NASHVILLE, TennesseeRegimens that contain oxaliplatin (Eloxatin) as well as
irintoecan (CPT-11, Camptosar) and fluorouracil (5-FU)/ leucovorin have
produced prolonged survival of 18 to 21 months in patients with advanced
colorectal cancer and should be considered for first-line therapy, according to
Mace L. Rothenberg, MD. Dr. Rothenberg, who is professor of medicine at
Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, reviewed the current
status of oxaliplatin-based regimens.
Oxaliplatin forms adducts that are bulkier and more hydrophobic than those
formed by cisplatin and as a result may be more difficult to repair. Dr.
Rothenberg said that oxaliplatin is also active against tumor cell lines that
are resistant to cisplatin in vitro. "Colon cancer cell lines are not very
sensitive to cisplatin or carboplatin (Paraplatin). Many are much more
sensitive to oxaliplatin," Dr. Rothenberg said.
Improved Survival Not Initially Seen
Three European phase III trials of 5-FU/leucovorin with or without
oxaliplatin showed a doubling or tripling of response rate and significant
increases in progression-free survival, Dr. Rothenberg said, but this did not
translate into an increase in overall survival. The US Food and Drug
Administration (FDA) Oncologic Drugs Advisory Committee recommended in March
2000 against approval of oxaliplatin for first-line treatment of advanced
"There is a requirement by the FDA that a therapy that adds toxicity must
offset that toxicity with a tangible benefit to patients (ie, survival)," Dr.
Rothenberg explained. "The committee also had knowledge of first-line
irinotecan data, to be presented that same day, demonstrating a survival
advantage in two phase III studies."
In analyzing why there was no improvement in survival despite improved time
to progression, Dr. Rothenberg said that the trials might have been
underpowered to detect a survival difference and might have been affected by
subsequent therapy, including oxaliplatin that was administered to patients
originally treated with 5-FU/leucovorin.