Safety, tolerability and pharmacokinetic properties of the novel triazene TriN 2755 in tumour bearing dogs – a phase I study^†

Abstract

TriN 2755 is an alkylating antineoplastic agent for intravenous (IV) use, carrying the triazene group as the cytotoxic principal. Using a standard 3 + 3 design, a phase I study was performed in tumour bearing dogs to determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT), and pharmacokinetic (PK) profile of TriN 2755. Thirty dogs were included in the study. TriN 2755 was administered over 20 min on two consecutive weeks per month for a total of three cycles. The starting dose was 25 mg kg and the MTD was 74.6 mg kg . Three dogs experienced DLT, which was characterized by gastrointestinal adverse events. The PKs of TriN 2755 and its main metabolites in plasma and sputum are described in a two-compartment model. The response rate for 19 of 30 dogs was 47.3% (six partial remission, three stable disease) and the median progression-free interval (PFI) for the responders was 47 days (range: 21-450 days).

Outcome comparison between radiation therapy and surgery as primary treatment for dogs with periarticular histiocytic sarcoma: An Italian Society of Veterinary Oncology study

“…Chemotherapy was started after a median of 14 days after RT (range, 1‐107). Thirty‐one (91.3%) dogs received post‐radiation lomustine at a median dosage of 80 mg/m 2 (range, 70‐90) every 21 days (median, 5 cycles; range, 1‐8 cycles); one (2.9%) dog was treated with an investigational drug (TRIN2755), 16 one (2.9%) received doxorubicin (4 cycles) and one (2.9%) received carboplatin and cyclophosphamide (4 cycles). Eleven (32.4%) dogs experienced adverse events: 4 of 34 dogs experienced bone marrow (BM) toxicity, four had hepatic toxicity, one dog had gastrointestinal (GI) and hepatic toxicity, one dog had BM and GI toxicity, and one dog experienced fever.…”