Pharmacists play key role in guiding adolescents, young adults through cancer survivorship
Adolescent and young adult cancer survivors are more likely than their peers to develop chronic health conditions, and pharmacists play a key role in helping to alleviate their symptoms, according to two presenters at HOPA Ahead 2019.
Joseph Sciasci, PharmD, BCOP, BCPS, clinical pharmacy specialist with the cancer center and blood and marrow transplant program at Children’s Hospital of Philadelphia, and Mary Mably, RPh, BCOP, pharmacy manager at UW Health in Wisconsin, provided an overview of how cancer treatment for adolescents and young adults (AYA) impacts their risk for long-term morbidity. They also identified opportunities for pharmacists to reduce incidence of long-term morbidity among AYA cancer survivors who received chemotherapy, explained treatment strategies for hormone-related symptoms, and offered insights into fertility preservation methods for this population.
Protocol-based chemotherapy plans have greatly benefited children, adolescents and young adults with cancer, helping to increase the cure rate for childhood malignancies to more than 80%. As the number of survivors has increased, however, so has incidence of therapy-related toxicity later in life.
Chronic conditions common
Research has revealed the connection between cancer treatment and treatment-associated conditions in children and adolescents. A study by Oeffinger and colleagues, published in 2006 in The New England Journal of Medicine, showed that 23% of survivors experience at least two significant toxicities by age 35 years.
In the retrospective cohort study, researchers monitored the health status of adults diagnosed with pediatric cancer between 1970 and 1986 and siblings without cancer. They tracked the prevalence of chronic conditions among 10,397 childhood cancer survivors (mean age, 26.6 years; range, 18-48) and 3,034 siblings (mean age, 29.2 years; range, 18-56). The researchers gave each condition a severity score, ranging from grade 1 (mild) to grade 4 (life-threatening).
The researchers found that among the survivors, 62.3% had at least one chronic condition, whereas 27.5% had a grade 3 or grade 4 condition.
Compared with siblings, the adjusted RR for a chronic condition in a survivor was 3.3 (95% CI, 3-3.5), whereas the adjusted RR for a severe or life-threatening condition was 8.2 (95% CI, 6.9-9.7).
At 30 years after cancer diagnosis, the survivors had cumulative incidence rates of 73.4% (95% CI, 69-77.9) for chronic health conditions and 42.4% (95% CI, 33.7-51.2) for severe/life-threatening conditions or death as a result of a chronic condition.
Childhood cancer survivors may face a wide variety of chronic health conditions, including psychosocial, orthopedic, endocrine or cardiovascular effects.
Oeffinger and colleagues also found that treatment-related toxicities that led to death — including secondary malignancy, or cardiac or pulmonary toxicities — represented 18% of the excess risk for death among children with cancer.
‘Consider therapy differences’
According to Sciasci, pharmacists can play an important role in minimizing toxicities in children with cancer.
“Decisions made during therapy will impact toxicities that occur after therapy,” Sciasci said during his presentation. “Pharmacists must consider therapy differences, both at protocol planning [or] design stages and while providing direct patient care.”
For example, among adolescent patients with acute lymphoblastic leukemia, those who received dexamethasone experienced significantly more toxicities than those who received prednisone, according to a study by Inaba and Pui. These included infection, bone fracture, osteoporosis, mood/behavioral problems and myopathy.
Sciasci added that these effects may ultimately cause patients to become noncompliant with their treatment.
“If a patient is having more toxicities, that can also decrease their adherence,” he said. “They don’t want to take a medication if they’re having a bad experience with it. Toxicities can also lead to delays in their chemotherapy; they may have to wait until they recover.”
Dexamethasone may also be linked to cognitive and behavioral issues among adolescent and young adult patients, Sciasci said. Hydrocortisone has been shown to yield improved psychological scores among patients with neuropsychological toxicities, he added.
Cisplatin can have a detrimental effect on hearing, which can hinder neurocognitive development. According to a 2017 study by Breglio and colleagues, this effect may be caused by the retention of cisplatin in the cochlea for months to years following chemotherapy treatment.
The use of sodium thiosulfate or amifostine may reduce the effect of chemotherapy on hearing, Sciasci said.
“This is a bit of a controversial issue in many institutions. In our institution, we have not adopted this as our standard,” he said. “I think sometimes there are concerns about toxicities associated with either amifostine or sodium thiosulfate, as well as injection or infusion-type toxicities. However, as a patient’s hearing decreases, we start having this discussion. Right now, it’s more of a case-by-case discussion.”
