Nearly two-thirds of patients with biliary tract cancer
who received a novel regimen containing cetuximab, gemcitabine and oxaliplatin
achieved objective tumor response, according to recent findings.
Patients with biliary tract cancer have a poor prognosis
and no standard palliative chemotherapy options. Researchers from several
institutions in Austria aimed to investigate whether cetuximab with gemcitabine
and oxaliplatin was safe and effective as first-line therapy for biliary tract
Thirty patients with a median age of 68 years
(interquartile range, 62-73 years) who had unresectable locally advanced or
metastatic disease were sequentially enrolled and treated at one site in
Austria from Oct. 1, 2006, to July 26, 2008.
The regimen administered to all patients was IV infusion
of 500 mg/m2 cetuximab and 1,000 mg/m2 gemcitabine on day
1 and 100 mg/m2 oxaliplatin on day 2 every 2 weeks for 12 cycles.
All participants received at least two cycles (median 7.5 cycles; range 2-12).
Overall response rate was the primary outcome measure.
The study was an intention-to-treat analysis, and adverse events were assessed
according to NCI Common Toxicity Criteria.
Nineteen patients (63%; 95% CI, 56.2-69.8) achieved
objective tumor response and three patients (10%; 95% CI, 3.2-16.8) achieved
complete response. Partial response was observed in 16 patients (53%; 95% CI,
46.2-59.8). The researchers reported an overall disease control rate of 80%.
Seventeen patients completed the full scheduled regimen
before the end of planned treatment, disease progression or secondary surgical
reaction. Nine patients had a 25% reduction in the oxaliplatin dose, one had a
25% reduction in cetuximab and two had a 25% reduction in gemcitabine and
oxaliplatin. One patient experienced hypersensitivity to oxaliplatin in cycle
four and discontinued that drug.
After a major response to therapy, nine patients
underwent potentially curative secondary resection. Four of these patients had
intrahepatic cholangiocarcinoma that was initially not amenable to secondary
resection, according to the results. The other four patients in this group
presented with locally advanced extrahepatic tumors with vascular involvement
and were, therefore, unresectable. Major tumor shrinkage by at least 40% was
reported in eight of these nine patients, and all of them received major liver
No grade 4 adverse events were reported, but 13 patients
experienced grade 3 adverse events. These included skin rash (n=4), peripheral
neuropathy (n=4), thrombocytopenia (n=3), nausea (n=1), diarrhea (n=1) and
Median follow-up was 22 months for all 30 patients (95%
CI, 12.5-31.1). The median PFS duration was 8.8 months for all treated patients
(95% CI, 5.1-12.5).
The median PFS was 21.2 months among the nine patients
who underwent secondary resection (12.5-29.8) vs. 6.8 months among those who
did not (4.5-9.1; P=.0001).
For OS, the median duration was 15.2 months (9.9-20.5)
for all treated patients and 11.6 months (10.9-12.3) for patients not eligible
for secondary surgery. Among patients who underwent secondary resection, median
OS was not reached.