NEW YORK (Reuters Health) Mar 21 - Patients with metastatic urothelial carcinoma got some benefit from adding bevacizumab to cisplatin and gemcitabine in a phase II trial.
But the three-drug (CGB) regimen did not achieve its primary endpoint, and furthermore it was extremely toxic.
Most patients with metastatic urothelial carcinoma die from their cancer despite standard-of-care treatment with cisplatin and gemcitabine, according to Dr. Noah M. Hahn of Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, who led the phase II study, and his colleagues.
Adding bevacizumab to standard chemotherapy has helped improve outcomes for a variety of tumor types. In the current study, chemotherapy-na�ve patients with metastatic or unresectable urothelial carcinoma received cisplatin 70 mg/m2 on day 1, gemcitabine 1,000 to 1,250 mg/m2 on days 1 and 8 and bevacizumab 15 mg/kg on day 1, every 21 days, as reported online today in the Journal of Clinical Oncology.
The research team evaluated 43 patients for response and toxicity. Eight had a complete response (19%) and 23 (53%) had a partial response, for an overall response rate of 72%.
Four patients (9%) in the current trial had stable disease lasting 12 weeks or more; six patients (14%) had disease progression. Three patients who completed eight cycles of CGB and then stayed on bevacizumab monotherapy converted from stable disease to partial response or complete response.
These results "compare favorably" to the 49% response rate and 12% complete response rate reported in 2000 in the phase III first-line cisplatin/gemcitabine study conducted in a similar population of patients, the authors say.
But after a median follow up of 27.2 months, progression-free survival (PFS), the primary endpoint, was 8.2 months, which did not meet the study-defined goal of a 50% improvement in PFS (from 7.5 months with standard cisplatin/gemcitabine therapy to 11.25 months with the three-drug regimen).
The median overall survival time was 19.1 months, similar to other studies, which have reported overall survival times ranging from 13.8 to 18.3 months.
Treatment-associated toxicity was common and significant. There were three treatment-related deaths - one episode each of aortic dissection, sudden cardiac death and CNS hemorrhage.
Grade 3 to 4 hematologic toxicities included neutropenia (35%), anemia (12%), thrombocytopenia (12%), and neutropenic fever (2%). Other Grade 3 to 5 toxicities included deep vein thrombosis/pulmonary embolism (DVT/PE; 21%), hemorrhage (7%), cardiac (7%), hypertension (5%) and proteinuria (2%).
Due to the high DVT/PE rates, the researchers reduced the dose of gemcitabine from 1,250 to 1,000 mg/m2, which brought down the DVT/PE rates.
Nonetheless, the authors say their "enthusiasm for this regimen is tempered by significant toxicity rates observed in this phase II trial."
Results of a phase III study that's now underway will provide more information on toxicity and efficacy, the research team adds.
SOURCE: http://bit.ly/i18dDM
J Clin Oncol 2011.
But the three-drug (CGB) regimen did not achieve its primary endpoint, and furthermore it was extremely toxic.
Most patients with metastatic urothelial carcinoma die from their cancer despite standard-of-care treatment with cisplatin and gemcitabine, according to Dr. Noah M. Hahn of Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, who led the phase II study, and his colleagues.
Adding bevacizumab to standard chemotherapy has helped improve outcomes for a variety of tumor types. In the current study, chemotherapy-na�ve patients with metastatic or unresectable urothelial carcinoma received cisplatin 70 mg/m2 on day 1, gemcitabine 1,000 to 1,250 mg/m2 on days 1 and 8 and bevacizumab 15 mg/kg on day 1, every 21 days, as reported online today in the Journal of Clinical Oncology.
The research team evaluated 43 patients for response and toxicity. Eight had a complete response (19%) and 23 (53%) had a partial response, for an overall response rate of 72%.
Four patients (9%) in the current trial had stable disease lasting 12 weeks or more; six patients (14%) had disease progression. Three patients who completed eight cycles of CGB and then stayed on bevacizumab monotherapy converted from stable disease to partial response or complete response.
These results "compare favorably" to the 49% response rate and 12% complete response rate reported in 2000 in the phase III first-line cisplatin/gemcitabine study conducted in a similar population of patients, the authors say.
But after a median follow up of 27.2 months, progression-free survival (PFS), the primary endpoint, was 8.2 months, which did not meet the study-defined goal of a 50% improvement in PFS (from 7.5 months with standard cisplatin/gemcitabine therapy to 11.25 months with the three-drug regimen).
The median overall survival time was 19.1 months, similar to other studies, which have reported overall survival times ranging from 13.8 to 18.3 months.
Treatment-associated toxicity was common and significant. There were three treatment-related deaths - one episode each of aortic dissection, sudden cardiac death and CNS hemorrhage.
Grade 3 to 4 hematologic toxicities included neutropenia (35%), anemia (12%), thrombocytopenia (12%), and neutropenic fever (2%). Other Grade 3 to 5 toxicities included deep vein thrombosis/pulmonary embolism (DVT/PE; 21%), hemorrhage (7%), cardiac (7%), hypertension (5%) and proteinuria (2%).
Due to the high DVT/PE rates, the researchers reduced the dose of gemcitabine from 1,250 to 1,000 mg/m2, which brought down the DVT/PE rates.
Nonetheless, the authors say their "enthusiasm for this regimen is tempered by significant toxicity rates observed in this phase II trial."
Results of a phase III study that's now underway will provide more information on toxicity and efficacy, the research team adds.
SOURCE: http://bit.ly/i18dDM
J Clin Oncol 2011.
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