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Phase I/II Trials Suggest Capecitabine Could Be Good Partner When Used With Oxaliplatin or Irinotecan

Phase I/II Trials Suggest Capecitabine Could Be Good Partner When Used With Oxaliplatin or Irinotecan

NEW HAVEN, Connecticut—Capecitabine (Xeloda) was developed as an oral
tumor-activated alternative to fluorouracil (5-FU) and now appears set to
replace that agent in some combination regimens for colorectal cancer according
to Edward Chu, MD. Dr. Chu reported that phase II trials suggest that either
capecitabine/oxaliplatin (Eloxatin) or capecitabine/irinotecan (CPT-11,
Camptosar) might be effective replacements for 5-FU-based regimens. Dr. Chu is
professor of medicine and pharmacology at Yale University School of Medicine
and associate director of the Yale Cancer Center, New Haven, Connecticut.

"Capecitabine should replace infusional 5-FU/leucovorin as the combination
partner for oxaliplatin. It offers improved convenience over regimens
incorporating infusional 5-FU, and the combination requires only one clinic
visit for oxaliplatin administration every 3 weeks," Dr. Chu said.

Attractive Option

"Phase II trials data show that capecitabine/oxaliplatin (Xelox) is a highly
active first-line therapy for metastatic colorectal cancer," he continued. "It
produced a 55% response rate with consistently high response rates, over 50%,
in all patient subgroups. Thirty-two percent of patients had disease
stabilization, and this lasted more than 3 months in all patients. Median time
to progression was 7.6 months, and median survival was 19 months. Toxicity is
manageable and is similar to that of the FOLFOX4 (fluorouracil, leucovorin,
oxaliplatin) regimen."

Capecitabine/oxaliplatin would be an attractive option because oral
capecitabine is metabolized to 5-FU by thymidine phosphorylase, an enzyme found
in higher concentrations in tumors than in normal tissue. The result is
preferential production at the tumor site. "Oral administration of capecitabine
mimics the mechanism of action of continuous infusion 5-FU but without the
complications and inconvenience associated with continuous infusion," Dr. Chu

The capecitabine/oxaliplatin combination is theoretically appealing because
the two drugs have different molecular mechanisms of action and no overlap of
key toxicities. Previous studies have also shown improved clinical efficacy
when oxaliplatin was added to 5-FU/leucovorin.

The main grade 3 or 4 toxicity with capecitabine/oxaliplatin is diarrhea,
which afflicted 35% of patients treated with a higher-dose regimen (capecitabine
1,250 mg/m2 bid and oxaliplatin 130 mg/m2) as first-line
therapy and 50% of those treated with a higher-dose regimen as second-line
therapy. Three percent of patients suffered grade 3 hand-foot syndrome in an
international phase II trial of capecitabine/oxaliplatin as first-line
treatment for metastatic colorectal cancer. There were no grade 4 hematologic
toxicities, and 60-day all-cause mortality was 2%, according to Dr. Chu. The US
gastrointestinal intergroup is planning a phase III trial of capecitabine/oxaliplatin


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