Trimodality therapy for stage II-III carcinoma of the esophagus: A dose-ranging study of concurrent capecitabine, docetaxel, and thoracic radiotherapy

Matthew Wood, Bassem I. Zaki, Stuart R. Gordon, John E. Sutton, Mikhail Lisovsky, Jiang Gui, Jeffrey A. Bubis, Konstantin H. Dragnev, James R. Rigas

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

PURPOSE: 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. CONCLUSION: 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.

Original languageEnglish (US)
Pages (from-to)487-494
Number of pages8
JournalJournal of Thoracic Oncology
Volume8
Issue number4
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

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docetaxel
Esophagus
Cohort Studies
Radiotherapy
Thorax
Carcinoma
Endosonography
Therapeutics
Chemoradiotherapy
Capecitabine
Esophagectomy
Maximum Tolerated Dose
Carboplatin

Keywords

  • Capecitabine
  • Chemoradiotherapy
  • Clinical trial
  • Esophageal carcinoma
  • Phase 2 dose-escalation study
  • Trimodality therapy

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Trimodality therapy for stage II-III carcinoma of the esophagus : A dose-ranging study of concurrent capecitabine, docetaxel, and thoracic radiotherapy. / Wood, Matthew; Zaki, Bassem I.; Gordon, Stuart R.; Sutton, John E.; Lisovsky, Mikhail; Gui, Jiang; Bubis, Jeffrey A.; Dragnev, Konstantin H.; Rigas, James R.

In: Journal of Thoracic Oncology, Vol. 8, No. 4, 01.01.2013, p. 487-494.

Research output: Contribution to journalArticle

Wood, Matthew ; Zaki, Bassem I. ; Gordon, Stuart R. ; Sutton, John E. ; Lisovsky, Mikhail ; Gui, Jiang ; Bubis, Jeffrey A. ; Dragnev, Konstantin H. ; Rigas, James R. / Trimodality therapy for stage II-III carcinoma of the esophagus : A dose-ranging study of concurrent capecitabine, docetaxel, and thoracic radiotherapy. In: Journal of Thoracic Oncology. 2013 ; Vol. 8, No. 4. pp. 487-494.
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abstract = "PURPOSE: 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. CONCLUSION: 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.",
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AU - Zaki, Bassem I.

AU - Gordon, Stuart R.

AU - Sutton, John E.

AU - Lisovsky, Mikhail

AU - Gui, Jiang

AU - Bubis, Jeffrey A.

AU - Dragnev, Konstantin H.

AU - Rigas, James R.

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N2 - PURPOSE: 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. CONCLUSION: 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.

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