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Authors: Hahn NM et al, ASCO 2009. Reviewed by: Dr. Lori Wood Abstract: 5018

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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Authors: Hahn NM et al, ASCO 2009. Reviewed by: Dr. Lori Wood Abstract: 5018

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  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

  2. 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

  3. 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

  4. 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)

  5. 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%

  6. 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.

  7. 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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