Phase I study of docetaxel with concomitant thoracic radiation therapy.
OBJECTIVE
The taxanes have demonstrated activity as radiation sensitizers in preclinical studies. This study was designed to determine the maximum-tolerated dose (MTD), optimal schedule, and toxicities of docetaxel in combination with concomitant standard chest radiotherapy.


METHODS
Twenty-nine patients with advanced non-small-cell lung or esophageal cancer enrolled in this phase I study to evaluate escalating docetaxel doses at three schedules. Docetaxel was administered as two 21-day cycles at doses of 40, 60, and 75 mg/m2 per cycle. Docetaxel administration schedules were as follows: schedule A, once every 3 weeks; schedule B, 2 of 3 weeks; or schedule C, weekly. Six weeks of concomitant standard chest radiotherapy in 1.8- to 2.0-Gy daily fractions was delivered to 60 Gy total.


RESULTS
Dose-limiting esophagitis and neutropenia were encountered with schedules A and B at docetaxel doses of 60 mg/m2 per cycle. The docetaxel MTD for schedules A and B was 40 mg/m2 per cycle. Dose-limiting esophagitis was also observed with schedule C; however, there was no neutropenia. For schedule C, we identified the MTD as 60 mg/m2 per cycle (20 mg/m2/wk). Other toxicities encountered included thrombocytopenia, hypersensitivity reaction, and pulmonary infiltrates (fatal in two patients). Late toxicity of esophageal stricture occurred in five patients.


CONCLUSIONS
Esophagitis and neutropenia are the dose-limiting toxicities of docetaxel administered with concomitant chest radiotherapy. Weekly administration of docetaxel allows for the highest total docetaxel dose during chest radiotherapy. We identified the recommended phase II docetaxel dose as 20 mg/m2 administered weekly with concomitant chest radiotherapy for 6 weeks.
Mauer
A M
AM
University of Chicago Department of Medicine, IL 60637, USA.
Masters
G A
GA
Haraf
D J
DJ
Hoffman
P C
PC
Watson
S M
SM
Golomb
H M
HM
Vokes
E E
EE
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D000077143:Docetaxel; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D004941:Esophagitis / Q000209:etiology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D011879:Radiotherapy Dosage; D043823:Taxoids; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel