1. ¹Division of Hematology, Oncology and Transplantation, the Vascular Biology Center, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA
2. ²Department of Therapeutic Radiology, University of Minnesota, Minneapolis, MN 55455, USA
3. ³Breast Cancer Research Program, Department of Radiation Oncology, University of Arkansas for medical Sciences, Little Rock, AR 72205, USA

Correspondence: Dr K Gupta, E-mail: gupta014@umn.edu

Revised 1 October 2007; Accepted 4 October 2007; Published online 30 October 2007.

Abstract

Morphine and its congener opioids are the main therapy for severe pain in cancer. However, chronic morphine treatment stimulates angiogenesis and tumour growth in mice. We examined if celecoxib (a cyclooxygenase-2 (COX-2) inhibitor) prevents morphine-induced tumour growth without compromising analgesia. The effect of chronic treatment with celecoxib (by gavage) and/or morphine (subcutaneously), or PBS on tumour prostaglandin E₂ (PGE₂), COX-2, angiogenesis, tumour growth, metastasis, pain behaviour and survival was determined in a highly invasive SCK breast cancer model in A/J mice. Two weeks of chronic morphine treatment at clinically relevant doses stimulates COX-2 and PGE₂ (4.5-fold compared to vehicle alone) and angiogenesis in breast tumours in mice. This is accompanied by increased tumour weight (35%) and increased metastasis and reduced survival. Co-administration of celecoxib prevents these morphine-induced effects. In addition, morphine and celecoxib together provided better analgesia than either agent alone. Celecoxib prevents morphine-induced stimulation of COX-2, PGE₂, angiogenesis, tumour growth, metastasis and mortality without compromising analgesia in a murine breast cancer model. In fact, the combination provided significantly better analgesia than with morphine or celecoxib alone. Clinical trials of this combination for analgesia in chronic and severe pain in cancer are warranted.