Img Alt - Mobile header
Back
General Topics

Oral therapies for cancer: a boon for treatment and bane for adherence

  • Oral therapies have revolutionized cancer treatment with their ease of administration.
  • However, they are prone to non-adherence as drugs are administered by patients away from health care settings1.
  • Cancer therapies are now akin to treatments for chronic ailments, lasting for several years. Therefore, the medication adherence barriers that pertain to chronic disease have become significant in cancer management2,3.

Cancer is among the leading cause of death across the globe. More than 18 million new cases were diagnosed in the year 20184, which is set to reach 29.4 million by 2040 (source: The cancer Atlas)5. The change in world demography due to high life expectancy is expected to further fuel cancer incidences. The technological and pharmaceutical advances have resulted in a better 5-year relative survival for cancer patients6. As per SEER registry data from the United States, survival for cancer patients has improved from 50% to upto 68% by 20207. Therefore, more patients are now dependent on anti-cancer medication either for reducing the tumor size or for protection from a future relapse, that too for longer periods. Cancer has become similar to chronic diseases in its outlook3. Non-adherence to oral medication for cancer treatment has become a major issue with the increasing use of oral anticancer drugs for cancer treatment1,2.

Challenges for adherence in Cancer therapy

Cancer patients are thought to be generally adherent to medication due to the impact of disease on survival, but reports show it is otherwise3. The last two decades have seen a steep rise in the approval of oral therapies for cancer and an increase in their prescription1. With this, the onus of administering medicines has shifted to patients rather than medical professionals8. Several cancers like ovarian, breast, prostate, leukemia, and lymphomas are comparable to chronic diseases in their long-term nature with patients expected to use cancer medications for several years for either protection or treatment2. It has led to a change in attitude toward cancer medication resulting in non-adherence ranging from 40 – 100% in cancer patients9.

Most robust non-adherence data is available for breast cancer that shows an alarmingly low rate of adherence (50%) for adjuvant hormone therapy owing to adverse effects and the long-term usage10. Similar to other chronic diseases, barriers for non-adherence to cancer therapies can be largely grouped into three categories – therapy-related, healthcare-related, and patient-related, discussed below in detail.

A. Therapy-related factors

  • The complexity of the dosage regimen: Oral therapy for cancer is often complex, with a period of active administration followed by a deliberate inactive period when no drug is taken to reduce the cytotoxic effects of the drug. Additionally, multiple drugs may be required to be administered in an overlapping or completely different schedule. This is often a cause of confusion among patients leading to incomplete dosage or inappropriate dosage11.
  • Enhanced adverse effects: Cancer therapy often does not differentiate between cancerous and healthy cells leading to severe adverse effects8. These adverse effects are major deterrents to therapy. For example, one-fourth of breast cancer patients are intentionally non-adherent to therapy due to the enhanced side effects and its impact on the quality of life12. Another study reported a perceived addiction to opioids as the reason for missing out on pain medications prescribed for cancer treatment13.
  • Shift towards oral medication: As more medicines for cancer therapy are being prescribed to be administered orally, patients are faltering in adherence as medication management becomes patients and families responsibility1.
  • Higher comorbidity: Cancer is mostly a disease associated with aging. With older age, people are also likely to suffer from other comorbidities. This results in the complexity of the regimen and lowering of adherence14.

B. Patients-related factors:

  • Beliefs: Personal beliefs are rooted in life experiences and current psychological state. Opinions about the importance of medications and their side effects are a salient hindrance to adherence forming the core of “necessity vs. concern belief15.
  • Socio-economic factors: Socioeconomic status is not just an important risk factor for cancer but also an important predictor of adherence to therapy.
  • Support network: Patients with a good support network, either family or friends rate high on adherence10.

C. Healthcare-related factors:

  • Personalized care plan: Cancer treatment requires visiting specialist care (oncologists, radiologists, or pathologists) in a specialized health center. Continued care in the same hospital, personalized care plan, and follow-up with medical oncologists were associated with improved adherence10.
  • Effective and frequent communication: Communication between the healthcare practitioner and patient is of utmost importance (See our article: Healthcare Providers: a potential springboard for adherence success). Patients giving high value to the doctor’s opinion were more adherent to treatment10.
  • Costs: Longer treatment periods for cancer treatment is also a financial burden on patients. Lower out-of-pocket costs are associated with higher adherence10

Table 1 lists the average rate of medication adherence in major types of cancers and the key barriers to adherence16.

