NASHVILLE--Combined neoadjuvant therapy with paclitaxel (Taxol),
carboplatin (Paraplatin), fluorouracil (5-FU), and irradiation,
followed by surgery, resulted in complete pathologic responses in
almost half of a group of patients with advanced esophageal cancer.
Another third of the patients had only microscopic residual disease
after surgery. Though median follow-up is only 7 months, the results
"This is one of the highest rates of pathologic complete
response reported thus far," Anthony Meluch, MD, said at an ASCO
poster session. "The follow-up is short at this point, but if
the numbers hold up with continued follow-up, the results may have
real meaning in the future."
In comparison to other trials that have used a standard
cisplatinum-5-FU regimen, he said, "the toxicity profiles seem
to be significantly better, and the surgical morbidity is acceptable."
Phase II Study
The findings came from a phase II clinical evaluation of the
neoadjuvant chemoradiation therapy regimen in 49 patients with stages
III-IV esophageal cancer.
All the patients had squamous cell or adenocarcinoma of the esophagus
or gastroesophageal junction, and all were acceptable surgical
candidates, said Dr Meluch, a medical oncologist with Tennessee
Oncology and the Sarah Cannon Cancer Center, Nashville.
Neoadjuvant chemotherapy consisted of paclitaxel at a dose of 200
mg/m², carboplatin dosed to an AUC of 6, and 5-FU at a dose of
225 mg/m². The 5-FU was administered via 24-hour continuous
infusion for 7 weeks. Paclitaxel and carboplatin were given during
weeks 1 and 4.
Each patient had radiation therapy during weeks 1 to 6, at a dose of
180 cGy in 25 fractions for a total dose of 4,500 cGy. Restaging
occurred during week 9, and surgery was performed on week 10 or 11.
Dr. Meluch reported that 41 of 49 patients completed therapy and were
evaluable for response. The neoadjuvant regimen produced objective
responses in 38 patients, all of whom were eligible for surgery.
Subsequently, 34 of the 38 responders had surgery, which was
definitive in 33 cases.
Among the 34 resected patients, 17 had a pathologic complete
response. An additional 12 patients had a partial response with
microscopic residual disease. The remaining five patients each had a
partial response with macroscopic residual disease.
At a median follow-up of 7 months, 27 patients remain alive with no
evidence of relapsed disease. Three other patients are alive after
relapse. One-year survival in the cohort is 68%, and 2-year survival
Dr. Meluch said that the neoadjuvant regimen was well tolerated, and
adverse effects of therapy affected neither the feasibility of
surgery nor the perioperative morbidity or mortality. Grade 3-4
leukopenia occurred in 30 patients, but severe thrombocytopenia and
anemia were uncommon.
Nonhematologic toxicities were infrequent and generally mild, with
esophagitis (14 cases grade 3-4) and dehydration (10 cases grade 3)
the most common.
"The pathologic complete response rate of 46% compares favorably
with previously reported neoadjuvant regimens, which had complete
responses in the range of 23% to 42%," Dr. Meluch said. "The
response was similar in squamous cell and adenocarcinoma histology."
Dr. Meluch said that the researchers plan to continue patient accrual
and complete the trial, to define the therapys impact on
survival. "We think that evaluation of the regimen in a phase
III trial may be warranted."