Cyclooxygenase-2 inhibitor and cisplatin combination as a radiosensitizer in the treatment of head and neck cancer patients

We read with interest the study by Nix et al. [1Go], in which they attempted to investigate the possible relationship between cox-2 protein expression and treatment failure in early-stage laryngeal cancer treated with radiotherapy. They found that overexpression was significantly associated with radio-resistant tumors (P=0.004) and suggested that cox-2 inhibitors might have a role in enhancing the effects of radiotherapy. Two important and recently published randomized trials clearly showed that in patients with operable high-risk head and neck cancer, concurrent use of radiotherapy and chemotherapy is superior to radiotherapy alone with regard to disease-free survival and/or overall survival [2Go, 3Go]. In these trials, in the concurrent arm, radiotherapy was combined with cisplatin, which is the most common and effective radiosensitizer of all chemotherapeutic agents. A recent study reported that the cox-2 inhibitor JTE-522–cisplatin combination elicited a synergistic and additive antitumor effect in different gastric cancer lines [4Go]. A study by Peng et al. [5Go] also demonstrated that the cox-2 inhibitor NS398 potently augmented chemotherapeutic drug-induced apoptosis in hypopharyngeal cancer. NS398 also radiosensitizes head and neck squamous cell carcinoma cell lines, possibly by inhibiting radiation-induced expression of cox-2 [6Go]. These preclinical and clinical data suggest that the cox-2 inhibitor–cisplatin combination may be more useful than cisplatin alone as a radiosensitizer in the treatment of head and neck cancer that overexpresses cox-2 protein.

O. Altundag, K. Altundag*, P. Morandi1 and M. Gunduz2

Department of Medical Oncology, Hacettepe University Faculy of Medicine, Ankara, Turkey; 1 Department of Medical Oncology, S. Bortolo General Hospital, Vicenza, Italy; 2 Department of Oral Pathology and Medicine, Graduate School of Medicine and Dentistry, Okayama University, Japan

(*); Email: drkadri{at}usa.net

References

1. Nix P, Lind M, Greenman J et al. Expression of Cox-2 protein in radioresistant laryngeal cancer. Ann Oncol 2004; 15: 797–801.[Abstract/Free Full Text]

2. Cooper JS, Pajak TF, Forastiere AA et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004; 350: 1937–1944.[Abstract/Free Full Text]

3. Bernier J, Domenge C, Ozsahin M et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004; 350: 1945–1952.[Abstract/Free Full Text]

4. Sugiura T, Saikawa Y, Kubota T et al. Combination chemotherapy with JTE-522, a novel selective cyclooxygenase-2 inhibitor, and cisplatin against gastric cancer cell lines in vitro and in vivo. In Vivo 2003; 17: 229–233.[ISI][Medline]

5. Peng JP, Liu LT, Chang HC, Hung WC. Enhancement of chemotherapeutic drug-induced apoptosis by a cyclooxygenase-2 inhibitor in hypopharyngeal carcinoma cells. Cancer Lett 2003; 201: 157–163.[CrossRef][ISI][Medline]

6. Amirghahari N, Harrison L, Smith M et al. NS 398 radiosensitizes an HNSCC cell line by possibly inhibiting radiation-induced expression of COX-2. Int J Radiat Oncol Biol Phys 2003; 57: 1405–1412.[CrossRef][ISI][Medline]





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