Oxaliplatin

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Background

Oxaliplatin inhibits DNA synthesis, primarily by conforming DNA adducts. Oxaliplatin, a platinum compound, has a broad spectrum of anti-tumor activity and has demonstrated a lack of cross-resistance with other platinum compounds. Oxaliplatin induces primary and secondary DNA lesions that lead to cell apoptosis.
In vitro: Oxaliplatin is active against human melanoma cell lines C32 and G361 with the IC50 values of 0.98 mM and 0.14 mM, respectively. Oxaliplatin effectively inhibited bladder carcinoma cell lines RT4 and TCCSUP, ovarian carcinoma cell line A2780, colon carcinoma cell line HT-29, glioblastoma cell lines U-87MG and U-373MG, and melanoma cell lines SK-MEL-2 and HT-144 with the IC50 values of 11 μM, 15 μM, 0.17 μM, 0.97 μM, 17.6 μM, 2.95 μM, 30.9 μM and 7.85 μM, respectively.
In vivo: A weekly injection of Oxaliplatin (10 mg/kg, i.p.) to nude mice bearing hepatocellular HCCLM3 tumors significantly reduces tumor volume and apoptotic index. Oxaliplatin (5 mg/kg, i.v. on days 1, 5 and 9) was active on T-leukemia-lymphoma L40 AKR with T/C of 1.77. Oxaliplatin was also efficient on intracerebrally grafted L1210 leukemia, B16 melanoma xenografts, MA 16-C xenografts, Lewis lung xenografts and C26 colon carcinoma xenografts. Oxaliplatin induced impairment of retrograde neuronal transport in mice.
Clinical Trials: In patients with metastatic colorectal cancer, in combination with fluorouracil/folinic acid, Oxaliplatin showed its activity against metastatic colorectal, both as a first-line therapy and in patients refractory to previous chemotherapy. In addition, oxaliplatin has also shown efficacy in patients with platinum-pretreated ovarian cancer, non-Hodgkin's lymphoma, breast cancer, mesothelioma and non-small cell lung cancer.

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