Specialty Pharmaceuticals: 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

Generic Name

Brand Name

Manufacturer

Therapeutic Category

Dosage Form

Anastrozole

Arimidex

AstraZeneca

Aromatase inhibitor

Oral tablet

Bexarotene

Targretin

Eisai Inc

Synthetic retinoid

Oral capsule

Bicalutamide

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

Lapatinib

Tykerb

GlaxoSmithKline

TKI, EGFR inhibitor

Oral tablet

Lomustine

CeeNU

Bristol-Myers Squibb

Alkylating agent

Oral capsule

Melphalan

Alkeran

GlaxoSmithKline

Alkylating agent

Oral tablet

Nilotinib

Tasigna

Novartis

TKI

Oral capsule

Pazopanib

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

Thalidomide

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)

Melphalan

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

Lomustine

Intracranial tumor

130 mg/m²

By mouth

Once every 6 weeks

Hodgkin’s Lymphoma

130 mg/m²

By mouth

Once every 6 weeks

Bicalutamide

Metastatic prostate cacer

50 mg

By mouth

Once daily (in combination with an LHRH analogue)

Imatinib

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)

Erlotinib

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

Nilotinib

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

Temozolomide

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

Thalidomide

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)

Lapatinib

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

Capecitabine

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

References

• 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.
• 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.
• 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.
• Arimidex (anastrozole) package insert. Available at: www1.astrazeneca-us.com/pi/arimidex.pdf.
• Targretin (bexarotene) package insert. Available at: www.eisai.com/pdf_files/prescribing_caps_information.pdf
• Casodex (bicalutamide) package insert. Available at: www1.astrazeneca-us.com/pi/casodex.pdf.
• Xeloda (capecitabine) package insert. Available at: www.xeloda.com/pdf/patient-pi.pdf.
• Sprycel (dasatinib) package insert. Available at: http://packageinserts.bms.com/pi/pi_sprycel.pdf.
• Tarceva (erlotinib) package insert. Available at : www.gene.com/gene/products/information/pdf/tarceva-prescribing.pdf.
• Afinitor (everolimus) package insert. Available at: www.pharma.us.novartis.com/product/pi/pdf/afinitor.pdf.
• Iressa (gefitinib) package insert. Available at: www1.astrazeneca-us.com/pi/iressa.pdf
• Gleevec (imatinib) package insert. Available at: www.pharma.us.novartis.com/product/pi/pdf/gleevec_tabs.pdf.
• Tykerb (lapatinib) package insert. Available at: http://us.gsk.com/products/assets/us_tykerb.pdf
• Ceenu (lomustine) package insert. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2009/017588s034lbl.pdf
• Alkeren (melphalan) package insert. Available at: http://us.gsk.com/products/assets/us_alkeran_tablets.pdf.
• Tasigna (nilotinib) package insert. Available at: www.pharma.us.novartis.com/product/pi/pdf/tasigna.pdf
• Votrient (pazopanib HCl) package insert. Available at: http://us.gsk.com/products/assets/us_votrient.pdf
• Nexavar website. Available at: http://nexavar-us.com/scripts/pages/en/hcp/
• Nexavar (sorafenib) package insert. Available at: http://berlex.bayerhealthcare.com/html/products/pi/Nexavar_PI.pdf
• Sutent (sunitinib) package insert. Available at: www.pfizer.com/files/products/uspi_sutent.pdf
• Temodar (temozolomide) package insert. Available at: www.spfiles.com/pitemodar.pdf
• Hycamtin (topotecan) package insert. Available at: http://us.gsk.com/products/assets/us_hycamtin_capsules.pdf
• Zolinza (vorinostat) package insert. Available at: www.merck.com/product/usa/pi_circulars/z/zolinza/zolinza_pi.pdf
• Revlimid (lenalidomide) package insert. Available at: www.revlimid.com/pdf/REVLIMID_PI.pdf
• Thalomid (thalidomide) package insert. Available at: www.thalomid.com/pdf/Thalomid%20PI%2072991-10.pdf