Type of cancerName of the therapyAdherence
Rate		Major barrierSource
Breast cancerHormone therapy (Tamoxifen)31-73%Adverse effects,
Mental health		Brett et al., 201612
Acute Lymphoblastic Leukemia (ALL)6-mercaptopurine Methotrexate85%
81%		Adolescent age, Racial minorities,
poor insurance		Yelena et al., 201817
Chronic myeloid leukemiaTyrosine kinase inhibitors50%Forgetfulness
Longer treatment duration		Rychter et al., 201718
Non-hodgkin lymphomaOral targeted therapy (ibrutinib)76 – 96%Adverse effects ComorbiditiesWilliams et al., 201919
Colorectal cancerCapecitabine88.3% – 94%Metastatic disease,
Dyspnea		Figueiredo Junior et al., 201420
Bladder cancerIntravesical instillation therapy (BCG)55%Adverse effectsTapiero et al., 201821
Kidney cancerSorafenib
Sunitinib
90.7 % – 84.8%Side effects
Racial minorities		Murphy et al., 202122
Lung cancerErlotinib50 – 80 %Family structure
Treatment concerns
Information access		Zhou et al., 202223
Prostrate cancerApalutamide, Enzalutamide or Abiraterone acetate42.8 – 53.9 %Older age,
Racial minority
Costs		Pilon et al., 202224
Multiple myelomaImmunomodulatory drugs

70 %Cost,
Adverse effects, Long-term intake		Cransac et al., 201925

Demography vulnerable to non-adherence in cancer therapy:

A. Women:

Women are less adherent to medication as compared to men for the same disease26. The adherence rates for breast cancer are higher in well-informed women and lower in patients with negative beliefs about the risk-benefit ratio. Non-adherence is associated with young, very old, and non-white women12,16.

B. Teenage-young adults:

About 38-50% of adolescents are non-adherent to their oral cancer therapy27, the lowest among all pediatric cancers28. Major challenges are lower self-esteem, peer pressure, mental health, and perceived beliefs about illness severity, treatment efficacy, and parent-child discordance27.

C. Older adults:

Non-adherence to medication is higher in older patients due to cognitive & sensory impairment. Older patients are also more likely to be suffering from other comorbidities leading to non-adherence14.

Overcoming barriers to adherence in cancer therapy:

  • Patient-provider interaction: Interventions that increase the quality and frequency of patient-provider communication and patients’ overall satisfaction with the healthcare visit are crucial for adherence. It lowers concern-beliefs and raises their confidence in the necessity of the treatment29.
  • Tailored communication: Educational communications tailored to match the patient’s treatment level in written or digital form can enhance adherence. The information could include mechanisms, adverse effects, and the importance of therapy along with remedies to mitigate them. It should also discuss ways to improve lifestyle and should list helpline numbers for further assistance16. COMPAS trial, reported significantly enhanced adherence in patients receiving such interventions (64.7% v.s.48% in the control group30. Web-based applications that remind about medication, allow reporting adverse events, and receive appropriate care will help30.

Conclusion:

Although cancer cure is largely dependent on timely detection and effective treatment breaking the adherence barriers will be the tipping point toward the success of cancer treatment in real-world practice. The paradigm shift in cancer care towards oral therapies prescribed for longer durations is mirroring the difficulties faced for chronic diseases. This brings the spotlight on medication adherence to achieve the expected treatment benefits from cancer therapy11.

“Cure sometimes, treat often, and comfort always.”― Hippocrates

References

1.  Given BA, Spoelstra SL, Grant M. The challenges of oral agents as antineoplastic treatments. Semin Oncol Nurs. May 2011;27(2):93-103. doi:10.1016/j.soncn.2011.02.003

2.  The American Cancer Society medical and editorial content team. Managing Cancer as a Chronic Illness. American Cancer Society. 2019;1.800.227.2345

3.  Partridge AH, Avorn J, Wang PS, Winer EP. Adherence to therapy with oral antineoplastic agents. J Natl Cancer Inst. 2002;94(9):652-61. doi:10.1093/jnci/94.9.652

4.  Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

5.  American Cancer Society, Atlantic 57, and Language Dept.The burden of cancer.American Cancer Society. 2019

6.  Allemani C, Matsuda T, Di Carlo V, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet. Mar 17 2018;391(10125):1023-1075. doi:10.1016/S0140-6736(17)33326-3

7.  Miller KD, Nogueira L, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin. 2019 Sep;69(5):363-385. doi: 10.3322/caac.21565.

8.  Schlichtig K, Durr P, Dorje F, Fromm MF. New Oral Anti-Cancer Drugs and Medication Safety. Dtsch Arztebl Int. Nov 15 2019;116(46):775-782. doi:10.3238/arztebl.2019.0775

9.  Bassan F, Peter F, Houbre B, et al. Adherence to oral antineoplastic agents by cancer patients: definition and literature review. Eur J Cancer Care (Engl). Jan 2014;23(1):22-35. doi:10.1111/ecc.12124

10.    Yussof I, Mohd Tahir NA, Hatah E, Mohamed Shah N. Factors influencing five-year adherence to adjuvant endocrine therapy in breast cancer patients: A systematic review. Breast. Apr 2022;62:22-35. doi:10.1016/j.breast.2022.01.012

11.    Krikorian S, Pories S, Tataronis G, et al.Adherence to oral chemotherapy: Challenges and opportunities. J Oncol Pharm Pract. 2019 Oct;25(7):1590-1598.

