Randomized clinical trial of adenosine 5'-triphosphate in patients with advanced non-small-cell lung cancer.
BACKGROUND
Extracellular adenosine 5'-triphosphate (ATP) is involved in the regulation of a variety of biologic processes, including neurotransmission, muscle contraction, and liver glucose metabolism, via purinergic receptors. In nonrandomized studies involving patients with different tumor types including non-small-cell lung cancer (NSCLC), ATP infusion appeared to inhibit loss of weight and deterioration of quality of life (QOL) and performance status. We conducted a randomized clinical trial to evaluate the effects of ATP in patients with advanced NSCLC (stage IIIB or IV).


METHODS
Fifty-eight patients were randomly assigned to receive either 10 intravenous 30-hour ATP infusions, with the infusions given at 2- to 4-week intervals, or no ATP. Outcome parameters were assessed every 4 weeks until 28 weeks. Between-group differences were tested for statistical significance by use of repeated-measures analysis, and reported P values are two-sided.


RESULTS
Twenty-eight patients were allocated to receive ATP treatment and 30 received no ATP. Mean weight changes per 4-week period were -1.0 kg (95% confidence interval [CI] = -1.5 to -0.5) in the control group and 0.2 kg (95% CI = -0.2 to +0.6) in the ATP group (P =.002). Serum albumin concentration declined by -1.2 g/L (95% CI= -2.0 to -0.4) per 4 weeks in the control group but remained stable (0.0 g/L; 95% CI = -0.3 to +0.3) in the ATP group (P =.006). Elbow flexor muscle strength declined by -5.5% (95% CI = -9.6% to -1. 4%) per 4 weeks in the control group but remained stable (0.0%; 95% CI= -1.4% to +1.4%) in the ATP group (P =.01). A similar pattern was observed for knee extensor muscles (P =.02). The effects of ATP on body weight, muscle strength, and albumin concentration were especially marked in cachectic patients (P =.0002, P =.0001, and P =. 0001, respectively, for ATP versus no ATP). QOL score changes per 4-week period in the ATP group showed overall less deterioration than in the control group-physical scores (-0.2% versus -2.4%; P =. 0002); functional scores (+0.4% versus -5.5%; P =.02); psychologic scores (-0.7% versus -2.4%; P =.11); overall QOL score (+0.1% versus -3.5%; P =.0001).


CONCLUSIONS
This randomized trial demonstrates that ATP has beneficial effects on weight, muscle strength, and QOL in patients with advanced NSCLC.
Agteresch
H J
HJ
Department of Internal Medicine, Erasmus University Medical Center Rotterdam, The Netherlands.
Dagnelie
P C
PC
van der Gaast
A
A
Stijnen
T
T
Wilson
J H
JH
D000255:Adenosine Triphosphate / Q000627:therapeutic use*; D000368:Aged; D001835:Body Weight; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D018908:Muscle Weakness / Q000188:drug therapy / Q000209:etiology; D010166:Palliative Care / Q000379:methods*; D011788:Quality of Life; D012709:Serum Albumin / Q000378:metabolism; D016896:Treatment Outcome; D019282:Wasting Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control
D012709:Serum Albumin; D000255:Adenosine Triphosphate