The pharmacology, pharmacokinetics, clinical efficacy, adverse effects
, and dosage and administration of gemcitabine are reviewed. Gemcitabi
ne is a deoxycytidine-analogue antimetabolite with activity against so
me solid tumors. Gemcitabine is phosphorylated intracellularly to difl
uorodeoxycytidine triphosphate, which terminates DNA-chain elongation
and competitively inhibits DNA polymerase and ribonucleotide reductase
. After i.v. administration, gemcitabine is rapidly distributed into t
otal body water. The drug is deaminated in the plasma to inactive difl
uorodeoxyuridine; both gemcitabine and difluorodeoxyuridine are primar
ily renally eliminated. In clinical studies, gemcitabine reduced pain
and improved function in patients with advanced pancreatic cancer. Gem
citabine has shown some activity against non-small-cell lung cancer, p
articularly 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 symp
toms, nausea, vomiting, and rash. Gemcitabine has FDA-approved labelin
g for use in the treatment of locally advanced and metastatic pancreat
ic cancer. The recommended dosage for this indication is 1000 mg/m(2)
(as the hydrochloride salt) i.v. given over 30 minutes weekly for seve
n weeks, followed after one week of rest by 1000 mg/m(2) i.v. given ov
er 30 minutes weekly for three weeks every four weeks. Gemcitabine pal
liates symptoms in patients with advanced or metastatic pancreatic can
cer. More study is needed to determine gemcitabine's role in the treat
ment of non-small-cell lung cancer, ovarian cancer, and breast cancer.