A Phase II Study of Celecoxib with Irinotecan, 5-Fluorouracil, and Leucovorin in Patients with Previously Untreated Advanced or Metastatic Colorectal Cancer

Emerson Y. Chen, Charles Blanke, Daniel G. Haller, Al B. Benson, Tomislav Dragovich, Heinz Josef Lenz, Carlos Robles, Hong Li, Motomi (Tomi) Mori, Nora Mattek, Rachel E. Sanborn, Charles Lopez

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective: Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Cyclooxygenase-2 (COX-2) overexpression is associated with increased tumor invasiveness and proliferation in CRC, and COX-2 inhibition has demonstrated chemopreventive activity. This study investigated the addition of celecoxib, a selective COX-2 inhibitor, to the irinotecan, 5-fluorouracil, and leucovorin (IFL) regimen for patients with previously untreated metastatic CRC. Patients and Methods: Forty-seven patients enrolled in this single-arm phase II study received celecoxib at 400 mg orally twice daily in combination with weekly irinotecan (125 mg/m2), 5-fluorouracil (500 mg/m2), and leucovorin (20 mg/m2) for 4 weeks every 6 weeks. The primary endpoint was response rate (RR) as measured by Response Evaluation Criteria in Solid Tumors. The protocol was amended midway to additionally exclude patients with Eastern Cooperative Oncology Group performance status 2 and require all patients with specific cardiovascular risk factors to take daily aspirin (81 mg). Results: The objective RR was 31.9% (95% confidence interval [CI], 19%-47%). Median progression-free survival was 8.7 months (95% CI, 5.8-10.6), and the median overall survival was 19.7 months (95% CI, 15.4-22.8). All cardiac events were observed before protocol modification. The median overall survival before and after protocol modification was 11.4 versus 24.2 months, respectively (P< 0.0001); tumor RR and progression-free survival were not statistically different before or after protocol modification. The trial was halted after an interim analysis demonstrated that the primary endpoint would not be met. Conclusions: Celecoxib plus IFL chemotherapy for patients with metastatic CRC is tolerable, but does not appear to increase the efficacy of IFL.

Original languageEnglish (US)
Pages (from-to)1193-1198
Number of pages6
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume41
Issue number12
DOIs
StatePublished - Dec 1 2018

Fingerprint

irinotecan
Celecoxib
Leucovorin
Fluorouracil
Colorectal Neoplasms
Confidence Intervals
Cyclooxygenase 2
Disease-Free Survival
Neoplasms
Survival
Cyclooxygenase 2 Inhibitors
Aspirin
Cause of Death

Keywords

  • 5-fluorouracil (5-FU)
  • celecoxib
  • colorectal cancer
  • cyclooxygenase-2 (COX-2) inhibitor
  • irinotecan

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A Phase II Study of Celecoxib with Irinotecan, 5-Fluorouracil, and Leucovorin in Patients with Previously Untreated Advanced or Metastatic Colorectal Cancer. / Chen, Emerson Y.; Blanke, Charles; Haller, Daniel G.; Benson, Al B.; Dragovich, Tomislav; Lenz, Heinz Josef; Robles, Carlos; Li, Hong; Mori, Motomi (Tomi); Mattek, Nora; Sanborn, Rachel E.; Lopez, Charles.

In: American Journal of Clinical Oncology: Cancer Clinical Trials, Vol. 41, No. 12, 01.12.2018, p. 1193-1198.

Research output: Contribution to journalArticle

Chen, Emerson Y. ; Blanke, Charles ; Haller, Daniel G. ; Benson, Al B. ; Dragovich, Tomislav ; Lenz, Heinz Josef ; Robles, Carlos ; Li, Hong ; Mori, Motomi (Tomi) ; Mattek, Nora ; Sanborn, Rachel E. ; Lopez, Charles. / A Phase II Study of Celecoxib with Irinotecan, 5-Fluorouracil, and Leucovorin in Patients with Previously Untreated Advanced or Metastatic Colorectal Cancer. In: American Journal of Clinical Oncology: Cancer Clinical Trials. 2018 ; Vol. 41, No. 12. pp. 1193-1198.
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abstract = "Objective: Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Cyclooxygenase-2 (COX-2) overexpression is associated with increased tumor invasiveness and proliferation in CRC, and COX-2 inhibition has demonstrated chemopreventive activity. This study investigated the addition of celecoxib, a selective COX-2 inhibitor, to the irinotecan, 5-fluorouracil, and leucovorin (IFL) regimen for patients with previously untreated metastatic CRC. Patients and Methods: Forty-seven patients enrolled in this single-arm phase II study received celecoxib at 400 mg orally twice daily in combination with weekly irinotecan (125 mg/m2), 5-fluorouracil (500 mg/m2), and leucovorin (20 mg/m2) for 4 weeks every 6 weeks. The primary endpoint was response rate (RR) as measured by Response Evaluation Criteria in Solid Tumors. The protocol was amended midway to additionally exclude patients with Eastern Cooperative Oncology Group performance status 2 and require all patients with specific cardiovascular risk factors to take daily aspirin (81 mg). Results: The objective RR was 31.9{\%} (95{\%} confidence interval [CI], 19{\%}-47{\%}). Median progression-free survival was 8.7 months (95{\%} CI, 5.8-10.6), and the median overall survival was 19.7 months (95{\%} CI, 15.4-22.8). All cardiac events were observed before protocol modification. The median overall survival before and after protocol modification was 11.4 versus 24.2 months, respectively (P< 0.0001); tumor RR and progression-free survival were not statistically different before or after protocol modification. The trial was halted after an interim analysis demonstrated that the primary endpoint would not be met. Conclusions: Celecoxib plus IFL chemotherapy for patients with metastatic CRC is tolerable, but does not appear to increase the efficacy of IFL.",
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T1 - A Phase II Study of Celecoxib with Irinotecan, 5-Fluorouracil, and Leucovorin in Patients with Previously Untreated Advanced or Metastatic Colorectal Cancer

