Cancer is a common illness and a major health problem worldwide, carrying a substantial social and economic impact on individuals, families, and the community. In 2020, approximately 150,000 Australians were diagnosed with cancer, and just under 50,000 died as a result of the disease. At current rates, it is expected that one in two Australians will be diagnosed with cancer by the age of 851, 2.
Cancer can arise in any cell of the body as a result of the accumulation of mutations that inhibit the mechanisms that regulate how cells grow and multiply. As a result of these multiple genetic changes, cells continue to grow and multiply abnormally to form a primary tumour which can impact the normal function of tissues and organs. In a process called “metastasis”, many tumours also shed cells that travel though the lymphatic system and blood vessels to settle in and form secondary tumours in distant organs.
Cancer is a complex disease. There are more than 100 different types of cancer, but in Australia the most commonly diagnosed cancers are prostate, breast, colorectal, melanoma, and lung1, 2. The highest risk factor for developing cancer is ageing, but many cancers can be prevented, or their incidence delayed by modification of significant lifestyle risk factors such as smoking, sun exposure, poor diet, alcohol consumption and inadequate physical activity2.
Standard cancer therapies
Advances in knowledge about prevention, early detection and treatment mean that more than 66% of people diagnosed with cancer today can be effectively treated and almost nine out of 10 children with cancer are effectively treated and go on to live normal lives2. Standard-of-care treatment varies depending on the type of cancer, location, and stage, but generally involves surgery (scalpel, cryosurgery, laser)3, chemotherapy (toxic agents, inhibitors, antibodies)4, and radiation therapy (x rays, subatomic particles)5, used either alone or in combination.
Advanced and emerging cancer therapies
Normally, cells of the immune system (e.g. T cells, NK cells) can prevent or slow the growth of tumours, but cancer cells develop ways to hide from the immune system, for example by undergoing genetic changes that make them less visible, by expressing proteins on their surface that block the action of immune cells, or by changing the cells around them so that they interfere with immune cells. Immunotherapy harnesses the patient’s immune system to overcome these blocks6. Immunotherapies include immune checkpoint inhibitors (ICIs) (e.g. nivolumab, ipilimumab, pembrolizumab)7, monoclonal antibodies (e.g rituximab, blinatumomab)8, T-cell transfer therapy (e.g. TIL, CART T)9, cancer vaccines (e.g. Sipuleucel-T, T-VEC)10, and immune system modulators (e.g. cytokines, BCG, immunomodulatory drugs)11, 12.
The diversity of genetic changes that transform normal cells to cancerous cells leads to a large number of different cancers involving specific tissue types and cancer mechanisms that must be targeted in order to eradicate tumours. Thus, standard-of-care therapy is often used with advanced therapies to increase treatment efficacy and improve patient outcomes. In addition, new therapies are constantly being developed and tested in clinical trials. Some of these include combinations of different ICIs, combining ICIs with radiotherapy, discovering new ICIs, and nanoparticle-based cancer drug delivery systems13.
In spite of the success of current treatments and improved patient survival, cancer patients still experience significant symptom burden that often increases in intensity over time. Symptoms include pain, fatigue, chemotherapy-induced nausea and vomiting (CINV), anxiety, depression, anorexia, weight loss, mucositis, and bladder and bowel problems14, 15.
Managing cancer- and treatment-related symptoms
Although significant progress has been made in the development of techniques for both diagnosis and treatment of most cancers, fewer advances have been made in the field of evaluation and treatment of cancer pain16. Radiotherapy, radiofrequency ablation, surgery and chemotherapy is often used for pain relief as well as for the treatment for cancer. Analgesics (including opioid medications) may be replaced by epidurals, nerve blocks, or neurosurgery when analgesics have failed to control pain, and anti-nausea medication is normally prescribed in conjunction with chemotherapy or radiotherapy17.
In spite of these options, many patients with cancer still have inadequate symptom control and poor quality of life (QoL)18. In addition to pain, CINV remains a significant cause of illness despite the best current treatments19. About 46-57% of patients experience significant nausea and 9-37% experience vomiting20. Therefore, although most cancer patients respond to standard-of-care medications (e.g. opioids for the control of pain), there is a small but significant percentage who do not, and a larger significant percentage who experience moderate to severe side effects. There is therefore a need for new strategies that can effectively supplement standard-of-care in patients with insufficient symptom control.
Non-pharmaceutical options. According to Cancer Australia, relaxation, massage, acupuncture, and distraction may help patients improve QoL17. A recently published systematic review looked at the efficacy of various complementary therapies in 1,845 European cancer patients. Although there was very limited availability of studies to reach a strong conclusion, the authors found some efficacy with a number of interventions, including auriculotherapy and acupuncture, laser moxibustion, electroacupuncture, progressive muscle relaxation and guided imagery, phytotherapy, music therapy and traditional Chinese medicine21.
