Oxaliplatin

Oxaliplatin (CAS 61825-94-3) is a platinum-based antitumor agent that primarily inhibits DNA synthesis by forming DNA adducts. It exhibits broad-spectrum antitumor activity and lacks cross-resistance with other platinum compounds; it induces primary and secondary DNA damage, triggering apoptosis.

Oxaliplatin is active against the human melanoma cell lines C32 and G361, with IC50 values of 0.98 mM and 0.14 mM, respectively. Oxaliplatin effectively inhibits the bladder cancer cell lines RT4 and TCCSUP, the ovarian cancer cell line A2780, the colon cancer cell line HT-29, the glioblastoma cell lines U-373MG and U-87MG, and the melanoma cell lines SK-MEL-2 and HT-144, with IC50 values of 11 micromol/L, 15 micromol/L, 0.17 micromol/L, 0.97 micromol/L, 2.95 micromol/L, 17.6 micromol/L, 30.9 micromol/L, and 7.85 micromol/L, respectively.

In vivo, in nude mice bearing HCCLM3 hepatocellular tumors, intraperitoneal injection of 10 mg/kg oxaliplatin once weekly significantly reduces tumor volume and the apoptotic index. Intravenous injection of 5 mg/kg oxaliplatin on days 1, 5, and 9 shows activity against T-lymphoma L40 AKR, with a T/C of 1.77. Oxaliplatin shows potent activity in models of intracerebrally transplanted L1210 leukemia, MA16-C xenografts, B16 melanoma xenografts, Lewis lung xenografts, and C26 colon cancer xenografts. In the experiments, cisplatin (3 mM) was dissolved in saline, while carboplatin (27 mM) and oxaliplatin (12.6 mM) were dissolved in water.

In patients with metastatic colorectal cancer, oxaliplatin in combination with fluorouracil/folinic acid is active against metastatic colorectal cancer and can be used as first-line therapy, as well as in patients refractory to prior chemotherapy. In addition, oxaliplatin is effective in patients with platinum-pretreated ovarian cancer, non-Hodgkin lymphoma, breast cancer, mesothelioma, and non-small cell lung cancer.

Oxaliplatin is commonly used to establish chemotherapy-induced peripheral neuropathy (cold allodynia) animal models, for studying the mechanisms of peripheral neuropathy and neuroprotective drugs.

References: [1]. Culy CR, Clemett D, Wiseman LR. Oxaliplatin. A review of its pharmacological properties and clinical efficacy in metastatic colorectal cancer and its potential in other malignancies. Drugs. 2000 Oct;60(4):895-924.

[2]. Raymond E, Faivre S, Chaney S et al. Cellular and molecular pharmacology of oxaliplatin. Mol Cancer Ther. 2002 Jan;1(3):227-35.

[3]. Stein A, Arnold D. Oxaliplatin: a review of approved uses. Expert Opin Pharmacother. 2012 Jan;13(1):125-37.

[4]. Hoff PM, Saad ED, Costa F et al. Literature review and practical aspects on the management of oxaliplatin-associated toxicity. Clin Colorectal Cancer. 2012 Jun;11(2):93-100.

[5]. Hall MD, et al. Say no to DMSO: dimethylsulfoxide inactivates cisplatin, carboplatin, and other platinum complexes. Cancer Res. 2014 Jul 15;74(14):3913-22.