Lung tumor resection does not affect debrisoquine metabolism.
Some authors have reported an association of extensive metabolism of debrisoquine with increased lung cancer risk, although others have found no association. Debrisoquine metabolism is controlled by a cytochrome P-450 isozyme encoded at the CYP2D6 locus, which is inducible by antipyrine and rifampicin. Because lung tumors may produce a variety of humoral substances, we wanted to determine whether the tumor induced debrisoquine metabolism. As part of a case-control study of lung cancer, debrisoquine metabolism was measured in patients with histologically confirmed non-small cell lung cancer before and after surgical resection with curative intent. One hundred four incident patients with curative intent. One hundred four incident patients with pathological stage I, II, or IIIA non-small cell lung cancer took debrisoquine (10 mg) orally at 10 p.m. and collected the subsequent 8-h urine both before and after surgery. We compared the values of the metabolic ratio, which is the percentage of the dose excreted as debrisoquine to the percentage of the dose excreted as the principal metabolite. The pre- and postoperative metabolic ratios were highly correlated (Pearson correlation coefficient = 0.96), and did not differ in value significantly (P = 0.88). Using traditional cutpoints (metabolic ratio, 1.0 and 12.6) to categorize the three metabolic phenotypes, the preoperative and postoperative phenotypes were well correlated (kappa = 0.78). These results show that the ability to metabolize debrisoquine is not induced by the presence of a primary lung tumor.
Shaw
G L
GL
National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Falk
R T
RT
Deslauriers
J
J
Nesbitt
J C
JC
McKneally
M F
MF
Frame
J N
JN
Feld
R
R
Issaq
H J
HJ
Ruckdeschel
J C
JC
Hoover
R N
RN
D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000601:surgery* / Q000652:urine; D016022:Case-Control Studies; D003647:Debrisoquin / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000601:surgery* / Q000652:urine; D008297:Male; D008657:Metabolic Clearance Rate / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D011013:Pneumonectomy; D012307:Risk Factors
D003647:Debrisoquin