TY - JOUR
T1 - P27 Kip1 in stage III colon cancer
T2 - Implications for outcome following adjuvant chemotherapy in cancer and leukemia group B protocol 89803
AU - Bertagnolli, Monica M.
AU - S.Warren, Robert
AU - Niedzwiecki, Donna
AU - Mueller, Elke
AU - Compton, Carolyn C.
AU - Redston, Mark
AU - Hall, Margaret
AU - Hahn, Hejin P.
AU - Jewell, Scott D.
AU - Mayer, Robert J.
AU - Goldberg, Richard M.
AU - Saltz, Leonard B.
AU - Loda, Massimo
PY - 2009/3/15
Y1 - 2009/3/15
N2 - Background: In retrospective studies, loss of p27 Kip1 (p27), a cyclin-dependent kinase inhibitor, has been associated with poor prognosis following colorectal cancer treatment. In a prospective study, we validated this relationship in patients enrolled on a trial of adjuvant chemotherapy for stage III colon cancer. Methods: Cancer and Leukemia Group B protocol 89803 randomized 1,264 stage III colon cancer patients to receive weekly bolus 5-fluorouracil/leucovorin or weekly bolus irinotecan, 5-fluo-rouracil, and leucovorin (lFL). The primary end point was overall survival (OS); disease-free survival was a secondary endpoint. Expression of p27 and DNA mismatch repair proteins were determined by immunohistochemistry in primary tumor and normal tissue from paraffin blocks. Data were analyzed using log-rank test. Results: Of 601 tumors analyzed, 207 (34.4%) showed p27 loss, 377 (62.8%) retained p27, and 17 (2.8%) were indeterminate. Patients with p27-negative tumors showed reduced OS [5-year OS 66%: 95% confidence interval (95% CI), 0.59-0.72 versus 75%: 95% CI, 0.70-0.79; log-rank P = 0.021]. This relationship was not influenced by treatment arm. Combination of p27 status with mismatch repair status, however, identified a small subset of patients that may benefit from lFL (n = 36; 5-year disease-free survival 81%: 95% CI, 0.64-0.98 versus 47%: 95% CI, 0.21-0.72; log-rank P = 0.042; 5-year OS 81%: 95% CI, 0.64-0.98 versus 60%: 95% CI, 0.35-0.85; log-rank P = 0.128). Conclusions: Loss of p27 is associated with reduced survival in stage III colon cancer but by itself does not indicate a significant difference in outcome between patients treated lFL or 5-fluorouracil/leucovorin.
AB - Background: In retrospective studies, loss of p27 Kip1 (p27), a cyclin-dependent kinase inhibitor, has been associated with poor prognosis following colorectal cancer treatment. In a prospective study, we validated this relationship in patients enrolled on a trial of adjuvant chemotherapy for stage III colon cancer. Methods: Cancer and Leukemia Group B protocol 89803 randomized 1,264 stage III colon cancer patients to receive weekly bolus 5-fluorouracil/leucovorin or weekly bolus irinotecan, 5-fluo-rouracil, and leucovorin (lFL). The primary end point was overall survival (OS); disease-free survival was a secondary endpoint. Expression of p27 and DNA mismatch repair proteins were determined by immunohistochemistry in primary tumor and normal tissue from paraffin blocks. Data were analyzed using log-rank test. Results: Of 601 tumors analyzed, 207 (34.4%) showed p27 loss, 377 (62.8%) retained p27, and 17 (2.8%) were indeterminate. Patients with p27-negative tumors showed reduced OS [5-year OS 66%: 95% confidence interval (95% CI), 0.59-0.72 versus 75%: 95% CI, 0.70-0.79; log-rank P = 0.021]. This relationship was not influenced by treatment arm. Combination of p27 status with mismatch repair status, however, identified a small subset of patients that may benefit from lFL (n = 36; 5-year disease-free survival 81%: 95% CI, 0.64-0.98 versus 47%: 95% CI, 0.21-0.72; log-rank P = 0.042; 5-year OS 81%: 95% CI, 0.64-0.98 versus 60%: 95% CI, 0.35-0.85; log-rank P = 0.128). Conclusions: Loss of p27 is associated with reduced survival in stage III colon cancer but by itself does not indicate a significant difference in outcome between patients treated lFL or 5-fluorouracil/leucovorin.
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U2 - 10.1158/1078-0432.CCR-08-2674
DO - 10.1158/1078-0432.CCR-08-2674
M3 - Article
C2 - 19276255
AN - SCOPUS:63449140852
SN - 1078-0432
VL - 15
SP - 2116
EP - 2122
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 6
ER -