Acupuncture for dyspnea in advanced cancer: a randomized, placebo-controlled pilot trial [ISRCTN89462491]

Acupuncture for dyspnea in advanced cancer: a randomized, placebo-controlled pilot trial [ISRCTN89462491]
Received: 11 April 2005
Accepted: 18 August 2005
Published: 18 August 2005
Andrew J Vickers1,2 , Marc B Feinstein3 , Gary E Deng1 and Barrie R Cassileth1
BMC Palliative Care 2005
BioMed Central

1Integrative Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, USA
2Biostatistics Service, Memorial Sloan-Kettering Cancer Center, New York, USA
3Pulmonary Service, Memorial Sloan-Kettering Cancer Center, New York, USA

Abstract

Background
Dyspnea, or shortness of breath, is a common symptom in patients with advanced cancer. Pharmacologic management is of proven benefit, but it does not help all patients. Preliminary data suggest that acupuncture can relieve dyspnea in a variety of populations, including cancer patients. We conducted a pilot study (ISRCTN89462491) preparatory to a fully powered randomized, placebo-controlled trial to determine whether acupuncture reduces dyspnea in patients with lung or breast cancer.

Methods
The study sample was comprised of forty-seven patients with lung or breast cancer presenting with dyspnea. Patients receiving symptomatic treatments were not excluded as long as no changes in management were planned during the trial. Patients were randomized to receive a single session of true or placebo acupuncture in addition to their existing dyspnea treatments. Semi-permanent acupuncture "studs" were then inserted: patients applied pressure to these studs twice a day to provide ongoing stimulation to acupuncture points. The subjective sensation of dyspnea was assessed with a 0 Ò 10 numerical rating scale immediately before and after acupuncture treatment and daily for a week thereafter.

Results
All but two of 47 randomized patients provided follow-up data. Dyspnea scores were slightly higher for patients receiving true versus placebo acupuncture, for both the period immediately following acupuncture treatment and for the daily one week follow-up (differences between means of 0.34, 95% C.I. -0.33, 1.02 and 0.56, 95% C.I. -0.39, 1.51). The 95% confidence interval excludes the prespecified minimum clinically significant difference of a 20% greater improvement in dyspnea for patients receiving acupuncture.

Conclusion
The acupuncture technique used in this trial is unlikely to have effects on dyspnea importantly larger than placebo for patients with advanced cancer.

Background
Dyspnea, or shortness of breath, is defined as the subjective experience of difficulty breathing. It is a common symptom in cancer patients, particularly those with advanced cancer. For example, in a general survey of 100 outpatients and 140 inpatients at a Veterans' Affairs Medical Center, at least some dyspnea was reported by 50% of patients [1]. Studies of patients with advanced disease find that 50 Ò70% experience significant dyspnea[2,3]. Although dyspnea is most commonly associated with lung cancer[3], high rates also occur in patients with breast cancer with pulmonary metastases[4].

Dyspnea in cancer patients has numerous causes. It may result from complications of the cancer itself, such as pulmonary embolism, pleural effusion, anemia, and endobronchial obstruction or from conditions associated with a risk factor such as chronic obstructive pulmonary disease (COPD) in smokers. It may also result from disorders not directly attributable to the lungs, such as congestive heart failure or anemia. Treatment of these patients is typically guided by the identification of a specific underlying abnormality. Pleural effusions, for instance, are treated by thoracentesis, COPD is treated by bronchodilators and/or steroids, and anemia is treated by transfusion.

Unfortunately, a specific lung or cardiac pathology is not identifiable in approximately one-quarter of patients[2]. Moreover, dyspnea may result from causes in which definitive treatment has been unsuccessful or not practical. A number of interventions have been attempted for such patients, who often have advanced cancer within the lung parenchyma or endobronchial disease refractory to external beam radiation. Several randomized trials have shown that both opioids and supplemental oxygen can alleviate the subjective sensation of dyspnea among patients with advanced cancer.

For example, in a randomized, double-blind, crossover trial, dyspnea sensation fell by 25 mm on a 100 mm visual analog scale after morphine, with little change on placebo (p < 0.01 for difference between groups)[5]. Using a similar randomized, crossover design, Bruera et al. reported highly significant differences between periods when patients received oxygen as compared to periods when unsupplemented air was administered [6]. However, such measures are not effective in all patients, and the problem of dyspnea in the cancer patient is often frustratingly difficult to treat. A multinational study of end-of life-care found that dyspnea required sedation in 25 to 50% of patients during the last week of life[7]. It is for these difficult to treat cancer patients that additional therapeutic options are needed.

A number of randomized controlled trials have examined acupuncture for shortness of breath in patients without cancer. For example, a randomized, double-blind, placebo-controlled trial of acupuncture for methacholine-induced asthma reported significant differences in favor of acupuncture[8]. A similar study involved a standardized running test to induce bronchorestriction in asthmatics. Exercise-induced reductions in lung function were significantly lower in real compared to placebo acupuncture[9]. A trial in COPD reported significant differences between groups for subjective breathlessness. Thirty-one patients were randomized to self-administer finger pressure ("acupressure") at true or sham acupuncture points on a double-blind, crossover basis. Acupressure led to approximately a one-third reduction of scores on a VAS of dyspnea compared to about a 20% improvement in placebo controls[10].

Only one trial has been reported in cancer. Although uncontrolled, the results are provocative. Thirty cancer patients in palliative care received a single session of acupuncture. The mean visual analog score for breathlessness before acupuncture treatment was 42; this fell to 24 immediately following 10 minutes of needle insertion, an improvement that was maintained at six hour follow-up. Symptom scores returned to baseline 24 hours later[11].

Given these data, we believed it would be worthwhile to investigate whether cancer-related dyspnea can be relieved by acupuncture. Acupuncture is a complementary therapy, and therefore was administered as a supplement to use of pharmacologics or oxygen for dyspnea. Placebo control was employed because our endpoint was subjective and because acupuncture had not previously been found superior to placebo for cancer-related dyspnea. Our overall objective was to determine whether true acupuncture was more effective than placebo for alleviating dyspnea in patients with advanced lung or breast cancer. Here we report the results of a pilot study that aimed to refine the methodology for an anticipated definitive trial.

© 2005 Vickers et al; licensee BioMed Central Ltd.
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