Oxaliplatin - A review of its pharmacological properties and clinical efficacy in metastatic colorectal cancer and its potential in other malignancies

Oxaliplatin is a platinum compound that inhibits DNA synthesis, primarily b y causing intrastrand cross-links in DNA. Oxaliplatin has a broad spectrum of antineoplastic activity and has demonstrated a lack of cross-resistance with other platinum compounds. In patients with metastatic colorectal cancer, intravenous oxaliplatin has been trialled as a monotherapy and in combination with other agents. The hi ghest response rates were achieved when oxaliplatin was used in combination with fluorouracil/folinic acid (leucovorin; calcium folinate), typically g reater than or equal to 50% in the first-line setting and 13 to 45% as a se cond-line therapy. First-line triple therapy with oxaliplatin and fluorouracil/folinic acid ac hieved significantly higher response rates and longer median progression-fr ee survival than fluorouracil/folinic acid therapy alone. However, no signi ficant difference in the median duration of overall survival was found. Thi s may be a consequence of the subsequent use of oxaliplatin and/or surgery after disease progression in patients who relapsed after fluorouracil/folin ic acid therapy alone. Neoadjuvant therapy with oxaliplatin/fluorouracil/folinic acid has proven b eneficial in enabling surgical removal of previously unresectable liver met astases. In 2 studies, surgery with curative intent was performed in 16 and 51% of patients with initially unresectable liver metastases following oxa liplatin/fluorouracil/folinic acid therapy; the 5-year survival rates were 40 and 50%, respectively. In patients with advanced ovarian cancer, first-line therapy with oxaliplat in/cyclophosphamide achieved an objective response rate which did not diffe r significantly from that of cisplatin/cyclophosphamide (33 vs 42%). In add ition, oxaliplatin has shown efficacy in patients with platinum-pretreated ovarian cancer and achieved objective response rates similar to paclitaxel in this setting (16 vs 17%). Promising results have also been found with oxaliplatin in patients with no n-Hodgkin's lymphoma, breast cancer, mesothelioma and non-small cell lung c ancer. Reversible, cumulative, peripheral sensory neuropathy is the principle dose -limiting factor of oxaliplatin therapy. Haematological and gastrointestina l toxicities occur frequently but are generally mild to moderate in intensi ty. Conclusion: Oxaliplatin in combination with fluorouracil/folinic acid is an effective treatment option for patients with metastatic colorectal cancer, both as a first-line therapy and in patients refractory to previous chemot herapy. Although preliminary results failed to show any overall survival ad vantage of this regimen over fluorouracil/folinic acid alone, this may be a consequence of trial design and requires further examination. Additional c linical investigation of oxaliplatin in patients with other cancers is warr anted given the promising results achieved in early trials, most notably in patients with platinum-pretreated ovarian cancer.