Phase I trial of escalating-dose irinotecan given weekly with cisplatin and concurrent radiotherapy in locally advanced esophageal cancer Journal Article


Authors: Ilson, D. H.; Bains, M.; Kelsen, D. P.; O'reilly, E.; Karpeh, M.; Coit, D.; Rusch, V.; Gonen, M.; Wilson, K.; Minsky, B. D.
Article Title: Phase I trial of escalating-dose irinotecan given weekly with cisplatin and concurrent radiotherapy in locally advanced esophageal cancer
Abstract: Purpose: To identify the maximum-tolerated dose and dose-limiting toxicity (DLT) of weekly irinotecan combined with cisplatin and radiation in esophageal cancer. Patients and Methods: Nineteen patients with clinical stage II to III esophageal squamous cell or adenocarcinoma were treated on this phase I trial. Induction chemotherapy with weekly cisplatin 30 mg/m2 and irinotecan 65 mg/m2 was administered for four treatments during weeks 1 to 5. Radiotherapy was delivered weeks 8 to 13 in 1.8-Gy daily fractions to a dose of 50.4 Gy. Cisplatin 30 mg/m2 and escalating-dose irinotecan (40, 50, 65, and 80 mg/m2) were administered on days 1, 8, 22, and 29 of radiotherapy. DLT was defined as a 2-week delay in radiotherapy for grade 3 to 4 toxicity. Results: Minimal toxicity was observed during chemoradiotherapy, with no grade 3 or 4 esophagitis, diarrhea, or stomatitis. DLT caused by myelosuppression was seen in two of six patients treated at the 80-mg/m 2 dose level, thus irinotecan 65 mg/m2 was defined as the recommended phase II dose. Dysphagia improved or resolved after induction chemotherapy in 13 (81%) of 16 patients who reported dysphagia before therapy. Only one patient (5%) required a feeding tube. Six complete responses (32%) were observed, including four pathologic complete responses in 15 patients selected to undergo surgery (27%). Conclusion: Cisplatin, irinotecan, and concurrent radiotherapy can be administered on a convenient schedule with relatively minimal toxicity and an acceptable rate of complete response in esophageal cancer. Further phase II evaluation of this regimen is ongoing. A phase III comparison to fluorouracil or taxane-containing chemoradiotherapy should be considered. © 2003 by American Society of Clinical Oncology.
Keywords: adult; clinical article; controlled study; treatment outcome; aged; middle aged; clinical trial; cisplatin; advanced cancer; diarrhea; dose response; multimodality cancer therapy; cancer radiotherapy; combined modality therapy; antineoplastic agent; controlled clinical trial; bone marrow suppression; esophagitis; stomatitis; antineoplastic combined chemotherapy protocols; camptothecin; pathology; irinotecan; drug dose escalation; dysphagia; drug derivative; adenosquamous carcinoma; maximum tolerated dose; phase 1 clinical trial; esophagus cancer; esophageal adenocarcinoma; tube feeding; esophagus tumor; esophageal neoplasms; esophageal squamous cell carcinoma; carcinoma, adenosquamous; humans; human; male; female; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 21
Issue: 15
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2003-08-01
Start Page: 2926
End Page: 2932
Language: English
DOI: 10.1200/jco.2003.02.147
PUBMED: 12885811
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Valerie W Rusch
    651 Rusch
  2. Bruce Minsky
    258 Minsky
  3. Mithat Gonen
    701 Gonen
  4. Martin S Karpeh
    93 Karpeh
  5. Daniel Coit
    415 Coit
  6. David H Ilson
    269 Ilson
  7. Eileen O'Reilly
    316 O'Reilly
  8. Manjit S Bains
    227 Bains
  9. David P Kelsen
    332 Kelsen
  10. Katie   Wilson
    1 Wilson