Pediatric Patient Education on Oral Chemotherapy at Home: Comparison
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Please note this is a comparison between Version 2 by Sirius Huang and Version 1 by Anika Patel.

Oral chemotherapy (OC) has been increasingly used in pediatric patients diagnosed with cancer, which is primarily managed in the outpatient setting. Different from adults, pediatric patients face unique challenges in administering these hazardous medications at home. Because of the complexity of pediatric pharmaceutical care and the hazardous nature of chemotherapy agents, comprehensive patient education is imperative to mitigate the potential safety risks associated with OC administration at home. Pharmacists play a vital role in patient education and medication consultations. 

  • oral chemotherapy
  • patient education
  • pediatric patients
  • pharmacists

1. Oral Chemotherapy Agents for At-Home Administration

Cancer management has been significantly impacted by innovations in precision medicine in the past two decades. This has led to the increased development and approval of novel oral chemotherapy (OC) agents for targeted therapy. In 2020 alone, the FDA approved ten new oral medications for cancer treatment, with reports estimating that oral medications consist of 25–35% of anti-cancer drugs currently in development [1,2][1][2]. OC refers to medications for anti-cancer treatment with different mechanisms of action administered via mouth or enteral feeding tubes [3]. OC drugs include classic oncolytic or cytotoxic drugs (i.e., 6-mercaptopurine, methotrexate, gemcitabine, arsenic trioxide, and temozolomide), drugs for hormonal treatment (i.e., selective estrogen receptor modulators, aromatase inhibitors, GnRH agonists and antagonists, and anti-androgens), and various anti-neoplastic drugs for targeted therapy (i.e., receptor tyrosine inhibitors, and small molecule inhibitors targeting epidermal growth factor receptor, mTOR, KRas, Bcl-2, and fibroblast growth factor receptor) [4,5][4][5].
The use of OCs offers many benefits and advantages, including convenience of administration, enhanced patient autonomy and privacy, less disruption in the patient’s daily routine, elimination of the need for parenteral line placement thereby minimizing the risk of infection, and avoidance of transportation and hospitalization. In addition, OCs typically present with lower emetic risk and are associated with milder adverse effects when compared to intravenous (IV) chemotherapeutic drugs, contributing to an improved quality of life for patients while continuing active anti-cancer treatment [6,7][6][7]. Drug delivery by this route is far less invasive providing an ease of administration that can allow for treatment in the comfort of the patient’s home. Moreover, many IV chemotherapy agents are vesicants and carry the risk of extravasation, which would be avoided with the use of oral agents. The utilization of OCs has transformed care delivery for oncology patients. Given the convenience and accessibility of OCs, administration of the medication is now predominantly managed by the patients or caregivers, reducing the reliance on healthcare professionals. As a result, there is a significant demand for developing a best practice model for patient education that particularly focuses on the outpatient setting for medication safety.
Cancer is one of the leading causes of death in children (5–14 years) in the United States [8]. OCs demonstrate essential value in pediatric oncology patients. The most common pediatric malignancy is acute lymphoblastic leukemia (ALL), where first-line anti-cancer therapy involves induction-maintenance regimens [9,10][9][10]. Once remission is achieved, maintenance chemotherapy using an OC such as 6-mercaptopurine lasts 2 to 3 years to prevent or delay cancer relapse [9,10][9][10]. Continuation of anti-cancer therapy at home is of particular benefit for pediatric patients, allowing them to maintain relatively regular routines, reduce their inpatient hospital stays, manage emotional distress associated with hospitalization, and attain an improved quality of life. A study conducted at the Children’s Hospital of Philadelphia found that IV chemotherapy given at home was superior to IV therapy administered in the hospital based on quality-of-life variables including patient’s sense of well-being, appetite, ability to do schoolwork, and improved mood [11]. Parents of the pediatric patients in this study also reported better capacity to keep up with household chores and work responsibilities and spend more time with their spouse and other children in their family.

