Oxaliplatin

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Eloxatin (Sanofi-Synthelabo)
vials containing 50 mg or 100 mg as lyophilised powder
Approved indication: colorectal cancer
Australian Medicines Handbook Section 14.1

Metastatic colorectal cancer has a poor prognosis. Only about 5% of patients will survive for five years, but their chances may be improved with chemotherapy. Regimens containing 5-fluorouracil and calcium folinate have an established role in therapy.

Oxaliplatin is an analogue of platinum. It has a wide spectrum of cytotoxicity and is active against tumours which are usually insensitive to platinum. Although oxaliplatin has been studied as monotherapy for colorectal cancer, it has been approved for use in combination with 5-fluorouracil and calcium folinate.

Most studies have involved regimens with continuous infusion of 5-fluorouracil. Oxaliplatin is given as a 2-6 hour infusion every two or three weeks. After two hours only 15% of the platinum is present in the circulation and no intact oxaliplatin remains. The platinum is distributed to the tissues and binds irreversibly to red blood cells. Most of the platinum is eliminated in the urine with approximately half the dose being excreted within five days. Renal impairment reduces clearance.

One clinical trial compared the efficacy of 5-fluorouracil and calcium folinate with or without oxaliplatin in 200 patients with previously untreated metastatic colorectal cancer. Treatment was repeated every three weeks. There was an objective response in 34% of the patients who received oxaliplatin and 12% in those who did not. The median progression-free survival was 8.3 months as opposed to 4.2 months.1 Although these results favour oxaliplatin, there was no improvement in survival and oxaliplatin's approval has now been restricted to patients whose cancer has progressed.

A study of oxaliplatin as second-line therapy included 97 patients whose disease had progressed despite treatment with 5-fluorouracil and calcium folinate. These patients only have a few months to live, but adding oxaliplatin to the regimen induced a response in 20 patients. The patients had a median survival time of 11 months.

Like other platinum-based drugs, oxaliplatin is very toxic. Most patients will have vomiting, diarrhoea, anaemia and altered liver function tests. The incidence of adverse effects increases when oxaliplatin is added to 5-fluorouraciland calcium folinate. Treatment is limited by neurotoxicity. Up to 95% of patients will develop a peripheral neuropathy.

Adding oxaliplatin as second-line therapy results in a median progression-free survival of 4.7 months. Patients and their doctors will have to decide if this outcome is offset by the toxicity of treatment.

References

  1. Giacchetti S, Perpoint B, Zidani R, Le Bail N, Faggiuolo R, Focan C, et al. Phase III multi center randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol 2000;18:136-47.