Cisplatin, Gemcitabine, and Lapatinib as Neoadjuvant Therapy for Muscle-Invasive Bladder Cancer / Journal of the Korean Cancer Association, 대한암학회지
Cancer Research and Treatment
;
: 1084-1091, 2016.
Artigo
em Inglês
| WPRIM
| ID: wpr-68886
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 ANDMETHODS:
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Trombocitopenia
/
Bexiga Urinária
/
Neoplasias da Bexiga Urinária
/
Cistectomia
/
Cisplatino
/
Terapia Neoadjuvante
/
Dose Máxima Tolerável
/
Diarreia
/
Tratamento Farmacológico
/
Terapia de Alvo Molecular
Limite:
Humanos
Idioma:
Inglês
Revista:
Cancer Research and Treatment
Ano de publicação:
2016
Tipo de documento:
Artigo
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