Background:
Cisplatin is used to treat head and neck cancer. People who take this drug are at risk for hearing loss. Atorvastatin is a drug used to treat high cholesterol. It might reduce the risk of cisplatin-induced hearing loss.
Objective:
To find out if atorvastatin reduces hearing loss in people treated with cisplatin and radiation.
Eligibility:
People ages 18 and older with squamous cell carcinoma of the head and neck who will undergo treatment with cisplatin-based chemotherapy and radiation
Design:
Participants will be screened with their medical records.
Participants currently taking a cholesterol-lowering statin medication are invited to participate in the observational arm of the study. Those not taking such a medication are invited to participate in the interventional arm of the study.
All participants will have 3 study visits for the purpose of evaluating hearing. One before starting cisplatin treatment, one within 3 months of completing cancer treatment, and one within 2 years of completing cancer treatment. They will have tympanograms. A small flexible tip will be placed in the ear canal. A puff of air will be delivered to assess mobility of the ear drum. They will have hearing tests. They will wear headphones. They will listen to tones that vary in loudness. They will be asked to indicate when they hear a sound. They will complete 3 questionnaires at the time of each hearing test.
Participants will have 2 visits for blood tests. These will occur upon consent and 12 weeks after. They will be randomly assigned to take the study drug or placebo orally, once daily. They will take it during cisplatin treatment and for 3 months after treatment.
Long-term follow up will include a chart review 2 years after participants complete their cisplatin therapy.
Willingness and ability to comply with and participate in all study procedures and availability for the duration of the study
Ability to provide consent and provision of signed and dated informed consent form
Adult subjects, aged >=18
Diagnosed with squamous cell carcinoma of the head and neck, confirmed by a pathologic review of surgical or biopsy specimen(s), who meet standard clinical and laboratory criteria and will undergo treatment with concomitant cisplatin-based chemotherapy and radiation with curative intent or treatment with neoadjuvant chemotherapy (NAC). This includes subjects who will be treated with either intensity-modulated radiation therapy (IMRT) or proton radiotherapy, with planned dose to the cochlea <35 Gy (to limit confounding effects of radiation64-67). Patients receiving immunotherapy in addition to cisplatin chemoradiation are eligible. Subjects treated with either high-dose cisplatin (typically 100 mg/m² x 2-3 doses every three weeks) or low-dose, weekly cisplatin (typically 40 mg/m² x 6-7 doses weekly) may enroll. Cisplatin in the neo-adjuvant setting may be given within a combination chemotherapy regimen (e.g TPF= Docetaxel, Cisplatin and 5FU or DC = Docetaxel Cisplatin)
Subjects currently taking a statin drug
Subjects with bilateral flat, Type B tympanogram
Subjects with bilateral cochlear implants
Pre-existing liver or kidney disease that in the opinion of the investigator would interfere with taking Atorvastatin 40 mg daily.
Parallel
Placebo
Other interventionPlacebo will be formulated to also contain a white powder such that the atorvastatin and placebo are indistinguishable even if a capsule is opened.
Atorvastatin
DrugSubjects will be provided with atorvastatin (40 mg) or placebo to be taken daily by mouth or by feeding tube. The tablets may be taken whole or crushed according to patient swallowing capabilities and preference.
To determine the effectiveness of atorvastatin (20 mg) at reducing the incidence and severity of cisplatin-induced hearing loss in patients with head and neck squamous cell carcinoma (HNSCC).
The primary endpoint is the change in hearing sensitivity (as measured by pure-tone audiometry) between the pre-treatment (before cisplatin therapy) hearing test and the post-treatment (after completion of cisplatin therapy) audiogram. Hearing loss will be defined according to CTCAE criteria and will be compared in subjects taking atorvastatin vs. subjects not taking any statin drug. Hearing sensitivity will be compared between audiograms collected at baseline (prior to treatment) to a repeated audiogram at the end of treatment (within 2-4 months of cessation of cisplatin administration).
To examine the extent to which atorvastatin 40 mg alters overall survival and disease-free survival.
It is important to confirm that atorvastatin use does not reduce overall response, survival or disease- free survival in subjects with HNSCC. To date, only two retrospective studies have compared survival in HNSCC subjects taking statins.
To compare the incidence of grade (Bullet)3 AEs through 4 weeks after CRT with atorvastatin versus placebo.
It is important to confirm that atorvastatin does not increase the overall toxicity associated with CRT.
To determine the effectiveness of atorvastatin (40 mg) at reducing changes in hearing sensitivity relative to baseline, as defined by ASHA criteria, in subjects treated with cisplatin- based CRT for head and neck squamous cell carcinoma (HNSCC).
The American Speech-Langauge-Hearing Association (ASHA) ototoxicity criteria can be used for early detection based on changes in hearing sensitivity in extended high frequencies (\>8 kHz). While ASHA does not assign grades to indicate severity, it may provide early diagnosis of hearing loss that has not yet spread to speech-related frequency regions of the cochlea (\<8 kHz).
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