Table 3.
Changes in results from prostaglandin assays and COX-1 and -2 expression after 24 weeks of treatment*
| Lowgrade stratum |
High-grade stratum |
Combined |
|||||||
|---|---|---|---|---|---|---|---|---|---|
| Compound | Celecoxib (n = 20) | Placebo (n = 16) | P† | Celecoxib (n = 8) | Placebo (n = 8) | P† | Celecoxib (n = 28) | Placebo (n = 24) | P† |
| PGE2, ng/mg of protein (IQR) | |||||||||
| −Arachidonic acid | |||||||||
| Median at baseline | 0.13 (−0.22 to 48) | 0.30 (−0.13 to 0.73) | .32 | 0.18 −0.89 to 1.25) | 0.04 (−0.81 to 0.89) | .49 | 0.14 (−0.28 to 0.56) | 0.23 (−0.23 to 0.69) | .81 |
| Median change | 0.00 (−0.26 to 0.26) | −0.06 (−0.40 to 0.28) | .37 | +0.15 −0.24 to 0.54) | +0.01 (−0.96 to 0.98) | .07 | +0.02 (−0.21 to 0.25) | −0.04 (−0.44 to 0.36) | 11 |
| +Arachidonic acid | |||||||||
| Median at baseline | 1.57 (−1.65 to 4.79) | 2.40 (−0.83 to 5.63) | .73 | 1.77 −1.47 to 5.01) | 1.61 (−1.50 to 4.72) | .53 | 1.57 (−1.68 to 4.82) | 1.75 (−1.47 to 4.97) | .96 |
| Median change | −0.11 (−2.38 to 2.16) | −0.06 (−4.22 to 4.10) | .95 | + 1.08 −1.83 to 3.99) | 0.00 (−3.72 to 3.72) | .09 | +0.08 (−2.53 to 2.69) | −0.01 (−3.53 to 3.51) | .39 |
| PGD2, ng/mg of protein (IQR) | |||||||||
| −Arachidonic acid | |||||||||
| Median at baseline | 0.09 (−0.13 to 0.31) | 0.22 (−0.16 to 0.60) | .26 | 0.180 to 0.36) | 0.08 (−0.4 to 0.20) | .12 | 0.12 (−0.09 to 0.33) | 0.13 (−0.18 to 0.44) | .79 |
| Median change | 0.00 (−0.16 to 0.16) | −0.06 (−0.35 to 0.23) | .34 | +0.08−0.24 to 0.40) | −0.00 (−0.26 to 0.26) | .21 | +0.02 (−0.19 to 0.23) | −0.03 (−0.28 to 0.22) | 14 |
| +Arachidonic acid | |||||||||
| Median at baseline | 0.93 (−0.64 to 2.50) | 1.46 (−2.11 to 5.03) | .36 | 1.25 −0.21 to 2.71) | 0.93 (−0.37 to 2.23) | .60 | 0.98 (−0.60 to 2.56) | 1.26 (−1.42 to 3.94) | .65 |
| Median change | −0.40 (−1.84 to 1.04) | −0.28 (−2.30 to 1.74) | .77 | + 1.09 −1.36 to 3.54) | −0.29 (−1.55 to 0.97) | .29 | −0.20 (−1.86 to 1.46) | −0.28 (−1.94 to 1.38) | .52 |
| PGF2α, ng/mg of protein (IQR) | |||||||||
| −Arachidonic acid | |||||||||
| Median at baseline | 0.21 (−0.20 to 0.62) | 0.17 (−0.68 to 1.02) | .86 | 0.15 −1.16 to 1.46) | 0.10 (−0.07 to 0.27) | .25 | 0.19 (−0.46 to 0.84) | 0.14 (−0.22 to 0.50) | .65 |
| Median change | +0.02 (−0.14 to 0.18) | −0.02 (−0.47 to 0.43) | .52 | +0.04 −0.29 to 0.37) | −0.02 (−0.40 to 0.36) | .83 | +0.02 (−0.14 to 0.18) | −0.02 (−0.28 to 0.22) | .57 |
| +Arachidonic acid | |||||||||
| Median at baseline | 1.63 (−1.37 to 4.63) | 3.16 (−2.80 to 9.12) | .31 | 1.63 −0.85 to 4.11) | 1.82 (−6.12 to 9.76) | 1.0 | 1.63 (−0.74 to 4.00) | 2.59 (−3.43 to 8.61) | .36 |
| Median change | −0.32 (−4.97 to 4.33) | −0.77 (−8.45 to 6.95) | .50 | +0.85 −2.65 to 4.35) | +0.10 (−2.28 to 2.48) | 0.67 | −0.14 (−4.19 to 3.91) | −0.48 (−4.44 to 3.48) | .53 |
|
Thromboxane B2, ng/mg of protein (IQR) |
|||||||||
