Treatment of lung cancer using clinically relevant oral doses of the cyclooxygenase-2 inhibitor rofecoxib: potential value as adjuvant therapy after surgery

Ann Surg. 2005 Jan;241(1):168-78. doi: 10.1097/01.sla.0000149427.84712.d9.


Objective: To investigate the uses and limitations of cyclooxygenase- (COX) 2 inhibition using clinically relevant doses of oral rofecoxib in the treatment of murine models of non-small-cell lung cancer (NSCLC).

Summary background data: Overexpression of COX-2 has been reported in lung cancer. Several studies have demonstrated that high doses of COX-2 inhibitors could inhibit the growth of rodent and human lung cancer cell lines. The potential uses and limitations of COX-2 inhibition at doses equivalent to those currently approved for use in humans have not been well studied.

Methods: Three murine NSCLC cell lines were injected into the flanks of mice to establish tumor xenografts. Mice were treated orally with low doses of a COX-2 inhibitor (rofecoxib chow, 0.0075%). Mechanisms were evaluated by analysis of tumor-infiltrating lymphocytes. To study rofecoxib as adjuvant therapy, large established tumors (14-18 days after tumor inoculation) were surgically debulked and animals were treated with rofecoxib starting 3 days before surgery. Recurrence of the tumor after debulking was monitored.

Results: Rofecoxib significantly slowed the growth of small (0-120 mm) tumors (P < 0.01-0.05) in all 3 cell lines, with higher efficacy in the more immunogenic tumors. Minimal responses were noted in larger tumors. Rofecoxib appeared to augment CD8 T cell infiltration in immunogenic tumors. Rofecoxib significantly reduced the recurrence rate after debulking (P < 0.01).

Conclusions: Clinically relevant doses of the COX-2 inhibitor rofecoxib given orally were effective in inhibiting the growth of small (but not large) tumors in 3 murine NSCLC cell lines tested and in preventing recurrences after surgical debulking. Depending on the immunogenicity of human tumors, COX-2 inhibition might be useful as adjuvant therapy for surgically resectable NSCLC.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Cell Line, Tumor
  • Chemotherapy, Adjuvant
  • Cyclooxygenase Inhibitors / administration & dosage*
  • Female
  • Lactones / administration & dosage*
  • Lung Neoplasms / drug therapy*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Recurrence, Local / prevention & control
  • Pneumonectomy
  • Sulfones / administration & dosage*
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • Cyclooxygenase Inhibitors
  • Lactones
  • Sulfones
  • rofecoxib