MONTEGO BAY, JAMAICA-
"Weekly carboplatin (Paraplatin)
and paclitaxel (Taxol) given concurrently
with definitive radiotherapy
and daily amifostine (Ethyol)
was well-tolerated by patients with
advanced squamous cell head and
neck cancers, and the cytoprotective
agent amifostine appeared
to decrease treatment-related
toxicity," according to Mohan
Suntharalingam, MD, vice chair
of radiation oncology at the University
of Maryland Greenebaum
Cancer Center, Baltimore. Dr.
Suntharalingam reported data
from a prospective phase II trial
evaluating the role of amifostine
with this concurrent chemotherapy
regimen at the 4th International
Chemoradiation Doubles Toxicity
"Few solid tumor sites have
shown such good outcomes with
combination radiation and chemotherapy
as head and neck cancers,
and combined-modality therapy is
here to stay," Dr. Suntharalingam
said. However, he noted that the
regimens can result in a doubling
of the rates of grade 3 or 4 mucosal
toxicity, from about 24% with either
chemotherapy or radiotherapy
alone to about 43% with the
combination. To address that
problem, he and his colleagues conducted
a prospective phase II trial
to determine whether adding the
cytoprotective agent amifostine
could reduce mucosal toxicity
without reducing tumor response.
Dr. Suntharalingam reported
data for 60 evaluable patients with
unresectable stage III or IV squamous
cell carcinomas of the head
or neck. Patients were treated with
daily radiation to the primary site
up to 70.2 Gy (1.8 Gy/d) delivered
with the shrinking field technique.
Clinically involved nodes received
the full dose, while uninvolved
nodes received up to 50.4 Gy.
Amifostine 500 mg IV was given
less than 1 hour prior to radiotherapy.
Concurrent weekly chemotherapy
comprised of carboplatin
100 mg/m2 as a 30-minute infusion
to AUC 1.5 and paclitaxel 40
mg/m2 IV as a 3-hour infusion.
Dr. Suntharalingam reported
that 82% of patients had complete
responses (CR) at the primary site,
and pathologic examination
showed a CR rate of 73% in nodepositive
patients. "Overall, 75% of
patients had no evidence of disease
following therapy," he said.
Sixty percent of patients required
treatment breaks, with a
median duration of 1 day. Breaks
were most often secondary to nausea/
vomiting (36%), dehydration
(18%), dermatitis (11%), mucositis
(5%), or neutropenia (5%).
Most patients received all planned
doses of amifostine. Three patients
discontinued amifostine because
of hypotension or nausea and
"It feels as if we are getting more
therapy into these patients [with
amifostine]," Dr. Suntharalingam
said. He reported that the frequency
of grade 3 xerostomia was 20%
with amifostine, and noted that
there was also only 20% grade 3
skin toxicity (no grade 4 toxicity).
With regard to nonhematologic
toxicities, patients who received
amifostine seemed to experience
toxicity later in the treatment period
and require fewer treatment
breaks, Dr. Suntharalingam said
(see Figure 1).
Leukopenia was somewhat
higher with amifostine, but there
was no decrease in efficacy.
"Radiotherapy plus weekly carboplatin/
paclitaxel is a well-tolerated
outpatient regimen with a complete
response rate of 75% and an
overall 5-year survival of 38%,"
Dr. Suntharalingam concluded.
"Initial experience with the addition
of amifostine suggests a benefit
in terms of mucosal protection
and xerostomia, while maintaining