Concept: Oral Anticancer Agents (OAAs) - Method of Identification

Introduction

This concept contains information on the methods used to identify oral anticancer agents (OAAs) and non-OAA medications covered by the Manitoba Home Cancer Drug Program. The concept also provides a list of limitations of the data used in identifying these medications. Information for this concept is taken directly from the deliverable Outpatient Oral Anticancer Agents in Manitoba by Raymond et al.(2018).

Oral Anticancer Agents (OAAs) are drugs used to treat cancer and are taken by mouth. They are grouped into 3 categories: traditional, targeted and hormonal. Recently, there has been a dramatic increase in the number of OAAs available as they are more convenient for cancer patients during therapy and may therefore be more acceptable to patients compared to traditional intravenous chemotherapy.

Safety issues related to OAAs are important to consider as these agents become a standard treatment option for many types of cancer. Examples of issues include: a lack of communication between pharmacist and patient, lack of standardized monitoring, and in-depth knowledge about OAAs among pharmacists that dispense these agents. Another major concern is that patients are accountable for ensuring the proper use of these agents, and there are currently no standard protocols for ensuring adherence to OAAs at home. Patients are also responsible for the safe handling of OAAs to avoid inadvertently exposing family members without cancer to the drugs.

Data Sources

The data sources used to identify the OAAs and non-OAAs in this research include:


• Drug Program Information Network (DPIN) data, and the
  
• Manitoba Home Cancer Drug Program (HCDP) database (project data).

Method of Identifying Oral Anticancer Agents (OAAs)

The OAAs examined included all oral formulations (e.g., tablet, capsule) for cancer treatment medications prescribed in Manitoba during the study period of April 1, 2003 to March 31, 2016. The list was compiled by examining the following Anatomical Therapeutic Chemical (ATC) categories found in the DPIN data:


• L01 (antineoplastic agents);
  
• L02 (endocrine therapy); and
  
• L04 (immunosuppressants)

Manitoba Health’s Drug Identification Number (DIN) Master File also aided in compiling the list, as well as consulting with stakeholders and clinical experts. These medications were covered by the HCDP for eligible patients as of April 1, 2012; however, the researchers were interested in how patterns of use changed over time, and so they included prescriptions for these medications for all years of the study in the analyses.

OAAs were classified as:


1. Traditional agents - e.g.: alkylating agents, antimetabolites, plant alkaloids. These standard or traditional chemotherapy medications act on and often kill all types of rapidly dividing cells, including normal and cancerous cells. Because methotrexate is covered under the HCDP for some leukemia, it was included in the analysis as a medication covered by the HCDP, even though it is often excluded from this category.
   
   
2. Targeted agents - e.g.: protein kinase inhibitors. Targeted cancer therapies are medications that block the growth and spread of cancer by interfering with specific molecules ("molecular targets") that are involved in the growth, progression, and spread of cancer. These medications are also known as "molecularly targeted" drugs or therapies. ( National Cancer Institute - Targeted Cancer Therapies web page - https://www.cancer.gov/cancertopics/factsheet/Therapy/targeted - accessed May 15, 2019).
   
   
3. Hormonal agents - hormone therapy to treat estrogen receptor-positive breast cancer and prostate cancer.

OAAs were also classified according to their mechanism of action using the ATC system. This system divides medications into different groups according to the organ or system on which they act and the therapeutic or chemical characteristics of the medication. There are five levels of classification for this system. For example, all alkylating agents (e.g., cyclophosphamide) were grouped together.

The following is a list of the Oral Anticancer Agents (OAAs) organized by Drug Group (from the National Cancer Institute), Drug Category and ATC Code (to the third or fourth level) and the specific name of the drugs in the category.

1. Traditional Agents

• Alkylating Agents - ATC Code = L01A
  
  • Busulfan
    
  • Chlorambucil
    
  • Cyclophosphamide
    
  • Lomustine
    
  • Melphalan
    
  • Mitotane
    
  • Procarbazeine
    
  • Temozolomide
  
  
• Antimetabolites - ATC Code = L01B
  
  • Capecitabine
    
  • Fludarabine Phosphate ++
    
  • Mercatopurine
    
  • Thioguanine
  
  
• Plant alkaloids - ATC Code = L01CB
  
  • Etoposide
  
  
• Other older anticancer agents - ATC Code = L01XX
  
  • Hydroxyurea
    
  • Tretinoin
  
  
• Lenalidomide and Others - ATC Code = L04AX
  
  • Lenalidomide
    
  • Pomalidomide
    
  • Thalidomide ++
  
  ++ - NOTE: There are no prescriptions for thalidomide or fludarabine as they are not included in DPIN.

