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Clinical significance of UDP-glucuronosyltransferase 1A1*6 for toxicities of combination chemotherapy with irinotecan and cisplatin in gynecologic cancers: a prospective multi-institutional study.

AbstractBACKGROUND:
To investigate the effects of UDP-glucuronosyltransferase 1A1 (UGT1A1) *28, *6 and *27 in patients with gynecologic cancer who received chemotherapy with irinotecan and cisplatin.
METHODS:
Patients eligible for this study had cervical or ovarian cancer treated with chemotherapy; a course of the regimen consisted of 60 mg/m(2) of irinotecan on days 1, 8 and 15, and 60 mg/m(2) of cisplatin on day 1 every 4 weeks. UGT1A1 polymorphisms and toxicities were analyzed.
RESULTS:
From March 2007 to December 2007, 30 Japanese patients were enrolled; 24 ovarian carcinoma patients and 6 cervical cancer patients. The following genotypes of UGT1A1 were found: wild type in 17 patients (57%), *28 in 4 patients (13%), *6 in 8 patients (27%), *28*6 in 1 case (3%) and no case of *27 (0%). Grade 3/4 neutropenia, thrombocytopenia and diarrhea were significantly more frequent in *6 patients compared with wild-type patients. Also, in *6 patients irinotecan administration on days 8 or 15 was significantly more often omitted due to toxicities. In patients with *28 or *28*6, side effects were similar to those in patients with *6.
CONCLUSION:
In addition to UGT1A1*28, UGT1A1*6 might also be a key candidate to determine the dose of combination chemotherapy with irinotecan and cisplatin.
AuthorsMasashi Takano, Masafumi Kato, Tomoyuki Yoshikawa, Naoki Sasaki, Junko Hirata, Kenichi Furuya, Michiko Takahashi, Harushige Yokota, Nao Kino, Koji Horie, Tomoko Goto, Keiichi Fujiwara, Kenji Ishii, Yoshihiro Kikuchi, Tsunekazu Kita
JournalOncology (Oncology) Vol. 76 Issue 5 Pg. 315-21 ( 2009) ISSN: 1423-0232 [Electronic] Switzerland
PMID19299905 (Publication Type: Journal Article, Multicenter Study)
CopyrightCopyright 2009 S. Karger AG, Basel.
Chemical References
  • Irinotecan
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Cisplatin
  • Camptothecin
Topics
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
  • Camptothecin (administration & dosage, analogs & derivatives)
  • Cisplatin (administration & dosage)
  • Female
  • Genotype
  • Glucuronosyltransferase (genetics)
  • Humans
  • Irinotecan
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Staging
  • Ovarian Neoplasms (drug therapy, genetics, pathology)
  • Polymorphism, Genetic
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Treatment Outcome
  • Uterine Cervical Neoplasms (drug therapy, genetics, pathology)
  • Young Adult

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