To reconcile dosage modification guidelines for doxorubicin in a patient with hyperbilirubinemia of Gilbert's syndrome (GS).
CASE SUMMARY:
A 62-year-old white man with concurrent diagnoses of large-cell non-Hodgkin's lymphoma and GS was treated with standard doses of a doxorubicin-containing chemotherapy regimen. No increase of end-organ toxicity was observed during four treatment cycles.
DISCUSSION:
The relative prevalence of GS coupled with the rising incidence of non-Hodgkin's lymphoma increases the probability that both disorders will be present in the same individual. A MEDLINE search (1966 through July 1997) revealed little, and often conflicting, information pertaining to drug metabolism and disposition in GS. In addition, no information has been reported regarding the metabolic fate of doxorubicin in these patients. It is important to emphasize that the lack of enhanced extramedullary toxicity in this patient is not conclusive evidence that the hepatic abnormality of GS had no effect on doxorubicin metabolism.
CONCLUSIONS:
Based on information regarding mechanisms for hepatic clearance, dosage modification of doxorubicin may not be necessary in hyperbilirubinemia of GS.
McKelveyEMGottliebJAWilsonHEHautATalleyRWStephensRHydroxydaunomycin (Adriamycin) combination chemotherapy in malignant lymphoma. Cancer1976;38:1484–93.
2.
ArmitageJOFyfeMALewisJ. Long-term remission durability and functional status of patients treated for diffuse histiocytic lymphoma with the CHOP regimen. J Clin Oncol1984;2:898–902.
3.
SkarinATCanellosGPRosenthalDSCaseDCJrMacIntyreJMPinkusGSImproved prognosis of diffuse histiocytic and undiffer-entiated lymphoma by use of high-dose methotrexate alternating with standard agents (M-BACOD). J Clin Oncol1983;1:91–8.
4.
FisherRIDeVitaVTJrHubbardSMLongoDLWesleyRChabnerBADiffuse aggressive lymphomas: Increased survival after alternating flexible sequences of ProMACE and MOPP chemotherapy. Ann Intern Med1983;98:304–9.
5.
LeeRCabanillasFBodeyGPFreireichEJ. A 10-year update of CHOP-Bleo in the treatment of diffuse large-cell lymphoma. J Clin Oncol1986;4:1455–61.
6.
ColemanMGersteinGTopilowALebowiczJBerhardtBChiarieriDAdvances in chemotherapy for large cell lymphoma. Semin Hematol1987;24(suppl 1):8–20.
7.
KlimoPConnorsJM. MACOP-B chemotherapy for the treatment of diffuse large cell lymphoma. Ann Intern Med1985;102:596–602.
8.
KlimoPConnorsJM. Updated clinical experience with MACOP-B. Semin Hematol1987;24(suppl 1):26–34.
9.
BenjaminRS. A practical approach to Adriamycin (NSC-123127) toxicology. Cancer Chemother Rep1975;6:191–4.
10.
MyersCE. Anthracyclines. In: ChabnerB, ed. Pharmacologic principles of cancer treatment. Philadelphia: WB Saunders, 1982:426–51.
11.
PowellLWHemingwayEBillingBHSherlockS. Idiopathic unconjugated hyperbilirubinemia (Gilbert's syndrome): A study of 42 families. N Engl J Med1967;277:1108–12.
12.
DeMoraisSMUetrechtJPWellsPG. Decreased glucuronidation and increased bioactivation of acetaminophen in Gilbert's syndrome. Gastroenterology1992;102:577–86.
13.
ThompsonRPH. Genetic transmission of Gilbert's syndrome. In: OkolicsanyiL, ed. Familial hyperbilirubinemia. New York: John Wiley, 1981:91–7.
14.
BosmaPJChowdhuryJRBakkerCGantlaSde BoerAOostraBAThe genetic basis of the reduced expression of bilirubin UDP—glucuronosyltransferase 1 in Gilbert's syndrome. N Engl J Med1995;333: 1171–5.
15.
Gilbert's syndrome: More questions than answers. Lancet1987;1:1071.
16.
ScharschmidtBF. Bilirubin metabolism, hyperbilirubinemia, and approach to the jaundiced patient. In: BennettJCPlumF, eds. Cecil textbook of medicine. 20th ed. Philadelphia: WB Saunders, 1996:755–9.
17.
OkolicsanyiLFeveryJBillingBBerthelotPThompsonRPSchmidRHow should mild, isolated unconjugated hyperbilirubinemia be investigated?Semin Liver Dis1983;3:36–41.
18.
RiggsCEBenjaminRSSerpickAABachurNR. Biliary disposition of Adriamycin. Clin Pharmacol Ther1977;22:234–41.
19.
GentileSTiribelliCBaldiniGLunazziGSottocasaGL. Sex differences of nicotinate-induced hyperbilirubinemia in Gilbert's syndrome. J Hepatol1985;1:417–29.
20.
RollinghoffWPaumgartnerGPreisigR. Nicotinic acid test in the diagnosis of Gilbert's syndrome: Correlation with bilirubin clearance. Gut1981;22:663–8.
21.
WangJIJacksonTLKaplanDL. Isotretinoin-associated normalization of hyperbilirubinemia in patients with Gilbert's syndrome. J Am Acad Dermatol1995;32:136–8.
22.
CarulliNDe LeonM PonsMauroEManentiFFerrariA. Alteration of drug metabolism in Gilbert's syndrome. Gut1976;17:581–7.
23.
CummingsMHWattsGF. Drug treatment of hypercholesterolaemia in a patient with Gilbert's syndrome. Ann Clin Biochem1994;31:83–5.
24.
PluharW. A case of possible lovastatin-induced pancreatitis in concomitant Gilbert's syndrome. Wien Klin Wochenschr1989;101:551–4.
25.
PosnerJCohenAFLandGWintonCPeckAW. The pharmacokinetics of lamotrigine (BW430C) in healthy subjects with unconjugated hyperbilirubinaemia (Gilbert's syndrome). Br J Clin Pharmacol1989;28: 117–20.
26.
ShaderRIDivollMGreenblattGJ. Kinetics of oxazepam and lorazepam in two subjects with Gilbert's syndrome. J Clin Psychopharmacol1981;11:400–2.
27.
UllrichDSiegABlumeRBockKWSchroterWBircherJ. Normal pathways for glucuronidation, sulphation and oxidation of paracetamol in Gilbert's syndrome. Eur J Clin Invest1987;17:237–40.
28.
SchmidRHammakerK. Glucuronide formation in patients with constitutional hepatic dysfunction (Gilbert's syndrome). N Engl J Med1959;260:1310–4.
29.
DouglasAPSavageRLRawlinsMD. Paracetamol (acetaminophen) kinetics in patients with Gilbert's syndrome. Eur J Clin Pharmacol1978;13:209–12.
30.
BrennerDEWiernikPHWesleyMBachurNR. Acute doxorubicin toxicity: Relationship to pretreatment liver function, response, and pharmacokinetics in patients with acute nonlymphocytic leukemia. Cancer1984;53:1042–8.
31.
OhkuboHOkudaKIidaS. Effects of corticosteroids on bilirubin metabolism in patients with Gilbert's syndrome. Hepatology1981;1:168–72.
