Pharmacy Purchasing & Products: What are the benefits of oral vs IV chemotherapy?

Kelly Gaertner, PharmD, BCOP, BCPS: Oral anticancer medications are becoming an increasingly integral part of hematology/oncology treatment. Recent years have witnessed an increase in the approval of new oral anticancer drugs and expanded indications for existing medications. Oral anticancer therapy offers several benefits compared with IV therapy, as oral therapy is less invasive, more flexible, and more convenient. For patients, this may result in fewer trips to the infusion center and improved quality of life.¹ Furthermore, patients receiving palliative chemotherapy often prefer oral chemotherapy, as long as efficacy is not sacrificed²; a more recent review also suggests that patients prefer oral to IV anticancer therapy.³

PP&P: What unique concerns accompany oral chemotherapy use?

Gaertner: Although oral anticancer medications offer a more convenient route of administration for the patient compared with IV chemotherapy, use of oral chemotherapy agents is accompanied by additional considerations.

• Drug-Drug Interactions. Clinically relevant drug-drug interactions (DDIs) are more common with oral versus IV therapy. DDIs can be categorized as either pharmacokinetic or pharmacodynamic.⁴ Pharmacokinetic interactions arise when the absorption, distribution, metabolism, or elimination of a drug is affected; interactions impacting absorption and metabolism are most commonly encountered. Pharmacodynamic interactions result in synergistic, additive, or antagonistic pharmacologic effects.⁴ Failure to identify and appropriately manage DDIs may result in reduced efficacy and/or increased toxicity of the affected medication.
  Consider that the absorption of several oral anticancer medications may be affected when administered concurrently with acid-suppressing medications. Therefore, in certain instances, such as with the oral kinase inhibitors erlotinib and neratinib, concurrent use of proton pump inhibitors is discouraged.^5,6 H2-receptor antagonists and antacids may be permissible with certain oral anticancer agents, but must be administered at specific time intervals around the oral anticancer medications. Pharmacists should help identify appropriate therapy options to minimize DDIs and counsel patients on proper administration. As acid suppressive medications are commonly prescribed and available over the counter, it is imperative that health care providers query patients and counsel them on the use of these medications while on oral anticancer therapy.

• Drug-Food Interactions. Patients should also be educated on drug-food interactions, an issue that is a much less common concern with IV therapy. Numerous oral anticancer medications carry recommendations to avoid consumption of grapefruit and grapefruit juice while on therapy; Seville oranges should also be avoided with certain medications. Oral anticancer medications typically carry specific directions on administration around food intake. Taking oral agents with or without food may alter absorption and subsequently impact efficacy or toxicity.¹ Others may be taken without regard to food, but taken in a particular way may reduce nausea.1 Less commonly, dose adjustments may be indicated if the patient is a current cigarette smoker, as is the case with erlotinib.⁵

• Challenges with Obtaining Medication. A variety of issues may arise for patients trying to obtain oral anticancer medications. Once the prescription is sent to the specialty pharmacy, processing time, prior authorization, and/or the need to obtain financial assistance, are all possible roadblocks.⁷ Getting the medication into the patient’s hands may take days to weeks. Furthermore, the high cost of the oral anticancer medication may present a significant issue. Patients may encounter high copays that could become a recurring problem with monthly refills.

• Patient Perception. Patients may have misconceptions regarding the convenience and side effects of oral therapy. They may incorrectly perceive oral anticancer therapy to be less toxic and therefore safer than IV medications.⁸ Although they often carry different side effect profiles than IV therapy, oral anticancer medications are definitely not benign and can cause serious toxicity. Routine laboratory monitoring is generally advised, and more frequent checks may be necessary following treatment initiation. With a number of oral anticancer medications, additional monitoring is recommended, such as cardiac function measurements, regular ophthalmology visits, and/or dermatologic assessments. 

• Increased Complexity. Some patients may find oral anticancer regimens to be complex and confusing, particularly if regimens and schedules vary greatly. Oral anticancer therapy may be administered as monotherapy or in combination with IV or other oral therapy. Use of oral anticancer medication frequently requires multiple tablets per dose. In rare instances, the oral anticancer medication may come in various dosage strengths, and the use of two different tablet strengths may be required to achieve the optimal dose for the patient. This can result in patients not only taking multiple tablets or capsules once or twice daily, but possibly having to use different tablets or capsules in combination. Use of multiple tablets or capsules and/or dosage strengths, twice daily dosing, and/or lack of a continuous dosing schedule may prove challenging to some patients. Finally, certain oral anticancer medications require the use of supportive medications, such as antiemetics, antidiarrheals, or venous thromboembolism prophylaxis, adding to the overall pill burden of the oral anticancer regimen.

PP&P: What are the benefits of developing a formal plan to monitor and manage these drugs?

