GEMCITABINE - A CYTIDINE ANALOG ACTIVE AGAINST SOLID TUMORS

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.