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Advanced BCC may be more common in elderly patients but many cannot tolerate surgery or radiation. Many elderly patients have comorbidities and limitations that limit therapeutic options for aBCC. Vismodegib and other medications that are under study are novel options to help manage their aBCC.
Basal cell carcinoma (BCC) is the most common type of skin cancer with an estimated 2.8 million cases diagnosed annually in the United States 1. Close to 40 percent to 50 percent of people who live to age 65 will have at least one non-melanoma skin cancer with BCC being the most common type. BCC more frequently affects older adults and, with an aging U.S. population, the incidence is likely to rise. Advanced basal cell carcinoma (aBCC) is a subset of BCCs that have extensive, invasive or metastatic involvement and are often recalcitrant to standard treatments.
Although aBCC is an unusual variant of BCC, when it does occur, it is often in the elderly population. Later-stage or more complicated lesions in the geriatric population may be caused by both a delay in seeking medical care as well as limited therapeutic options. James Sligh, M.D., Ph.D., associate professor and dermatology division chief at University of Arizona, adds that “locally advanced BCC in older patients tends to have evolved more often from previously treated, recurrent BCC than in younger patients” and presents with a “higher tumor burden”.
Seniors, adults aged 65 and older, represent about 13.7 percnet (about 1 in 7 people) of the United States population.2 Over 90 percent of seniors have at least one chronic medical condition and approximately 75 percent have at least two conditions. Close to 40 percent of seniors will have some type of disability including difficulty in hearing, vision, cognition, ambulation, self-care, or independent living. With many comorbidities, disabilities and a limited life span, treatment of aBCC in the geriatric population can present a difficult challenge.
The benign neglect or watchful waiting approach has often been an option for aBCC patients who are severely-ill. However, even with metastatic BCC, the median overall survival from the time of diagnosis was found to be seven years in a small case series from the Stanford University School of Medicine.3 In that time period, tumors can begin to ulcerate, bleed and cause significant disability and disfigurement. Therefore, it is reasonable to treat elderly patients with even the most advanced cases, unless a severe comorbidity is likely to lead to death in the very near future. Gary Goldenberg, M.D., assistant clinical professor of dermatology at the Icahn School of Medicine at Mount Sinai, emphasizes that oral medication “can be used just for a few months...to reduce symptoms, especially bleeding or ulceration.” There is “no ceiling for treatment,” according to Dr. Sligh, adding, “I believe that elderly patients can benefit greatly from medical management of locally advanced BCC and in many cases are ideal for treatment with non-surgical modalities.”
NEXT: aBCC treatment options for elderly
Treatment options for aBCC in the geriatric population do not differ from other populations but can be more complicated depending on the health status of the patient. Surgery, including Mohs micrographic surgery or wide local excision is still the treatment of choice if the patient could reasonably be expected to tolerate the procedure and as long as it doesn’t subsequently cause significant morbidity.
Patients with significant dementia, tremor or Parkinson’s disease may not be able to stay sedentary for a procedure under local anesthesia. General anesthesia would lend many more risks in this population as well. 4
Radiotherapy is a good treatment option for patients with aBCC who are unable to tolerate surgery. Again, like surgery with local anesthesia, patients would need to remain motionless during the radiation sessions. In addition, transportation for the radiation therapy needs to be considered as treatments are often two to three times per week over several weeks.
Smoothened inhibitors, such as vismodegib (Erivedge, Genentech) and other drugs under study, present new options for patients who refuse or are unable to tolerate procedures. Studies on the safety of vismodegib included patients up to 101 years old with locally aBCC and 92 years old with metastatic aBCC. 5
Vismodegib and its metabolites are eliminated primarily via the hepatic route. Unfortunately, the effect of hepatic or renal impairment on the systemic exposure of vismodegib has not been studied. However, population pharmacokinetic analyses have shown that creatinine clearance as low as 30 mL/min, weight up to 140 kg (308lbs), and age up to 89 years did not have a clinically meaningful influence on the systemic effects of vismodegib. 6
It may prove prudent to assess pre-treatment and periodic complete metabolic panels to gather information on electrolytes, hepatic and renal function in the elderly. In clinical trials, although rare, azotemia, hyponatremia and hypokalemia were observed. Dr. Goldenberg recommends that visit to the primary care doctor and a baseline CPK may be appropriate for elderly patients about to start vismodegib therapy.
NEXT: Polypharmacy considerations
Another consideration in the elderly population is the prevalence of polypharmacy and risk of medication interactions or toxicity. Vismodegib is excreted predominantly as an unaltered drug but has several minor metabolites produced by hepatic CYP enzymes, CYP2C9 and CYP3A4. 6 It does not appear to be altered when coadministered with CYP3A4 inducers or inhibitors.
Medications that inhibit the efflux transporter P-glycoprotein (e.g. clarithromycin, erythromycin, azithromycin) may increase systemic levels of vismodegib leading to more adverse effects and should be monitored closely. Medications that alter the pH of the upper GI tract may alter the absorption and bioavailability of vismodegib.
