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Article Excerpt
The National Cancer Institute (2007) estimates that 12,500 children are diagnosed with cancer each year. Survival rates for childhood cancer have dramatically improved over the past two decades; 80.2% of young children diagnosed before age five, 78.3% of children diagnosed between ages 5 and 9 years, and 70.3% of children diagnosed with cancer during adolescence will survive (American Cancer Society, 2008). This increased survival rate for children with cancer has led to a need for primary care practitioners to become familiar with the long-term effects of cancer and cancer treatment protocols.
Most childhood malignancies are treated with a combination of intense chemotherapy agents, surgery, and/or radiation therapy. Although these treatments are largely successful in putting children's cancer into remission, they also expose children to related toxicities that may affect children's normal health and development. This article will review the long-term ototoxic effects of cisplatin, a common chemotherapy agent used to treat many childhood malignancies, ways to screen for auditory toxicity in the primary care setting, and current options for monitoring and managing these children's sensorineural hearing loss in the primary care setting.
Methodology
A literature review investigating cisplatin ototoxicity in children and childhood cancer survivors was conducted. The Cumulative Index to Nursing and Allied Health Literature (CINAHL, 1990-2008), PsychINFO (1967-2008), Ovid Medline (1990-2008), Google Scholar ([c] 2008), and Google ([c] 2008) databases were searched for all human studies and review articles published in English that included one or more of the following key words or search terms: "cisplatin," "ototoxicity," "hearing loss," "hearing impairment," "sensorineural hearing loss," "children," "cancer," "childhood cancer," and "childhood cancer survivors." Articles found were reviewed and included if they pertained to ototoxicity that occurred as a consequence of cisplatin treatment for childhood cancer. Ancestry searching of the references of these pertinent articles was also performed. Articles that referenced cisplatin ototoxicity in adults with cancer were excluded.
Review of Literature
Mechanism of Action of Cisplatin
Cisplatin or cis-diamminedichloridoplatinum (CDDP) is an antineoplastic platinum compound. It was the first drug of its class, and as such, it is the most widely studied. Other platinum-containing compounds currently used to treat cancer include carboplatin and oxaliplatin. Platinum agents exert their effect by interfering with cell division or mitosis. They do so by forming platinum complexes within cells. The complexes cause cross-linking between and within strands of DNA (Lehne, 2007; Li, 2006). This damages the DNA of cells and prevents cell mitosis from occurring. It also activates apoptosis pathways to cause cell death.
Current Usages of Cisplatin
Cisplatin is currently utilized in many childhood cancer clinical trials overseen by the Children's Oncology Group, which is the main research organization involved in developing pediatric oncology treatment protocols. Cisplatin and other platinum compounds are used in the treatment of cancers of the bone, connective tissue and muscles, brain and nerve tissues, head, neck, lungs, eyes, kidneys, adrenal glands, lymph tissues, liver, and reproductive organ tissues (see Figure 1) (CureSearch, National Childhood Cancer Foundation, & Children's Oncology Group, 2008; Mayo Clinic, 2008). For these treatment regimens, cisplatin is administered intravenously, and the timing and dosage of cisplatin is dependent on the specific type and grading of the cancer metastasis.
Figure 1. Childhood Cancers Treated with Cisplatin and Other Platinum Compounds * Bone (osteosarcomas) * Connective tissues and muscles (rhabdomyosarcomas) * Lungs * Eyes (retinoblastomas) * Kidneys and adrenal glands (Wilms' tumor) * Lymph tissues (non-Hodgkin's lymphoma) * Liver (hepatoblastomas) * Reproductive organ tissues (testicular, endometrial ovarian, cervical cancers) Sources: CureSearch, National Childhood Cancer Foundation, & Children's Oncology Group, 2008; Mayo Clinic, 2008.
Side Effects of Cisplatin
Common side effects of cisplatin include nausea, vomiting, decreased appetite, metallic taste, alopecia, and tinnitus (Mayo Clinic, 2008). It can also cause electrolyte disturbances in children, including hypomagnesaemia, hypokalemia, and hypocalcaemia (CureSearch et al., 2008; Mayo Clinic, 2008). Other more serious adverse effects of cisplatin include nephrotoxicity, peripheral neuropathy, acute bone marrow suppression, and ototoxicity (CureSearch et al., 2008; Lehne, 2007; Li, 2006; Mayo Clinic, 2008). During cisplatin treatment, children are monitored for most of these toxicities. Kidney function tests, including glomerular filtration rate, blood urea nitrogen, and creatinine clearance, are measured to monitor for nephrotoxicity; physical assessments are conducted to detect any peripheral neuropathies; and complete blood counts with differentials are drawn to monitor for cisplatin-induced myelosupression. Although in the past children's hearing was not monitored, today efforts are being made to routine]y assess children's hearing before, during, and after cisplatin treatment.
Cisplatin-Induced Sensorineurai Hearing Loss
Normal hearing physiology. Human ear anatomy is divided into outer, middle, and inner ear segments. The outer ear includes the pinna and external auditory canal; the middle ear consists of the tympanic membrane and the boney ossicles (malleus, incus, and stapes); and the inner ear consists of the oval window, the cochlea (which houses the organ responsible for hearing), the semicircular canals, and vestibule (which are responsible for balance and equilibrium) (Fontana & Porth, 2005).
Once a sound wave travels through the external auditory canal and into the middle ear, it causes the tympanic membrane to vibrate. The vibration of the tympanic membrane causes the ossicles to vibrate in turn, with the stapes eventually pressing upon the oval window of the inner ear. When the oval window begins to vibrate, it causes the fluid in the cochlea to oscillate along the Organ of Corti, which is lined with hair cells that serve as our hearing receptors. When the hair cells are stimulated by this fluid movement, they transmit nerve impulses through the cochlear nerve to cranial nerve VIII, the vestibulocochlear nerve. From there, the nerve impulses travel to the temporal lobe auditory processing centers of the brain, and audition is perceived (Fontana & Porth, 2005; Huether & Defriez, 2006).
Conductive vs. sensorineural hearing loss. Hearing loss is divided into two classifications: conductive or sensorineural. Conductive hearing loss occurs when there is a malfunction somewhere in the auditory...
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