HOUSTON-In head and
neck cancer, intensity-modulated
radiotherapy (IMRT) may reduce
some, but does not eliminate treatment
toxicity, according to studies
comparing IMRT vs standard radiotherapy
in this patient population.
Investigators have found reduced
rates of xerostomia but little
difference in acute grade 3 mucositis,
reported David I.
Rosenthal, MD, associate professor
of radiation oncology at
The University of Texas M. D.
Anderson Cancer Center.
Dr. Rosenthal is therefore undertaking
a phase II study to determine
whether cytoprotection with
amifostine can reduce those side
effects. "IMRT leaves 70% of patients
with at least some symptoms
of dry mouth ," he said.
He added that IMRT can reduce
xerostomia for many patients but
is still associated with mucositis.
Late grade 2 to 3 xerostomia was
reported as 84% with conventional
RT vs 30% with IMRT, but grade
3 or 4 mucositis was more common
with IMRT vs conventional
RT (42% vs 25%), and more IMRT
patients required G-tubes (25% vs
18%); these differences are not
Dr. Rosenthal said that some of
these effects might be explained by
the fact that while IMRT provides
relative sparing of the parotid
gland, it does not reliably spare the
25 Gy Threshold
"There appears to be a steep
section of the dose-response curve
for xerostomia at about 25 Gy, that
some have referred to as a threshold.
Patients who get more dose
have little recovery of salivary gland
function at 12 months," he noted.
"If the planned mean dose to the
parotid gland is more than 24 to 26
Gy, then IMRT may have little if
any benefit compared with conventional
radiotherapy, and there
is considerable increased cost."
He explained that two-thirds of
stimulated salivary flow is from
the parotid gland, and said the majority
of unstimulated salivary flow
comes from the submandibular
gland. "The majority of xerostomia
symptoms are related to lack
of basal unstimulated salivary
gland flow that is primarily from
the submandibular gland, and not
related to the parotids," he said. In
the normal setting, stimulated flow
occurs for less than 1 hour per day,
during eating. Some studies suggest
that the submandibular gland
may contribute as much as 90% of
total salivary output when patients
are not eating.
Phase II Study
Dr. Rosenthal's phase II study
in head and neck cancer patients
will assess whether amifostine (500
mg SC daily prior to radiation) can
reduce IMRT-associated xerostomia
and mucositis and preserve
function of the submandibular and
sublingual salivary glands.
The treatment regimen includes
definitive treatment with 66 Gy of
radiation in 30 fractions or postoperative
treatment with 60 Gy in
30 fractions. The primary endpoint
is the preservation of submandibular
and sublingual salivary flow,
plus subjective xerostomia scores.
Secondary endpoints include the
parotid dose-volume histogram,
mucositis in lower-dose RT areas,
scalp hair-loss patterns, and dysphagia
as measured by the Performance
"Our hypothesis is that
combined physical radiotherapy
dose-sparing by IMRT and
amifostine cytoprotection will
improve global salivary sparing
and decrease xerostomia," Dr.
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