Entry Detail
| General information | |
| Database: | DB00558 |
| Objective: | They investigated the efficacy and safety of gemcitabine, cisplatin, and sunitinib (GCS) in mUC and MIBC in parallelphase II trials. |
| Authors: | Galsky MD, et al |
| Title: | Gemcitabine, Cisplatin, and sunitinib for metastatic urothelial carcinoma and as preoperative therapy for muscleinvasive bladder cancer. |
| Journal: | Clin Genitourin Cancer |
| Year: | 2013 |
| PMID: | 23228446 |
| Trial Design | |
| Clinical Trial Id: | NCT00821327 NCT00859339. |
| Agent: | sunitinib |
| Target: | FL cytokine receptor Mast/stem cell growth factor receptor Vascular endothelial growth factor receptor 2 Plateletderived growth factor receptor |
| Cancer Type: | Urothelial Carcinoma |
| Cancer Subtype: | urothelial cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | gemcitabine+ cisplatin+ sunitinib (GCS) |
| Study Type: | an open label, phase II study |
| Key Patients Feature: | Trial 1 patients required histologic documentation of a diagnosis of urothelial cancer of the bladder, urethra, ureter, or renalpelvis, and the presence of unresectable or metastatic measurabledisease (cT4b or N1/2 or M1). The patients could not have received prior chemotherapy for mUC, but chemotherapy in theperioperative setting was permitted if treatment was completed 12 months before enrollment. In trial 2, eligibility requirements included a diagnosis of muscleinvasive urothelial cancer ofthe bladder and no lymph node or metastatic disease (T2T4, N0, M0). Both trials required adequate performance status (trial 1:Karnofsky Performance Status 70%; trial 2: Eastern Cooperative Oncology Group performance status 01); adequate cardiac, bone marrow, and hepatic function; and a creatinine clearance 60 mL/min determined by CockcroftGault formula calculation. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | GCS was given as firstline treatment for patients with mUC and as neoadjuvant therapy for patients with MIBC. The Simon minimax 2stage design was used for an objective response rate in trial 1 and for the pathologic complete response rate in trial 2. |
| Primary End Point: | rials 1 and 2:response rate and pathologic complete response, respectively |
| Secondary End Point: | NA |
| Patients Number: | 45 |
| Trial Results | |
| DLT_MTD: | The doses of gemcitabine and cisplatin were subsequently reduced to 800 and 60 mg/m(2), respectively, without an improvement in drug delivery, and the trial was closed. |
| Objective Response Rate: | In trial 1, the response rate was 49% (95% CI, 31%67%); in trial 2, the pathologic complete response was 22% (2/9). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The median progression free survival for the intenttotreat population was 8.0 months (95% CI, 7.014.0 months) |
| Median OS A vs. C: | the median overall survival was 13.8 months (95% CI, 10.122.9 months) |
| Adverse Event(agent arm): | Grade 3 to 4 hematologic toxicities occurred in 70% (23/33) of patients in trial 1 and 22% (2/9) of patients in trial 2. |
| Conclusions: | Delivery of GCS was hampered by excessive toxicity in both advanced and neoadjuvant settings. |