Of the new generation platinum compounds that have been evaluated, tho
se with the 1,2-diaminocyclohexane carrier ligand - including oxalipla
tin - have been focused upon in recent years. Molecular biology studie
s and the National Cancer Institute in vitro cytotoxic screening showe
d that diaminocyclohexane platinums such as oxaliplatin belong to a di
stinct cytotoxic family, differing from cisplatin and carboplatin, wit
h specific intracellular target(s), mechanism(s) of action and/or mech
anism(s) of resistance. In phase I trials, the dose-limiting toxicity
of oxaliplatin was characterized by transient acute dysesthesias and c
umulative distal neurotoxicity, which was reversible within a few mont
hs after treatment discontinuation. Moreover, oxaliplatin did not disp
lay any, auditory, renal and hematologic dose-limiting toxicity at the
recommended dose of 130 mg/m(2) q three weeks or 85 mg/m(2) q two wee
ks given as a two-hour i.v. infusion. Clinical phase II experiences on
the antitumoral activity of oxaliplatin have been conducted in hundre
ds of patients with advanced colorectal cancers (ACRC). Single agent a
ctivity reported as objective response rate in ACRC patients is 10% an
d 20% overall in ACRC patients with 5-fluorouracil (5-FU) pretreated/r
efractory and previously untreated ACRC, respectively. Synergistic cyt
otoxic effects in preclinical studies with thymidylate synthase inhibi
tors, cisplatin/carboplatin and topoisomerase I inhibitors, and the ab
sence of hematologic dose-limiting toxicity have made oxaliplatin an a
ttractive compound for combinations. Phase II trials combining oxalipl
atin with 5-FU and folinic acid ACRC patients previously treated/refra
ctory to 5-FU showed overall response rates ranging from 21% to 58%, a
nd survivals ranging from 12 to 17 months. In patients with previously
untreated ACRC, combinations of oxaliplatin with 5-FU and folinic aci
d showed response rates ranging from 34% to 67% and median survivals r
anging from 15 to 19 months. Two randomized trials totaling 620 previo
usly untreated patients with ACRC, comparing 5-FU and folinic acid to
the same regimen with oxaliplatin, have shown a 34% overall response r
ate in the oxaliplatin group versus 12% in the 5-FU/folinic acid group
for the first trial; and 51.2% vs. 22.6% in the second one. These sta
tistically significant differences were confirmed in time to progressi
on advantage for the oxaliplatin arm (8.7 vs. 6.1 months, and 8.7 vs.
6.1 months, respectively). A small but consistent number of histologic
al complete responses have been reported in patients with advanced col
orectal cancer treated with the combination of oxaliplatin with 5-FU/f
olinic acid, and secondary metastasectomy is increasingly done by onco
logists familiar with the combination. Based on preclinical and clinic
al reports showing additive or synergistic effects between oxaliplatin
and several anticancer drugs including cisplatin, irinotecan, topotec
an, and paclitaxel, clinical trials of combinations with other compoun
ds have been performed or are still ongoing in tumor types in which ox
aliplatin alone showed antitumoral activity such as ovarian, non-small
-cell lung, breast cancer and non-Hodgkin lymphoma. Its single agent a
nd combination therapy data in ovarian cancer confirm its non-cross re
sistance with cisplatin/carboplatin. While the role of oxaliplatin in
medical oncology is yet to be fully defined, it appears to be an impor
tant new anticancer agent.