PURPOSE: Preclinical 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). METHODS: In 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. RESULTS: All 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. CONCLUSION: In 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.
PURPOSE: Preclinical 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). METHODS: In 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. RESULTS: All 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. CONCLUSION: In 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 NSCLCpatients after treatment with paclitaxel and carboplatin. Confirmatory trials are planned.
Authors: C T Tong; S A Howard; H R Shah; K R Van Quill; E T Lin; H E Grossniklaus; J M O'Brien Journal: Br J Ophthalmol Date: 2005-09 Impact factor: 4.638
Authors: Terry W Moody; Christopher Switzer; Wilmarie Santana-Flores; Lisa A Ridnour; Marc Berna; Michelle Thill; Robert T Jensen; Anna Sparatore; Piero Del Soldato; Grace C Yeh; David D Roberts; Giuseppe Giaccone; David A Wink Journal: Lung Cancer Date: 2009-07-23 Impact factor: 5.705
Authors: Florian Hohla; Andrew V Schally; Celia A Kanashiro; Stefan Buchholz; Benjamin Baker; Chandrika Kannadka; Angelika Moder; Elmar Aigner; Christian Datz; Gabor Halmos Journal: Proc Natl Acad Sci U S A Date: 2007-11-14 Impact factor: 11.205
Authors: Santosh Kesari; David Schiff; John W Henson; Alona Muzikansky; Debra C Gigas; Lisa Doherty; Tracy T Batchelor; Janina A Longtine; Keith L Ligon; Susan Weaver; Andrea Laforme; Naren Ramakrishna; Peter McL Black; Jan Drappatz; Abigail Ciampa; Judah Folkman; Mark Kieran; Patrick Y Wen Journal: Neuro Oncol Date: 2008-04-10 Impact factor: 12.300