Limits...
Carbonic anhydrase 9 is a predictive marker of survival benefit from lower dose of bevacizumab in patients with previously treated metastatic colorectal cancer.

Hong YS, Cho HJ, Kim SY, Jung KH, Park JW, Choi HS, Oh JH, Kim BC, Sohn DK, Kim DY, Chang HJ - BMC Cancer (2009)

Bottom Line: The DCR was significantly higher in patients with a lower CA9 expression score compared to those with a higher score (80.0% vs. 27.3%, respectively, P = 0.004).However, VEGF expression was not associated with the DCR and survival.Lower degree of CA9 expression was associated with better clinical outcomes in patients with mCRC treated with lower dose bevacizumab-based chemotherapy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea. fahr27@gmail.com

ABSTRACT

Background: Carbonic anhydrase 9 (CA9) is a marker for hypoxia and acidosis, which is linked to a poor prognosis in human tumors. The purpose of this comparative analysis was to evaluate whether CA9 and VEGF expression are associated with survival outcomes in patients with metastatic colorectal cancer (mCRC) after treatment with bevacizumab as second or later line treatment.

Methods: Thirty-one mCRC patients who were treated with bevacizumab-containing chemotherapy as second or later line treatment and who had analyzable tumor paraffin blocks were selected for this study. The planned dose of bevacizumab was 5 mg/kg/2-week. Immunohistochemical (IHC) staining of CA9 and VEGF was performed and their expression was scored by the intensity multiplied by percentage of stained area.

Results: The overall response rate was 19.4% and the disease control rate (DCR) was 61.3% with 6 partial responses and 13 cases of stable disease. The DCR was significantly higher in patients with a lower CA9 expression score compared to those with a higher score (80.0% vs. 27.3%, respectively, P = 0.004). The patients with a low CA9 expression score also showed better outcomes with regard to the median progression-free survival (P = 0.028) and overall survival (P = 0.026). However, VEGF expression was not associated with the DCR and survival.

Conclusion: Lower degree of CA9 expression was associated with better clinical outcomes in patients with mCRC treated with lower dose bevacizumab-based chemotherapy. Prospective studies are now needed to determine the correlation between CA9 expression and clinical outcomes after bevacizumab treatment, at different doses and in varied settings.

Show MeSH

Related in: MedlinePlus

Survival outcomes according to the CA9 expression scores. The median PFS was 3.9 months and median OS with bevacizumab was 11.4 months; after the 17.6 months of median follow up of all 31 patients. There were statistically significant differences between the 2 groups according to the score in terms of median PFS (4.7 mo vs. 2.4 mo, p = 0.028) and median OS (24.1 mo vs. 10.2 mo, p = 0.026).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2719665&req=5

Figure 2: Survival outcomes according to the CA9 expression scores. The median PFS was 3.9 months and median OS with bevacizumab was 11.4 months; after the 17.6 months of median follow up of all 31 patients. There were statistically significant differences between the 2 groups according to the score in terms of median PFS (4.7 mo vs. 2.4 mo, p = 0.028) and median OS (24.1 mo vs. 10.2 mo, p = 0.026).

Mentions: The survival outcomes are shown in Figures 2 and 3. The median PFS was 3.9 months (95% CI, 1.7 – 6.1) and the median OS with bevacizumab was 11.4 months (95% CI, 9.5 – 13.4), after the median 17.6 months of follow up (range, 3.8 – 43.9). The median OS from initiation of first-line treatment was 32.4 months (95% CI, 25.7 – 39.1). The PFS was better, with borderline significance, in patients that received second line bevacizumab compared to those that received third or later line bevacizumab (5.0 vs. 2.4 months, hazard ratio (HR) 0.49 [95% CI, 0.23–1.05], P = 0.060); the OS was not statistically different according to the line of bevacizumab treatment (16.4 vs. 11.2 months, HR 0.67 [95% CI, 0.24–1.83], P = 0.426).