2. Patient Education and Medication Counseling for Children

Pediatric patients who receive medications at home face unique challenges in medication administration and in predicting medication response due to the high percentage of off-label use [12]. There are many notable differences in drug absorption, distribution, metabolism, and excretion observed in children and neonates compared to adults. At different growth stages, the rate of gastric emptying, gastric pH, surface area available for drug absorption, hepatic metabolic enzyme levels, and renal clearance vary significantly [13]. Pediatric patients require individually tailored dosing regimens based on their age and body weight to account for their pharmacokinetic differences. As such, ensuring accurate and age-appropriate doses and regimens is vital for medication safety and therapeutic effectiveness.
In addition, to facilitate oral administration of medications, especially for neonates and infants, liquid formulations are commonly preferred due to the ease of individualized dosing. However, most medications for children are used off-label and may not have age-appropriate formulations to accommodate their needs [12,14][12][14]. Extemporaneous compounding of medications may be restricted by lack of information on stability, storage conditions, impact on drug absorption and bioavailability, drug efficacy, and palatability [15,16][15][16]. These challenges further complicate the pharmaceutical care provided to children and increase the risk of medication errors due to possible miscalculations, incorrect dilutions and measurements, and the use of inappropriate ingredients [17,18][17][18]. Unlike adults who in general can conduct self-care independently, most pediatric patients rely on their parents and other care providers. In a study conducted on outpatient pediatric care, 84% of medical treatment errors were classified as medication errors, with 11% specifically related to medication administration [19]. The primary cause of these reported medical errors was identified as problematic communication and/or insufficient handoffs. Enhancing communication between providers/pharmacists and parents has been shown as an effective approach to mitigating medication errors in pediatric patient care [19].
Medication counseling and education are even more crucial for patients diagnosed with cancer. Oncology patients are at a higher risk of medication errors due to polypharmacy, comorbidities, and the immunocompromising effects of anti-cancer agents [20]. Chemotherapy regimens are frequently intricate and tailored to the individual patient. Studies demonstrated that chemotherapy errors affect 1–3% of adult and pediatric oncology patients, occurring at a rate of about 1–4 per 1000 orders [20]. Medical errors were reported throughout the entire process of anti-cancer treatment, including prescribing, dispensing, administration, and monitoring of chemotherapy agents across diverse healthcare settings. As targeted therapy continues to advance rapidly, oral chemotherapy drugs pose an increasing risk of errors. In an earlier study on OC, 38.8% of errors were reported as incorrect doses and 10% as missed doses [21]. Pediatric patients are more vulnerable to medication errors given the constant dose adjustments based on body weight and the prolonged anti-cancer treatment (e.g., the maintenance therapy for acute lymphoblastic leukemia lasting 2–3 years) [22]. Efforts should be made to address any barriers that hinder effective communication between healthcare providers and patients/caregivers to improve medication counseling and education.

