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Adjuvant chemotherapy for stage III colon cancer: relative dose intensity and survival among veterans.

Aspinall SL, Good CB, Zhao X, Cunningham FE, Heron BB, Geraci M, Passero V, Stone RA, Smith KJ, Rogers R, Shields J, Sartore M, Boyle DP, Giberti S, Szymanski J, Smith D, Ha A, Sessions J, Depcinski S, Fishco S, Molina I, Lepir T, Jean C, Cruz-Diaz L, Motta J, Calderon-Vargas R, Maland J, Keefe S, Tague M, Leone A, Glovack B, Kaplan B, Cosgriff S, Kaster L, Tonnu-Mihara I, Nguyen K, Carmichael J, Clifford L, Lu K, Chatta G - BMC Cancer (2015)

Bottom Line: Receipt of >70% RDI was associated with better 5-year OS (p < 0.001) and 3-year DFS (P = 0.009) than was receipt of ≤70% RDI, with 5-year OS rates of 66.3% and 50.5%, respectively and 3-year DFS rates of 66.1% and 52.7%, respectively.In the multivariable analysis of 5-year OS, oxaliplatin + 5-FU/LV (versus 5-FU/LV) (HR = 0.55; 95% CI = 0.34-0.91), >70% RDI at the first year (HR = 0.58; 95% CI = 0.37-0.89) and married status (HR = 0.66; 95% CI = 0.45-0.97) were associated with significantly decreased risk of death, while age ≥75 (versus 55-64) (HR = 2.06; 95% CI = 1.25-3.40), Charlson Comorbidity Index (HR = 1.17; 95% CI = 1.06-1.30), T4 tumor status (versus T1/T2) (HR = 5.88; 95% CI = 2.69-12.9), N2 node status (HR = 1.68; 95% CI = 1.12-2.50) and bowel obstruction (HR = 2.32, 95% CI = 1.36-3.95) were associated with significantly increased risk.Similar associations were observed for DFS.

View Article: PubMed Central - PubMed

Affiliation: VA Pharmacy Benefits Management Services, Hines, IL, USA. sherrie.aspinall@va.gov.

ABSTRACT

Background: Given the paucity of information on dose intensity, the objective of this study is to describe the use of adjuvant chemotherapy for stage III colon cancer, focusing on relative dose intensity (RDI), overall survival (OS) and disease-free survival (DFS).

Methods: Retrospective cohort of 367 patients diagnosed with stage III colon cancer in 2003-2008 and treated at 19 VA medical centers. Kaplan-Meier curves summarize 5-year OS and 3-year DFS by chemotherapy regimen and RDI, and multivariable Cox proportional hazards regression was used to model these associations.

Results: 5-fluorouracil/leucovorin (FU/LV) was the most commonly initiated regimen in 2003 (94.4%) and 2004 (62.7%); in 2005-2008, a majority of patients (60%-74%) was started on an oxaliplatin-based regimen. Median RDI was 82.3%. Receipt of >70% RDI was associated with better 5-year OS (p < 0.001) and 3-year DFS (P = 0.009) than was receipt of ≤70% RDI, with 5-year OS rates of 66.3% and 50.5%, respectively and 3-year DFS rates of 66.1% and 52.7%, respectively. In the multivariable analysis of 5-year OS, oxaliplatin + 5-FU/LV (versus 5-FU/LV) (HR = 0.55; 95% CI = 0.34-0.91), >70% RDI at the first year (HR = 0.58; 95% CI = 0.37-0.89) and married status (HR = 0.66; 95% CI = 0.45-0.97) were associated with significantly decreased risk of death, while age ≥75 (versus 55-64) (HR = 2.06; 95% CI = 1.25-3.40), Charlson Comorbidity Index (HR = 1.17; 95% CI = 1.06-1.30), T4 tumor status (versus T1/T2) (HR = 5.88; 95% CI = 2.69-12.9), N2 node status (HR = 1.68; 95% CI = 1.12-2.50) and bowel obstruction (HR = 2.32, 95% CI = 1.36-3.95) were associated with significantly increased risk. Similar associations were observed for DFS.

