“Real world” effectiveness of different postoperative adjuvant chemotherapy regimens in stage III colon cancer patients.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 754-754
Author(s):  
Jy Ming Chiang ◽  
Hsin Yuan Hung

754 Background: In clinical practice, choosing oral chemotherapy or FOLFOX may depend to drug toxicity and patients’ age and comorbidities, in addition to heterogeneous stage III colon cancer. The benefit of oxaliplatin in the real world practice remained further clarified. Methods: 688 stage III colon cancer patients were collected. Treatment outcomes were retrospectively compared based on the type of chemotherapy in terms of OS and DFS. Multivariate Cox-regression modeling was used to adjust for the potential confounders. Results: This study included capecitabine (259 patients), fluorouracil-leucovorin plus oxaliplatin (FOLFOX) (283 patients) and Tegafur-uracil(146 patients). Comparing patients with capecitabine and tegafur regimens, patients receiving FOLFOX were significantly younger (mean age 56.5 yrs v.s. 65,1 yrs and 66,9 yrs ), more poor differentiation (15.9% v.s. 8.1% and 8.2%), deeper tumor invasion (T4 lesion 25.1% v.s. 15.8% and 17.1%), more advanced nodal involvement (N2/3 51.9% v.s. 18.1% and 20.5%) and had less comorbidity (50.2% v.s. 61.4% and 65.1%). Rate of completeness of chemotherapies (88.0% v.s. 87.6% and 81.5%) was no significant difference. Comparing treatment outcome, by univariate analysis, demonstrated significant (p = 0.0258) difference in OS for N2/3 patients but no difference in N1 patiens. However, by balancing confounding factors including co-morbidities, multivariate analysis showed that impact on overall survival in patients receiving capecitabine was statistically significant better than Tegafur (HR = 0.59, p = 0. 03) while no difference comparing with FOLFOX regimen (HR = 0.76, p = 0.3219). However, disease free survival (DFS) was no significantly different for FOLFOX comparing with capecitabine HR 0.97 and Tegafur HR 0.89 by multivariate Cox regression analyses. Conclusions: As post-operative adjuvant setting, oral chemotherapy either Capecitabine or Tegafur-uracil showed similar effectiveness as folfox in terms of DFS while in terms of OS, Capecitabine demonstrated similar effectiveness to folfox but better than Tegafur-urecil.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11594-11594
Author(s):  
Nils Brunner ◽  
Jan Stenvang ◽  
Eva Budinska ◽  
Sune Boris Nygaard

11594 Background: FOLFIRI as adjuvant treatment in primary colon cancer was previously tested in two pivotal prospective randomized clinical trials (PETACC-3 and CALGB 89803), both of which failed to demonstrate significant beneficial effects when adding irinotecan to 5FU. As a consequence, FOLFIRI is presently not used as adjuvant treatment for colon cancer. Methods: The study included 580 patients with mRNA expression data performed on tumor samples (FFPE) from stage III colon cancer patients enrolled in the PETACC-3 study, which randomized the patients to 5FU plus Leucovorin +/- irinotecan. Primary end-points were recurrence-free survival (RFS) and overall survival (OS). Median ABCG2 and the 75 percentile TOP-1 mRNA expression data were used to allocate the patients into one of two groups: One with high ABCG2 expression (above median) and low TOP-1 expression (below 75 percentile) (n = 167) and another group including all other combinations of these two genes. Kaplan Meier curves and Cox proportional hazards model were used to visualize differences between groups and calculate p-values (log-rank test). Results: The survival statistics showed a significant difference for both RFS (HR: 0.63 (0.44-0.92); p = 0.017) and OS (HR: 0.6 (0.39-0.93); p = 0.021) between the two groups when the patients received FOLFIRI. In contrast, no significant differences were observed between the groups when patients received 5FU and Leucovorin alone (p-values: RFS: 0.58; OS: 0.75). Conclusions: We here show that the combination of two independent gene expression abundance with a strong association to irinotecan treatment (high ABCG2 drug efflux pump and low TOP-1, the latter being the target for irinotecan) identified a group of stage III colon cancer patients who will not benefit from FOLFIRI adjuvant treatment while patients with other combinations of expression of these two genes appear to significantly benefit from adjuvant FOLFIRI treatment. The lack of a similar effect in patients receiving treatment with 5FU and Leucovorin only, points to a predictive value of ABCG2 and TOP-1 measurements.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 591-591 ◽  
Author(s):  
Nils Brunner ◽  
Sune Boris Nygaard ◽  
Eva Budinska ◽  
Jan Stenvang

