Primary chemotherapy with low-dose prolonged infusion gemcitabine and cisplatin in patients with bladder cancer: A Phase II trial

Khaled, Hussein; Emara, Mohamed E.; Gaafar, Rabab M.; Mansour, Osman; Abdel Warith, Ahmed; Zaghloul, Mohamed S.; El Malt, Osama

doi:10.1016/j.urolonc.2007.01.013

« Previous Next »Urologic Oncology: Seminars and Original Investigations
Volume 26, Issue 2 , Pages 133-136, March 2008

Primary chemotherapy with low-dose prolonged infusion gemcitabine and cisplatin in patients with bladder cancer: A Phase II trial

Hussein Khaled, M.D.
- Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt
- Corresponding author. Tel.: +00-201-22151040; fax: +368-9711.
Mohamed E. Emara, M.D.
- Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt
Rabab M. Gaafar, M.D.
- Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt
Osman Mansour, M.D.
- Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt
Ahmed Abdel Warith, M.D.
- Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt
Mohamed S. Zaghloul, M.D.
- Department of Radiation Oncology, National Cancer Institute, Cairo University, Cairo, Egypt
Osama El Malt, M.D.
- Department of Surgical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt

Received 21 August 2006; received in revised form 8 January 2007; accepted 8 January 2007. published online 15 January 2008.

Abstract

Background

Gemcitabine is an active agent in the treatment of bladder cancer. The enzyme deoxycytidine kinase catalyzes the phosphorylation of gemcitabine into the active gemcitabine triphosphate. After an infusion during 30 minutes, this enzyme will be saturated, therefore, accumulation of higher intracellular concentrations of the active gemcitabine triphosphate could be achieved by prolonging the infusion time of gemcitabine.

Patients and methods

Based on previously published Phase I trials, the efficacy and safety of a combination of cisplatin and gemcitabine given as prolonged infusion were tried in a Phase II study of 57 untreated patients with stage III/IV bladder cancer, which is the most common malignant tumor among Egyptian males. Patients received gemcitabine (250 mg/m² during 6-hour infusion) on days 1 and 8, and cisplatin (70 mg/m²) on day 2 every 21-day cycle.

Results

The 41 males and 16 females had a median age of 55 years (range 37–77). A total of 37 patients had transitional cell, 15 had squamous cell, 2 had adenocarcinoma, and 3 had undifferentiated cell carcinoma. The median number of cycles given to these 57 patients was 4 (range 1–6). Of 54 evaluable patients, 5 (9.4%) had complete remission, and 27 (50%) partial remission, for an overall response rate of 59.4%. These results are comparable to those of a previous Phase II study of the same combination but with gemcitabine given in the standard dose and schedule. Responses were observed at all disease sites. Both hematologic and nonhematologic toxicity were treatable and not severe.

Conclusions

Prolonged infusion of gemcitabine and cisplatin is an effective treatment for advanced bilharzial-related bladder cancer. Toxicity, especially myelosuppression, is surprisingly mild. This combination deserves to be tried in other different disease categories.

Keywords: Chemotherapy, Bladder cancer, Low dose, Prolonged infusion, Gemcitabine, Cisplatin