Gaertner: Ensuring patient safety is the primary objective when developing a formal plan to monitor and manage oral anticancer therapy. Because oral anticancer therapy is associated with a wide range of potential adverse effects, close monitoring is key to symptom identification and management.

Toxicity management may also improve adherence, which in turn can improve patient outcomes, and thus should be continually assessed. Incorporating a routine toxicity and adherence evaluation into the formal monitoring program can help to achieve maximal drug benefit. Follow-up within 7 and 14 days after the start of treatment, and prior to each refill, is suggested.⁹

PP&P: What is the role of the pharmacist in managing oral chemotherapy?

Gaertner: As the medication experts, pharmacists should be closely involved with patient counseling, assessing adherence, managing side effects and drug-drug interactions, and facilitating a patient-provider relationship of communication.

• Patient Counseling. Pharmacists should be integrally involved in patient counseling. Key areas of discussion include the process of obtaining the medication, regimen schedule and start date, administration, management of any drug and/or food interactions, possible adverse events, monitoring, self-management strategies, when and how to contact the clinic or seek immediate medical attention, and plans for follow-up.⁹ It is imperative that patients have a thorough understanding of potential adverse events, what to monitor for, and when to seek help. Safe handling and storage of the oral anticancer medication should be reviewed, including proper disposal methods of any unused medication. Pharmacists should play a central role in providing oral anticancer education at the onset of therapy and reinforce key points with the patient throughout their course of therapy.

• Ordering. Pharmacists can assist with medication ordering to ensure correct dose, directions, and any special administration instructions are included on the prescription. Pharmacists can identify if any dose adjustments are required for renal or hepatic impairment, or for DDIs with concomitant medications. In addition, they can evaluate for appropriate use of the medication and place in therapy as well as assess any comorbid conditions or patient-specific concerns with a particular therapy. Pharmacists can also confirm orders for any necessary supportive medications. Although numerous types of errors may occur with oral chemotherapy, having a pharmacist involved in the ordering of these medications can serve to minimize the risk of errors.¹⁰
  On a higher level, pharmacists can be involved in the development of oral anticancer medication order sets.⁹ Finally, the pharmacist should be notified when a new oral anticancer medication is ordered, so they can perform a thorough review before the order is sent to the specialty pharmacy.

• Assessing Adherence. Pharmacists can assist with assessing patient adherence to therapy. Nonadherence may result for any number of reasons, including patient-specific factors such as spiritual beliefs, physical challenges, a lack of understanding or support, poor communication from the provider or health system, the complexity of the regimen, toxicity, and/or financial burden.¹¹ Whether via phone or during clinic visits, pharmacists are well trained to identify any barriers to adherence and discuss ways to overcome them with patients.

• Assessing Toxicity. Pharmacists are well suited to aid in oral anticancer toxicity assessments. A thorough understanding of drug mechanisms and associated toxicities allows for a comprehensive review of actual or potential adverse events and management strategies. Pharmacists can identify which adverse events to monitor for and help determine whether side effects are drug-related. As DDIs are more frequently encountered with oral anticancer medications, it is crucial that a pharmacist perform a thorough DDI check prior to oral anticancer therapy initiation. It is also important that during follow-up visits with the patient, pharmacists determine whether any new prescription or over-the-counter medications have been started.

• Facilitating Robust Communication. Pharmacists can help facilitate patient-provider communication by serving as a patient advocate and liaison to clinic staff. In the outpatient setting, pharmacists often are the point of contact for patients and should be actively involved with therapy. Poor communication with the health care team may negatively affect patient adherence to medication.¹¹ Pharmacists can help maintain lists of patients receiving oral chemotherapy, and work closely with providers to note any changes in therapy. Assisting with coordination of monitoring and communicating with clinic staff can help to ensure smooth patient care and avoid any therapy interruptions. Optimally, a multidisciplinary approach will be employed for the management of oral anticancer therapies.

  Without pharmacist consultation and recommendation, unconventional methods of administration should not be routinely advised. Rather, in general, patients should be counseled to swallow tablets or capsules whole, not crush, chew, or dissolve them. However, if patients are having difficulty swallowing the medication in its commercial dosage form, pharmacists can assist with identifying any literature or recommendations that may allow the tablet or capsule to be crushed, opened, or dissolved into an alternative form to ensure patient adherence and maximize the drug benefit.

PP&P: What strategies can be employed to ensure patient adherence to oral anticancer medication?

