Cisplatin, Gemcitabine, and Lapatinib as Neoadjuvant Therapy for Muscle-Invasive Bladder Cancer.
- Author:
Vivek NARAYAN
1
;
Ronac MAMTANI
;
Stephen KEEFE
;
Thomas GUZZO
;
S Bruce MALKOWICZ
;
David J VAUGHN
Author Information
- Publication Type:Original Article
- Keywords: Urothelial carcinoma; Drug therapy; Molecular targeted therapy; Epidermal growth factor receptor; Cystectomy
- MeSH: Cisplatin*; Cystectomy; Diarrhea; Drug Therapy; Humans; Maximum Tolerated Dose; Molecular Targeted Therapy; Neoadjuvant Therapy*; Receptor, Epidermal Growth Factor; Thrombocytopenia; Urinary Bladder Neoplasms*; Urinary Bladder*
- From:Cancer Research and Treatment 2016;48(3):1084-1091
- CountryRepublic of Korea
- Language:English
- Abstract: 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.
