The aim of this study was to compare the efficacy and safety of modafinil and dexamethasone in the management of cancer-related fatigue and their effects on quality of life (QoL). A prospective randomized controlled study was conducted, enrolling 80 cancer patients experiencing moderate or severe fatigue following at least three cycles of chemotherapy or a course of palliative/curative radiotherapy. Patients received either oral modafinil 100 mg or dexamethasone 4 mg daily for 14 days. Levels of fatigue, QoL and symptom severity were compared after 14–21 days. Both drugs were efficacious and safe in the management of fatigue and QoL. However, modafinil performed marginally better. Although modafinil demonstrated marginal superiority, both modafinil and dexamethasone can improve fatigue and QoL in cancer patients.

Clinical trials registry of India: CTRI/2018/05/014046 (www.ctri.nic.in)

Lay abstract

Cancer-related fatigue is a common and nagging problem that needs best evidence-based management. Modafinil, a brain stimulant, and dexamethasone, a corticosteroid, have been shown in separate studies to provide benefit, but there are little data regarding which one is superior. The present study compared modafinil with dexamethasone in a randomized controlled trial. Modafinil was found to be marginally superior in treating cancer-related fatigue and several domains of quality of life, though dexamethasone also demonstrated significant improvement of fatigue. This study provides a valuable guide for future larger studies for implementation of the findings in the form of better patient care.

Tweetable abstract

Oral doses of the #psychostimulant #modafinil and #corticosteroid #dexamethsasone can improve #cancer-related #fatigue and #qualityoflife without major #sideeffects. #Modafinil was marginally superior.

Keywords:

