Oxaliplatin is a
cytotoxic agent which, like other
platinum compounds, acts primarily by causing inter- and intra-strand cross-links in
DNA, thereby inhibiting
DNA synthesis.
Oxaliplatin has a bulky carrier
ligand which is thought to enhance cytotoxicity and abolish cross-resistance between
oxaliplatin and other
platinum compounds. Phase II and III clinical trials have found
oxaliplatin combined with
fluorouracil/
calcium folinate (
leucovorin/
folinic acid) to be an effective first- and second-line treatment for patients with metastatic
colorectal cancer. First-line triple
therapy with
oxaliplatin and
fluorouracil/
calcium folinate achieved significantly higher response rates than
fluorouracil/
calcium folinate alone in 2 phase III studies (objective response rates 59 vs 23% and 50.7 vs 22.3%). In addition, median progression-free survival was longer with triple
therapy in both studies (8.9 vs 5.2 and 8.75 vs 6.0 months). However, there was no significant difference in median duration of survival between treatment groups, although this may be a consequence of the subsequent use of
oxaliplatin and/or surgery in patients who relapsed during
therapy with
fluorouracil/
calcium folinate alone. About 30 to 45% of patients (whose disease progressed during or after
fluorouracil-based
therapy) responded to second-line combination
therapy with
oxaliplatin and
fluorouracil/
calcium folinate. Median progression-free survival ranged from 7 to 10 months and the median duration of survival from 10 to 17 months. Objective responses were achieved in 20 and 24% of patients in 2 small trials of first-line
oxaliplatin monotherapy and in about 10% of patients given the
drug as a second-line option. Peripheral sensory neuropathy is the dose-limiting toxicity associated with
oxaliplatin. Severe neurotoxicity has been estimated to occur in 10% of patients after 6 treatment cycles and in 50% after 9 cycles of an
oxaliplatin dosage of 130 mg/m2 once every 3 weeks. It is cumulative, but reversible on discontinuation of
therapy.
Nausea,
vomiting and diarrhoea are common, but are usually mild to moderate. Myelosuppression is also observed, but is usually mild.
CONCLUSION:
oxaliplatin is a promising treatment option for patients with metastatic
colorectal cancer. It appears to be particularly advantageous (in terms of response rate and duration of progression-free survival) when used in combination with
fluorouracil/
calcium folinate as both a first- and second-line option, although preliminary studies have failed to show any survival advantage over
fluorouracil/
calcium folinate alone. Promising results have been found in studies of the
drug as monotherapy, and
oxaliplatin may also prove useful in the neoadjuvant setting in patients with unresectable liver
metastases; however, data are limited at present.