2. Targeted Agents **

• Protein Kinase Inhibitors for Haematological Malignancies - ATC Code = L01XE
  
  • Bosutinib
    
  • Dasatinib
    
  • Imatinib Mesylate
    
  • Nioltinib
    
  • Ruxolitinib
  
  
• Protein Kinase Inhibitors for Solid Tumors - ATC Code = L01XE
  
  • Afatanib
    
  • Axitinib
    
  • Crizotinib
    
  • Dabrafenib
    
  • Erlotinib
    
  • Gefitnib
    
  • Ibrutinib
    
  • Lapatinib
    
  • Pazopanib
    
  • Regorafenib
    
  • Sorafenib
    
  • Sunitinib
    
  • Trametinib
    
  • Vandetanib
    
  • Vemurafenib
  
  
• Other newer anticancer agents
  
  • Everolimus - ATC Codes = L01XE, L04AA
    
  • Vismodegib - ATC Code = L01XX

3. Hormonal Agents

• Hormone therapy for breast cancer
  
  • Anastrozole - ATC Code = L02BG
    
  • Exemestane - ATC Code = L02BG
    
  • Letrozole - ATC Code = L02BG
    
  • Tamoxifen - ATC Code = L02BA
  
  
• Hormone therapy for prostate cancer
  
  • Abiraterone - ATC Code = L02BX
    
  • Bicalutamide - ATC Code = L02BB
    
  • Enzalutamide - ATC Code = L02BB
    
  • Flutamide - ATC Code = L02BB
    
  • Nilutamide - ATC Code = L01BB

Table 2.1: Oral Anticancer Agents List in the online Deliverable contains a list of the OAAs included in this research, organized by Drug Group (from the National Cancer Institute), drug category and specific drug name, and the corresponding ATC code.

Method of Identifying Non-Oral Anticancer Agents

In addition to OAAs, several non-OAA medications covered by the HCDP were included in the analyses. These medications (listed below) are generally used as part of the patient’s cancer treatment (for example, to treat nausea) or prescribed through CancerCare Manitoba by an oncologist if for a non-cancer indication. Parenteral (injectable) formulations of chemotherapy and anticancer agents were excluded. The non-OAA medications covered by the HCDP since its inception on April 1, 2012 we included were anti-nauseants, steroids, supportive treatments such as megestrol for cancer or treatment-related appetite suppression, and agents to treat a specific disease (e.g., anagrelide).

The following lists the non-OAA medications covered by the Home Cancer Drug Program (HCDP) that were investigated in this research:


• Supportive Treatments
  
  • Estradiol - ATC Code G03CA
    
  • Megestrol - ATC Code G03AC, G03DB, L02AB
  
  
• Disease Treatments
  
  • Acitretin - ATC Code D05BB
    
  • Anagrelide - ATC Code L01XX
    
  • Celecoxib - ATC Code L01XX, M01AH
    
  • Imiquimod - ATC Code D06BB
    
  • Isotretinoin - ATC Code D10AD, D10BA
    
  • Ketoconazole - ATC Code D01AC, G01AF, J02AB
    
  • Methotrexate - ATC Code L01BA, L04AX
  
  
• Anti-nauseants
  
  • Aprepitant - ATC Code A04AD
    
  • Domperidone - ATC Code A03FA
    
  • Granisetron - ATC Code A04AA
    
  • Metoclopramide - ATC Code A03FA
    
  • Nabilone - ATC Code A04AD
    
  • Olanzapine - ATC Code N05AH
    
  • Ondansetron - ATC Code A04AA
    
  • Prochlorperazine - ATC Code N05AB
  
  
• Steroids
  
  • Dexamethasone - ATC Code H02AB, H02AB
    
  • Hydrocortisone - ATC Code H02AB, H02AB
    
  • Prednisone - ATC Code A07EA, H02AB

Table 2.2: Non-Oral Anticancer Agent Medications Covered by the Home Cancer Drug Program (HCDP) in the online Deliverable contains a list of the non-OAAs included in this research, organized by Drug Group (from the National Cancer Institute), drug category and specific drug name, and the corresponding ATC code(s).

Cautions / Limitations

There are several limitations in using the DPIN data for research into OAAs:


• The DPIN system contains records of prescriptions dispensed from outpatient dispensaries. Because not everyone who seeks medical attention and receives a prescription actually fills the prescription, the analyses in this report may underestimate the number of prescriptions written for OAAs and non-OAA medications covered by the HCDP. In addition:
  
  
  • Medication use not captured in the DPIN system may include physician samples, although the possibility is low for these types of medications.
    
  • There are some systems of compassionate use or dispensing outside of DPIN system for OAAs; notable examples include thalidomide, which is dispensed through a pharmaceutical company, and oral fludarabine, which is not included in DPIN as it is dispensed through the CancerCare Manitoba pharmacy.
    
  • The DPIN system does not contain records for Manitobans who are incarcerated or members of the RCMP, and approximately 25% of personal care homes in Manitoba do not fill prescriptions at community pharmacies, and are therefore also not included in the DPIN system.