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Journal of Clinical Oncology, Vol 26, No 25 (September 1), 2008: pp. 4225 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2008.18.3566
Pharmacologic Intervention for Cancer-Related DyspneaRegional Palliative Care Program of Extremadura, Palliative Care Team of Badajoz, Spain To the Editor: We have read with great interest the work carried out by Ben-Aharon et al1, who conducted a systematic review of randomized controlled trials assessing all pharmacologic and nonpharmacologic intervention for dyspnea palliation in patients with cancer. We would like to make some comments. It is surprising that in the search terms for PubMed, chlorpromazine was not included (decreases breathlessness without affecting ventilation or producing sedation in healthy subjects).2 In an open-labeled trial, McIver et al3 found chlorpromzine effective for relief of dyspnea in advanced cancer. The authors do not explain, within the study population, if those patients with cancer and other comorbidity (mainly chronic obstructive pulmonary disease) are excluded. We believe that this information is important, because if there is comorbidity, we can not discern if the cause of breathlessness was cancer or chronic obstructive pulmonary disease. In the longitudinal study conducted by our group,4 there were two or more causes to explain the etiology of dyspnea at the end of life (both the equal importance). As the authors note, the single trial that assessed the role of midazolam as adjunct therapy5 to morphine, demonstrated that the beneficial effects of morphine in controlling baseline levels of dyspnea could be improved by the addition of midazolam, without increased somnolence. However, no other benzodiazepines were assessed in randomized controlled trials. Moreover, there are studies in nononcological terminal respiratory illness, which suggest the possibility of an improvement in terminal breathlessness treated with other benzodiazepines.6 We think it is important to emphasize in the final discussion, one aspect that is essential for clinicians, and reflecting a common practice in our midst: our terminally ill patients with cancer who are already receiving regular doses of opioids have almost equal benefit from a supplemental equivalent of 25% to 50% of their 4-hourly oral or suncutaneous regular opioid dose, to improve their breathlessness.7 At present, our group is conducting a phase II randomized controlled trial to determine the efectiveness of oral transmucose fentanyl citrate for the exertion dyspnea treatment in seriously ill patients with cancer and to contribute to drug security data in that population. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Ben-Aharon I, Gafter-Gvili A, Paul M, et al: Interventions for alleviating cancer-related dyspnea: A systematic review. J Clin Oncol 26:2396-2404, 2008 2. O'Neil PA, Morton PB, Stara RD: Chlorprmazine: A specific effect on breathlessness? Br J Clin Pharmacol 19:793-797, 1985[Medline] 3. McIver B, Walsh D, Nelson K: The use of chlorpromazine for symptom control in dying cancer patients. J Pain Symptom Manage 9:341-345, 1994[CrossRef][Medline] 4. Cuervo Pinna MA, Mota Vargas R, Redondo Moralo MJ, et al: Etiology factors of the dyspnea at the end of life. Med Pal 15:143-148, 2008 5. Navigante AH, Cerchietti LC, Castro MA, et al: Midazolam as adjunct therapy to morphine in the alleviation of severe dyspnea perception in patients with advanced cancer. J Pain Symptom Manage 31:38-47, 2006[CrossRef][Medline] 6. Man GC, Hsu K, Sproule BJ: Effects of alprazolam on exercise and dyspnea in patients with chronic obstructive pulmonary disease. Chest 90:832-836, 1986[CrossRef][Medline] 7. Allard P, Lamontagne C, Bernard P, et al: How effective are supplementary doses of opioids for dyspnea in terminally ill cancer patients? A randomized continuous sequential clinical trial. J Pain Symptom Manage 17:256-265, 1999[CrossRef][Medline]
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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