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Sequential Cisplatin/Gemcitabine Plus Docetaxel Shows Benefits as First-Line Treatment for Urothelial Carcinoma: Presented at ICACT

By Chris Berrie

PARIS, FRANCE -- February 4, 2005 -- A sequential schedule of cisplatin plus gemcitabine followed by docetaxel is active and relatively well tolerated as first-line treatment for patients with advanced or metastatic urothelial carcinoma, according to a trial presented here February 3^rd at the 16^th International Conference on Anti-Cancer Treatment.

"Bladder cancer is among the most common cancers in developed countries, and it is a chemosensitive disease, as shown by the overall response rates during the 1980s," said Dr. Ioannis Boukovinas, MD, Medical Oncologist, 2^nd Medical Oncology Department, Anticancer Institute of Thessaloniki "Theagenio", Thessaloniki, Greece. Dr. Boukovinas presented the data on behalf of the Hellenic Oncology Research Group.

Although cisplatin-based combination chemotherapy is the standard of care and the response rates obtainable have improved over the past 15 years, Dr. Boukovinas said that as this has been achieved at the expense of major toxicity. There remains the need for novel, more effective and less toxic chemotherapy combinations, he said.

To evaluate the efficacy and safety of the sequential use of cisplatin plus gemcitabine followed by docetaxel as first-line treatment in patients with advanced urothelial carcinoma, Dr. Boukovinas and colleagues designed a multicentre, phase 2 study and enrolled 38 patients with locally advanced or recurrent urothelial carcinoma.

Patients were 84.2% male and their median age was 67 years (range, 40-75 years), 37% had locally advanced or recurrent disease. The Eastern Cooperative Oncology Group performance status range was 0 and 1, with a stage III in 13.2% and IV in 86.8%. Histology showed 97.4% of patients with transitional cell carcinoma, while the majority had a pelvic site without distant metastases (71.1%) and only 1 or 2 organs involved (66%; median 2).

Treatment started with gemcitabine IV 1,000 mg/m² over 30 minutes on days 1 and 8, and cisplatin IV 70 mg/m² over 60 minutes on day 2. Treatment was maintained by repeating the cisplatin/gemcitabine every 21 days for a total of 4 cycles before changing to docetaxel IV 100 mg/m² over 60 minutes on day 1 of this new cycle. Similarly, this docetaxel cycle was repeated every 21 days for a total of 4 cycles. Thus the patients would receive a total of 8 cycles, unless disease progression or toxicity occurred.

A total of 250 cycles were applied (median per patient, 8; range, 2-8), which subdivided into the two cycle sets, with medians of 4 cycles for both cisplatin/gemcitabine (range 2-4) and docetaxel (range, 1-4). Of the 250 cycles, a total of 29% were delayed (cisplatin/gemcitabine, 42 cycles; docetaxel, 21 cycles); however, these were mainly due to practical problems and patient compliance.

The overall response (OR) rate of 55.3% (complete, 15.8%; partial, 39.5%) was accompanied by 23.7% of patients achieving stable disease, although 13.2% underwent progressive disease and a small fraction were not evaluable (7.9%). The median response duration was 5 months.

With respect to the individual datasets for cisplatin/gemcitabine and docetaxel, Dr. Boukovinas noted that following on from an OR of 47.4% (complete, 5.3%; partial, 42.1%) from the first 4 cycles, there were a further 5 (17.2%) complete responses and 5 partial responses (17.2%) in the 30 patients evaluable for the second 4 cycles. Also, while 4 patients (13.3%) reached stable disease, 11 (36.7%) showed disease progression.

All patients were available for toxicity evaluations, and the only World Health Organisation grade 3/4 toxicities were neutropenia (55.2% overall), thrombocytopenia (10.5%) and anaemia (5.2%). There was also one episode of G3 febrile neutropenia that required hospitalisation, but there were no toxic deaths.

With a median follow-up of 9.8 months (range, 1.5-25.4), the median time to progression was 7.7 months (range, 1.0-25.0), with an overall survival of 15.6 months (range, 12.3-18.9).

Dr. Boukovinas indicated that this treatment regimen is not only very active as first-line therapy for patients with advanced urothelial carcinoma, but is also safe and shows a manageable overall toxicity.

"It seems that monotherapy as part of the treatment is not enough, since a number of patients did not continue to respond during the second phase of the schedule," he noted.


[Study Title: Sequential Administration of Cisplatin+Gemcitabine and Docetaxel as First-Line Treatment in Patients With Bladder Cancer. a Multicentre Phase 2 Trial.]

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