| General information |
| Database: | DB00548 |
| Objective: | Novel approaches are needed for patients with metastatic urothelial cancer (UC). This trial assessed the efficacy and toxicity of bevacizumab in combination with cisplatin and gemcitabine (CGB) as firstline treatment for patients with metastatic UC. |
| Authors: | Hahn NM, et al |
| Title: | Phase II trial of cisplatin, gemcitabine, and bevacizumab as firstline therapy for metastatic urothelial carcinoma: Hoosier Oncology Group GU 0475. |
| Journal: | J Clin Oncol. |
| Year: | 2011 |
| PMID: | 21422406 |
| Trial Design |
| Clinical Trial Id: | NCT00234494 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | Urothelial Carcinoma |
| Cancer Subtype: | advanced urothelial carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | cisplatin, gemcitabine, and bevacizumab |
| Study Type: | Phase II Trial |
| Key Patients Feature: | Institutional review board approval was obtained from all participatingcenters. All patients provided written informed consent. Eligibility criteriaincluded the following: age 18 years; metastatic or unresectable predominantlyurothelialcellcarcinomaoftheurethra, bladder, orupperurinarytract;measurable disease per Response Evaluation Criteria in Solid Tumors(RECIST); and Eastern Cooperative Oncology Group (ECOG) performancestatus (PS) of 0 or 1. patients were required to have adequate bone marrowfunction (absolute neutrophil count [ANC] 1, 500/ L, platelet count 100, 000/ L, and hemoglobin 8 g/dL with transfusion or erythropoieticgrowth factor support), coagulation parameters (international normalizedratio[INR] 1.5), renalfunction(creatinine 1.5mg/dLandurineproteintocreatinine ratio 1.0), and hepatic function (bilirubin 1.5 mg/dL andALT 5 upper limit of normal for patients with liver metastases or ALT 2.5 upperlimitofnormalforpatientswithoutlivermetastases). |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | performance status of 0 (n = 26) or 1 (n = 17) |
| Treatment Info: | Chemotherapynaive patients with metastatic or unresectable UC received cisplatin 70 mg/m(2) on day 1, gemcitabine 1, 000 to 1, 250 mg/m(2) on days 1 and 8, and bevacizumab 15 mg/kg on day 1, every 21 days. |
| Primary End Point: | PFS |
| Secondary End Point: | NA |
| Patients Number: | 43 |
| Trial Results |
| DLT_MTD: | Grade 3 to 4 hematologic toxicity included neutropenia(35%), thrombocytopenia (12%), anemia (12%), and neutropenic fever (2%). Grade 3 to 5nonhematologic toxicity included deep vein thrombosis/pulmonary embolism (21%), hemorrhage(7%), cardiac (7%), hypertension (5%), and proteinuria (2%). |
| Objective Response Rate: | complete response in eight patients (19%) andpartial response in 23 patients (53%), for an overall response rate of 72%. Stable diseaselasting 12 weeks occurred in four patients (9%), and progressive disease occurred in six patients(14%) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 8.2 months (95% CI, 6.8 to 10.3 months) |
| Median OS A vs. C: | 19.1 months (95% CI, 12.4 to 22.7 months) |
| Adverse Event(agent arm): | Grade 3 to 4 hematologic toxicity included neutropenia (35%), thrombocytopenia (12%), anemia (12%), and neutropenic fever (2%). Grade 3 to 5 nonhematologic toxicity included deep vein thrombosis/pulmonary embolism (21%), hemorrhage (7%), cardiac (7%), hypertension (5%), and proteinuria (2%). Three treatmentrelated deaths (CNS hemorrhage, sudden cardiac death, and aortic dissection) were observed. |
| Conclusions: | CGB demonstrates promising OS and antiangiogenic treatmentrelated toxicities in thephase II setting of metastatic UC. The full riskbenefit profile of CGB in patients with metastatic UC will be determined by an ongoingphase III intergroup trial. |