Cisplatin, Gemcitabine, and Lapatinib as Neoadjuvant Therapy for Muscle-Invasive Bladder Cancer

Vivek Narayan; Ronac Mamtani; Stephen Keefe; Thomas Guzzo; S. Bruce Malkowicz; David J. Vaughn

Cisplatin, Gemcitabine, and Lapatinib as Neoadjuvant Therapy for Muscle-Invasive Bladder Cancer

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Type: Academic journal

Author: Vivek Narayan Ronac Mamtani Stephen Keefe Thomas Guzzo S. Bruce Malkowicz David J. Vaughn

Journal: 대한암학회 Cancer Research and Treatment Cancer Research and Treatment 제48권 제3호 KCI Accredited Journals

Published: 2016.1

Pages: 1,084 - 1,091 (8page)

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Cisplatin, Gemcitabine, and Lapatinib as Neoadjuvant Therapy for Muscle-Invasive Bladder Cancer

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Purpose We sought to investigate the safety and efficacy of gemcitabine, cisplatin, and lapatinib (GCL) as neoadjuvant therapy in patients with muscle-invasive bladder cancer (MIBC) planned for radical cystectomy. Materials and Methods Four cycles of GCL were administered as neoadjuvant therapy for patients with MIBC. Although initially designed as a phase II efficacy study with a primary endpoint of pathologic complete response at the time of radical cystectomy, the dose selected for investigation proved excessively toxic. A total of six patients were enrolled. Results The initial four patients received gemcitabine 1,000 mg/m2 intravenously on days 1 and 8 and cisplatin 70 mg/m2 intravenously on day 1 of each 21-day treatment cycle. Lapatinib was administered as 1,000 mg orally daily starting one week prior to the initiation of cycle 1 of gemcitabine and cisplatin (GC) and continuing until the completion of cycle 4 of GC. These initial doses were poorly tolerated, and the final two enrolled patients received a reduced lapatinib dose of 750 mg orally daily. However, reduction of the lapatinib dose did not result in improved tolerance or drug-delivery, and the trial was terminated early due to excessive toxicity. Grade 3/4 toxicities included diarrhea (33%), nausea/vomiting (33%), and thrombocytopenia (33%). Conclusion The addition of lapatinib to GC as neoadjuvant therapy for MIBC was limited by excessive treatment-related toxicity. These findings highlight the importance of thorough dose-escalation investigation of combination therapies prior to evaluation in the neoadjuvant setting, as well as the limitations of determination of maximum tolerated dose for novel targeted combination regimens.

#Urothelial carcinoma #Drug therapy #Molecular targeted therapy #Epidermal growth factor receptor #Cystectomy

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References (25)

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Stein JP / 2006 / Radical cystectomy for invasive bladder cancer : long-term results of a standard procedure / World J Urol 24:296~304

Grossman HB / 2003 / Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer / N Engl J Med 349:859~866

Advanced Bladder Cancer(ABC)Meta-analysis Collaboration / 2005 / Neoadjuvant chemotherapy in invasive bladder cancer : update of a systematic review and meta-analysis of individual patient data advanced bladder cancer(ABC)meta-analysis collaboration / Eur Urol 48:202~205

National Comprehensive Cancer Network / NCCN guidelines:bladder cancer

von der Maase H / 2000 / Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer : results of a large, randomized, multinational, multicenter, phase III study / J Clin Oncol 18:3068~3077

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