References

1. Ferlay J, Colombet M, Soerjomataram I et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int. J. Cancer 144(8), 1941–1953 (2019).
Medline CASGoogle Scholar
2. Weis J. Cancer-related fatigue: prevalence, assessment and treatment strategies. Expert Rev. Pharmacoecon. Outcomes Res. 11(4), 441–446 (2011).
MedlineGoogle Scholar
3. Banipal RPS, Singh H, Singh B. Assessment of cancer-related fatigue among cancer patients receiving various therapies: a cross-sectional observational study. Indian J. Palliat. Care 23(2), 207–211 (2017).
MedlineGoogle Scholar
4. Hickok JT, Roscoe JA, Morrow GR, Mustian K, Okunieff P, Bole CW. Frequency, severity, clinical course, and correlates of fatigue in 372 patients during 5 weeks of radiotherapy for cancer. Cancer 104(8), 1772–1778 (2005).
MedlineGoogle Scholar
5. Lawrence DP, Kupelnick B, Miller K, Devine D, Lau J. Evidence report on the occurrence, assessment, and treatment of fatigue in cancer patients. J. Natl Cancer Inst. Monographs (32), 40–50 (2004).
MedlineGoogle Scholar
6. Jean-Pierre P, Mustian K, Kohli S, Roscoe JA, Hickok JT, Morrow GR. Community-based clinical oncology research trials for cancer-related fatigue. J. Support Oncol. 4(10), 511–516 (2006).
MedlineGoogle Scholar
7. Berger AM, Mooney K, Banerjee Chandana O. NCCN clinical practice guidelines in oncology (NCCN guidelines^®) version 2.2020 cancer-related fatigue. J. Natl Compr. Canc. Netw. 65 (2020).
Google Scholar
8. Olson K. A new way of thinking about fatigue: a reconceptualization. Oncol. Nurs. Forum 34(1), 93–99 (2007).
MedlineGoogle Scholar
9. Hofman M, Ryan JL, Figueroa-Moseley CD, Jean-Pierre P, Morrow GR. Cancer-related fatigue: the scale of the problem. Oncologist 12(Suppl. 1), 4–10 (2007).
MedlineGoogle Scholar
10. Glaus A, Crow R, Hammond S. A qualitative study to explore the concept of fatigue/tiredness in cancer patients and in healthy individuals. Support Care Cancer 4(2), 82–96 (1996).
Medline CASGoogle Scholar
11. Hofman M, Morrow GR, Roscoe JA et al. Cancer patients' expectations of experiencing treatment-related side effects: a University of Rochester Cancer Center--Community Clinical Oncology Program study of 938 patients from community practices. Cancer 101(4), 851–857 (2004).
MedlineGoogle Scholar
12. Bower JE, Ganz PA, Desmond KA, Rowland JH, Meyerowitz BE, Belin TR. Fatigue in breast cancer survivors: occurrence, correlates, and impact on quality of life. J. Clin. Oncol. 18(4), 743–753 (2000).
Medline CASGoogle Scholar
13. Jones JM, Olson K, Catton P et al. Cancer-related fatigue and associated disability in post-treatment cancer survivors. J. Cancer Surviv. 10(1), 51–61 (2016).
MedlineGoogle Scholar
14. Yennurajalingam S, Palmer JL, Zhang T, Poulter V, Bruera E. Association between fatigue and other cancer-related symptoms in patients with advanced cancer. Support Care Cancer 16(10), 1125–1130 (2008).
MedlineGoogle Scholar
15. Smets EM, Visser MR, Willems-Groot AF et al. Fatigue and radiotherapy: (A) experience in patients undergoing treatment. Br. J. Cancer 78(7), 899–906 (1998).
Medline CASGoogle Scholar
16. Yucel B, Akkaş EA, Okur Y et al. The impact of radiotherapy on quality of life for cancer patients: a longitudinal study. Support Care Cancer 22(9), 2479–2487 (2014).
MedlineGoogle Scholar
17. Fosså SD, Dahl AA, Loge JH. Fatigue, anxiety, and depression in long-term survivors of testicular cancer. J. Clin. Oncol. 21(7), 1249–1254 (2003).
MedlineGoogle Scholar
18. Vardy JL, Dhillon HM, Pond GR et al. Fatigue in people with localized colorectal cancer who do and do not receive chemotherapy: a longitudinal prospective study. Ann. Oncol. 27(9), 1761–1767 (2016).
Medline CASGoogle Scholar
19. Jean-Pierre P, Figueroa-Moseley CD, Kohli S, Fiscella K, Palesh OG, Morrow GR. Assessment of cancer-related fatigue: implications for clinical diagnosis and treatment. Oncologist 12(Suppl. 1), 11–21 (2007).
MedlineGoogle Scholar
20. Berger AM, Mooney K. Dissemination and implementation of guidelines for cancer-related fatigue. J. Natl Compr. Canc. Netw. 14(11), 1336–1338 (2016).
MedlineGoogle Scholar
21. Mercadante S, Fulfaro F, Casuccio A. The use of corticosteroids in home palliative care. Support Care Cancer 9(5), 386–389 (2001).
Medline CASGoogle Scholar
