Gemcitabine and Ifosfamide As a Second-Line Systemic Chemotherapy for Cisplatin -Failed Advanced TCC

Cisplatin-based combination chemotherapy produces a response rate of 40-70% in TCC patients. However, only less than 10% of the patients can achieve long-term remission. Until now, there is no standard chemotherapy for cisplatin-failed TCC patients. Both gemcitabine and ifosfamide have been identified to have response rates of 20% or more in pretreated TCC patients. It is thus reasonable to combine these two active drugs as a second-line treatment for TCC.

Patients enrolled must have a pathologically proven urothelial transitional cell carcinoma (TCC) and must have exposed to one cisplatin-based combination chemotherapy for the advanced disease. GI regimen will be continued until maximal response.

Inclusion criteria

• Histologically or cytologically confirmed transitional cell carcinoma
• Advanced / metastatic disease failed to prior chemotherapy (diagnostically confirmed disease progression during the treatment of last chemotherapy or within 6 months after the end of last chemotherapy)
• Presence of at least one measurable disease which is defined as lesion that can be measured in at least 1 dimension as ³ 20 mm with conventional technique or ³ 10 mm with spiral CT scan
• Performance status of ECOG 0, 1, 2
• Age 20 years or older
• Life expectancy more than 3 months
• Adequate hematopoietic function as defined below:

• WBC ³ 3,000/uL
• Platelets ³ 75,000/Ul
• Adequate organ function as defined below:

• Total bilirubin £ 1.5 ´ ULN
• ALT / AST£ 5 ´ ULN
• Creatinine £ 1.5 mg/dL
• Adequate serum electrolyte concentration:

• 4 mmol/L<[K+] <5.3 mmol/L
• 0.74 mmol/L<[Mg2+] <1.03 mmol/
• 2.02 mmol/L<[Ca2+]<2.60 mmol/L
• Result of ECG assessment: QTC < 460 msec
• Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria

• Received chemotherapy, radiotherapy, surgery, or other investigational drug within 4weeks prior to entering the study
• Receiving other concurrent palliative chemotherapy, radiotherapy, hormonal therapy, or other investigational drug except non-disease related conditions (e.g. insulin for diabetes) during study period
• Presence of CNS metastasis
• Previous or current malignancy with the exception of curatively treated non- melanoma skin cancer or cervical carcinoma in situ
• Presence of serious concomitant illness which might be aggravated by study medication:

• Uncontrolled infection (active serious infections that are not controlled by antibiotics)
• Peripheral neuropathy grade 2 or higher (by NCI common toxicity criteria in sensory or motor neuropathy)
• Clinically significant arrhythmia (electrocardiogram QTc greater than 500 msec)
• Prior myocardial infarction or serious coronary arterial disease within the last 12 months
• Mental status is not fit for clinical trial.
• Women of child-bearing potential (pregnancy or breast feeding)