Conclusion: Patients with stage III colon cancer who received >70% RDI had improved 5-year OS. The association between RDI and survival needs to be examined in studies of adjuvant chemotherapy for colon cancer outside of the VA.

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Kaplan-Meier estimates of survival by chemotherapy regimen received. A. Kaplan-Meier estimates of overall survival by chemotherapy regimen received. B. Kaplan-Meier estimates of disease-free survival by chemotherapy regimen received.
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Fig2: Kaplan-Meier estimates of survival by chemotherapy regimen received. A. Kaplan-Meier estimates of overall survival by chemotherapy regimen received. B. Kaplan-Meier estimates of disease-free survival by chemotherapy regimen received.

Mentions: Of the 367 patients who received adjuvant chemotherapy in the VA during the study period, 132 (36.0%) died by year 5, and 146 (39.8%) died or had a recurrence of their colon cancer by year 3. Oxaliplatin plus 5-FU/LV was associated with better OS than was 5-FU/LV (p = 0.04); the 5-year OS rates were 69.5% and 54.0%, respectively (Figure 2A). Similar estimates were obtained for 3-year DFS (69.6% and 56.6%, respectively), and between-regimen differences in DFS were of borderline statistical significance (P = 0.06, Figure 2B). Receipt of >70% RDI was associated with better 5-year OS (p < 0.001) and 3-year DFS (P = 0.009) than was receipt of ≤70% RDI, with 5-year OS of 66.3% and 50.5%, respectively and 3-year DFS rates of 66.1% and 52.7%, respectively (Figures 3A and B). The Kaplan-Meier plot of OS also indicates some attenuation over time in the apparently protective effect of >70% RDI.Figure 2


Adjuvant chemotherapy for stage III colon cancer: relative dose intensity and survival among veterans.

Aspinall SL, Good CB, Zhao X, Cunningham FE, Heron BB, Geraci M, Passero V, Stone RA, Smith KJ, Rogers R, Shields J, Sartore M, Boyle DP, Giberti S, Szymanski J, Smith D, Ha A, Sessions J, Depcinski S, Fishco S, Molina I, Lepir T, Jean C, Cruz-Diaz L, Motta J, Calderon-Vargas R, Maland J, Keefe S, Tague M, Leone A, Glovack B, Kaplan B, Cosgriff S, Kaster L, Tonnu-Mihara I, Nguyen K, Carmichael J, Clifford L, Lu K, Chatta G - BMC Cancer (2015)

Kaplan-Meier estimates of survival by chemotherapy regimen received. A. Kaplan-Meier estimates of overall survival by chemotherapy regimen received. B. Kaplan-Meier estimates of disease-free survival by chemotherapy regimen received.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4352567&req=5

Fig2: Kaplan-Meier estimates of survival by chemotherapy regimen received. A. Kaplan-Meier estimates of overall survival by chemotherapy regimen received. B. Kaplan-Meier estimates of disease-free survival by chemotherapy regimen received.
Mentions: Of the 367 patients who received adjuvant chemotherapy in the VA during the study period, 132 (36.0%) died by year 5, and 146 (39.8%) died or had a recurrence of their colon cancer by year 3. Oxaliplatin plus 5-FU/LV was associated with better OS than was 5-FU/LV (p = 0.04); the 5-year OS rates were 69.5% and 54.0%, respectively (Figure 2A). Similar estimates were obtained for 3-year DFS (69.6% and 56.6%, respectively), and between-regimen differences in DFS were of borderline statistical significance (P = 0.06, Figure 2B). Receipt of >70% RDI was associated with better 5-year OS (p < 0.001) and 3-year DFS (P = 0.009) than was receipt of ≤70% RDI, with 5-year OS of 66.3% and 50.5%, respectively and 3-year DFS rates of 66.1% and 52.7%, respectively (Figures 3A and B). The Kaplan-Meier plot of OS also indicates some attenuation over time in the apparently protective effect of >70% RDI.Figure 2

