Docetaxel has demonstrated activity as a radiosensitizer in numerous preclinical studies, probably due to its role as a cell cycle synchronizer for the G2/M radiosensitive phase of the cell cycle. We conducted a phase I trial to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of
docetaxel with concurrent thoracic
radiation therapy (TRT) to patients with unresectable stage III
non small-cell lung cancer (NSCLC). Fifteen patients were entered into this study.
Docetaxel was administered as a 1-hour intravenous (I.V.) infusion, repeated every week for 6 weeks with starting dose of 20 mg/m2. Doses were escalated in 10 mg/m2 increments in successive cohorts of three new patients, if tolerated. Unacceptable toxicity was defined as grade = 3 nonhematologic or hematologic toxicity according to Eastern Cooperative Oncology Group (ECOG) toxicity criteria. TRT was administered to the primary
tumor and regional lymph nodes (40 Gy) followed by a boost to the
tumor (20 Gy). At the first dose level (20 mg/m2/week), one patient developed grade 4
hyperglycemia and accrual was expanded to five patients. At the second level (30 mg/m2/week), two out of six patients developed grade 3
esophagitis. At the third level (40 mg/m2/week), two out of four patients developed grade 3
esophagitis and one patient developed grade 3 pulmonary toxicity. The weekly
docetaxel MTD with concurrent
radiation therapy (RT) was found to be 30 mg/m2. The DLT was
esophagitis and pulmonary toxicity. Other toxicities encountered included skin reaction,
nausea and
vomiting, as well as
diarrhea. Additionally, there were no treatment-related mortalities or late-occurring toxicities.
Esophagitis was the principal DLT of concurrent weekly
docetaxel and thoracic radiation in the outpatient setting. The MTD of concurrent weekly
docetaxel with TRT is 30 mg/m2 weekly for 6 weeks. This study is still open to accrual with weekly
docetaxel and TRT in locally advanced NSCLC patients.