12.    Brett J, Fenlon D, Boulton M, et al. Factors associated with intentional and unintentional non-adherence to adjuvant endocrine therapy following breast cancer. Eur J Cancer Care (Engl). Jan 2018;27(1)doi:10.1111/ecc.12601

13.    Seangrung R, Ahuja M, Pasutharnchat K, Mahawan R. Factors influencing non-adherence to opioids in cancer patients: a mixed-methods cross-sectional study. F1000Res. 2020;9:1471. doi:10.12688/f1000research.27725.2

14.    Puts MTE, Tu HA, Tourangeau A, et al. Factors influencing adherence to cancer treatment in older adults with cancer: a systematic review. Ann Oncol. Mar 2014;25(3):564-577. doi:10.1093/annonc/mdt433

15.    Thorneloe RJ, Horne R, Side L, Wolf MS, Smith SG, Investigators E. Beliefs About Medication and Uptake of Preventive Therapy in Women at Increased Risk of Breast Cancer: Results From a Multicenter Prospective Study. Clin Breast Cancer. Feb 2019;19(1):e116-e126. doi:10.1016/j.clbc.2018.10.008

16.    Ruddy K, Mayer E, Patridge A. Patient adherence and persistence with oral anticancer treatment.CA Cancer J Clin. 2009 Jan-Feb;59(1):56-66. doi: 10.3322/caac.20004.

17.    Wu YP, Stenehjem DD, Linder LA, et al. Adherence to Oral Medications During Maintenance Therapy Among Children and Adolescents With Acute Lymphoblastic Leukemia: A Medication Refill Analysis. J Pediatr Oncol Nurs. Mar/Apr 2018;35(2):86-93. doi:10.1177/1043454217741877

18.    Rychter A, Jerzmanowski P, Holub A, et al. Treatment adherence in chronic myeloid leukaemia patients receiving tyrosine kinase inhibitors. Med Oncol. Jun 2017;34(6):104. doi:10.1007/s12032-017-0958-6

19.    Williams AM, Baran AM, Casulo C, et al. Ibrutinib Dose Adherence and Therapeutic Efficacy in Non-Hodgkin Lymphoma: A Single-Center Experience. Clin Lymphoma Myeloma Leuk. Jan 2019;19(1):41-47. doi:10.1016/j.clml.2018.10.005

20.    Figueiredo Junior AG, Forones NM. Study on adherence to capecitabine among patients with colorectal cancer and metastatic breast cancer. Arq Gastroenterol. Jul-Sep 2014;51(3):186-91. doi:10.1590/s0004-28032014000300004

21.    Tapiero S, Helfand A, Kedar D, et al. Patient Compliance With Maintenance Intravesical Therapy for Nonmuscle Invasive Bladder Cancer. Urology. Aug 2018;118:107-113. doi:10.1016/j.urology.2018.04.039

22.    Murphy CC, Fullington HM, Gerber DE, et al. Adherence to oral therapies among patients with renal cell carcinoma: Post hoc analysis of the ECOG-ACRIN E2805 trial. Cancer Med. Sep 2021;10(17):5917-5924. doi:10.1002/cam4.4140

23.    Zhou H, Wang X, Yu D, et al. Adherence to Oral Targeted Anti-Lung Cancer Therapy: A Qualitative Interview Study. Patient Prefer Adherence. 2022;16:995-1004. doi:10.2147/PPA.S341966

24.    Pilon D, LaMori J, Rossi C, et al. Medication adherence among patients with advanced prostate cancer using oral therapies. Future Oncol. Jan 2022;18(2):231-243. doi:10.2217/fon-2021-0992

25.    Cransac A, Aho S, Chretien ML, Giroud M, Caillot D, Boulin M. Adherence to immunomodulatory drugs in patients with multiple myeloma. PLoS One. 2019;14(3):e0214446. doi:10.1371/journal.pone.0214446

26.    Manteuffel M, Williams S, Chen W, Verbrugge RR, Pittman DG, Steinkellner A. Influence of patient sex and gender on medication use, adherence, and prescribing alignment with guidelines. J Womens Health (Larchmt). Feb 2014;23(2):112-9. doi:10.1089/jwh.2012.3972

27.    Hullmann SE, Brumley LD, Schwartz LA. Medical and psychosocial associates of nonadherence in adolescents with cancer. J Pediatr Oncol Nurs. Mar-Apr 2015;32(2):103-13. doi:10.1177/1043454214553707

28.    Kondryn HJ, Edmondson CL, Hill J, Eden TO. Treatment non-adherence in teenage and young adult patients with cancer. Lancet Oncol. Jan 2011;12(1):100-8. doi:10.1016/S1470-2045(10)70069-3

29.    Sutton AL, Salgado TM, He J, Hurtado-de-Mendoza A, Sheppard VB. Sociodemographic, clinical, psychosocial, and healthcare-related factors associated with beliefs about adjuvant endocrine therapy among breast cancer survivors. Support Care Cancer. Sep 2020;28(9):4147-4154. doi:10.1007/s00520-019-05247-5 30.       Finitsis DJ, Vose BA, Mahalak JG, Salner AL. Interventions to promote adherence to endocrine therapy among breast cancer survivors: A meta-analysis. Psychooncology. Feb 2019;28(2):255-263. doi:10.1002/pon.4959