Bottom Line: Receipt of >70% RDI was associated with better 5-year OS (p < 0.001) and 3-year DFS (P = 0.009) than was receipt of ≤70% RDI, with 5-year OS rates of 66.3% and 50.5%, respectively and 3-year DFS rates of 66.1% and 52.7%, respectively.In the multivariable analysis of 5-year OS, oxaliplatin + 5-FU/LV (versus 5-FU/LV) (HR = 0.55; 95% CI = 0.34-0.91), >70% RDI at the first year (HR = 0.58; 95% CI = 0.37-0.89) and married status (HR = 0.66; 95% CI = 0.45-0.97) were associated with significantly decreased risk of death, while age ≥75 (versus 55-64) (HR = 2.06; 95% CI = 1.25-3.40), Charlson Comorbidity Index (HR = 1.17; 95% CI = 1.06-1.30), T4 tumor status (versus T1/T2) (HR = 5.88; 95% CI = 2.69-12.9), N2 node status (HR = 1.68; 95% CI = 1.12-2.50) and bowel obstruction (HR = 2.32, 95% CI = 1.36-3.95) were associated with significantly increased risk.Similar associations were observed for DFS.

View Article: PubMed Central - PubMed

Affiliation: VA Pharmacy Benefits Management Services, Hines, IL, USA. sherrie.aspinall@va.gov.

ABSTRACT

Background: Given the paucity of information on dose intensity, the objective of this study is to describe the use of adjuvant chemotherapy for stage III colon cancer, focusing on relative dose intensity (RDI), overall survival (OS) and disease-free survival (DFS).

Methods: Retrospective cohort of 367 patients diagnosed with stage III colon cancer in 2003-2008 and treated at 19 VA medical centers. Kaplan-Meier curves summarize 5-year OS and 3-year DFS by chemotherapy regimen and RDI, and multivariable Cox proportional hazards regression was used to model these associations.

Results: 5-fluorouracil/leucovorin (FU/LV) was the most commonly initiated regimen in 2003 (94.4%) and 2004 (62.7%); in 2005-2008, a majority of patients (60%-74%) was started on an oxaliplatin-based regimen. Median RDI was 82.3%. Receipt of >70% RDI was associated with better 5-year OS (p < 0.001) and 3-year DFS (P = 0.009) than was receipt of ≤70% RDI, with 5-year OS rates of 66.3% and 50.5%, respectively and 3-year DFS rates of 66.1% and 52.7%, respectively. In the multivariable analysis of 5-year OS, oxaliplatin + 5-FU/LV (versus 5-FU/LV) (HR = 0.55; 95% CI = 0.34-0.91), >70% RDI at the first year (HR = 0.58; 95% CI = 0.37-0.89) and married status (HR = 0.66; 95% CI = 0.45-0.97) were associated with significantly decreased risk of death, while age ≥75 (versus 55-64) (HR = 2.06; 95% CI = 1.25-3.40), Charlson Comorbidity Index (HR = 1.17; 95% CI = 1.06-1.30), T4 tumor status (versus T1/T2) (HR = 5.88; 95% CI = 2.69-12.9), N2 node status (HR = 1.68; 95% CI = 1.12-2.50) and bowel obstruction (HR = 2.32, 95% CI = 1.36-3.95) were associated with significantly increased risk. Similar associations were observed for DFS.

Conclusion: Patients with stage III colon cancer who received >70% RDI had improved 5-year OS. The association between RDI and survival needs to be examined in studies of adjuvant chemotherapy for colon cancer outside of the VA.

Show MeSH
Related in: MedlinePlus