GEMCITABINE - A REVIEW OF ITS PHARMACOLOGY AND CLINICAL POTENTIAL IN NONSMALL CELL LUNG-CANCER AND PANCREATIC-CANCER

Gemcitabine [2'-deoxy-2',2'-difluorocytidine monohydrochloride (beta i somer); dFdC] is a novel deoxycytidine analogue which was originally i nvestigated for its antiviral effects but has since been developed as an anticancer therapy. Gemcitabine monotherapy produced an objective t umour response in 18 to 26% of patients with advanced non-small cell l ung cancer (NSCLC)and appears to have similar efficacy to cisplatin ph s etoposide. Objective response rates ranging from 26 to 54% were reco rded 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 c isplatin, in 3 clinical trials. Gemcitabine appears to be cast effecti ve compared with best supportive care for NSCLC. In addition, direct c osts 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 gemcit abine pills cisplatin was associated with a lower cost per tumour resp onse than cisplatin plus etoposide or cisplatin plus vinorelbine, acco rding to a retrospective cost-effectiveness analysis. In a single comp arative 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 pal liative efficacy in patients refractory to fluorouracil. Gemcitabine a ppears to be well tolerated, although further comparisons with other c hemotherapy regimens are required. The available data indicate that ge mcitabine monotherapy is better tolerated than cisplatin plus etoposid e in patients with NSCLC. Data from noncomparative studies suggest tha t the combination of gemcitabine and cisplatin has an acceptable toler abilty profile. In a single trial in patients with pancreatic cancer f luorouracil 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 adv anced NSCLC, given their limited life expectancy and the toxicity asso ciated with many other chemotherapy regimens. More detailed characteri sation of its risk-benefit profile compared with those of current and developing regimens for NSCLC should be possible once results from sev eral ongoing studies are available. Gemcitabine is a valuable new chem otherapy option for patients with advanced pancreatic cancer, a diseas e considered incurable at present. Its apparent survival and palliativ e 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.