Abstract
Background
Over one half of the patients diagnosed with advanced lung cancer experience anorexia. In addition to its high incidence, cancer-induced anorexia promotes the development of the anorexia-cachexia syndrome, which is related to poor clinical outcomes. Recently, drugs derived from cannabinoids, such as Nabilone, have been recognized for their appetite improvement properties; however, clinical trials to support their use in cancer patients are necessary.
Methods
This is a randomized, double-blind, placebo-controlled clinical trial to assess the effect of Nabilone vs. placebo on the appetite, nutritional status, and quality of life in patients diagnosed with advanced Non-small cell lung cancer (NSCLC) (NCT02802540).
Results
A total of 65 patients from the outpatient clinic at the National Institute of Cancer (INCan) were assessed for eligibility and 47 were randomized to receive Nabilone (0.5 mg/2 weeks followed by 1.0 mg/6 weeks) or placebo. After 8 weeks of treatment, patients who received Nabilone increased their caloric intake (342-kcal) and had a significantly higher intake of carbohydrates (64 g) compared to patients receiving placebo (p = 0.040). Quality of life also showed significant improvements in patients in the experimental arm of the trial, particularly in role functioning (p = 0.030), emotional functioning (p = 0.018), social functioning (p = 0.036), pain (p = 0.06), and insomnia (p = 0.020). No significant change in these scales was seen in the control group.
Conclusion
Nabilone is an adequate and safe therapeutic option to aid in the treatment of patients diagnosed with anorexia. Larger trials are necessary in order to draw robust conclusions in regard to its efficacy in lung cancer patients.
Similar content being viewed by others
References
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65(2):87–108
Arrieta O, Carmona A, Ramírez-Tirado LA, Flores-Estrada D, Macedo-Pérez EO, Martínez-Hernández JN, Corona-Cruz JF, Cardona AF, de la Garza J (2016) Survival of patients with advanced non-small cell lung cancer enrolled in clinical trials. Oncology 91:185–193
Arrieta O et al (2013) National consensus of diagnosis and treatment of non-small cell lung cancer. Rev Invest Clin 65(Suppl 1):S5–S84
Miyauchi E, Inoue A, Usui K, Sugawara S, Maemondo M, Saito H, Fujita Y, Kato T, Suzuki T, Harada T, Watanabe H, Nakagawa T, Ichinose M (2017) Phase II study of modified carboplatin plus weekly nab-paclitaxel in elderly patients with non-small cell lung cancer: North Japan lung cancer study group trial 1301. In: Oncologist, vol 22, pp 640–e59
Nasrah R et al (2016) Defining the role of dietary intake in determining weight change in patients with cancer cachexia. Clin Nutr
Cardona AF, Rojas L, Wills B, Arrieta O, Carranza H, Vargas C, Otero J, Cuello M, Corrales L, Martín C, Ortiz C, Franco S, Rosell R, CLICaP (2016) Pemetrexed/carboplatin/bevacizumab followed by maintenance pemetrexed/bevacizumab in Hispanic patients with non-squamous non-small cell lung cancer: outcomes according to thymidylate synthase expression. PLoS One 11(5):e0154293
Ming-Hua C, Bao-Hua Z, Lei Y (2016) Mechanisms of anorexia cancer cachexia syndrome and potential benefits of traditional medicine and natural herbs. Curr Pharm Biotechnol 17(13):1147–1152
Orozco-Morales M et al (2016) Interplay between cellular and molecular inflammatory mediators in lung Cancer. Mediat Inflamm 2016:3494608
Arrieta O, de la Torre-Vallejo M, Lopez-Macias D, Orta D, Turcott J, Macedo-Perez EO, Sanchez-Lara K, Ramirez-Tirado LA, Baracos VE (2015) Nutritional status, body surface, and low lean body mass/body mass index are related to dose reduction and severe gastrointestinal toxicity induced by afatinib in patients with non-small cell lung cancer. Oncologist 20(8):967–974
Jatoi A, Windschitl HE, Loprinzi CL, Sloan JA, Dakhil SR, Mailliard JA, Pundaleeka S, Kardinal CG, Fitch TR, Krook JE, Novotny PJ, Christensen B (2002) Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a north central cancer treatment group study. J Clin Oncol 20(2):567–573
Temel JS, Abernethy AP, Currow DC, Friend J, Duus EM, Yan Y, Fearon KC (2016) Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials. Lancet Oncol 17(4):519–531
Sanchez-Lara K et al (2014) Effects of an oral nutritional supplement containing eicosapentaenoic acid on nutritional and clinical outcomes in patients with advanced non-small cell lung cancer: randomised trial. Clin Nutr 33(6):1017–1023
Brisbois TD, de Kock IH, Watanabe SM, Mirhosseini M, Lamoureux DC, Chasen M, MacDonald N, Baracos VE, Wismer WV (2011) Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo-controlled pilot trial. Ann Oncol 22(9):2086–2093
Wilson MM, Philpot C, Morley JE (2007) Anorexia of aging in long term care: is dronabinol an effective appetite stimulant?—a pilot study. J Nutr Health Aging 11(2):195–198