Prior research also demonstrated a dose-dependent risk for long-term cardiac toxicities with anthracyclines. Dexrazoxane — although not consistently used — has been shown to reduce anthracycline-induced cardiomyopathy (RR = 0.29; 95% CI, 0.2-0.41) and should be considered when lifetime anthracycline exposure is anticipated to be greater than 300 mg/m2 doxorubicin equivalents, Sciasci said.
Sciasci said concerns that dexrazoxane may have had negative effects on a patient’s response to chemotherapy previously hindered its use.
“Subsequent data has suggested that this might not be as much of a concern, that patients don’t do worse in terms of overall survival when treated with dexrazoxane,” he said. “Overall, dexrazoxane does result in a reduction in anthracycline-induced cardiomyopathy, and at my institution, we consider including dexrazoxane when anthracycline doses are expected to exceed 300 mg/m2 doxorubicin equivalents.”
Effects of immunotherapy
Although the availability of many immunotherapies has expanded treatment options, their differing toxicity profiles must be considered, Sciasci added
“Increased use of targeted agents, such as chimeric antigen receptor T-cell therapies, has reduced the burden of additional chemotherapy exposure in some relapsed/refractory patient subsets,” Sciasci said. “As use of targeted agents continues to grow, we expect the number of survivors to increase. Reduced exposure to chemotherapy may lead to less toxicities, but [CAR T-cell therapy] and other targeted therapies may present their own unique long-term effects.”
Many institutions have created survivorship or late-effects clinics to help AYA patients transition from pediatric or acute care and build relationships with family or adult internal medicine practitioners, Sciasci said. This allows for a health assessment after therapy that can serve as a baseline for subsequent monitoring and also can help address compliance issues that may arise with health issues — such as hypertension or diabetes — that these patients develop, he added.
When caring for young adult cancer survivors, it is important to consider their mental state, health behaviors and sexual function, Mably said.
“Survivors are at greater risk for distress, anxiety, depression and fear of recurrence,” she said during her presentation. “They should be monitored regularly — particularly at times of stress, such as times of scans looking for recurrence, screening for cancer, major life events or times of loss in their life.”
Survivors should be referred to mental health services as necessary. Although pharmacologic interventions are available, nonpharmacologic interventions also can be helpful, Mably said.
“As pharmacists, we sometimes forget about these,” she said. “If you can identify the source of their anxiety or distress — such as pain, sleep disturbances or substance abuse — those should be treated. Also, assuring patients that this is common among survivors provides them with emotional support and a feeling that they are not alone in this.”
Mindfulness and meditation also should be considered, Mably said.
Health behaviors that can influence future cancer risk also must be carefully evaluated, Mably said. These include maintaining a healthy weight, eating a plant-based diet, getting sufficient exercise and undergoing recommended cancer screenings.
As many as 80% of patients with cancer take dietary supplements — often without their health care team’s knowledge — even though there is no evidence to suggest any benefit in the absence of deficiencies or comorbidities, Mably said.
“Although the FDA does regulate some dietary supplements, analyses of supplements from multiple manufacturers showed many products don’t contain the purported active ingredients and can contain unlisted ingredients, such as fillers or banned pharmaceutical ingredients that can be harmful to our patients. ... It’s really important to tease that out ... as part of doing a medication history.”
Mably also provided an overview of fertility preservation options for young cancer survivors.
“Providers should have the earliest possible discussion, before treatment, with patients treated during their reproductive years, as well as parents or guardians of children or adolescents,” she said. “Patients should be referred to appropriate specialists and, of course, the discussion with these patients or their parents should be documented appropriately in the electronic health record.” – by Mark Leiser and Jennifer Byrne
- References:
- Breglio AM, et al. Nat Commun. 2017;doi:10.1038/s41467-017-01837-1.
- Inaba H and Pui CH. Lancet Oncol. 2010;doi:10.1016/S1470-2045(10)70114-5.
- Oeffinger KC, et al. N Engl J Med. 2006;doi:10.1056/NEJMsa060185.
- Sciasci J and Mably M. Survivorship in young adults and adolescents: Current and future challenges. Presented at: HOPA Ahead 2019; April 3-6, 2019; Fort Worth, Texas.
Disclosures: Mably reports advisory board roles with Alnylam Pharmaceuticals, Juno Therapeutics and Stemline Therapeutics. Sciasci reports no relevant financial disclosures. Please see the studies for all other authors’ relevant financial disclosures.
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