GEMCITABINE IN SOLID TUMORS - PRESENT STATUS AND FURTHER DEVELOPMENT

Gemcitabine [Gemzar(R)] is a nucloside analogue with clinical signific ant activity against different solid tumors. Currently, clinical resea rch concentrates mainly on pancreatic, bladder, breast, ovary and non- small-cell lung cancer (NSCLC). In pan creatic cancer, it has been sho wn that the drug has meaningful impact on survival and disease-related symptoms which is superior to 5-Fluorouracil. In locally advanced and metastatic NSCLC, several phase II studies involving more than 400 pa tients showed validated response rates with gemcitabine in more than 2 0% of the patients. This has been confirmed in a randomized study show ing equal activity of gemcitabine monotherapy compared to combination therapy with cisplatin/etoposide. Combination therapy with cisplatin i n NSCLC yields response rates in the range of 30 to 54%. Early phase I I studies in patients with metastatic breast cancer have shown promisi ng results with response rates between 46 and 25% in chemonaive and pr etreated patients. In urogenital tumors, gemcitabine has activity in f irst-and second-line treatment, even in cisplatin-refractory tumors, w ith response rates of 20-30% in bladder cancer and 19-24% in ovarian c ancer. Compared to other cytostatic drugs, gemcitabine is well tolerat ed in the majority of patients with mild myelosuppression and flu-like symptoms as the most reported side effects. Current research and furt her development concentrates on dose and schedule modifications of gem citabine and on combination with other drugs or radiation which should lead to increased response rates and survival of patients with solid tumors.