Maida V, Ennis M, Irani S, Corbo M, Dolzhykov M (2008) Adjunctive nabilone in cancer pain and symptom management: a prospective observational study using propensity scoring. J Support Oncol 6(3):119–124
Abrams DI (2016) Integrating cannabis into clinical cancer care. Curr Oncol 23(2):S8–S14
Bedi G, Cooper ZD, Haney M (2013) Subjective, cognitive and cardiovascular dose-effect profile of nabilone and dronabinol in marijuana smokers. Addict Biol 18(5):872–881
Turcott JG, Juárez-Hernández E, de la Torre-Vallejo M, Sánchez-Lara K, Luvian-Morales J, Arrieta O (2016) Value: changes in the detection and recognition thresholds of three basic tastes in lung cancer patients receiving cisplatin and paclitaxel and its association with nutritional and quality of life parameters. Nutr Cancer 68(2):241–249
Cannabis In Cachexia Study, G et al (2006) Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the cannabis-in-cachexia-study-group. J Clin Oncol 24(21):3394–3400
Muscaritoli M, Anker SD, Argilés J, Aversa Z, Bauer JM, Biolo G, Boirie Y, Bosaeus I, Cederholm T, Costelli P, Fearon KC, Laviano A, Maggio M, Fanelli FR, Schneider SM, Schols A, Sieber CC (2010) Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by special interest groups (SIG) “cachexia-anorexia in chronic wasting diseases” and “nutrition in geriatrics”. Clin Nutr 29(2):154–159
Hernandez-Avila M et al (1998) Validity and reproducibility of a food frequency questionnaire to assess dietary intake of women living in Mexico City. Salud Publica Mex 40(2):133–140
Yamanaka T, Matsumoto S, Teramukai S, Ishiwata R, Nagai Y, Fukushima M (2007) The baseline ratio of neutrophils to lymphocytes is associated with patient prognosis in advanced gastric cancer. Oncology 73(3–4):215–220
Arrieta O, Núñez-Valencia C, Reynoso-Erazo L, Alvarado S, Flores-Estrada D, Angulo LP, Oñate-Ocaña LF (2012) Health-related quality of life in patients with lung cancer: validation of the Mexican-Spanish version and association with prognosis of the EORTC QLQ-LC13 questionnaire. Lung Cancer 77(1):205–211
Bergman B, Aaronson NK, Ahmedzai S, Kaasa S, Sullivan M (1994) The EORTC QLQ-LC13: a modular supplement to the EORTC Core quality of life questionnaire (QLQ-C30) for use in lung cancer clinical trials. EORTC study group on quality of life. Eur J Cancer 30A(5):635–642
Sanchez-Lara K et al (2013) Brain activity correlated with food preferences: a functional study comparing advanced non-small cell lung cancer patients with and without anorexia. Nutrition 29(7–8):1013–1019
Sanchez-Lara K et al (2012) Association of nutrition parameters including bioelectrical impedance and systemic inflammatory response with quality of life and prognosis in patients with advanced non-small-cell lung cancer: a prospective study. Nutr Cancer 64(4):526–534
Arrieta O, Angulo LP, Núñez-Valencia C, Dorantes-Gallareta Y, Macedo EO, Martínez-López D, Alvarado S, Corona-Cruz JF, Oñate-Ocaña LF (2013) Association of depression and anxiety on quality of life, treatment adherence, and prognosis in patients with advanced non-small cell lung cancer. Ann Surg Oncol 20(6):1941–1948
Arrieta O, J L-M, Turcott JG, Oñate-Ocaña LF (2018) Quality of life and anorexia/cachexia in lung cancer: validation of the Spanish version of the FAACT instrument
Turcott JG, Ramirez-Tirado LA, Oñate-Ocaña L., Flores-Estrada D., Zatarain-Barron Z., Soca-Chafre G., Arrieta O. (2017) FAACT-anorexia cachexia scale: cut-off value for the anorexia diagnosis in non-small cell lung cancer patients
Cote M et al (2016) Improving quality of life with nabilone during radiotherapy treatments for head and neck cancers: a randomized double-blind placebo-controlled trial. Ann Otol Rhinol Laryngol 125(4):317–324
Maida V (2006) The synthetic cannabinoid nabilone improves pain and symptom management in cancer patients., In SABCS: San Antonio. p. Abstract 3145
Arrieta O, Michel Ortega RM, Villanueva-Rodríguez G, Serna-Thomé MG, Flores-Estrada D, Diaz-Romero C, Rodríguez CM, Martínez L, Sánchez-Lara K (2010) Association of nutritional status and serum albumin levels with development of toxicity in patients with advanced non-small cell lung cancer treated with paclitaxel-cisplatin chemotherapy: a prospective study. BMC Cancer 10:50
Funding
Nabilone and placebo were donated by vealent pharmaceutical without any further participation in the trial.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest statement
The authors declare that they have no conflict of interest.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Electronic supplementary material
ESM 1
(DOCX 55 kb)
Rights and permissions
About this article
Cite this article
Turcott, J.G., del Rocío Guillen Núñez, M., Flores-Estrada, D. et al. The effect of nabilone on appetite, nutritional status, and quality of life in lung cancer patients: a randomized, double-blind clinical trial. Support Care Cancer 26, 3029–3038 (2018). https://doi.org/10.1007/s00520-018-4154-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00520-018-4154-9