SCLC is the most aggressive and lethal form of lung cancer, typically very sensitive to cytotoxic therapy when first diagnosed, but associated with a high incidence of tumour relapse and a very poor life expectancy. Combination chemotherapy based on cisplatin or carboplatin and etoposide represents the most widely used regimen. Despite of the high response rate, approximately 80% of patients with limited disease and nearly all patients with extended disease develop disease relapse or progression. Topotecan is, at present, the only approved second line treatment in Europe. The search of a new therapeutic agent that could alter the natural history of SCLC would be an important goal to be reached. LBH589 (Panobinostat) is a histone deacetylase (HDAC) inhibitor available for intravenous and oral administration. LBH589 could be classified as PAN-DAC inhibitor targeting both histone and non histone proteins and as such it could be suitable for combination with cytotoxics. Three phase I dose escalation studies with both the intravenous and the oral formulation of LBH589, examining various dose schedules of administration have been conducted in advanced solid tumours and haematological malignancies. Single agent activity was observed in phase I in patients with haematological cancer. In solid tumours one response (Hormone-refractory Prostatic Cancer) and some prolonged stabilizations have been observed with intravenous formulation. Phase II studies are now in progress.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
21
25 mg/5 ml solution packaged in 6 ml type I glass vials and given as a 30 minutes infusion at the dose of 20 mg/m2 i.v., on day 1 and 8, every 21 days.
Klinik für Onkologie und Haematologie
Frankfurt am Main, Germany
Klinikum Kassel Innere Medizin
Kassel, Germany
Azienda Ospedaliera "S. G. Moscati"
Avellino, AV, Italy
Istituto Nazionale Ricerca sul Cancro
Genova, GE, Italy
U.O. di Oncologia Medica
Palermo, PA, Italy
Ospedale Maggiore di Parma
Parma, PR, Italy
Azienda Ospedaliera San Camillo Forlanini
Rome, RM, Italy
Az. San. Ospedaliera Molinette S. Giovanni Battista di Torino
Torino, TO, Italy
Objective response rate
Objective response rate measured according to the RECIST (Response Evaluation Criteria In Solid Tumours).
Time frame: 12-18 weeks (foreseen participation of the patient in the study)
Duration of antitumor activity
Time-to-progression, duration of response and disease stabilization
Time frame: 12-18 weeks (foreseen participation of the patient in the study)
Drug safety profile
Evaluation of adverse events, physical examination, vital signs, concomitant medications, laboratory (hematology and chemistry) and instrumental data (i.e. ECG) considered for safety analyses
Time frame: 28 days following the last dose
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