Gemcitabine. A review of its pharmacology and clinical potential in non-small cell lung cancer and pancreatic cancer.

Gemcitabine [2'-deoxy-2',2'-difluorocytidine monohydrochloride (beta isomer); dFdC] is a novel deoxycytidine analogue which was originally investigated for its antiviral effects but has since been developed as an anticancer therapy. Gemcitabine monotherapy produced an objective tumour response in 18 to 26% of patients with advanced non-small cell lung cancer (NSCLC) and appears to have similar efficacy to cisplatin plus etoposide. Objective response rates ranging from 26 to 54% were recorded when gemcitabine was combined with cisplatin, and 1-year survival duration after such treatment ranged from 35 to 61%. Improvements in a range of NSCLC disease symptoms and/or in general performance status occurred in many patients who received gemcitabine, with or without cisplatin, in 3 clinical trials. Gemcitabine appears to be cost effective compared with best supportive care for NSCLC. In addition, direct costs associated with administration of gemcitabine monotherapy may be lower than those for some other NSCLC chemotherapy options, according to retrospective cost-minimisation analyses. The combination of gemcitabine plus cisplatin was associated with a lower cost per tumour response than cisplatin plus etoposide or cisplatin plus vinorelbine, according to a retrospective cost-effectiveness analysis. In a single comparative study in patients with advanced pancreatic cancer, gemcitabine was more effective than fluorouracil with respect to survival duration and general clinical status. It also showed modest antitumour and palliative efficacy in patients refractory to fluorouracil. Gemcitabine appears to be well tolerated, although further comparisons with other chemotherapy regimens are required. The available data indicate that gemcitabine monotherapy is better tolerated than cisplatin plus etoposide in patients with NSCLC. Data from noncomparative studies suggest that the combination of gemcitabine and cisplatin has an acceptable tolerabilty profile. In a single trial in patients with pancreatic cancer, fluorouracil was better tolerated than gemcitabine; however, gemcitabine was generally well tolerated overall in this study. Thus, gemcitabine (with or without cisplatin) may prove attractive to patients with advanced NSCLC, given their limited life expectancy and the toxicity associated with many other chemotherapy regimens. More detailed characterisation of its risk-benefit profile compared with those of current and developing regimens for NSCLC should be possible once results from several ongoing studies are available. Gemcitabine is a valuable new chemotherapy option for patients with advanced pancreatic cancer, a disease considered incurable at present. Its apparent survival and palliative benefits over fluorouracil require confirmation, but are encouraging, as the need to improve both the duration and quality of survival in these patients is well recognised.