Phase I study of docetaxel (TXT) and 5-fluorouracil (5-FU) with concurrent radiotherapy in patients with advanced esophageal cancer.
This phase I study was designed to determine the maximum-tolerated dose (MTD) of docetaxel (TXT) and toxicities of combining weekly administration of TXT and continuous infusion of 5-fluorouracil (5-FU) with concomitant radiotherapy for advanced esophageal cancer.


METHODS
Patients received TXT by i.v. infusion over 1 h on days 1, 8, 22 and 29. They were also given 5-FU 250 mg/m2/day by continuous infusion for 24 h on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40 and 43-45. Fractionated radiotherapy was performed on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40 and 43-45, and a total dose of 60 to 66 Gy was delivered. The starting dose level (Level 1) of TXT was set at 7.5 mg/m2. Dose escalation was conducted in increments of 25 mg/m2, until the dose reached Level 4 (15 mg/m2). At least three patients were enrolled at each level.


RESULTS
Seven patients (median age, 64 years) were enrolled. Six patients had stage III (T4NIMO) and one had stage IVb (T4N1M1b) esophageal cancer; six had squamous cell carcinoma and one had carcinosarcoma. No patient had received prior chemotherapy or radiotherapy, and two patients had undergone esophageal bypass surgery using a whole stomach tube without resection of primary or metastatic lesions. In the 7patients, the regimen was well-tolerated, with esophagitis as the most common toxicity (grade 3: n=1; grade 4: n=3). In general, hematological toxicity was mild. Dose-limiting toxicity (DLT) was observed at Level 2 (TXT 10 mg/m2) when three patients developed grade 4 esophagitis and this dose was deemed the MTD for this regimen. In the 7 assessable patients, the overall clinical response rate was 85.7%.


CONCLUSIONS
The MTD of TXT in this regimen was 10 mg/m2 and the recommended dose of TXT was 7.5 mg/m2. Although esophagitis was the dose-limiting and the most frequent toxicity, the regimen was safe and well-tolerated, and demonstrated the possibility of good efficacy in patients with advanced esophageal cancer.
Hihara
Jun
J
Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Yoshida
Kazuhiro
K
Hamai
Yoichi
Y
Emi
Manabu
M
Yamaguchi
Yoshiyuki
Y
Wadasaki
Koichi
K
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D003131:Combined Modality Therapy; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
D043823:Taxoids; D000077143:Docetaxel; D005472:Fluorouracil