TAS-102 + oxaliplatin

TAS-102 + oxaliplatin is a combination chemotherapy regimen being investigated for the treatment of metastatic colorectal cancer (mCRC). This combination pairs TAS-102 (trifluridine/tipiracil), an oral antitumor drug, with oxaliplatin, an established chemotherapeutic agent. ## Drug Information TAS-102 + oxaliplatin (also known as TAS-OX) is a combination therapy that has shown promising results in clinical trials for patients with metastatic colorectal cancer who have previously received standard treatments. The combination has been studied in various dosing schedules, typically with TAS-102 administered on days 1-5 and oxaliplatin on day 1 of 14-day cycles[1][3]. The recommended dosage established in phase I studies is TAS-102 35 mg/m² twice daily on days 1-5, with oxaliplatin 85 mg/m² administered as an intravenous infusion on day 1 of each 14-day cycle[1][3]. This dosing schedule differs from the standard 28-day TAS-102 cycle to reduce the additive toxicity of the chemotherapy combination[1]. ## Mechanism of Action TAS-102 consists of trifluridine, a thymidine-based nucleoside analogue, and tipiracil hydrochloride, a thymidine phosphorylase inhibitor[8][9]. Trifluridine is incorporated into DNA, interfering with DNA synthesis and function. Tipiracil prevents the rapid degradation of trifluridine, maintaining its therapeutic concentration. Oxaliplatin is a platinum-based compound that forms crosslinks in DNA, preventing DNA replication and transcription, ultimately leading to cell death. The combination of these agents appears to have enhanced antitumor effects compared to either agent alone. Preclinical studies suggest that TAS-102 plus oxaliplatin may sensitize microsatellite stable (MSS) metastatic colorectal cancer to anti-PD-1 immune checkpoint inhibitors, potentially improving responses to immunotherapy[1]. ## Clinical Development Several clinical trials have evaluated this combination: 1. A phase I study determined the recommended dose for TAS-102 in combination with oxaliplatin[3][4]. 2. A phase Ib expansion study assessed the safety and efficacy of TAS-OX in patients with metastatic colorectal cancer previously treated with oxaliplatin[3][9]. 3. A phase II trial investigated TAS-102 and oxaliplatin in treating patients with stage IV colon cancer[6]. 4. A multicohort phase I study evaluated TAS-102 plus oxaliplatin in combination with either bevacizumab or nivolumab in patients with metastatic colorectal cancer who had received at least one line of standard chemotherapy[1]. ## Safety Profile The safety profile of TAS-102 + oxaliplatin appears manageable. In clinical studies, most adverse events were grade 1 or 2 in severity and could be managed with supportive care, dose reductions, or delays[3]. The most common adverse events associated with TAS-102 (based on its individual profile) include anemia, neutropenia, asthenia/fatigue, nausea, thrombocytopenia, decreased appetite, diarrhea, vomiting, abdominal pain, and pyrexia[5]. Studies have shown that the combination does not appear to potentiate the toxicity of either individual drug, and full doses of each can safely be administered together[3]. No treatment-related deaths were reported in the clinical trials reviewed[3]. ## Current Status TAS-102 + oxaliplatin remains investigational for metastatic colorectal cancer. While TAS-102 alone is approved for previously treated patients with metastatic colorectal cancer[1][5], the combination with oxaliplatin is still being evaluated in clinical trials to determine its efficacy and optimal use in the treatment landscape.

Brand names

LonsurfEloxatin

Other names

TAS-102 with oxaliplatinTAS102 with oxaliplatinTAS 102 with oxaliplatinTAS-102 plus oxaliplatinTAS102 plus oxaliplatinTAS 102 plus oxaliplatinTAS-102 and oxaliplatinTAS102 and oxaliplatinTAS 102 and oxaliplatinTASOX