22. Tanioka H, Miyamoto Y, Tsuji A et al. Prophylactic effect of dexamethasone on regorafenib-related fatigue and/or malaise: a randomized, placebo-controlled, double-blind clinical study in patients with unresectable metastatic colorectal cancer (KSCC1402/HGCSG1402). Oncology 94(5), 289–296 (2018).
Medline CASGoogle Scholar
23. Yennurajalingam S, Frisbee-Hume S, Palmer JL et al. Reduction of cancer-related fatigue with dexamethasone: a double-blind, randomized, placebo-controlled trial in patients with advanced cancer. J. Clin. Oncol. 31(25), 3076–3082 (2013).
Medline CASGoogle Scholar
24. Shih A, Jackson KC. Role of corticosteroids in palliative care. J. Pain Palliat. Care Pharmacother. 21(4), 69–76 (2007).
MedlineGoogle Scholar
25. Yennurajalingam S, Bruera E. Role of corticosteroids for fatigue in advanced incurable cancer: is it a “wonder drug” or “deal with the devil”. Curr. Opin. Support Palliat. Care 8(4), 346–351 (2014).
MedlineGoogle Scholar
26. Sodji Q, Kaminski J, Willey C et al. Management of metastatic spinal cord compression. South. Med. J. 110(9), 586–593 (2017).
MedlineGoogle Scholar
27. Yennurajalingam S, Tannir NM, Williams JL et al. A double-blind, randomized, placebo-controlled trial of panax ginseng for cancer-related fatigue in patients with advanced cancer. J. Natl Compr. Canc. Netw. 15(9), 1111–1120 (2017).
MedlineGoogle Scholar
28. Carroll JK, Kohli S, Mustian KM, Roscoe JA, Morrow GR. Pharmacologic treatment of cancer-related fatigue. Oncologist 12(Suppl. 1), 43–51 (2007).
Medline CASGoogle Scholar
29. Boele FW, Douw L, de Groot M et al. The effect of modafinil on fatigue, cognitive functioning, and mood in primary brain tumor patients: a multicenter randomized controlled trial. Neuro. Oncol. 15(10), 1420–1428 (2013).
Medline CASGoogle Scholar
30. Cooper MR, Bird HM, Steinberg M. Efficacy and safety of modafinil in the treatment of cancer-related fatigue. Ann. Pharmacother. 43(4), 721–725 (2009).
Medline CASGoogle Scholar
31. Spathis A, Dhillan R, Booden D, Forbes K, Vrotsou K, Fife K. Modafinil for the treatment of fatigue in lung cancer: a pilot study. Palliat. Med. 23(4), 325–331 (2009).
Medline CASGoogle Scholar
32. Rabkin JG, Gordon PH, McElhiney M, Rabkin R, Chew S, Mitsumoto H. Modafinil treatment of fatigue in patients with ALS: a placebo-controlled study. Muscle Nerve 39(3), 297–303 (2009).
Medline CASGoogle Scholar
33. Lam JY, Freeman MK, Cates ME. Modafinil augmentation for residual symptoms of fatigue in patients with a partial response to antidepressants. Ann. Pharmacother. 41(6), 1005–1012 (2007).
Medline CASGoogle Scholar
34. Zifko UA, Rupp M, Schwarz S, Zipko HT, Maida EM. Modafinil in treatment of fatigue in multiple sclerosis. Results of an open-label study. J. Neurol. 249(8), 983–987 (2002).
Medline CASGoogle Scholar
35. Spathis A, Fife K, Blackhall F et al. Modafinil for the treatment of fatigue in lung cancer: results of a placebo-controlled, double-blind, randomized trial. J. Clin. Oncol. 32(18), 1882–1888 (2014).
Medline CASGoogle Scholar
36. Laird BJA, Scott AC, Colvin LA et al. Pain, depression, and fatigue as a symptom cluster in advanced cancer. J. Pain Symptom Manage. 42(1), 1–11 (2011).
MedlineGoogle Scholar
37. Cella D. The Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale: a new tool for the assessment of outcomes in cancer anemia and fatigue. Semin. Hematol. 34(3 Suppl. 2), 13–19 (1997).
Medline CASGoogle Scholar
38. Cella DF, Tulsky DS, Gray G et al. The Functional Assessment of Cancer Therapy scale: development and validation of the general measure. J. Clin. Oncol. 11(3), 570–579 (1993).
Medline CASGoogle Scholar
39. Bruera E, Kuehn N, Miller MJ, Selmser P, MacMillan K. The Edmonton Symptom Assessment System (ESAS): a simple method for the assessment of palliative care patients. J. Palliat. Care 7(2), 6–9 (1991).
Medline CASGoogle Scholar
40. Hui D, Bruera E. The Edmonton Symptom Assessment System 25 years later: past, present, and future developments. J. Pain Symptom Manage. 53(3), 630–643 (2017).
MedlineGoogle Scholar
41. Oldenmenger WH, de Raaf PJ, de Klerk C, van der Rijt CCD. Cut points on 0–10 numeric rating scales for symptoms included in the Edmonton Symptom Assessment scale in cancer patients: a systematic review. J. Pain Symptom Manage. 45(6), 1083–1093 (2013).
MedlineGoogle Scholar
