Pilot study on antitumor efficacy of intravenously applied synergistic combinations of salicylic acids in patients with advanced solid tumors

e13508 Background: Due to chronic hypoxia cancer cells are growing in a more acidic environment compared to physiological tissue. Using this differentiation a new therapy method has been developed for targeted chemotherapy. Recent preclinical in vitro and in vivo data have shown direct pH-sensitive anti-tumor activity by pore formation and apoptosis when synergistically acting combinations of diflunisal, paraaminosalicylic acid (PAS) and aspirin were applied. Therefore, a pilot study was performed to evaluate its clinical relevance. Methods: A total of 30 patients (n=30) with advanced solid tumors and the lack of standard treatments were treated with a protocol consisting of 3-5 weeks with 2 daily i.v. infusions of diflunisal and aspirin for 4 days per week after they had signed an informed consent form. Response evaluation was assessed by PET/CT differentiating in metabolic and metric (RECIST) response. Results: Out of 30 patients treated 4 patients suffered from colorectal cancer, 11 from breast cancer, 2 from ovarian cancer, 2 from lung cancer, 2 from gastric cancer, 2 from glioblastoma, 1 from CUP, 1 from hemangioendothelioma, 1 from pleuramesothelioma, 1 from non-Hodgkin lymphoma, 1 from pancreatic cancer, 1 from choledochus cancer, 1 from prostate cancer, respectively. Side effects related to the therapy have been fatigue (6,7%), nausea (13,3%), tinnitus (10%), hypertension (6,7%), dyspnea (3,3%) and burning sensation in tumor areas (3,3%). Out of 30 patients treated, until today 14 were evaluable for metric response, 12 for metabolic and 13 for tumor marker response assessment. For tumor marker follow up 2 patientis (6,7 %) had a CR, 6 (20 %) a PR, 4 (13,3 %) a SD of > 3 month and 1 (3,3 %) a PD. For metric follow up 0 patients (0 %) had a CR, 6 (20 %) a PR, 5 (16,7 %) a SD of > 3 month and 3 (10 %) a PD. For metabolic follow up 1 patients (3,3 %) had a CR, 3 (10 %) a PR, 5 (16,7 %) a SD of > 3 month and 3 (10 %) a PD. Conclusions: This pilot study confirms a direct pH-sensitive synergistic anti-tumor activity of intravenous salicylic acids in patients with advanced solid tumors. Therefore, a further evaluation in a controlled clinical phase II study will be performed.