Cancer-related fatigue, quality of life, pharmacological treatment

CORRESPONDENCE

Cancer-related fatigue, quality of life, pharmacological treatment

Maira Paschoin de Oliveira Campos

MD; Research Coordinator, Endocrinology and Metabolism, University of Miami, Miami, Florida, USA - [e-mail]

We agree with the concerns raised regarding the safety of amphetamines such as methylphenidate/dexmethylphenidate¹. In fact, we generally support the use of non-pharmacological interventions, such as cognitive behavioral therapy or energy conservation and activity management, in all patients after the diagnosis of fatigue is made by one of the multiple tools available such as FACIT-F, Visual Analogue Scale, Chalder scale, Brief Fatigue Inventory², and others. If fatigue does not improve or if it is severe, pharmacological therapy should then be judiciously considered.

While the abuse potential of methylphenidate is an understandable concern, orally administered methylphenidate at doses prescribed for a therapeutic effect has few reinforcing properties³. In fact, psychostimulant abuse among patients with cancer-related fatigue has not been reported. Finally, a recent systematic review and metanalysis evaluating psychostimulants for the management of cancer-related fatigue included 426 patients and found that there was no difference in the frequency of adverse events of methylphenidates. Placebo with a combined odds ratio of 1.24 (95% CI 0.42, 3.62)⁴.

We agree that modafinil certainly may be considered an option for treatment-associated cancer-related fatigue (chemotherapy or radiotherapy), and recent evidence recommends its use in cases of severe fatigue and in patients with advanced disease^5-7. However, evidence supporting the use of modafinil in mild or moderate fatigue does not exist. Although the authors state otherwise, they refer to a review article that makes no specific assertion regarding the use of modafinil according to fatigue severity, and primarily references the study by Jean-Pierre et al. that found modafinil to be effective only in severe fatigue⁸.

Regarding the use of erythropoietin stimulating agents (ESA), our review described the recent evidence and recommendations on this topic thoroughly, including the concerns related to prothrombotic states and the recently raised possibility of ESAs stimulating tumor growth^9-12.

Guarana (Paullinia cupana) is a plant native to the central Amazon, known for its stimulant and aphrodisiac properties, and popular for its use in energy drinks^13,14. In a randomized, double-blinded, crossover clinical trial published by our group, guarana demonstrated favorable effects on fatigue during chemotherapy¹⁵. The stimulant properties of guarana are generally taken to reflect the presence of caffeine, which comprises only 2.5%-5% of the extract's dry weight, although other purine alkaloids (theophylline and theobromine) are present in smaller quantities. The doses we used in this study (50 mg PO BID) would have negligible amounts of caffeine. Furthermore, no significant increase in cardiovascular events has been demonstrated in any study to date, but larger trials are needed to evaluate this promising therapeutic option for cancer-related fatigue.

REFERENCES

1. Campos MPO, Hassan BJ, Riechelmann R, Del Giglio A. Fadiga relacionada ao câncer: uma revisão. Rev Assoc Med Bras. 2011;57(2):211-9.

2. Mock V, Atkinson A, Barsevick A, Cella D, Cimprich B, Cleeland C, et al. NCCN practice guidelines for cancer-related fatigue. Oncology. 2000;14 (11A):151-61.

3. Volkow ND, Swanson JM. Variables that affect the clinical use and abuse of methylphenidate in the treatment of ADHD. Am J Psychiatry. 2003;160(11):1909-18.

4. Minton O, Richardson A, Sharpe M, Hotopf M, Stone PC. Psychostimulants for the management of cancer-related fatigue: a systematic review and metaanalysis. J Pain Symptom Manage. 2011;41(4):761-7.

5. Portela MA, Rubiales AS, Centeno C. The use of psychostimulants in cancer patients. Curr Opin Support Palliat Care. 2011;5(2):164-8.

6. Escalante CP, Manzullo EF. Cancer-related fatigue: the approach and treatment. J Gen Intern Med. 2009;24(Suppl 2):S412-6.

7. Cooper MR, Bird HM, Steinberg M. Efficacy and safety of modafinil in the treatment of cancer-related fatigue. Ann Pharmacother. 2009;43(4):721-5.

8. Jean-Pierre P, Morrow GR, Roscoe JA, Heckler C, Mohile S, Janelsins M, 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. 2010;116(14):3513-20.

9. Littlewood TJ, Bajetta E, Nortier JW, Vercammen E, Rapoport B; Epoetin Alfa Study Group. Effects of epoetin alfa on hematologic parameters and quality of life in cancer patients receiving nonplatinum chemotherapy: results of a randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2001;19(11): 2865-74.

10. Osterborg A, Brandberg Y, Molostova V, Iosava G, Abdulkadyrov K, Hedenus M, et al. Epoetin Beta Hematology Study Group. Randomized, double-blind, placebo-controlled trial of recombinant human erythropoietin, epoetin beta, in hematologic malignancies. J Clin Oncol. 2002;20(10):2486-94.

11. Fujisaka Y, Sugiyama T, Saito H, Nagase S, Kudoh S, Endo M, et al. Randomised, phase III trial of epoetin-β to treat chemotherapy-induced anaemia According to the EU regulation. Br J Cancer. 2011;105(9):1267-72.

12. Cancer and chemotherapy-induced anemia. National Comprehensive Cancer Network clinical practice guidelines in oncology. [cited 2011 nov 30 ]. Available from: http://www.nccn.org/professionals/physician_gls/f.guidelines.asp.

13. Smith N, Atroch AL. Guarana's journey from regional tonic to aphrodisiac and global energy drink. Evid Based Complement Alternat Med. 2010;7(3):279-82.

14. Weckerle CS, Stutz MA, Baumann TW. Purine alkaloids in Paullinia. Phytochemistry. 2003;64(3):735-42.

15. Oliveira Campos MP, Riechelmann R, Martins LC, Hassan BJ, Casa FB, Del Giglio A. Guarana (Paullinia cupana) improves fatigue in breast cancer patients undergoing systemic chemotherapy. J Altern Complement Med. 2011; 17(6):505-12.

Publication Dates

• Publication in this collection
  04 May 2012
• Date of issue
  Apr 2012