Challenges and Opportunities with Oral Oncology Agents

Pharmacists can collaborate with oncologists to maximize patient outcomes through appropriate dispensing, side-effect monitoring, and adherence.

                               
Todd Cooperman, PharmD, RPh, PAHM        Russel Allinson, RPh, MS

Oral oncology agents reflect a significant divergence from traditional treatment regimens for the treatment of oncologic diagnosis, and represent new challenges and opportunities for the pharmacist. Prior to the introduction of oral agents, patients were monitored primarily at the point of oncolytic infusion. After their introduction, it became apparent that patients taking these drugs did not receive the same level of monitoring for adverse effects and adherence.

Results of a study by Weingart et al concluded that there was limited and inconsistent monitoring of patients on oral oncology products. In addition, in those practices that offered pharmacist consultation and monitoring, only 58% of patients accepted these services. The study results also revealed that only one third of the organizations provided special training to their clinicians to ensure proper education of patients.¹

In a secondary study by Weingart et al, the most common types of medication errors that occurred with oral oncology agents included the wrong dose, wrong drug, and wrong number of days supplied. Of these errors, 39.3% of the wrong number of days of therapy supplied resulted in the patient having an adverse event.²

As a result of these problems, there has been a trend to limit some of the oral oncolytics to a restricted number of pharmacies. In addition, the FDA has mandated additional safety measures, including:

Follow FDA-mandated REMS. The passage of the FDA Act of 2007 (FDAAA) gave the FDA the authority to require additional safety processes when a marketed drug potentially creates a significant risk to the patient. Prior to the passage of the FDAAA, drugs that fell under the risk evaluation and mitigation strategies (REMS) category were approved with a mandated implementation of a risk minimization action plan (RiskMAP). The RiskMAP required the manufacturer to ensure that a robust risk management strategy was in place to minimize the occurrence of an adverse event.³

Enhance tracking of drug distribution and inventories. Manufacturers may have a need to maintain enhanced tracking of drugs released to the market. This may occur with drugs that have a rather complex synthesis process that results in limited production volumes and/or drugs susceptible to counterfeiting.

Ensure training of dispensing pharmacist or treating clinicians. When training is a component of a submitted REMS program, the manufacturer is required to report to the FDA the training elements received by those individuals who will be dispensing the drugs. They may also be required to demonstrate that a specific level of care is being administered to the patient. Frequently, the manufacturer must demonstrate REMS compliance through a specific reporting process. Even though only a select number of oral oncology agents fall under REMS guidelines, they all require greater scrutiny and patient support in order to avoid adverse drug reactions, ensure proper use, and improve patient adherence. In fact, the majority of oral oncolytics could potentially be dispensed in the retail setting. This creates an opportunity for pharmacists to fill in the clinical gap in appropriate prescribing and monitoring.

Opportunities for Pharmacists
The pharmacist represents the last clinician in the prescribing chain and is best qualified to ensure that oral oncolytics are prescribed appropriately and that patients are monitored for adverse effects. There is a 2-step process that can be taken to implement such a program.

Step 1: Drug Knowledge and Monitoring
The first step is to develop a deep knowledge of the drugs and the cancers they treat. The pharmacist must ensure that a prescription received for an oral oncolytic is written properly. If there are any questions regarding the prescription, the pharmacist must consult the prescribing oncologist. In addition, pharmacists should document the diagnosis on the prescription to ensure that they can evaluate the dosing scheme properly. Finally, capturing a complete treatment regimen for the oncologic diagnosis ensures that the pharmacist can properly complete a drug utilization review.

Step 2: Standardization and Documentation of Clinical Activities
Through the use of either a clinical record or a therapeutic monitoring tool, the pharmacist should document his or her activities and interventions. This documentation should include the exact treatment regimen that has been prescribed and the agents being administered by the physician or infusion clinic. Through these 2 activities, the pharmacist can ensure that all pharmacologic issues are identified and addressed appropriately. An electronic record can facilitate the exchange of information and provides reporting to multiple parties, including the oncologists, nurses, and other clinicians. The pharmacist can also facilitate the appropriate treatment coordination of the patient with their clinicians. Documentation secondarily serves as a reference to ensure that a patient is consistently monitored for the relevant adverse events.

Through the standardization of the care process and documentation of their clinical activities, pharmacists can collaborate with oncologists to maximize patient outcomes through appropriate dispensing, side-effect monitoring, and adherence.  