AU - Chen, Emerson Y.

AU - Blanke, Charles

AU - Haller, Daniel G.

AU - Benson, Al B.

AU - Dragovich, Tomislav

AU - Lenz, Heinz Josef

AU - Robles, Carlos

AU - Li, Hong

AU - Mori, Motomi (Tomi)

AU - Mattek, Nora

AU - Sanborn, Rachel E.

AU - Lopez, Charles

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Objective: Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Cyclooxygenase-2 (COX-2) overexpression is associated with increased tumor invasiveness and proliferation in CRC, and COX-2 inhibition has demonstrated chemopreventive activity. This study investigated the addition of celecoxib, a selective COX-2 inhibitor, to the irinotecan, 5-fluorouracil, and leucovorin (IFL) regimen for patients with previously untreated metastatic CRC. Patients and Methods: Forty-seven patients enrolled in this single-arm phase II study received celecoxib at 400 mg orally twice daily in combination with weekly irinotecan (125 mg/m2), 5-fluorouracil (500 mg/m2), and leucovorin (20 mg/m2) for 4 weeks every 6 weeks. The primary endpoint was response rate (RR) as measured by Response Evaluation Criteria in Solid Tumors. The protocol was amended midway to additionally exclude patients with Eastern Cooperative Oncology Group performance status 2 and require all patients with specific cardiovascular risk factors to take daily aspirin (81 mg). Results: The objective RR was 31.9% (95% confidence interval [CI], 19%-47%). Median progression-free survival was 8.7 months (95% CI, 5.8-10.6), and the median overall survival was 19.7 months (95% CI, 15.4-22.8). All cardiac events were observed before protocol modification. The median overall survival before and after protocol modification was 11.4 versus 24.2 months, respectively (P< 0.0001); tumor RR and progression-free survival were not statistically different before or after protocol modification. The trial was halted after an interim analysis demonstrated that the primary endpoint would not be met. Conclusions: Celecoxib plus IFL chemotherapy for patients with metastatic CRC is tolerable, but does not appear to increase the efficacy of IFL.

AB - Objective: Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Cyclooxygenase-2 (COX-2) overexpression is associated with increased tumor invasiveness and proliferation in CRC, and COX-2 inhibition has demonstrated chemopreventive activity. This study investigated the addition of celecoxib, a selective COX-2 inhibitor, to the irinotecan, 5-fluorouracil, and leucovorin (IFL) regimen for patients with previously untreated metastatic CRC. Patients and Methods: Forty-seven patients enrolled in this single-arm phase II study received celecoxib at 400 mg orally twice daily in combination with weekly irinotecan (125 mg/m2), 5-fluorouracil (500 mg/m2), and leucovorin (20 mg/m2) for 4 weeks every 6 weeks. The primary endpoint was response rate (RR) as measured by Response Evaluation Criteria in Solid Tumors. The protocol was amended midway to additionally exclude patients with Eastern Cooperative Oncology Group performance status 2 and require all patients with specific cardiovascular risk factors to take daily aspirin (81 mg). Results: The objective RR was 31.9% (95% confidence interval [CI], 19%-47%). Median progression-free survival was 8.7 months (95% CI, 5.8-10.6), and the median overall survival was 19.7 months (95% CI, 15.4-22.8). All cardiac events were observed before protocol modification. The median overall survival before and after protocol modification was 11.4 versus 24.2 months, respectively (P< 0.0001); tumor RR and progression-free survival were not statistically different before or after protocol modification. The trial was halted after an interim analysis demonstrated that the primary endpoint would not be met. Conclusions: Celecoxib plus IFL chemotherapy for patients with metastatic CRC is tolerable, but does not appear to increase the efficacy of IFL.

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KW - colorectal cancer

KW - cyclooxygenase-2 (COX-2) inhibitor

KW - irinotecan

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