PHILADELPHIAConcurrent chemoradiotherapy seems likely to become
standard therapy for treating locally advanced lung cancer. That would make
preventing radiation-induced esophagitis even more important, according to
Maria Werner-Wasik, MD.
"The esophagus unfortunately is included in most standard
radiotherapy fields projecting over the vertebral bodies. Although many of
us want to believe that we exclude most of the esophagus in the off-cord
fields, that is not the case," she noted. Dr. Werner-Wasik is assistant
professor and clinical director, Department of Radiation Oncology, Kimmel
Cancer Center, Thomas Jefferson University Hospital, Philadelphia.
"The incidence of acute esophagitis varies with the type of
radiochemotherapy used. With standard radiation preceded by induction
chemotherapy, incidence of grade 3 or higher esophagitis is a low
1.3%," she said. "With concurrent cisplatin (Platinol)-based
regimens and standard radiation, there is 6% to 14% incidence of
esophagitis. When radiation intensity increases for hyperfractionated
regimens, the incidence of esophagitis rises to 24% to 34%. When the potent
radiosensitizer gemcitabine (Gemzar) is added to standard radiation, the
esophagitis incidence is as high as 49%."
Phase II Trial
The Jefferson researchers are conducting a phase II trial of induction
paclitaxel (Taxol) plus carboplatin (Paraplatin) followed by thoracic
radiation therapy with concurrent weekly low-dose paclitaxel for patients
with unresectable locally advanced non-small-cell lung cancer.
"In the first 11 evaluable patients, we observed 20% incidence of
grade 3 esophagitis. It was also our impression that esophagitis was quite
prolonged. Many patients suffered for weeks, in addition to having a
high-grade esophagitis. We decided to incorporate amifostine (Ethyol) in
treatment of the second cohort of patients because we knew from preclinical
data that amifostine provided significant protection against esophagitis in
mice treated with radiation. Data from a phase II trial at the University of
Wisconsin also suggested that amifostine given during induction and before
each fraction of radiation reduced the risk of esophagitis," Dr.
The second cohort of 12 patients received amifostine 500 mg given on the
day paclitaxel was given and again on the following day. For the 6-week
chemoradiotherapy cycle, patients receive 12 infusions of amifostine.