A feasibility study of carboplatin with fixed dose of gemcitabine in 'unfit' patients with advanced bladder cancer

For the purpose of a subsequent phase II/III European Organization for Rese arch and Treatment of Cancer (EORTC) trial, a gemcitabine/carboplatin feasi bility study in 'unfit' patients with advanced urothelial cell cancer was c onducted. Gemcitabine was given at 1000 mg/m(2) days 1 and 8 with carboplat in (area under the curve (AUC) 4.5 or 5) day 1 every 21 days. 16 patients w ere treated, median age 68 years (47-75) years, performance status (PS) 0/1 /2 in 3/10/3 patients. Creatinine clearance was > 1 ml/s in 3 patients, 0.5 -1 ml/s in 9 and <0.5 ml/s in 4 patients. Half of the patients had visceral disease. Median number of cycles given was 4 (range 2-6), for a total of 6 9 cycles. The first 8 patients received 33 cycles using a carboplatin AUC o f 5. World Health Organization (WHO) grade 3-4 toxicity was: haemoglobin 5 patients, platelets 6 patients, neutrophils 5 patients and febrile neutrope nia 2 patients. In view of this haematological toxicity in subsequent patie nts, the carboplatin AUC was decreased to 4.5. At this dose level, 8 patien ts received 36 cycles. WHO grade 3-4 toxicity was: anaemia I patient, plate lets 4 patients, neutrophils 4 patients with no febrile neutropenia. Thus, this dose level was regarded to be feasible. For the 16 evaluable patients, overall response rate was 44%, (1 complete response (CR), 6 partial respon se (PR)). In conclusion, the combination of gemcitabine with carboplatin Li t an AUC of 4.5 appears to be an active and well tolerated regimen with acc eptable toxicity in this unfit patient Population. Based on these data, a r andomised trial in the framework of the EORTC-Genito urinary (GU) group of gemcitabine/carboplatin versus carboplatin/methotrexate/vinblastine (MCAVI) is ongoing. (C) 2001 Elsevier Science Ltd. All rights reserved.