Invest New Drugs 2016 Nov 21. Epub 2016 Dec 21.
Luis Paz-Ares, Martin Forster, Valentina Boni, Sergio Szyldergemajn, Jesús Corral, Samantha Turnbull, Antonio Cubillo, Carlos Fernandez Teruel, Iker López Calderero, Mariano Siguero, Patrick Bohan, Emiliano Calvo .
Abstract
Background To determine the recommended dose (RD) of a combination of PM01183 and gemcitabine in patients with advanced solid tumors.
Methods Forty-five patients received escalating doses of PM01183/gemcitabine on Days 1 and 8 every 3 weeks (d1,8 q3wk) following a standard 3 + 3 design. Results PM01183 3.5 mg flat dose (FD)/gemcitabine 1000 mg/m(2) was the highest dose level tested. Dose-limiting toxicities (DLTs) were mostly hematological and resulted in the expansion of a lower dose level (PM01183 3.5 mg FD/gemcitabine 800 mg/m(2)); 19 patients at this dose level were evaluable but >30% had DLT and >20% had febrile neutropenia. No DLT was observed in 11 patients treated at PM01183 3.0 mg FD/gemcitabine 800 mg/m(2), which was defined as the RD.
This regimen was feasible and tolerable with manageable toxicity; mainly grade 3/4 myelosuppression. Non-hematological toxicity comprised fatigue, nausea, vomiting, and transaminases increases. Fifteen (33%) patients received ≥6 cycles with no cumulative hematological toxicity.
Pharmacokinetic analysis showed no evidence of drug-drug interaction. Nine of 38 patients had response as per RECIST (complete [3%] and partial [21%]), for an overall response rate (ORR) of 24% (95% Confidence Interval [CI] 12-40%). Eleven patients (29%) had disease stabilization ≥4 months.
Responses were durable (median of 8.5 months): overall median progression-free survival (PFS) was 4.2 months (95% CI, 2.7-6.5 months).
Conclusions The RD for this combination is PM01183 3.0 mg FD (or 1.6 mg/m(2))/Gemcitabine 800 mg/m(2) d1,8 q3wk. This schedule is well tolerated and has antitumor activity in several advanced solid tumor types.
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Gemzar ( Gemcitabine ) es un medicamento que pertenece al grupo de los análogos de nucleósidos y se utiliza como agente quimioterápico para el tratamiento de distintos tipos de cáncer, incluyendo cáncer de pulmón no microcítico, cáncer de páncreas, cáncer de vejiga y cáncer de mama. Se está investigando su utilidad para otros tumores como el cáncer de esófago y los linfomas. Ha sido comercializado con el nombre de Gemzar por la empresa Eli Lilly and Company. Se administra por vía intravenosa a una dosis de 1-1.2 g/m2. Puede utilizarse asociado al carboplatino con buenos resultados en el tratamiento del cáncer de pulmón no microcítico.