours prior to each subsequent course of high dose cisplatin Low dose cisplatin is monitored every 3 weeks 3, 6 and 12 months following completion of treatment Annually, for up to five years following completion of treatment

26 Monitoring Schedule: Carboplatin Schedule for monitoring Baseline within 1 week prior to beginning of treatment, or within 24 hours of administration Every 3 months during active treatment 3, 6 and 12 months following completion of treatment Annually, for up to five years following completion of treatment

27 Determining Ototoxicity Change in hearing sensitivity is always determined relative to baseline measures > 20 db decrease at any one frequency > 10 db decrease at any two adjacent frequencies Loss of response at three consecutive frequencies (American Speech-Language-Hearing Association, March, 1994)

28 Referrals: The Issue of Getting the Patient to You Attending rounds/presenting to Physicians Genitourinary Gynecology Head and Neck Pediatrics Thoracic medicine Alliances with pharmacists Alliances with Physicians Assistants, Nurse Practitioners, and Nurses

29 Implementing and Maintaining a Monitoring Program Determining the goals of the program Identification of hearing loss Prevention of hearing loss Minimization of hearing loss Rehabilitation when hearing loss is present Counseling the patient / family regarding expectations, communication strategies, rehabilitative assistance, etc.

30 Conclusions For all patients receiving treatment that may be considered to be potentially ototoxic, audiological assessment should be an essential part of the pre-treatment evaluation process, should be routinely performed throughout the treatment process, and should be a routine part of the follow-up process, in order to ultimately ensure optimal quality of life

31 Conclusions Many potentially ototoxic agents have been identified, of which the most concerning are aminoglycoside antibiotics and chemotherapeutic agents Monitoring potentially ototoxic agents serves to provide identification of the effects of the agents as early as possible The procedures for monitoring are well defined

32 Thank You!! James H. Hall, Jr., M.A., CCC-A 1515 Holcombe Blvd, Unit 340 Houston, TX Hilary H. Arnaud, Au.D., CCC-A 1515 Holcombe Blvd, Unit 340 Houston, TX