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: 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: The initial trial 1 GCS dose was gemcitabine 1000 mg/m(2) intravenously, days 1 and 8; cisplatin 70 mg/m(2) 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/m(2), 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: Delivery of GCS was hampered by excessive toxicity in both advanced and neoadjuvant settings.
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: 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: The initial trial 1 GCS dose was gemcitabine 1000 mg/m(2) intravenously, days 1 and 8; cisplatin 70 mg/m(2) 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/m(2), 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: Delivery of GCS was hampered by excessive toxicity in both advanced and neoadjuvant settings.
Authors: Matthew D Galsky; Marshall Posner; Randall F Holcombe; Karen M Lee; Krzysztof Misiukiewicz; Che-Kai Tsao; James Godbold; Rothschild Soto; Kiev Gimpel-Tetra; Nancy Lowe; William K Oh Journal: Cancer Chemother Pharmacol Date: 2014-07-15 Impact factor: 3.333
Authors: A Necchi; P Giannatempo; L Mariani; E Farè; D Raggi; M Pennati; N Zaffaroni; F Crippa; A Marchianò; N Nicolai; M Maffezzini; E Togliardi; M G Daidone; A M Gianni; R Salvioni; F De Braud Journal: Invest New Drugs Date: 2014-02-26 Impact factor: 3.850
Authors: Metin Kurtoglu; Nicole N Davarpanah; Rui Qin; Thomas Powles; Jonathan E Rosenberg; Andrea B Apolo Journal: Clin Genitourin Cancer Date: 2015-03-05 Impact factor: 2.872
Authors: Andrea B Apolo; Rosa Nadal; Yusuke Tomita; Nicole N Davarpanah; Lisa M Cordes; Seth M Steinberg; Liang Cao; Howard L Parnes; Rene Costello; Maria J Merino; Les R Folio; Liza Lindenberg; Mark Raffeld; Jeffrey Lin; Min-Jung Lee; Sunmin Lee; Sylvia V Alarcon; Akira Yuno; Nancy A Dawson; Kimaada Allette; Arpita Roy; Dinuka De Silva; Molly M Lee; Tristan M Sissung; William D Figg; Piyush K Agarwal; John J Wright; Yangmin M Ning; James L Gulley; William L Dahut; Donald P Bottaro; Jane B Trepel Journal: Lancet Oncol Date: 2020-07-06 Impact factor: 41.316