Gaertner: Patient adherence is yet another challenge with oral anticancer therapy, as compliance to therapy is more difficult to assess than with IV medications. Poor patient adherence may result in reduced efficacy and subsequently impact outcomes. Patients should be followed closely while on oral anticancer medication; however, the health care team may have less direct contact with the patient taking oral compared with IV anticancer medication. Ultimately, the use of oral anticancer therapy puts more responsibility on the patient, making patient adherence critical to achieving optimal outcomes and minimizing toxicity.^8,11

Multiple strategies can be employed to ensure patient adherence, including the following:

• Medication Calendars. Providing patients with descriptive calendars outlining their treatment regimen can help them visualize and keep track of the dosing and schedule. Patients should be encouraged to mark off each dose as it is taken.
• Cell Phone Alarms. Another option is to advise patients to set cell phone alarms to remind them to take their medications. This helps ensure the medication is taken at a consistent time each day.
• Store the Medication in a Prominent Place. Simple changes, such as keeping the medication in a place where the patient is most likely to see and remember to take it, can be helpful as well.
• Incorporate Medication into the Daily Routine. Taking the medication should be incorporated into the patient’s daily routine, such as after breakfast, if indicated to be taken with food.¹¹

The selected adherence tool should reflect the patient’s preference and be routinely used.¹¹ Given that oral anticancer medications are typically hazardous drugs, they must be kept in a separate pillbox, if one is used. However, it is important to review the storage and handling information for each drug, as some are recommended to be kept in their original packaging. Finally, patients should be counseled on what to do in the event of a missed dose.

PP&P: How can the pharmacy ensure patients receive appropriate financial assistance to support access to oral anticancer medications?

Gaertner: Obtaining oral anticancer medications is significantly more complex than the processes for most other medications. Oral anticancer medications usually must come from specialty mail order pharmacies and may have distribution restrictions. If the use of a particular specialty pharmacy is mandated, this information is usually noted on the product website. The patient’s insurance also may dictate the source of the prescription.

Oftentimes, the specialty pharmacy can assist with identifying financial assistance programs. It is important that the specialty pharmacy maintain open and ongoing communication with the clinic, so that the prescribing team is kept abreast of any insurance or copay issues and can discuss available options and next steps with the patient. It would also be helpful to have someone on the multidisciplinary care team who is able to facilitate use of patient assistance programs and assist with obtaining the medications.

PP&P: What specialized oral anticancer medication training should be provided to pharmacists?

Gaertner: Pharmacists should receive training on oral anticancer medication safe handling and administration, as well as monitoring. With regard to adverse event monitoring, pharmacists must be aware of class effects of medications, as well as important clinical pearls with individual medications. Pharmacists should also be knowledgeable about which supportive medications are necessary for each oral anticancer medication, as use of recommended supplemental medications may reduce adverse events. Finally, pharmacists must have access to drug information and interaction databases.

References

1. Segal EM, Flood MR, Mancini RS, et al. Oral chemotherapy food and drug interactions: a comprehensive review of the literature. J Oncol Pract. 2014;10(4):e255-e268.
2. Liu G, Franssen E, Fitch MI, et al. Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol. 1997;15(1):110-115.
3. Eek D, Krohe M, Mazar I, et al. Patient-reported preferences for oral versus intravenous administration for the treatment of cancer: a review of the literature. Patient Prefer Adherence. 2016;10:1609-1621.
4. Conde-Estévez D. Targeted cancer therapy: interactions with other medications. Clin Transl Oncol. 2017;19(1):21-30.
5. Tarceva [package insert]. Northbrook, IL: OSI Pharmaceuticals, LLC, an affiliate of Astellas Pharma US, Inc; 2016.
6. Nerlynx [package insert]. Los Angeles, CA: Puma Biotechnology, Inc, 2017.
7. Niccolai JL, Roman DL, Julius JM, et al. Potential obstacles in the acquisition of oral anticancer medications. J Oncol Pract. 2017;13(1):e29-e36.
8. Goldspiel B, Hoffman JM, Griffith NL, et al. ASHP guidelines on preventing medication errors with chemotherapy and biotherapy. Am J Health-Syst Pharm. 2015;72:e6-e35.
9. Mackler E, Segal EM, Muluneh B, et al. 2018 Hematology/Oncology Pharmacist Association best practices for the management of oral oncolytic therapy: pharmacy practice standard. J Oncol Pract. 2019;15(4):e346-e355.
10. Weingart SN, Toro J, Spencer J, et al. Medication errors involving oral chemotherapy. Cancer. 2010;116(10):2455-2464.
11. McCue DA, Lohr LK, Pick AM. Improving adherence to oral cancer therapy in clinical practice. Pharmacotherapy. 2014;34(5):481-494.

Kelly Gaertner, PharmD, BCOP, BCPS, is a hematology/oncology clinical pharmacy specialist practicing with Allegheny Health Network Cancer Institute in Pittsburgh, Pennsylvania. She received her Doctor of Pharmacy degree from Duquesne University in Pittsburgh and completed her oncology pharmacy training at the University of Virginia Health System in Charlottesville, Virginia. Kelly’s professional interests include breast cancer and gastrointestinal malignancies, supportive care, and oral chemotherapy
management.