Pilot Study of Lapatinib (Tyverb®) in Neoadjuvant Treatment for Patients With Locally Bladder Carcinoma Before Cystectomy
Patients with invasive bladder tumor , candidates for radical cystectomy. Patients will
receive Lapatinib during 3 weeks +/- 5 days, before cystectomy. A comparison of tissue from
the original biopsy and cystectomy after Lapatinib will allow this to occur.
TREATMENT AND STRATEGY Lapatinib in bladder carcinoma -Overall there are arguments for
considering that egf pathway is involved in bladder carcinoma and so far that drugs
inhibiting EGF pathway could have an impact for therapeutical endpoints.
Nevertheless it is unclear that from previous studies that adding egf inhibiting drug to
chemotherapy is clinically relevant, essentially by difficulties to measure a beneficial
endpoint while downstream EGF pathways have been modified by these drugs, as shown with
lapatinib (see 2.1.5).
Furthermore, there is no argument for initial selection of patients based on the initial
egfr and/or her 2 tumor profile, asking for more intense knowledge.
LAPATINIB TREATMENT Patients will receive lapatinib therapy at a daily standard dose of 1500
LAPATINIB TREATMENT DURATION Patients will then receive 3 weeks of lapatinib therapy +
possible 5 days. As the study is a non direct benefit study, the exposition to the drug is
proposed during the standard window of 3 to 4 weeks to organize a radical cystectomy in
patients with muscle invasive bladder carcinoma. In this study patients, the standard
procedure is not delayed for the purpose of the study.
The duration of exposition to lapatinib as to be long enough to have a continuous impact of
biological events to induce indeed inhibition of EGF pathway but also to impact on more
complex or more distal events as apoptosis and so to be able to measure it. This justifies a
3 weeks of treatment + possible up to 5 days more due to surgical organization procedures.
Surgery will take place on the last day of treatment, which is recommended due to the
half-life of lapatinib. Nevertheless for surgical purpose, the drug could be not given on
the day of surgery.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label
Effect on egf pathway at a molecular level of 3 weeks treatment by lapatinib.
The primary objective of the study is to evaluate the effect at a molecular level, of 3 weeks of neoadjuvant lapatinib, in locally advanced muscle-invasive transitional cell carcinoma of the bladder. A comparison of tissue from the original biopsy and cystectomy after lapatinib will allow this to occur. This effect will be evaluated by studying proliferation and apoptotic markers as well as the phosphorylation of proteins which are components of the egf signalling pathway.
At surgery (day 21-27)
Geneviève CHENE, Pr
France: Ministry of Health