591 Background: FOLFIRI as adjuvant treatment in primary colon cancer was previously tested in two pivotal prospective randomized clinical trials (PETACC-3 and CALGB 89803), both of which failed to demonstrate significant beneficial effects when adding irinotecan to 5FU. As a consequence, FOLFIRI is presently not used as adjuvant treatment for colon cancer. Methods: The study included 580 patients with mRNA expression data performed on tumor samples (FFPE) from stage III colon cancer patients enrolled in the PETACC-3 study, which randomized the patients to 5FU plus Leucovorin +/- irinotecan. Primary end-points were disease free survival (DFS) and overall survival (OS). Median ABCG2 and the 75 percentile TOP-1 mRNA expression data were used to allocate the patients into one of two groups: One with high ABCG2 expression (above median) and low TOP-1 expression (below 75 percentile) (n = 167) and another group including all other combinations of these two genes. Kaplan Meier curves and Cox proportional hazards model were used to visualize differences between groups and calculate p-values (log-rank test). Results: The survival statistics showed a significant difference for both RFS (HR: 0.63 (0.44-0.92); p = 0.017) and OS (HR: 0.6 (0.39-0.93); p = 0.021) between the two groups when the patients received FOLFIRI. In contrast, no significant differences were observed between the groups when patients received 5FU and Leucovorin alone (RFS: 0.58; OS: 0.75). Conclusions: We here show that the combination of two independent gene expression abundance with a strong association to irinotecan treatment (high ABCG2 drug efflux pump and low TOP-1, which is the target for irinotecan) identified a group of stage III colon cancer patients who will not benefit from FOLFIRI adjuvant treatment while patients with other combinations of expression of these two genes appear to significantly benefit from adjuvant FOLFIRI treatment. The lack of a similar effect in patients receiving treatment with 5FU and Leucovorin only, points to a predictive value of ABCG2 and TOP-1 measurements.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 555-555 ◽  
Author(s):  
Sang-Hee Cho ◽  
Jun Eul Hwang ◽  
Woo Kyun Bae ◽  
Ik-Joo Chung

555 Background: Tumors expressing PD-L1 can render immune inactivated via triggering of PD-1 receptor on T cells with various pathways. Based on these mechanism, the blockade PD-1/PD-L1 pathway based been used as a therapeutic target for metastatic CRC. In the present study, we evaluated the prognostic role of PD-L1 expression associated with microsatellite status in surgically resected stage III colon cancer patients. Methods: PD-L1 expression was performed by immunohistochemistry from 182 stage III colon cancer patients after curative resection. Using the immunohistochemical stain, percentages of PD-L1 positive tumor cells and staining intensity were evaluated and categorized as ‘strong’ and ‘weak’ positive group. Clinical and histopathologic parameters including of MSI status and survival outcomes were analyzed with IDO expression which stands for the suppressive immune environment. Results: Strong PD-L1 expression was observed in 29% of all patients. PNI and lymphocyte response response were more frequently shown in strong PD-L1 patients. Among these patients, MSI was shown in 23 patients (12%). Although there was no significant difference between MSI and PD-L1 status, strong PD-L1 tended to better OS in MSS colon cancer (P = 0.056). In contrast, strong PD-L1 expression significantly correlated with significantly worse prognosis in disease free survival (P = 0.001) and overall survival (P < 0.001) than weak PD-L1 expression inMSI patients regardless of adjuvant chemotherapy. In MSI patients, the strong IDO expression was tended to be more frequently shown in strong PD-L1 expression patients (36.4%) than weak PD-L1 expression patients (14.3%). Conclusions: The expression of PD-L1 is differently affected on the survival according to the status of microsatellite. There is no significant relationship between the expression of PD-L1 and prognosis in MSS stage III colon cancer patients. However, in MSI colon cancer which has been well known as a highly immunogenic property, strong PD-L1 expression is significantly associated with poor prognosis on survival outcomes reflecting of immunosuppressive microenvironment in curative resected stage III colon cancer patient.


