Phase I trial of combined-modality therapy for localized esophageal cancer: Escalating doses of continuous-infusion paclitaxel with cisplatin and concurrent radiation therapy Journal Article


Authors: Brenner, B.; Ilson, D. H.; Minsky, B. D.; Bains, M. S.; Tong, W.; Gonen, M.; Kelsen, D. P.
Article Title: Phase I trial of combined-modality therapy for localized esophageal cancer: Escalating doses of continuous-infusion paclitaxel with cisplatin and concurrent radiation therapy
Abstract: Purpose: To define the maximum-tolerated dose (MTD) of paclitaxel when given as a weekly 96-hour infusion with cisplatin and radiotherapy for patients with esophageal cancer. Patients and Methods: Thirty-four patients with locally advanced esophageal cancer and three patients with local recurrence or positive resection margins were treated. Weekly paclitaxel doses of 10, 20, 30, 40, 60, and 80 mg/m2, given as a continuous 96-hour infusion, were administered with weekly cisplatin, 30 mg/m2 on day 1, weeks 1 to 6, and concurrent radiation (50.4 Gy). Plasma paclitaxel steady-state levels were measured. Results: Dose-limiting toxicity, defined as a treatment break longer than 2 weeks for toxicity, occurred in one patient in the 80-mg/m2/wk dose level. Major causes for any (including ≤ 2 weeks) treatment breaks were mediport complications and neutropenic fever, which occurred mostly at that dose level. At a paclitaxel dose of 60 mg/m2/wk, myelosuppression, mostly neutropenia, was relatively mild and transient; stomatitis, esophagitis, diarrhea, and peripheral neuropathy were uncommon and usually of grade 2 or less. Therefore, the MTD was established at 60 mg/m2/wk. The mean steady-state concentration of paclitaxel at the MTD was 17.2 nmol/L. Complete (RO) resection was possible in 16 (73%) of 22 patients who underwent subsequent surgery, and the pathologic complete response rate was 24%. Conclusion: Weekly, 96-hour infusion of paclitaxel 60 mg/m2/wk, given with concurrent cisplatin and radiotherapy, is a safe and tolerable regimen for patients with localized esophageal cancer. Preliminary efficacy data are encouraging. This regimen is the basis of ongoing Radiation Therapy Oncology Group phase II randomized trials in esophageal and gastric cancers. © 2004 by American Society of Clinical Oncology.
Keywords: adult; clinical article; controlled study; treatment outcome; aged; middle aged; clinical trial; drug tolerability; neutropenia; cancer localization; cancer recurrence; cisplatin; diarrhea; dose response; drug safety; multimodality cancer therapy; paclitaxel; combined modality therapy; controlled clinical trial; neoplasm recurrence, local; bone marrow suppression; esophagitis; neuropathy; stomatitis; antineoplastic agents, phytogenic; dose-response relationship, drug; febrile neutropenia; blood sampling; carcinoma; drug blood level; maximum tolerated dose; phase 1 clinical trial; esophagus cancer; infusions, intravenous; esophageal neoplasms; humans; human; male; female; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 22
Issue: 1
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2004-01-01
Start Page: 45
End Page: 52
Language: English
DOI: 10.1200/jco.2004.05.039
PROVIDER: scopus
PUBMED: 14701767
DOI/URL:
Notes: J. Clin. Oncol. -- Cited By (since 1996):59 -- Export Date: 16 June 2014 -- CODEN: JCOND -- Source: Scopus
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MSK Authors
  1. William Ping-Yiu Tong
    119 Tong
  2. Baruch Brenner
    10 Brenner
  3. Bruce Minsky
    258 Minsky
  4. Mithat Gonen
    701 Gonen
  5. David H Ilson
    269 Ilson
  6. Manjit S Bains
    227 Bains
  7. David P Kelsen
    332 Kelsen