Table 1
Drugs Available in the Retail Setting

EGFR = epidermal growth factor receptor; EGFR-TKI = epidermal growth factor receptor-tyrosine kinase inhibitor; mTOR = mammalian target of rapamycin; TKI = tyrosine kinase inhibitor; VEGF = vascular endothelial growth factor.
 
Adapted from references 4-23.
 
 
Table 2
Oral Oncolytics Available through Limited Distribution

TNF = tumor necrosis factor.
Adapted from references 24 and 25.
 
Table 3
Dosing of Oral Oncolytics

Adapted from references 4-25.
 

Dr. Cooperman is director of research and development and Mr. Allinson is chief executive officer and chief clinical officer of Therigy, LLC

References

1. Weingart SN, Flug J,Brouillard D, Morway L, Partridge A, Bartel S, Shulman LN,Connor M. Oral chemotherapy safety practices at US cancer centres: questionnaire survey.  BMJ 2007;334:407-9.
2. Weingart SN, Toro J, Spencer J, Duncombe D, Gross A, Bartel S, Miransky J, Partridge A, Shulman L, Connor M. Medication errors involving oral chemotherapy. CANCER 2010;116:2455-2464.
3.  Guidance for Industry Format and Content of Proposed Risk Evaluation and Mitigation  trategies (REMS), REMS Assessments, and Proposed REMS Modifications. Available at: www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM184128.pdf . Accessed July 27, 2010.
4. Arimidex (anastrozole) package insert. Available at: www1.astrazeneca-us.com/pi/arimidex.pdf.
5. Targretin (bexarotene)  package insert. Available at: www.eisai.com/pdf_files/prescribing_caps_information.pdf
6. Casodex (bicalutamide) package insert. Available at: www1.astrazeneca-us.com/pi/casodex.pdf.
7. Xeloda (capecitabine) package insert. Available at: www.xeloda.com/pdf/patient-pi.pdf.
8. Sprycel (dasatinib) package insert. Available at:  http://packageinserts.bms.com/pi/pi_sprycel.pdf.
9. Tarceva (erlotinib) package insert. Available at : www.gene.com/gene/products/information/pdf/tarceva-prescribing.pdf.
10. Afinitor (everolimus) package insert. Available at: www.pharma.us.novartis.com/product/pi/pdf/afinitor.pdf.
11. Iressa (gefitinib) package insert. Available at: www1.astrazeneca-us.com/pi/iressa.pdf
12. Gleevec (imatinib) package insert. Available at: www.pharma.us.novartis.com/product/pi/pdf/gleevec_tabs.pdf.
13. Tykerb (lapatinib) package insert. Available at:  http://us.gsk.com/products/assets/us_tykerb.pdf
14. Ceenu (lomustine) package insert. Available at:  www.accessdata.fda.gov/drugsatfda_docs/label/2009/017588s034lbl.pdf
15. Alkeren (melphalan) package insert. Available at:  http://us.gsk.com/products/assets/us_alkeran_tablets.pdf.
16. Tasigna (nilotinib) package insert. Available at:  www.pharma.us.novartis.com/product/pi/pdf/tasigna.pdf
17. Votrient (pazopanib HCl) package insert. Available at:  http://us.gsk.com/products/assets/us_votrient.pdf
18. Nexavar website. Available at:  http://nexavar-us.com/scripts/pages/en/hcp/
19. Nexavar (sorafenib) package insert. Available at:  http://berlex.bayerhealthcare.com/html/products/pi/Nexavar_PI.pdf
20. Sutent (sunitinib) package insert. Available at:   www.pfizer.com/files/products/uspi_sutent.pdf
21. Temodar (temozolomide) package insert. Available at:   www.spfiles.com/pitemodar.pdf
22. Hycamtin (topotecan) package insert. Available at:  http://us.gsk.com/products/assets/us_hycamtin_capsules.pdf
23. Zolinza (vorinostat) package insert. Available at:  www.merck.com/product/usa/pi_circulars/z/zolinza/zolinza_pi.pdf
24. Revlimid (lenalidomide) package insert. Available at:  www.revlimid.com/pdf/REVLIMID_PI.pdf
25. Thalomid (thalidomide) package insert. Available at:  www.thalomid.com/pdf/Thalomid%20PI%2072991-10.pdf