3. Essential Subjects for Oral Chemotherapy Counseling in Pediatric Patients

3.1. Safety Considerations (Administration, Handling, and Disposal)

Like IV chemotherapeutic medications, OC agents are defined as hazardous drugs given their carcinogenicity, developmental toxicity (including teratogenicity), reproductive toxicity, and genotoxicity [23]. Although OC provides many advantages over IV agents, a shift from infusion to oral administration puts the responsibility of managing these hazardous medications in the hands of the patient and/or their caregivers. The National Institute for Occupational Safety and Health (NIOSH) recommends installing biological safety cabinets and providing personal protective equipment (PPE) to minimize occupational exposure to hazardous medications. United States Pharmacopeia (USP) <800> has also clearly outlined the requirements and regulations on compounding hazardous medications. However, these safety precautions are not applicable in the home setting. Consequently, unintended exposure to caregivers and family members may occur.
OC tablets and capsules are shown to produce particulates that could be released into the air and inhaled. This risk increases particularly when their outer coatings are damaged or if capsules are opened. Exposure may also occur via direct contact with contaminated body fluids or waste, as traces of drug or their active metabolites can be excreted through urine or feces [24]. Depending on their half-life, excretion of the active drug or its metabolites may extend for several days after treatment cessation. The International Society of Oncology Pharmacy Practitioners (ISOPP) recommends that patients on oral 6-mercaptopurine should continue to use PPE when in contact with urine for two days and feces for five days after administration [25]. If caregivers and family members are not aware of the need for stringent safeguards, mishandling in this context can lead to possible direct or indirect hazardous exposure [26].
Extemporaneous compounding of OC medications is becoming common practice when treating pediatric patients who cannot swallow entire tablets or capsules due to their younger age, individualized dosing requirements, or clinical morbidities. Hazardous compounding is generally performed by a well-trained pharmacy technician or pharmacist in a hospital or special compounding pharmacy. However, at home, handling and administration of OC is primarily carried out by patients and their caregivers with limited medical training.
Furthermore, disposal of hazardous medications can be challenging in certain areas, especially in rural or economically disadvantaged communities. Inappropriate disposal of hazardous OC agents can cause environmental contamination and create potential public health concerns. In 2012, Alameda County in California became the first local government to pass legislation requiring pharmaceutical companies to design, fund, and operate a program to safely collect and dispose of unwanted drugs, including hazardous medications [27]. Following that, several other California counties have successfully passed and implemented regulations regarding safe medication disposal [28,29,30,31][28][29][30][31]. However, an earlier study demonstrated that patients rarely received education and counseling on the proper disposal of unneeded OC drugs [32]. More efforts from all relevant stakeholders including national regulatory agencies and state boards of pharmacy are needed to advocate, develop, and standardize the safe disposal of hazardous medications in the home setting. Utilizing a patient education checklist may also aid pharmacists in ensuring sufficient counseling on the safe disposal of OC.

3.2. Medication Adherence for Optimal Treatment Effectiveness

With all the essential information about handling, administering, and disposing of OC, healthcare providers must also emphasize the importance of adherence in maximizing the benefits of their treatment. Inadequate adherence to chemotherapy regimens results in a shorter duration of remission, lack of complete response to the medication, increased costs of medical treatment, and overall reduced quality of life [33]. Many factors contribute to medication nonadherence in pediatric patients, including lack of understanding about the disease or treatment, socioeconomic status, drug taste, and the medication administration schedule [34]. In addition, certain psychosocial and demographic issues in oncology patients also adversely impact their medication compliance, such as comorbid conditions, depression, unmanaged side effects, and limited access to medications due to cost or location [35,36][35][36].
Adolescents (aged 12–18 years old) are known to be a particularly nonadherent group [37], and studies showed that 21–60% of adolescents and young adults with cancer are nonadherent to oral medications [38]. Although many factors contribute to their struggle with medication compliance, dosing medications during school time is a notable obstacle [34]. Potential solutions include utilizing technology to help remind them when to take their medications, altering the dosing schedule to take the next dose after school, and educating these patients while being cognizant of social stigma [34]. Supplementing patient education with motivational interviewing techniques has proven to be efficacious and feasible in improving OC compliance [39]. Healthcare providers should address potential barriers to compliance and explore solutions to ensure patients are adherent to their medication regimens and derive the maximum benefit from their treatment.
Caregivers are essential in providing and supporting pediatric medical care at home and ensuring medication adherence, especially for younger children [40,41][40][41]. A study showed that pediatric patient care provided by caregivers can be influenced by the attitude of the child toward the treatment [42]. As anti-cancer medications are always riddled with adverse reactions and side effects, child resistance to medication administration is very common and can be a real challenge for caregivers [42]. In an earlier study, 65% of caregivers of pediatric patients who were discharged home were given instructions on medication dosing, but none of them were taught how to administer the medication at home [43]. In addition, multigenerational care is common in pediatric patients and is often conducted by multiple caregivers [44]. Factors such as aging, low health literacy, and language barriers may restrict their ability to provide optimal medical care. It is crucial to equip all caregivers with the skills and resources to address these potential challenges in OC administration at home [45,46][45][46].

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