Pharmaceutical options. Poor symptom control and/or intolerable adverse effects attributed to opioids and other medications have encouraged the search for other therapeutic strategies such as cannabinoid-based medicines22. Current Therapeutic Goods Administration (TGA) guidelines list indications for which there is stronger scientific evidence regarding the therapeutic potential of cannabis medicines, including opioid-resistant cancer pain, anorexia, and overall QoL23. In the US, the US National Comprehensive Cancer Network (NCCN) guidelines list cannabinoids as options for breakthrough or treatment resistant CINV24, 25.
Recent clinical studies in patients with advanced cancer have shown benefits of cannabinoids in pain relief, reduction of nausea and vomiting, stimulation of appetite, and improved sleep, fatigue, and health-related QoL26-28. Further clinical studies in patients with CINV have shown benefit for medicinal cannabis29-33. To support this, a systematic review of 23 randomised controlled trials concluded that cannabis-based medications may be useful for treatment-refractory CINV. It found that patients were five times more likely to report complete absence of vomiting compared to placebo. However, cannabinoids were not found to be superior to conventional therapy34. On the other hand, a meta-analysis of 28 studies found more benefit from the use of cannabinoids than with comparative anti-nausea medication and placebos. The average number of patients showing complete prevention of nausea and vomiting was greater with cannabinoids than with placebo35.
In the US, a survey of 237 oncologists showed that 67% viewed cannabis medicines as a helpful adjunct to standard pain management strategies, and 65% thought cannabis medicines were equally or more effective than standard treatments for anorexia and cachexia36.
However, there still remains a need for high-quality randomised controlled trials to properly assess the effectiveness and safety of cannabinoids, compared with placebo and standard treatments, for cancer-related symptoms. A number of clinical trials in advanced cancer patients are currently underway in Australia (ACTRN12619000037101,ACTRN12619001534178p, ACTRN12619000513112, ACTRN12619000265178, ACTRN12616001036404, ACTRN12616000516482, ACTRN12619000037101), and overseas (NCT03948074, NCT03984214, NCT04585841). These and other studies planned for the future will continue to contribute to the evidence base required in this field.
- Cancer data in Australia.: Australian Institute of Health and Welfare; 2020 [Available from: https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/contents/cancer-summary-data-visualisation].
- Facts and Figures. Cancer statistics in Australia.: Cancer Council; 2021 [Available from: https://www.cancer.org.au/cancer-information/what-is-cancer/facts-and-figures].
- Surgery to treat cancer: National Cancer Institute. National Institute of Health. USA.; 2021 [Available from: https://www.cancer.gov/about-cancer/treatment/types/surgery].
- Amjad MT, Kasi A. Cancer Chemotherapy.StatPearls. Treasure Island (FL): StatPearls Publishing. Copyright © 2020, StatPearls Publishing LLC.; 2020.
- Maani EV, Maani CV. Radiation Therapy.StatPearls. Treasure Island (FL): StatPearls Publishing. Copyright © 2020, StatPearls Publishing LLC.; 2020.
- Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nature Reviews Immunology. 2020;20(11):651-68.
- Robert C. A decade of immune-checkpoint inhibitors in cancer therapy. Nat Commun. 2020;11(1):3801.
- Weiner LM, Surana R, Wang S. Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nature reviews Immunology. 2010;10(5):317-27.
- Perica K, Varela JC, Oelke M, Schneck J. Adoptive T cell immunotherapy for cancer. Rambam Maimonides Med J. 2015;6(1):e0004.
- Hollingsworth RE, Jansen K. Turning the corner on therapeutic cancer vaccines. npj Vaccines. 2019;4(1):7.
- Berraondo P, Sanmamed MF, Ochoa MC, Etxeberria I, Aznar MA, Pérez-Gracia JL, et al. Cytokines in clinical cancer immunotherapy. British Journal of Cancer. 2019;120(1):6-15.
- Larsen ES, Joensen UN, Poulsen AM, Goletti D, Johansen IS. Bacillus Calmette–Guérin immunotherapy for bladder cancer: a review of immunological aspects, clinical effects and BCG infections. APMIS. 2020;128(2):92-103.
- Dang Y, Guan J. Nanoparticle-based drug delivery systems for cancer therapy. Smart Materials in Medicine. 2020;1:10-9.
- Portenoy RK, Thaler HT, Kornblith AB, Lepore JM, Friedlander-Klar H, Coyle N, et al. Symptom prevalence, characteristics and distress in a cancer population. Qual Life Res. 1994;3(3):183-9.
- Van Lancker A, Velghe A, Van Hecke A, Verbrugghe M, Van Den Noortgate N, Grypdonck M, et al. Prevalence of symptoms in older cancer patients receiving palliative care: a systematic review and meta-analysis. J Pain Symptom Manage. 2014;47(1):90-104.
