Douglas B. Flieder

Celecoxib, a Selective Cyclo-Oxygenase-2 Inhibitor, Enhances the Response to Preoperative Paclitaxel and Carboplatin in Early-Stage Non–Small-Cell Lung Cancer

PURPOSEnPreclinical studies suggest that treatment with a selective cyclo-oxygenase-2 (COX-2) inhibitor may augment the antitumor effects of chemotherapy. In this study, patients with non-small-cell lung cancer (NSCLC) were preoperatively treated with celecoxib in combination with chemotherapy. End points were toxicity, response rates, and measurement of intratumoral levels of prostaglandin E2 (PGE2).nnnMETHODSnIn this phase II trial, 29 patients with stages IB to IIIA NSCLC were treated with two preoperative cycles of paclitaxel and carboplatin, as well as daily celecoxib, followed by surgical resection. Levels of PGE2 in the primary tumors and adjacent normal lung tissue were compared in 17 study patients versus 13 controls, who received preoperative paclitaxel/carboplatin without celecoxib.nnnRESULTSnAll patients completed preoperative chemotherapy, and 26 completed preoperative celecoxib. The overall clinical response rate was 65% (48% with partial response; 17% with complete response). Grade 3 or 4 neutropenia was observed in 18 patients (62%). Twenty-eight patients were explored and underwent complete resection of their tumors. There were no complete pathologic responses, but seven patients (24%) had minimal residual microscopic disease. The addition of celecoxib to a regimen of paclitaxel and carboplatin abrogated the marked increase in levels of PGE2 detected in primary tumors after treatment with paclitaxel and carboplatin alone.nnnCONCLUSIONnIn comparison with historically reported response rates, these data suggest that the addition of a selective COX-2 inhibitor may enhance the response to preoperative paclitaxel and carboplatin in patients with NSCLC. Moreover, treatment with celecoxib 400 mg twice daily was sufficient to normalize the increase in PGE2 levels found in NSCLC patients after treatment with paclitaxel and carboplatin. Confirmatory trials are planned.

Pathologic characteristics of drug-induced lung disease

The surgical pathologists role in the diagnosis of adverse pulmonary and pleural drug effect requires an appreciation of the clinico-radiologic scenario and particular knowledge of morphologic patterns of lung injury. Bronchoscopic biopsies may be helpful in some cases of DAD, eosinophilic pneumonia, or OP. Extrapolating patterns of lung involvement from small biopsies and cytologic preparations often is difficult and surgical lung biopsy is required. Although lung biopsies are not pathognomonic for drug toxicity and correlation with clinical, laboratory, and radiologic data is required, they can be a powerful tool in the evaluation of suspected drug-induced pulmonary disease by helping to exclude underlying disease or infection and documenting the pattern of lung injury. The latter information is helpful in making the diagnosis of drug toxicity as well as guiding the optimal management of the patient.

Proliferative myositis: A rare pseudosarcoma of the chest wall

Proliferative myositis is a rare, inflammatory tumor that is often misdiagnosed as sarcoma. The clinical course of proliferative myositis is benign, and local recurrence after simple excision is uncommon. Typically, the lesion presents in the extremities or the head and neck. We present an unusual case of proliferative myositis with involvement of the anterior chest wall.