SC, IV Amifostine Compared in Patients With Advanced NSCLC on Combined-Modality Therapy

PHILADELPHIA-While the Radiation Therapy Oncology Group (RTOG) study 98-01 did not demonstrate that amifostine(Drug information on amifostine) (Ethyol) significantly decreased grade ≥ 3 esophagitis in lung cancer patients treated with induction chemotherapy followed by concurrent hyperfractionated radiotherapy (RT) and consolidation chemotherapy, it did uncover some intriguing hints of benefit. According to Maria Werner- Wasik, MD, patient swallowing diaries suggested a reduction in swallowing dysfunction, particularly toward the end of RT and after its completion. There also appeared to be a benefit for women and for patients older than 65 years. "Unfortunately these late data were not captured well, so a study will be done to investigate these issues more closely," said Dr. Werner-Wasik, a radiation oncologist and associate professor at Kimmel Cancer Center, Jefferson Medical College, Philadelphia. The phase II trial will enroll 76 patients with inoperable nonsmall- cell lung cancer (NSCLC) at stage II, stage IIIA/B, or stage IV with oligometastases. Patients will be randomized to either daily amifostine 500 mg SC 30 to 60 min- utes before RT or to rapid IV bolus amifostine 15 to 30 minutes before each RT fraction (see Figure 1). They will be treated with concurrent thoracic RT to 64.0 Gy and weekly chemotherapy with paclitaxel (Taxol) 50 mg/m² IV and carboplatin(Drug information on carboplatin) (Paraplatin) to AUC 2 for 6 weeks. This will be followed by optional consolidation with four cycles of paclitaxel(Drug information on paclitaxel)/carboplatin. Metastases Permitted
Unlike most similar studies, this one will allow patients with small brain or liver metastases. "We believe that these patients, when treated adequately, may live long enough for us to assess endpoints, so we are allowing patients with local recurrence after previous surgery or with oligometastases that have been definitively treated," Dr. Werner-Wasik said. "The primary endpoint of the study is the frequency of severe (grade ≥ 3) nonhematologic toxicity, with emphasis on esophageal toxicity. If 34% of patients historically get grade ≥ 3 acute esophagitis and at most 20% of the 76 evaluable treated patients on this study develop grade ≥ 3 esophagitis, we can conclude that the treatment is effective in reducing toxicity," she added. Esophagitis will be evaluated weekly during RT and for 6 weeks after the last day of RT, then at 3 months and every 3 months thereafter for 1 year. Pulmonary function studies will be done at 1 and 3 months after RT, then every 3 months for 1 year.