Gemcitabine: A cytidine analogue active against solid tumors

被引:150
作者
Hui, YF
Reitz, J
机构
[1] UNIV MICHIGAN,MED CTR,DEPT PHARM SERV,ANN ARBOR,MI 48109
[2] UNIV CALIF SAN FRANCISCO,MED CTR,DEPT CLIN PHARM,SAN FRANCISCO,CA 94143
[3] UNIV MICHIGAN,MED CTR,OUTPATIENT HEMATOL ONCOL PROGRAM,ANN ARBOR,MI 48109
关键词
antincoplastic agents; dosage; gemcitabine; neoplasms; pharmacokinetics; toxicity;
D O I
10.1093/ajhp/54.2.162
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of gemcitabine are reviewed. Gemcitabine is a deoxycytidine-analogue antimetabolite with activity against some solid tumors. Gemcitabine is phosphorylated intracellularly to difluorodeoxycytidine triphosphate, which terminates DNA-chain elongation and competitively inhibits DNA polymerase and ribonucleotide reductase. After i.v. administration, gemcitabine is rapidly distributed into total body water. The drug is deaminated in the plasma to inactive difluorodeoxyuridine; both gemcitabine and difluorodeoxyuridine are primarily renally eliminated. In clinical studies, gemcitabine reduced pain and improved function in patients with advanced pancreatic cancer. Gemcitabine has shown some activity against non-small-cell lung cancer, particularly when combined with cisplatin or ifosfamide. The agent has also shown modest activity against advanced ovarian and breast cancer. Adverse effects include dose-limiting myelosuppression, flu-like symptoms, nausea, vomiting, and rash. Gemcitabine has FDA-approved labeling for use in the treatment of locally advanced and metastatic pancreatic cancer. The recommended dosage for this indication is 1000 mg/m(2) (as the hydrochloride salt) i.v. given over 30 minutes weekly for seven weeks, followed after one week of rest by 1000 mg/m(2) i.v. given over 30 minutes weekly for three weeks every four weeks. Gemcitabine palliates symptoms in patients with advanced or metastatic pancreatic cancer. More study is needed to determine gemcitabine's role in the treatment of non-small-cell lung cancer, ovarian cancer, and breast cancer.
引用
收藏
页码:162 / 170
页数:9
相关论文
共 69 条
  • [1] A PHASE-I CLINICAL, PLASMA, AND CELLULAR PHARMACOLOGY STUDY OF GEMCITABINE
    ABBRUZZESE, JL
    GRUNEWALD, R
    WEEKS, EA
    GRAVEL, D
    ADAMS, T
    NOWAK, B
    MINEISHI, S
    TARASSOFF, P
    SATTERLEE, W
    RABER, MN
    PLUNKETT, W
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 1991, 9 (03) : 491 - 498
  • [2] EFFICACY AND SAFETY PROFILE OF GEMCITABINE IN NON-SMALL-CELL LUNG-CANCER - A PHASE-II STUDY
    ABRATT, RP
    BEZWODA, WR
    FALKSON, G
    GOEDHALS, L
    HACKING, D
    RUGG, TA
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 1994, 12 (08) : 1535 - 1540
  • [3] ABRATT RP, 1996, P ANN M AM SOC CLIN, V15, P1136
  • [4] Allerheiligen S, 1994, P AN M AM SOC CLIN, V13, P338
  • [5] SINGLE-AGENT ACTIVITY OF WEEKLY GEMCITABINE IN ADVANCED NON-SMALL-CELL LUNG-CANCER - A PHASE-II STUDY
    ANDERSON, H
    LUND, B
    BACH, F
    THATCHER, N
    WALLING, J
    HANSEN, HH
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 1994, 12 (09) : 1821 - 1826
  • [6] ANDERSON H, 1994, P ANN M AM SOC CLIN, V13, P1238
  • [7] ANDERSON H, 1994, P ANN M AM SOC CLIN, V13, P1164
  • [8] ANTON A, 1996, P AN M AM SOC CLIN, V15, pA1134
  • [9] CHEMOTHERAPY OF NON-SMALL CELL LUNG-CANCER - A REAPPRAISAL AND A LOOK TO THE FUTURE
    BAKOWSKI, MT
    CROUCH, JC
    [J]. CANCER TREATMENT REVIEWS, 1983, 10 (03) : 159 - 172
  • [10] BEGBIE SD, 1995, P AM SOC CLIN ONCOL, V14, pA1172