Trimodality therapy for stage II-III carcinoma of the esophagus: a dose-ranging study of concurrent capecitabine, docetaxel, and thoracic radiotherapy.
OBJECTIVE
This dose-escalation study was performed to determine the recommended phase II dose of oral capecitabine to be delivered concurrently with thoracic radiation therapy and weekly docetaxel in patients with locally advanced esophageal carcinoma.


METHODS
Patients with operable stage II or III esophageal carcinoma were staged by endoscopic ultrasonography and computed tomography. Two cycles of docetaxel (80 mg/m) and carboplatin (target area under the concentration-time curve: 6 mg/ml × min) were delivered over 6 weeks. This was followed by concurrent weekly docetaxel (15 mg/m), thoracic radiotherapy (50.4 Gy in 28 fractions), and increasing doses of capecitabine (500-3500 mg) given before each fraction of radiotherapy. After restaging, responding patients continued to esophagectomy within 4 to 8 weeks of completing chemoradiotherapy.


RESULTS
Forty-four patients were enrolled, and 40 were assessable for the dose-ranging component of concurrent chemoradiotherapy. Endoscopic ultrasonography stages at enrollment were T3N1 (29 patients), T3N0 (4 patients), T2N1 (6 patients), and T4N0 (one patient). The maximum tolerated dose of capecitabine was 3500 mg. Thirty-six patients had surgery; 83% had R0 resection, and 17% had pathological complete response. Median overall survival was 23.5 months, with 34 and 27% alive at 3 and 5 years.


CONCLUSIONS
The recommended phase II dose of capecitabine is 3500 mg when given concurrently with 50.4 Gy of thoracic radiotherapy in 28 fractions and weekly docetaxel. This trimodality therapy for operable locally advanced esophageal carcinoma was very well tolerated and remarkably active. This regimen holds promise for the treatment of esophageal carcinoma and warrants further investigation.
Comprehensive Thoracic Oncology Program, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.
Matthew D
MD
Wood
Bassem I
BI
Zaki
Stuart R
SR
Gordon
John E
JE
Sutton
Mikhail
M
Lisovsky
Jiang
J
Gui
Jeffrey A
JA
Bubis
Konstantin H
KH
Dragnev
James R
JR
Rigas
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D019160:Endosonography; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016629:Esophagectomy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011879:Radiotherapy Dosage; D012074:Remission Induction; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D013899:Thoracic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D014057:Tomography, X-Ray Computed
D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000069287:Capecitabine; D005472:Fluorouracil