Cancer Res Treat.  2016 Jul;48(3):1084-1091. 10.4143/crt.2015.405.

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

• Narayan V
• Mamtani R
• Keefe S
• Guzzo T
• Malkowicz
• Vaughn DJ

• KMID: 2344082
• DOI: http://doi.org/10.4143/crt.2015.405

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.

Keyword

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

MeSH Terms

Cisplatin*
Cystectomy
Diarrhea
Drug Therapy
Humans
Maximum Tolerated Dose
Molecular Targeted Therapy
Neoadjuvant Therapy*
Receptor, Epidermal Growth Factor
Thrombocytopenia
Urinary Bladder Neoplasms*
Urinary Bladder*
Cisplatin
Receptor, Epidermal Growth Factor

Reference

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