p27Kip1 in Stage III Colon Cancer: Implications for Outcome following Adjuvant Chemotherapy in Cancer and Leukemia Group B Protocol 89803
| Autor: | Monica M. Bertagnolli, Robert J. Mayer, Richard M. Goldberg, Leonard B. Saltz, Massimo Loda, Mark Redston, Scott D. Jewell, Donna Niedzwiecki, Carolyn C. Compton, Robert S. Warren, Margaret Hall, Hejin P. Hahn, Elke Mueller |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Chemotherapy medicine.medical_specialty business.industry Colorectal cancer medicine.medical_treatment Cancer medicine.disease Gastroenterology Primary tumor Surgery Irinotecan Oncology Internal medicine medicine Clinical endpoint Bolus (digestion) Prospective cohort study business medicine.drug |
| Zdroj: | Clinical Cancer Research. 15:2116-2122 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-08-2674 |
| Popis: | Background: In retrospective studies, loss of p27Kip1 (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-fluorouracil, and leucovorin (IFL). The primary endpoint 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 IFL (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 IFL or 5-fluorouracil/leucovorin. |
| Databáze: | OpenAIRE |
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