Transcript Slide 1

A Multicentre Phase II Study of Cisplatin (C),
Gemcitabine (G), and Bevacizumab (B) as First-Line
Chemotherapy for Metastatic Urothelial Carcinoma
(UC): Hoosier Oncology Group GU-0475
Authors: Hahn NM et al, ASCO 2009.
Reviewed by: Dr. Lori Wood
Abstract: 5018
Date posted: June 12, 2009
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R
metastatic urothelial cancer
ECOG 0-1
Treatment
Cisplatin 70 mg/m2
Gemcitabine 1250 mg/m2 d1 and d8*
Bevacizumab 15 mg/kg d1 q21 days x 8
*After first 17 patients, 
venous thromboembolic
events and Gemcitabine  to
1000 mg/m2.
first-line
1 endpoint = PFS (by RECIST)
n = 40 to  PFS from 7.5m  11.25m
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STUDY RATIONALE
•Cisplatin/Gemcitabine would be considered standard first-line
chemotherapy for metastatic urothelial cancer in North America.
• Adding more chemotherapy (i.e.: the triplet of
Gemcitabine/Cisplatin/Taxol) did not improve outcome in a previous
phase III study. Unlikely to be further advantages to adding
more/other chemotherapy drugs.
• Therefore, reasonable to add targeted therapy to traditional
chemotherapy
• VEGF expression associated with poor prognosis in bladder
cancer.
• So, combination of Gemcitabine/Cisplatin and Bevacizumab studied
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RESULTS
• n = 43
• Median 6 cycles; 30% received all 8 and received maintenance
Bevacizumab
• Dose modifications 60%
• Discontinued secondary to toxicity 42%  21% secondary to DVT/PE
• Gemcitabine:
• 1250 mg/m2 = 39% grade 3-4 DVT/PE and 0% grade 3-4
hemorrhage
• 1000 mg/m2 = 8% grade 3-4 DVT/PE and 12% grade 3-5
hemorrhage
• Deaths = 3 (sudden cardiac, aortic dissection, CNS hemorrhage)
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RESULTS (CONTINUED)
• RECIST response rates:
• CR = 14%
• PR = 44%
• SD = 30%
• PD = 9%
• PFS = 8.2 months with median follow-up 14.6m
• PFS at 12m = 29%
• Overall survival = 19.1 months
• Overall survival at 12m = 65%
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STUDY COMMENTARY
• Significant toxicity with this combination, especially DVT/PE.
• CR + PR = 58% with PFS = 8.2m and OS = 19.1m.
• The PFS and OS is higher than with Gemcitabine/Cisplatin alone;
however, these were highly selected patients.
• Currently an ongoing phase I study of Carboplatin/Gemcitabine/
Bevacizumab.
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BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS
• This triplet is far from prime time.
• It is very important in the metastatic palliative setting to “do no harm”
and this combination looks like it does/could.
• Another example of how the tolerability of systemic therapy in
patients with bladder cancer is different than other cancer populations
• i.e.: lung cancer: doses of Carboplatin/Gemcitabine are an
AUC = 6 and full dose Gemcitabine
• i.e.: bladder cancer: just cannot get those doses in because of
myelosuppression
• Tough combination to move into a phase III study.
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