| −Arachidonic acid | |||||||||
| Median at baseline | 0.06 (−0.02 to 0.14) | 0.09 (−0.02 to 0.20) | .23 | 0.05 −0.18 to 0.28) | 0.03 (−0.06 to 0.1 2) | .40 | 0.06 (0.03 to 0.1 5) | 0.08 (−0.01 to 0.17) | .67 |
| Median change | 0.00 (−0.06 to 0.06) | −0.02 (−0.14 to 0.10) | .75 | +0.02 −0.04 to 0.08) | −0.00 (−0.10 to 0.10) | .53 | +0.01 (−0.06 to 0.08) | −0.02 (−0.13 to 0.09) | .56 |
| +Arachidonic acid | |||||||||
| Median at baseline | 0.21 (−0.38 to 0.80) | 0.58 (−0.31 to 1.47) | .32 | 0.26 −0.30 to 0.82) | 0.28 (−0.25 to 0.81) | .75 | 0.24 (−0.34 to 0.82) | 0.51 (−0.11 to 1.13) | .58 |
| Median change | −0.07 (−0.27 to 0.13) | −0.04 (−0.74 to 0.66) | .92 | +0.23 −0.60 to 1.06) | +0.02 (−0.21 to 0.25) | .53 | −0.05 (−0.44 to 0.34) | −0.01 (−0.54 to 0.52) | .80 |
|
6−keto−F1α,ng/mg of protein (IQR) |
|||||||||
| −Arachidonic acid | |||||||||
| Median at baseline | 0.14(0 to 0.28) | 0.19 (0.05 to 0.33) | 15 | 0.22 0.11 to 0.33) | 0.13 (0 to 0.26) | .07 | 0.17 (0.02 to 0.32) | 0.17 (−0.03 to 0.31) | .81 |
| Median change | −0.03 (−0.15 to 0.09) | −0.10 (−0.29 to 0.09) | .46 | +0.08 −0.19 to 0.35) | −0.01 (−0.19 to 0.17) | .46 | −0.02 (−0.1 6 to 0.12) | −0.05 (−0.25 to 0.1 5) | .40 |
| +Arachidonic acid | |||||||||
| Median at baseline | 0.30 (−0.07 to 0.67) | 0.37 (−0.31 to 1.05) | .52 | 0.53 0.30 to 0.76) | 0.36 (−0.10 to 0.82) | .34 | 0.36 (−0.05 to 0.77) | 0.37 (−0.18 to 0.92) | .94 |
| Median change | −0.05 (−0.31 to 0.21) | −0.01 (−0.54 to 0.52) | .73 | +0.26 −1.23 to 1.75) | +0.02 (−1.00 to 1.04) | .34 | −0.01 (−0.35 to 0.33) | +0.02 (−0.78 to 0.82) | .87 |
| COX−1 mRNA,fg/µg*(IQR) | |||||||||
| Median at baseline | 14 (−3 to 31) | 20 (−1 to 41) | .56 | 10 −5 to 25) | 13 (3 to 23) | .80 | 10 (−7 to 27) | 16 (6 to 26) | .48 |
| Median change | 2 (−43 to 47) | 10 (−19 to 39) | 1.00 | 11 −1 to 23) | 2 (−8 to 12) | .33 | 11 (−22 to 44) | 4 (−13 to 21) | .41 |
| No. | 2 | 3 | 5 | 4 | 7 | 7 | |||
| COX-2 mRNA,fg/µg†(IQR) | |||||||||
| Median at baseline | 10 (3 to 17) | 47 (17 to 77) | .08 | 15 1 to 29) | 5 (1 to 9) | .34 | 13 (−1 to 27) | 12 (−17 to 41) | .64 |
| Median change | 5(−1 to 11) | −10 (−24 to 4) | .08 | 14 −13 to 41) | 10 (2 to 18) | .75 | 8 (−19 to 35) | 0 (−24 to 24) | .27 |
| No. | 2 | 3 | 5 | 5 | 7 | 8 | |||
*
Changes were calculated by subtracting the baseline value from the value at 24 weeks. Arachidonic acid was included in the prostaglandin assays to enhance the sensitivity of detection (23; see “Patients and Methods”). COX = cyclooxygenase; PG = prostaglandin; IQR = interquartile range.
†
Derived from two-sided Wilcoxon rank sum test.
‡
Changes were calculated by subtracting the baseline value from the value at 24 weeks for 15 pairs in which the tissue biopsy sample that was used for COX expression analysis was from the area adjacent to the highest grade of dysplasia at both baseline and 24-week biopsy examinations.