Specialty Pharmaceuticals: Challenges and Opportunities with Oral Oncology Agents

AUGUST 16, 2010
Todd Cooperman, PharmD, RPh, PAHM, and Russel Allinson, RPh, MS
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
Generic Name Brand Name Manufacturer Therapeutic Category Dosage Form
Anastrozole Arimidex AstraZeneca Aromatase inhibitor Oral tablet
Bexarotene Targretin Eisai Inc Synthetic retinoid Oral capsule
Casodex AstraZeneca Nonsteroidal antiandrogen Oral tablet
Capecitabine Xeloda Roche Pyrimidine analog Oral tablet
Dasatinib Sprycel Bristol-Myers Squibb TKI Oral tablet
Erlotinib Tarceva Genentech, OSI Pharmaceuticals TKI; EGFR inhibitor Oral tablet
Everolimus Afinitor Novartis mTOR kinase inhibitor Oral tablet
Gefitinib Iressa AstraZeneca EGFR-TKI Oral tablet
Imatinib Gleevec Novartis TKI Oral tablet
Tykerb GlaxoSmithKline TKI, EGFR inhibitor Oral tablet
CeeNU Bristol-Myers Squibb Alkylating agent Oral capsule
Melphalan Alkeran GlaxoSmithKline Alkylating agent Oral tablet
Nilotinib Tasigna Novartis TKI Oral capsule
Votrient GlaxoSmithKline TKI, VEGF inhibitor Oral tablet
Sorafenib Nexavar Bayer HealthCare TKI, VEGF inhibitor Oral tablet
Sunitinib Sutent Pfizer TKI, VEGF Inhibitor Oral capsule
Temozolomide Temodar Schering Alkylating agent Oral capsule
Topotecan Hycamtin GlaxoSmithKline Topoisomerase-1 inhibitor Oral capsule
Vorinostat Zolinza Merck Histone deacetylase inhibitor Oral capsule
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
Generic Name Brand Name Manufacturer Therapeutic Category Dosage Form
Lenalidomide Revlimid Celgene Corp Angiogenesis inhibitor, systemic immunomodulator Oral capsule
Thalomid Celgene Corp Angiogenesis inhibitor, systemic immunomodulator, TNF inhibitor Oral capsule
TNF = tumor necrosis factor.
Adapted from references 24 and 25.

Table 3
Dosing of Oral Oncolytics
Generic Name Specific Indication Dose Route Frequency
Everolimus Renal cell carcinoma 10 mg By mouth  Once daily
Renal transplant rejection prophylaxis 0.75 mg By mouth Twice daily (adjust maintenance dose if needed at a 4- to 5-day interval based on serum concentrations, tolerability, and response)
Multiple myeloma 6 mg By mouth Once daily for 2-3 weeks, followed by up to 4 weeks rest, then a maintenance dose of 2 mg daily as hematologic recovery begins
Ovarian carcinoma 0.2 mg/kg By mouth Daily for 5 days, repeat every 4-5 weeks
Anastrozole Breast cancer 1 mg By mouth Once daily
Intracranial tumor 130 mg/m2 By mouth Once every 6 weeks
Hodgkin’s Lymphoma 130 mg/m2 By mouth Once every 6 weeks
Metastatic prostate cacer 50 mg By mouth Once daily (in combination with an LHRH analogue)
Ph+ CML(chronic phase) 400 mg By mouth Once daily (May be increased to 600 mg/day)
Ph+ CML(accelerated phase or blast crisis) 600 mg By mouth Once daily (May be increased to 400 mg twice daily)
Ph+ ALL (relapsed or refractory) 600 mg By mouth Once daily
GIST (adjuvant treatment following complete resection) 400 mg By mouth Once daily
GIST (unresectable and/or metastatic malignant) 400 mg By mouth Once daily (May be increased to 400 mg twice daily)
ASM with eosinophilia 100 mg By mouth Once daily (May titrate up to 400 mg once daily)
ASM without D816V c-Kit mutation or c-Kit mutation status unknown 400 mg By mouth Once daily
DFSP 400 mg By mouth Once daily
HES/CEL 400 mg By mouth Once daily
HES/CEL with FIP1L1-PDGFRα fusion kinase 100 mg By mouth Once daily (May titrate up to 400 mg once daily)
MDS/MPD 400 mg By mouth Once daily
Topotecan Small cell lung cancer 2.3 mg/m2 By mouth Daily for 5 days; repeated every 21 days
Gefitinib Non-small cell lung cancer (NSCLC) 250 mg By mouth Once daily
Sorafenib Renal cell carcinoma 400 mg By mouth Twice daily
Hepatocellular cancer 400 mg By mouth Twice daily
Lenalidomide Multiple myeloma 25 mg By mouth Once daily
Dasatinib CML (Chronic phase) 100 mg By mouth Once daily
CML (Accelerated or blast phase) 140 mg By mouth Once daily
Ph+ ALL 140 mg By mouth Once daily
Sunitinib Gastrointestinal stromal tumor 50 mg By mouth Once daily for 4 weeks of a 6-week treatment cycle (4 weeks on, 2 weeks off)
Renal cell carcinoma 50 mg By mouth Once daily for 4 weeks of a 6-week treatment cycle (4 weeks on, 2 weeks off)
Non-small cell lung cancer (refractory and maintenance therapy) 150 mg By mouth Once daily
Pancreatic cancer 100 mg By mouth Once daily in combination with gemcitabine
Bexarotene Cutaneous T-cell lymphoma 300-400 mg/m2 By mouth Once daily
Ph+ CML, newly-diagnosed (chronic phase) 300 mg By mouth Twice daily
Ph+ CML, resistant or intolerant (chronic or accelerated phase) 400 mg By mouth Twice daily
Anaplastic astrocytoma (refractory) 150 mg/m2 By mouth Once daily for 5 days repeat every 28 days
Glioblastoma multiforme (newly diagnosed, high-grade glioma) 75 mg/m2 By mouth Once daily for 42 days. Wait 4 weeks, then 150 mg/m2/day for 5 days; repeat every 28 days
Erythema nodosum leprosum 100-300 mg By mouth At bedtime with water (at least 1 hour after dinner) until active reaction subsides, then tapered in 50 mg decrements every 2-4 weeks
Multiple myeloma 200 mg By mouth Once daily (with dexamethasone 40 mg daily on days 1-4, 9-12, and 17-20 of a 28-day treatment cycle)
Breast cancer 1250 mg By mouth Once daily (in combination with capecitabine)
Breast cancer 1500 mg By mouth Once daily (in combination with letrozole)
Pazopanib HCL Renal cell carcinoma 800 mg By mouth Once daily
Metastatic breast cancer 1250 mg/m2 By mouth Twice daily for 2 weeks, every 21 days
Metastatic colorectal cancer 1250 mg/m2 By mouth Twice daily for 2 weeks, every 21 days
Dukes' C colon cancer 1250 mg/m2 By mouth Twice daily (8 cycles of 2 weeks of drug administration and 1 week rest period)
Vorinostat Cutaneous T-cell lymphoma 400 mg By mouth Once daily
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

  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

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