In 2001, the first oral chemotherapy agent (OCA), imatinib (Gleevec) was approved by the US FDA. Since then, more than 80 OCAs have entered the US market and are currently being used to treat multiple types of cancers.1
Over the past two decades, a significant portion of cancer treatment has shifted from directly observed IV chemotherapy to patient-administered oral chemotherapy.2 The most important advantage of OCAs is patient convenience, given the flexibility in timing and location of administration, when patients are able to receive chemotherapy in the comfort of their own homes. However, to ensure safe OCA use, this new treatment modality requires comprehensive patient education, monitoring, and support.
Managing Oral Chemotherapy
Because the incorporation of OCAs has shifted the mode of cancer treatment, certain issues must be carefully considered to ensure safe use, including patient adherence, drug-food interactions, and drug-drug interactions.
The ability to take OCAs at home without the direct supervision of a health care provider places increased responsibility on the patient to manage their own care. It is imperative that patients take their OCAs correctly; this includes appropriate dose, frequency, time in relation to food, and time in relation to other medications. Should patients not feel an immediate benefit from the medication, they may not see the need to continue the chemotherapy regimen. This is concerning, as nonadherence has been shown to worsen event-free survival in patients with chronic myelogenous leukemia (CML), for example.3
As such, counseling that emphasizes the importance of adherence should be presented by pharmacists upon initiation of therapy and throughout treatment. Daily reminders, cell phone apps, routines, and diaries can assist patients in taking their OCAs regularly. For regimens that require time off of the OCAs, calendars can be used to assist patients in understanding when to take them and when not to.
OCAs differ from IV treatment in that they may be affected by food interactions, whereas this is rarely the case with IV treatment. For some OCAs, food may alter the bioavailability and affect the clinical efficacy and/or increase toxicity of the treatment. For example, nilotinib (Tasigna) should be taken on an empty stomach, as concomitant administration with food will increase its absorption and consequently the risk of toxicities, such as potentially fatal QT prolongation.4 Conversely, capecitabine (Xeloda) should be taken with food to reduce potential side effects.5 Pharmacists should counsel patients and family members on the proper way to take their prescribed OCA in relation to food.
Drug interactions are also a significant consideration when managing patients taking OCAs, particularly elderly patients. Many cancers are diagnosed in the older population (eg, chronic myeloid leukemia, prostate cancer), and these patients tend to have multiple comorbidities and rely on a significant number of other medications to manage them. Approximately 50% of OCAs are substrates for cytochrome P450 (CYP) 3A4, which is the most common substrate of CYP450 interactions. Other CYP isozymes (eg, CYP2D6, CYP2C9, CYP2C19) and metabolism pathways (eg, P-glycoprotein) can also lead to drug-drug interactions, albeit less commonly.
Concomitant acid suppressive therapy should be evaluated for potential drug-drug interactions. Some OCAs, such as dasatinib, nilotinib, and erlotinib, require an acidic environment for optimal absorption4,6,7; concurrent proton pump inhibitor (PPI) treatment should be avoided in patients taking these OCAs. H2 antagonists can be considered, but depending on the agent, should be spaced apart from OCA administration. Interestingly, cola has been shown to increase the bioavailability of erlotinib with non-small cell lung cancer patients during esomeprazole treatment and can be considered for patients who have to take a PPI and an OCA that requires an acidic environment.8
Patients should undergo a detailed medication reconciliation prior to starting OCAs, which includes any over-the-counter medications, nutritional and herbal supplements, and prescription medications, in order to assess any potential drug-drug interactions. Whenever possible, patients’ medication regimens should be simplified to avoid potential drug-drug interactions and to improve adherence.9 Patients should also be counseled to check with a member of the health care team before starting any new medications while taking OCAs. If a drug-drug interaction arises, pharmacists should provide alternative agents that do not interact with the OCA.
Patient counseling, including information about toxicity, side effects, and safe handling practices, is critical to safe OCA use.
Toxicity of OCAs
It is important to inform patients that OCAs are not necessarily less toxic than traditional IV chemotherapy agents, and that they are, indeed, still chemotherapy. Although OCAs usually do not have the myelosuppressive side effect profile of traditional IV chemotherapy, they have their own unique toxicity profiles.
It is essential that patients be counseled on the potential side effects of their OCAs so they understand what to expect, as well as how to manage side effects at home. A common example of a side effect that can be managed at home is chemotherapy-induced diarrhea (CID), which has been reported in 50% to 80% of patients receiving OCAs. Uncomplicated CID can be treated with over-the-counter loperamide (4 mg orally initially and then 2 mg every 2 to 4 hours or after every unformed stool; maximum 16 mg/day). Guidelines also recommend tincture of opium and octreotide, while diphenoxylate/atropine is an additional option.10,11 Nonpharmacologic management includes avoiding foods that may aggravate the diarrhea, aggressive oral rehydration, and following a BRAT (ie, bananas, rice, applesauce, and toast) diet.
Patients and caregivers should be aware of safe handling practices with oral chemotherapy. As hazardous medications, OCAs should be handled only when wearing gloves, and patients and caregivers should wash their hands after handling OCAs. Patients should fully understand how to take their OCAs and keep a diary of any adverse effects. Patients should not crush or chew tablets, open capsules, or double up on doses unless instructed to do so.12 TABLE 1 provides some additional guidelines regarding OCA handling.
As medication experts, pharmacists should play a key role in OCA management by providing essential counseling to patients and caregivers, including the best way to take the OCAs and common adverse effects to expect. Pharmacists can also help improve adherence and outcomes in patients taking OCAs, and can serve a vital role in screening for potential drug-drug and drug-food interactions. Most importantly, pharmacists should use their knowledge, training, and background as a critical resource in ensuring safe use of OCAs.
Chung-Shien Lee, PharmD, BCPS, BCOP, is an assistant professor at St. John’s University College of Pharmacy and Health Sciences, in the department of clinical health professions, in Queens, New York.
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