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(Drug information on 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(Drug information on 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(Drug information on carboplatin) (Paraplatin) followed by thoracic radiation therapy with concurrent weekly low-dose paclitaxel(Drug information on 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(Drug information on 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. Werner-Wasik said.
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.