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

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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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Treatment Cisplatin 70 mg/m2 Gemcitabine 1250
mg/m2 d1 and d8 Bevacizumab 15 mg/kg d1 q21 days
x 8
R
After first 17 patients, ?? venous
thromboembolic events and Gemcitabine ? to 1000
mg/m2.
metastatic urothelial cancer ECOG
0-1 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/Gemcitabin
  e 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.