Phase II randomized study of two regimens of sequentially administered mitomycin C and irinotecan in patients with unresectable esophageal and gastroesophageal adenocarcinoma

Maryam B. Lustberg, Tanios Bekaii-Saab, Donn Young, Gregory Otterson, William Burak, Abbas Abbas, Barbara McCracken-Bussa, Mark E. Lustberg, Miguel A. Villalona-Calero

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Based on the observation of topoisomerase-1, upregulation by mitomycin C (MMC), and the phase I antitumor activity of sequential MMC/irinotecan in esophageal cancer, we conducted a phase II evaluation of two schedules of this combination in previously untreated stage III/IV esophageal/gastroesophageal junction adenocarcinomas. Patients and Methods: Patients (n = 76) were randomized to either 6 mg/m2 MMC on day 1 and 125 mg/m2 irinotecan on days 2 and 9 (arm A) or 3 mg/m2 MMC on days 1 and 8 and 125 mg/m irinotecan on days 2 and 9 (arm B). Each cycle was repeated every 28 days. Restaging was planned after two cycles, and resections were performed whenever possible. A two-stage Simon minimax design was used for each arm, with a "pick-the-winner" approach based on efficacy. Results: The response rate (complete response + partial response) in 73 evaluable patients was 52% (21 of 40 patients) for arm A and 33% (11/33) for arm B. Moderate or severe toxicity was similar. Twenty-seven patients were resected (20:7, arm A:B). There was one complete pathologic response; five others were node negative. Conclusion: Irinotecan/MMC is feasible in esophageal/gastroesophageal junction adenocarcinoma. MMC (6 mg/m) every 28 days for up to six cycles is the recommended modulatory dose for irinotecan in future trials.

Original languageEnglish (US)
Pages (from-to)713-718
Number of pages6
JournalJournal of Thoracic Oncology
Volume5
Issue number5
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

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irinotecan
Mitomycin
Adenocarcinoma
Esophagogastric Junction
Esophageal Neoplasms
Appointments and Schedules
Up-Regulation
Observation

Keywords

  • Gastroesophageal adenocarcinoma
  • Irinotecan
  • Mitomycin C
  • Topoisomerase I

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Phase II randomized study of two regimens of sequentially administered mitomycin C and irinotecan in patients with unresectable esophageal and gastroesophageal adenocarcinoma. / Lustberg, Maryam B.; Bekaii-Saab, Tanios; Young, Donn; Otterson, Gregory; Burak, William; Abbas, Abbas; McCracken-Bussa, Barbara; Lustberg, Mark E.; Villalona-Calero, Miguel A.

In: Journal of Thoracic Oncology, Vol. 5, No. 5, 01.01.2010, p. 713-718.

Research output: Contribution to journalArticle

Lustberg, Maryam B. ; Bekaii-Saab, Tanios ; Young, Donn ; Otterson, Gregory ; Burak, William ; Abbas, Abbas ; McCracken-Bussa, Barbara ; Lustberg, Mark E. ; Villalona-Calero, Miguel A. / Phase II randomized study of two regimens of sequentially administered mitomycin C and irinotecan in patients with unresectable esophageal and gastroesophageal adenocarcinoma. In: Journal of Thoracic Oncology. 2010 ; Vol. 5, No. 5. pp. 713-718.
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T1 - Phase II randomized study of two regimens of sequentially administered mitomycin C and irinotecan in patients with unresectable esophageal and gastroesophageal adenocarcinoma

AU - Lustberg, Maryam B.

AU - Bekaii-Saab, Tanios

AU - Young, Donn

AU - Otterson, Gregory

AU - Burak, William

AU - Abbas, Abbas

AU - McCracken-Bussa, Barbara

AU - Lustberg, Mark E.

AU - Villalona-Calero, Miguel A.

PY - 2010/1/1

Y1 - 2010/1/1

N2 - Background: Based on the observation of topoisomerase-1, upregulation by mitomycin C (MMC), and the phase I antitumor activity of sequential MMC/irinotecan in esophageal cancer, we conducted a phase II evaluation of two schedules of this combination in previously untreated stage III/IV esophageal/gastroesophageal junction adenocarcinomas. Patients and Methods: Patients (n = 76) were randomized to either 6 mg/m2 MMC on day 1 and 125 mg/m2 irinotecan on days 2 and 9 (arm A) or 3 mg/m2 MMC on days 1 and 8 and 125 mg/m irinotecan on days 2 and 9 (arm B). Each cycle was repeated every 28 days. Restaging was planned after two cycles, and resections were performed whenever possible. A two-stage Simon minimax design was used for each arm, with a "pick-the-winner" approach based on efficacy. Results: The response rate (complete response + partial response) in 73 evaluable patients was 52% (21 of 40 patients) for arm A and 33% (11/33) for arm B. Moderate or severe toxicity was similar. Twenty-seven patients were resected (20:7, arm A:B). There was one complete pathologic response; five others were node negative. Conclusion: Irinotecan/MMC is feasible in esophageal/gastroesophageal junction adenocarcinoma. MMC (6 mg/m) every 28 days for up to six cycles is the recommended modulatory dose for irinotecan in future trials.

AB - Background: Based on the observation of topoisomerase-1, upregulation by mitomycin C (MMC), and the phase I antitumor activity of sequential MMC/irinotecan in esophageal cancer, we conducted a phase II evaluation of two schedules of this combination in previously untreated stage III/IV esophageal/gastroesophageal junction adenocarcinomas. Patients and Methods: Patients (n = 76) were randomized to either 6 mg/m2 MMC on day 1 and 125 mg/m2 irinotecan on days 2 and 9 (arm A) or 3 mg/m2 MMC on days 1 and 8 and 125 mg/m irinotecan on days 2 and 9 (arm B). Each cycle was repeated every 28 days. Restaging was planned after two cycles, and resections were performed whenever possible. A two-stage Simon minimax design was used for each arm, with a "pick-the-winner" approach based on efficacy. Results: The response rate (complete response + partial response) in 73 evaluable patients was 52% (21 of 40 patients) for arm A and 33% (11/33) for arm B. Moderate or severe toxicity was similar. Twenty-seven patients were resected (20:7, arm A:B). There was one complete pathologic response; five others were node negative. Conclusion: Irinotecan/MMC is feasible in esophageal/gastroesophageal junction adenocarcinoma. MMC (6 mg/m) every 28 days for up to six cycles is the recommended modulatory dose for irinotecan in future trials.

KW - Gastroesophageal adenocarcinoma

KW - Irinotecan

KW - Mitomycin C

KW - Topoisomerase I

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