It is perhaps best to advise patients to avoid proton pump inhibitors, H2 receptor antagonists, and antacids within several hours of taking vismodegib. The only medication with serious interactions is ivacaftor, a medication for cystic fibrosis, which can systemically increase levels of vismodegib. 7 A more complete list of medication interactions can be found using medication interaction tools such as Epocrates or Medscape. 7,8
Side effects of vismodegib are likely to be similar in the elderly as other populations. However, Dr. Sligh advises that the clinician “watch elderly patients carefully for signs of weight loss or dehydration as they tend tolerate [these] potential side effects less than some younger patients might.”
Muscle spasms may be managed with hydration, massage, warm compresses and stretching exercises. Alopecia is more common in the elderly and may be less alarming to this population. Gentle hair care and topical minoxidil may be recommended for patients concerned with alopecia.
Dysgeusia and weight loss may be quite alarming for older adults. Smaller meals with high protein, high caloric content and strong flavors should be eaten more frequently throughout the day. Medications such as megestrol or dronabinol may help relieve anorexia and weight loss in patients on vismodegib. For a list of other helpful tips to combat adverse effects from vismodegib, see the discussion guide for providers and side effects brochure for patients available on the Genentech website. 9
NEXT: Alternatives to surgery
Although less than ideal, some patients are unsuitable for surgery and may prefer a nonradiotherapy or nonchemotherapeutic treatment. Topical and destructive therapies are generally associated with lower clearance rates and higher recurrence rates than surgery or radiotherapy but may be all the patient consents to or can tolerate.
Topical imiquimod is FDA approved for superficial BCCs and provides immunomodulator effects by increasing proinflammatory cytokines. For aBCC, combining therapies such as imiquimod with cryotherapy or curettage and electrodessication may prove better than doing nothing at all. 10,11 Imiquimod plus another destructive or debulking method may be an alternative treatment in elderly patients who have unwillingness or are poor candidates for surgery, vismodegib and/or radiotherapy.
Treatment of aBCC in the elderly is challenging. With a rising incidence of BCC and an aging population, cases of aBCC may be expected to rise. As more data on smoothened inhibitors in this population are published, dermatologists will be able to better guide patients on treatment options. Oral medications may allow us to address aBCC symptoms in non-surgical candidates such as ulceration, bleeding, pain and tumor size. In addition, combination therapy is likely to be a promising option for any patient with advanced BCC.
1. Basal Cell Carcinoma (BCC). Skin Cancer Found. 2014. Available at: http://www.skincancer.org/skin-cancer-information/basal-cell-carcinoma. Accessed August 1, 2014.
2. Profile of Older Americans. Adm Aging, Dep Health Hum Serv. 2013. Available at: http://www.aoa.gov/Aging_Statistics/Profile/Index.aspx. Accessed August 1, 2014.
3. Danial C, Lingala B, Balise R, et al. Markedly improved overall survival in 10 consecutive patients with metastatic basal cell carcinoma. Br J Dermatol. 2013;169:673-676. doi:10.1111/bjd.12333.
4. Li G, Warner M, Lang BH, Huang L, Sun LS. Epidemiology of anesthesia-related mortality in the United States, 1999-2005. Anesthesiology. 2009;110:759-765. doi:10.1097/ALN.0b013e31819b5bdc.
5. Sekulic A, Migden MR, Oro AE, et al. Efficacy and Safety of Vismodegib in Advanced Basal-Cell Carcinoma. N Engl J Med. 2012;366:2171-2179. doi:10.1056/NEJMoa1113713.
6. Erivedge (vismodegib) PRESCRIBING INFORMATION. Genentech USA, Inc. 2012. Available at: http://www.gene.com/download/pdf/erivedge_prescribing.pdf. Accessed August 1, 2014.
7. Vismodegib. Medscape Drugs Dis. 2014. Available at: http://reference.medscape.com/drug/erivedge-vismodegib-999716#3. Accessed August 1, 2014.
8. Erivedge (vismodegib): Drug Interactions. Epocrates, an athenahealth Co. 2014. Available at: https://online.epocrates.com/u/1046285/Erivedge/Drug+Interactions. Accessed August 1, 2014.
9. Erivedge: Resource Library. Genentech USA, Inc. 2014. Available at: http://www.erivedge.com/hcp/resources/index.html. Accessed August 1, 2014.
10. Gaitanis G, Nomikos K, Vava E, Alexopoulos EC, Bassukas ID. Immunocryosurgery for basal cell carcinoma: Results of a pilot, prospective, open-label study of cryosurgery during continued imiquimod application. J Eur Acad Dermatology Venereol. 2009;23:1427-1431. doi:10.1111/j.1468-3083.2009.03224.x.
11. Goldenberg G, Hamid O. Nonsurgical treatment options for basal cell carcinoma - focus on advanced disease. J Drugs Dermatol. 2013;12:1369-78.