PM01183 showed improved efficacy over topotecan in 81 PRROC patients in a randomized phase II trial [Poveda et al. 50th ASCO Annual Meeting 2014 .
Myelosuppression was manageable although dose-limiting.
Neutropenia was correlated with PM01183 area under the curve (AUC) as seen in prior Phase I studies.
Methods:
PRROC consenting patients with + 3 prior chemotherapy lines, adequate organ function and ECOG=0-2 were treated until progression or unacceptable toxicity with either PM01183 at 7 mg every three weeks (q3w) or topotecan on days (D)1-5 q3w or on D1, 8, 15 every four weeks in an IRB/IEC approved clinical trial. Primary endpoint was response rate (RR); secondary endpoints included progression-free-survival (PFS), overall-survival (OS), safety and PK/PD correlations. PK/PD modelling was used to link PM01183 plasma concentrations with changes over time of CA-125/tumor size and severity of neutropenia. An Emax-sigmoid model fits to determine the potency of each drug.
Results :
Calculated potency modelled as half maximal effective concentration (EC50) was 0.03/4.57 µg/L for PM01183/topotecan, respectively. The typical PM01183 PK-profile was well above this efficacy threshold during all the cycle. The model predicts that PM01183 given at 3.2 mg/m² q3w will still result in active plasma concentrations during all the cycle, while grade 4 neutropenia would be reduced by =20%.
Conclusions:
PM01183 is an Active Drug, Approximately 150 Times more Potent than Topotecan, in PRROC Patients. PK/PD models provide a suitable method to optimize the PM01183 benefit/risk ratio. A randomized phase III study in PRROC is underway to confirm these promising results.
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Nombre Genérico: Topotecán .
Nombre Comercial: Hycamptin® .
Farmaceutica : GlaxoSmithKline ( GSK ) .
El Topotecán es un fármaco de quimioterapia anticanceroso ("antineoplásico" o "citotóxico"). Este medicamento se clasifica como un "inhibidor de la topoisomerasa 1".
Para qué se utiliza este fármaco:
Este medicamento se utiliza para tratar el cáncer de ovarios cuando ya han fallado otros tratamientos .