2016 ◽  
Vol 61 ◽  
pp. 1-10 ◽  
Author(s):  
F.N. van Erning ◽  
L.G.E.M. Razenberg ◽  
V.E.P.P. Lemmens ◽  
G.J. Creemers ◽  
J.F.M. Pruijt ◽  
...  

Medical Care ◽  
2009 ◽  
Vol 47 (12) ◽  
pp. 1229-1236 ◽  
Author(s):  
Amy J. Davidoff ◽  
Thomas Rapp ◽  
Ebere Onukwugha ◽  
Ilene H. Zuckerman ◽  
Nader Hanna ◽  
...  

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3596-3596
Author(s):  
Jemma Megan Boyle ◽  
Angela Kuryba ◽  
Thomas E Cowling ◽  
Jan van der Meulen ◽  
Nicola S Fearnhead ◽  
...  

3596 Background: The optimal duration of adjuvant combination chemotherapy administered to patients with stage III colon cancer is debated. Our study assessed the effect of completed chemotherapy cycles on 3-year colon cancer-specific mortality, as well as the effect of dose reduction and early discontinuation of oxaliplatin in patients with 100% completion, within a real-world population. Methods: 4,147 patients undergoing major resection between 01 June 2014 and 30 April 2017 with pathological stage III colon cancer in the English National Health Service were identified. Chemotherapy data were obtained from linked administrative hospital records and a national chemotherapy dataset. Patients were stratified according to completion of < 50% ( < 6 FOLFOX cycles or < 4 CAPOX cycles), 50-92% (6-11 FOLFOX cycles or 4-7 CAPOX cycles) or 100% of cycles (12 FOLFOX cycles or 8 CAPOX cycles). Competing-risk regression analysis for 3-year colon cancer-specific death was performed with adjustment for patient, tumour and hospital-level characteristics to estimate subdistribution hazard ratios (sHR) as a measure of relative risk. Results: Patients included within our study were less fit and had increased rates of high-risk disease (T4 and/or N2 pathological staging) compared to the IDEA study. For FOLFOX, the 3-year cumulative incidence of colon cancer-specific death in patients completing 100% of cycles was 15.1% (95% CI, 12.8% to 17.6%), 18.2% (95% CI, 15.3% to 21.3%) for 50-92% of cycles and 26.4% (95% CI, 20.6% to 32.5%) for < 50% of cycles. For CAPOX, this was 12.0% (95% CI, 10.2% to 14.0%) for 100% completion of cycles, 18.2% (95% CI, 15.6% to 21.0%) for 50-92% of cycles, and 19.8% (95% CI, 15.8% to 24.1%) for < 50% cycles. Compared to 100% completion of FOLFOX cycles, colon cancer-specific death was higher in patients recorded as completing < 50% (sHR 2.17; 95% CI, 1.56 to 3.03; P = < 0.001) and 50-92% of FOLFOX cycles (sHR 1.40; 95% CI, 1.09 to 1.78; P = 0.007). Compared to 100% completion of CAPOX cycles, colon cancer-specific death was higher in patients recorded as completing < 50% (sHR 2.02; 95% CI 1.53 to 2.67; P< 0.001) and 50-92% of CAPOX cycles (sHR 1.63; 95% CI 1.27 to 2.10; P< 0.001). Dose reduction and early discontinuation of oxaliplatin did not have a statistically significant effect on mortality. Conclusions: Patients within the real world setting were more likely to have poor prognostic factors. Those who completed adjuvant chemotherapy for stage III colon cancer had improved survival rates regardless of dose reduction or early discontinuation of oxaliplatin.


Sign in / Sign up

Export Citation Format

Share Document