42. Uppsala Monitoring Centre. The use of the WHO-UMC system for standardised case causality assessment. Uppsala Monitoring Centre (UMC), WHO Collaborating Centre for International Drug Monitoring. https://www.who.int/medicines/areas/quality_safety/safety_efficacy/WHOcausality_assessment.pdf
Google Scholar
43. Morrow GR, Gillies LJ, Hickok JT, Roscoe JA, Padmanaban D, Griggs JJ. The positive effect of the psychostimulant modafinil on fatigue from cancer that persists after treatment is completed. J. Clin. Oncol. 23(Suppl. 16), 8012–8012 (2005).
MedlineGoogle Scholar
44. Jean-Pierre P, Morrow GR, Roscoe JA et al. A Phase 3 randomized, placebo-controlled, double-blind clinical trial of the effect of modafinil on cancer-related fatigue among 631 patients receiving chemotherapy: a University of Rochester Cancer Center Community Clinical Oncology Program Research base study. Cancer 116(14), 3513–3520 (2010).
Medline CASGoogle Scholar
45. Fukuoka S, Shitara K, Noguchi M et al. Prophylactic use of oral dexamethasone to alleviate fatigue during regorafenib treatment for patients with metastatic colorectal cancer. Clin. Colorectal Cancer 16(2), e39–e44 (2017).
MedlineGoogle Scholar
46. Inoue A, Yamada Y, Matsumura Y et al. Randomized study of dexamethasone treatment for delayed emesis, anorexia and fatigue induced by irinotecan. Support Care Cancer 11(8), 528–532 (2003).
MedlineGoogle Scholar
47. Kaleita TA, Wellisch DK, Graham CA et al. Pilot study of modafinil for treatment of neurobehavioral dysfunction and fatigue in adult patients with brain tumors. J. Clin. Oncol. 24(Suppl. 18), 1503–1503 (2006).
Google Scholar
48. Morrow GR, Gillies LJ, Hickok JT, Roscoe JA, Padmanaban D, Griggs JJ. The positive effect of the psychostimulant modafinil on fatigue from cancer that persists after treatment is completed. J. Clin. Oncol. 23(Suppl. 16), 8012–8012 (2005).
MedlineGoogle Scholar
49. Locke DEC, Decker PA, Sloan JA et al. Validation of single-item linear analog scale assessment of quality of life in neuro-oncology patients. J. Pain Symptom Manage. 34(6), 628–638 (2007).
MedlineGoogle Scholar
50. Vetter TR, Mascha EJ. Bias, confounding, and interaction: lions and tigers and bears, oh my! Anesth. Analg. 125(3), 1042–1048 (2017).
MedlineGoogle Scholar
51. Administration. Biases and confounding. (2010). https://www.healthknowledge.org.uk/public-health-textbook/research-methods/1a-epidemiology/biases
Google Scholar
52. Prajapati K, Desai M, Shah S, Panchal J, Kapadia J, Dikshit R. An analysis of serious adverse drug reactions at a tertiary care teaching hospital. Perspect. Clin. Res. 7(4), 181–186 (2016).
MedlineGoogle Scholar
53. Modi A, Desai M, Shah S, Shah B. Analysis of cutaneous adverse drug reactions reported at the regional ADR monitoring center. Indian J. Dermatol. 64(3), 250 (2019).
MedlineGoogle Scholar
54. Khan LM, Al-Harthi SE, Osman A-MM, Sattar MAAA, Ali AS. Dilemmas of the causality assessment tools in the diagnosis of adverse drug reactions. Saudi Pharm. J. 24(4), 485–493 (2016).
MedlineGoogle Scholar
55. Du W, Lehr VT, Lieh-Lai M et al. An algorithm to detect adverse drug reactions in the neonatal intensive care unit. J. Clin. Pharmacol. 53(1), 87–95 (2013).
MedlineGoogle Scholar

Vol. 17, No. 14

Metrics

Downloaded 290 times

History

Received 20 August 2020

Accepted 8 January 2021

Published online 2 March 2021

Published in print May 2021

Information

Keywords

Author contributions

Conception and design of the study: S Mukhopadhyay, U Deb, S Banerjee and S Biswas. Data collection: U Deb, B Bhattacharya and S Banerjee. Data analysis: U Deb and S Mukhopadhyay. Manuscript preparation: U Deb and S Mukhopadhyay. Interpretation of findings, critical review and revision of the manuscript: S Mukhopadhyay, U Deb, B Bhattacharya, S Banerjee and S Biswas. All authors read and approved the final manuscript and agree to be accountable for all aspects of the work.

Acknowledgments

The authors sincerely acknowledge FACIT.org for providing free license of FACIT-F and FACIT-Fatigue scales for using in this academic research. The authors also thank Dr. D Das, Dr. P Dutta and Dr. Aditya of the Department of Radiation Oncology and S Dutta of the Department of Pharmacology, Burdwan Medical College, Burdwan, India.

Financial & competing interests disclosure

This study was funded by the Indian Council of Medical Research (no. 3/2/Jan; 2018/PG-Thesis-HRD(10); date: 7.9.201). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

PDF download