Carbonic anhydrase 9 is a predictive marker of survival benefit from lower dose of bevacizumab in patients with previously treated metastatic colorectal cancer.

Hong YS, Cho HJ, Kim SY, Jung KH, Park JW, Choi HS, Oh JH, Kim BC, Sohn DK, Kim DY, Chang HJ - BMC Cancer (2009)

Survival outcomes according to the CA9 expression scores. The median PFS was 3.9 months and median OS with bevacizumab was 11.4 months; after the 17.6 months of median follow up of all 31 patients. There were statistically significant differences between the 2 groups according to the score in terms of median PFS (4.7 mo vs. 2.4 mo, p = 0.028) and median OS (24.1 mo vs. 10.2 mo, p = 0.026).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2719665&req=5

Figure 2: Survival outcomes according to the CA9 expression scores. The median PFS was 3.9 months and median OS with bevacizumab was 11.4 months; after the 17.6 months of median follow up of all 31 patients. There were statistically significant differences between the 2 groups according to the score in terms of median PFS (4.7 mo vs. 2.4 mo, p = 0.028) and median OS (24.1 mo vs. 10.2 mo, p = 0.026).
Mentions: The survival outcomes are shown in Figures 2 and 3. The median PFS was 3.9 months (95% CI, 1.7 – 6.1) and the median OS with bevacizumab was 11.4 months (95% CI, 9.5 – 13.4), after the median 17.6 months of follow up (range, 3.8 – 43.9). The median OS from initiation of first-line treatment was 32.4 months (95% CI, 25.7 – 39.1). The PFS was better, with borderline significance, in patients that received second line bevacizumab compared to those that received third or later line bevacizumab (5.0 vs. 2.4 months, hazard ratio (HR) 0.49 [95% CI, 0.23–1.05], P = 0.060); the OS was not statistically different according to the line of bevacizumab treatment (16.4 vs. 11.2 months, HR 0.67 [95% CI, 0.24–1.83], P = 0.426).

Bottom Line: The DCR was significantly higher in patients with a lower CA9 expression score compared to those with a higher score (80.0% vs. 27.3%, respectively, P = 0.004).However, VEGF expression was not associated with the DCR and survival.Lower degree of CA9 expression was associated with better clinical outcomes in patients with mCRC treated with lower dose bevacizumab-based chemotherapy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea. fahr27@gmail.com

ABSTRACT

Background: Carbonic anhydrase 9 (CA9) is a marker for hypoxia and acidosis, which is linked to a poor prognosis in human tumors. The purpose of this comparative analysis was to evaluate whether CA9 and VEGF expression are associated with survival outcomes in patients with metastatic colorectal cancer (mCRC) after treatment with bevacizumab as second or later line treatment.

Methods: Thirty-one mCRC patients who were treated with bevacizumab-containing chemotherapy as second or later line treatment and who had analyzable tumor paraffin blocks were selected for this study. The planned dose of bevacizumab was 5 mg/kg/2-week. Immunohistochemical (IHC) staining of CA9 and VEGF was performed and their expression was scored by the intensity multiplied by percentage of stained area.

Results: The overall response rate was 19.4% and the disease control rate (DCR) was 61.3% with 6 partial responses and 13 cases of stable disease. The DCR was significantly higher in patients with a lower CA9 expression score compared to those with a higher score (80.0% vs. 27.3%, respectively, P = 0.004). The patients with a low CA9 expression score also showed better outcomes with regard to the median progression-free survival (P = 0.028) and overall survival (P = 0.026). However, VEGF expression was not associated with the DCR and survival.

Conclusion: Lower degree of CA9 expression was associated with better clinical outcomes in patients with mCRC treated with lower dose bevacizumab-based chemotherapy. Prospective studies are now needed to determine the correlation between CA9 expression and clinical outcomes after bevacizumab treatment, at different doses and in varied settings.

Show MeSH
Related in: MedlinePlus