J Pharm Pharmacogn Res 2(Suppl. 1): S5, 2014
Special supplement with the abstract book of LATINFARMA 2013
CO 008: IMMUNOTRANS-ARTERIAL CHEMOEMBOLIZATION (ITACE) IN HEPATOCELLULAR CARCINOMA PATIENTS TREATED WITH ANTI-EGFR MAB NIMOTUZUMAB PLUS ADRIAMYCIN. PHASE I CLINICAL TRIAL, FINAL RESULTS
Ramos-Suzarte M1, Hernández JC2, Roque A2, Ugarte JC2, Jordán J2, Samada M2, Lorenzo P1, Fernández A1, Catalá M2, Fermín E2, Frías A1, Izquierdo M1, Cedeño M1, Rengifo E1, Frómeta M1, Crombet T.1
Introduction: Hepatocellular carcinoma (HCC) is a common complication of chronic liver disease. EGFR is well validated as a primary contributor of different tumor of epithelial origin included liver cancer in initiation and progression. Nimotuzumab is a humanized monoclonal antibody (mAbs) that recognizes the EGFR extracellular domain. While it has similar preclinical and clinical activity when compared to other anti-EGFR mAbs, it does not induce skin toxicity or hypomagnesaemia.
Methods: Phase I prospective clinical trial (RPCEC00000022) to evaluate safety and optimal biological doses of immunotrans-arterial chemoembolization (ITACE) with nimotuzumab in patients with unresectable HCC. In this trial were enrolled 3 patients in 4 different level doses of Mab: 50 mg, 100 mg, 200 mg and 400 mg maintaining the same concentration of cytostatic drug per level, just one administration per patients. The principal endpoint was evaluate safety and Optimal or Maxima Biological Doses in the treatment of HCC by Trans arterial chemoembolization (ITACE) by injecting nimotuzumab an doxorubicin mixed with a radiopaque contrast (e.g. Lipiodol) and an embolic agent Gel foam into hepatic artery.
Results: The maximum tolerable dose was 200 mg of nimotuzumab, was impossible complete the administration in 400 mg because the administration rout was intra-arterial and the limiting factor was the final volume. Was confirmed a gain for these patients, since the life expectancy of them were about 6 months however median survival of 13.01 months was found to be above expected. Nimotuzumab was safe in terms of intra-arterial administration and the combination with doxorubicin. Not anti-idiotipic response was detected in any treated patients. Was the first time that nimotuzumab was administered by intra-arterial rout but is a perfect way to be used in this tumor.
Conclusions: The maxima tolerated dose was 200 mg of nimotuzumab for ITACE. The administration of nimotuzumab was safety, increasing patient survival, which provides a longer period for the possibility for patients to receive a liver transplant. The combinations with chemotherapy not increase the toxicity of therapy.