A Phase II Trial of Celecoxib (CX), Irinotecan (I), 5-Fluorouracil (5FU), and Leucovorin (LCV) in Patients with Unresectable or Metastatic Colorectal Cancer (CRC)

Reviewer: Thomas Dilling, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 19, 2002

Presenter: C.D. Blanke
Presenter's Affiliation: Oregeon Health Sciences University
Type of Session: Scientific


  • Previous studies have shown that cyclooxygenase-II (COX-2) is present in the majority of CRCs, with expression associated with worse prognosis.
  • Celecoxib is a selective COX-2 inhibitor which has demonstrable anti-angiogenesis properties in vivo, and benefit when combined with chemotherapy.
  • Based on these data, a multi-institutional phase 2 trial was undertaken.

Materials and Methods

  • Inclusion criteria were patients with measurable disease which was deemed unresectable or metastatic. ECOG Performance Status 0-2.
  • Patients were excluded if they had had treatment in the prior 12 months with any agents except 5FU, or if they had a history of thromboembolic disease.
  • Patients received CX at 400 bid x 2 weeks, then IFL chemotherapy (the "Saltz regimen") concurrent with CX x 4 cycles, q43 days, continuing treatment until disease progressed or treatment-related toxicity was achieved.
  • Initially, standard dosing of these agents was undertaken (125 mg/m2 I, 500 mg/m2 F, 20 mg/m2 L).
  • The trial was closed for several months while interim data were analyzed. The trial was then reopened, with amendments, including restriction to ECOG performance status 0-1, as well as mild reductions in chemotherapy dosage due to reported grade 2 toxicities.
  • To date, 21 patients are evaluable for toxicity and 18 for response.


  • Grade 3/4 toxicities included neutropenia in 27%, diarrhea in 23%, nausea in 23%, and electrolyte disturbances in 18%.
  • Interestingly, the reported rate of neutropenia is lower than that previously described in patients undergoing IFL chemotherapy alone.
  • 3 thromboembolic events were reported, including two cerebrovascular accidents, one of which resulted in death, and one myocardial infarction. These 3 patients all had underlying vascular disease.
  • Patients have received from 1-9 cycles of treatment.
  • 24% had PR, with 43% demonstrating stable disease. 14% had frank progression. 19% were not assessed, but have been included in an intent-to-treat fashion
  • Median duration of PR was 6.0 months, with PFS of 6.8 months. Median survival is 10.1 months.

Author's Conclusions

  • To date, the trial has only accrued 1/2 of the patients planned, so these data are still somewhat immature.
  • Nonetheless, these very preliminary results do suggest some activity against CRC with COX-2 inhibition.

Clinical/Scientific Implications

  • As our knowledge of molecular functioning of tumor cells improves, researchers hope to create agents with increasing efficacy.
  • COX-2 inhibition is one of the important "first wave" of directed molecular therapies for oncologic tumors.
  • Additional patients will need to be accrued to this study to better ascertain the treatment toxicity profile, as well as the response rate of tumors to this therapy.
  • If these very early data are indicative, a phase 3 trial will probably be indicated to further ascertain the efficacy of this treatment modality.

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