Gemcitabine, Cisplatin, and Sunitinib for Metastatic Urothelial Carcinoma and as Preoperative Therapy for Muscle-Invasive Bladder Cancer
文摘
Background
Data support chemotherapy combined with antiangiogenic therapy in metastatic urothelial cancer (mUC) and muscle-invasive bladder cancer (MIBC). We investigated the efficacy and safety of gemcitabine, cisplatin, and sunitinib (GCS) in mUC and MIBC in parallel phase II trials.Patients and Methods
<p>Trial 1 enrolled 36 patients with mUC who were chemotherapy naive; trial 2 enrolled 9 patients with MIBC. The primary endpoints for trials 1 and 2 were response rate and pathologic complete response, respectively. GCS was given as first-line treatment for patients with mUC and as neoadjuvant therapy for patients with MIBC. The Simon minimax 2-stage design was used for an objective response rate in trial 1 and for the pathologic complete response rate in trial 2.Results
<p>The initial trial 1 GCS dose was gemcitabine 1000 mg/mp>2p> intravenously, days 1 and 8; cisplatin 70 mg/mp>2p> intravenously, day 1; and sunitinib 37.5 mg orally daily, days 1 to 14 of a 21-day cycle. These doses proved intolerable. The doses of gemcitabine and cisplatin were subsequently reduced to 800 and 60 mg/mp>2p>, respectively, without an improvement in drug delivery, and the trial was closed. This lower-dose regimen was applied in trial 2, which was stopped early due to excess toxicity. 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. In trial 1, the response rate was 49 % (95 % CI, 31 % -67 % ); in trial 2, the pathologic complete response was 22 % (2/9). Due to early closure secondary to toxicity, the sample sizes of both trials were small.Conclusions
<p>Delivery of GCS was hampered by excessive toxicity in both advanced and neoadjuvant settings.