- Gress KL, Charipova K, Kaye AD, Viswanath O, Urits I. An Overview of Current Recommendations and Options for the Management of Cancer Pain: A Comprehensive Review. Oncology and Therapy. 2020;8(2):251-9.
- Affected by cancer: Cancer Australia; 2021 [Available from: https://www.canceraustralia.gov.au/affected-cancer].
- Smith TJ, Temin S, Alesi ER, Abernethy AP, Balboni TA, Basch EM, et al. American Society of Clinical Oncology provisional clinical opinion: the integration of palliative care into standard oncology care. J Clin Oncol. 2012;30(8):880-7.
- Navari RM, Aapro M. Antiemetic Prophylaxis for Chemotherapy-Induced Nausea and Vomiting. N Engl J Med. 2016;374(14):1356-67.
- Mersiades AJ, Tognela A, Haber PS, Stockler M, Lintzeris N, Simes J, et al. Oral cannabinoid-rich THC/CBD cannabis extract for secondary prevention of chemotherapy-induced nausea and vomiting: a study protocol for a pilot and definitive randomised double-blind placebo-controlled trial (CannabisCINV). BMJ Open. 2018;8(9):e020745.
- Guerra-Martín MD, Tejedor-Bueno MS, Correa-Casado M. Effectiveness of Complementary Therapies in Cancer Patients: A Systematic Review. International Journal of Environmental Research and Public Health. 2021;18(3):1017.
- Cyr C, Arboleda MF, Aggarwal SK, Balneaves LG, Daeninck P, Neron A, et al. Cannabis in palliative care: current challenges and practical recommendations. Ann Palliat Med. 2018;7(4):463-77.
- Guidance for the use of medicinal cannabis in the treatment of palliative care patients in Australia, Version 1 (2017). Therapeutic Goods Administration, Department of Health, Australian Government, Canberra.
- Adel N. Overview of chemotherapy-induced nausea and vomiting and evidence-based therapies. Am J Manag Care. 2017;23(14 Suppl):S259-s65.
- Berger MJ, Ettinger DS, Aston J, Barbour S, Bergsbaken J, Bierman PJ, et al. NCCN Guidelines Insights: Antiemesis, Version 2.2017. J Natl Compr Canc Netw. 2017;15(7):883-93.
- Lichtman AH, Lux EA, McQuade R, Rossetti S, Sanchez R, Sun W, et al. Results of a Double-Blind, Randomized, Placebo-Controlled Study of Nabiximols Oromucosal Spray as an Adjunctive Therapy in Advanced Cancer Patients with Chronic Uncontrolled Pain. J Pain Symptom Manage. 2018;55(2):179-88 e1.
- Bar-Lev Schleider L, Mechoulam R, Lederman V, Hilou M, Lencovsky O, Betzalel O, et al. Prospective analysis of safety and efficacy of medical cannabis in large unselected population of patients with cancer. Eur J Intern Med. 2018;49:37-43.
- Darkovska-Serafimovska M, Serafimovska T, Arsova-Sarafinovska Z, Stefanoski S, Keskovski Z, Balkanov T. Pharmacotherapeutic considerations for use of cannabinoids to relieve pain in patients with malignant diseases. J Pain Res. 2018;11:837-42.
- Tramer MR, Carroll D, Campbell FA, Reynolds DJ, Moore RA, McQuay HJ. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ. 2001;323(7303):16-21.
- Machado Rocha FC, Stefano SC, De Cassia Haiek R, Rosa Oliveira LM, Da Silveira DX. Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis. Eur J Cancer Care (Engl). 2008;17(5):431-43.
- Duran M, Perez E, Abanades S, Vidal X, Saura C, Majem M, et al. Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting. Br J Clin Pharmacol. 2010;70(5):656-63.
- Meiri E, Jhangiani H, Vredenburgh JJ, Barbato LM, Carter FJ, Yang HM, et al. Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Curr Med Res Opin. 2007;23(3):533-43.
- Allan GM, Finley CR, Ton J, Perry D, Ramji J, Crawford K, et al. Systematic review of systematic reviews for medical cannabinoids: Pain, nausea and vomiting, spasticity, and harms. Can Fam Physician. 2018;64(2):e78-e94.
- Smith LA, Azariah F, Lavender VT, Stoner NS, Bettiol S. Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy. Cochrane Database Syst Rev. 2015(11):CD009464.
- Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, et al. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015;313(24):2456-73.
- Braun IM, Wright A, Peteet J, Meyer FL, Yuppa DP, Bolcic-Jankovic D, et al. Medical Oncologists’ Beliefs, Practices, and Knowledge Regarding Marijuana Used Therapeutically: A Nationally Representative Survey Study. J Clin Oncol. 2018;36(19):1957-62.