Hide Sidebar

Effect of Age on Survival Benefit of Adjuvant Chemotherapy in Elderly Patients with Stage III Colon Cancer

Effect of Age on Survival Benefit of Adjuvant Chemotherapy in Elderly Patients with Stage III Colon Cancer

Critique date: Wed, 01/27/2010 - 3:17pm
Institution: 
Mount Sinai School of Medicine
   
Article Citation
Citation: 
Zuckerman, Ilene H et al “Effect of Age on Survival Benefit of Adjuvant Chemotherapy in Elderly Patients with Stage III Colon Caner” JAG 200957:1403-1410
   
Clinical Bottom Lines

 

Elderly patients > 65 who receive adjuvant chemotherapy for stage III colon cancer have a higher probability of survival than those who do not receive standard adjuvant chemotherapy.

1.Survival benefit associated with treatment was not identical across all age catergories.

2.Treatment associated survival benefit declines with age.

   
Methods
Study Design: 
Cohort study
Follow-up Period: 
The average follow up time was 28 months ( range 1-84 months) Exact date of death was not available form the SEER data (only months and year are reported).
Patient Population: 

Population: Selected patients age 66 and older with stage 3 colon cancer

Control: Patients with colon cancer who did not receive standard adjuvant chemotherapy with 5-FU or leucovorin

Patients were aged 66 and older and had a diagnosis of Stage III colon cancer between 1997-2002. Patients were followed from surgery to time of death or censorship. Data was obtained from the National Cancer Institutes Surveillance, Epidemiology, and End Results (SEER) database and linked Medicare enrollment and claims database were used.

Selected patients had a diagnosis of stage III colon cancer between 1997-2002 and treated with 5-fluorouracil or leucovorin within six months of surgery. Patients had continuous Medicare Part A and B enrollment without HMO enrollment. Data obtained within 16 SEER cancer registries.

Significant Exclusions: 

Patient’s with claims for other cancer diagnosis, HIV, AIDS, or organ transplant during the five years before the colon cancer diagnosis. Patients were further excluded if missing, incomplete, inconsistent information, those with neo-adjuvant chemotherapy, and those treated with non-standard adjuvant regimens (capecitabine or irinotecan).

Intervention/Exposure: 

Intervention: Treatment with 5-Fluorouracil or leucovorin within 6 month of surgery

The purpose of the study was to look at how age could effect survival benefit associated with adjuvant chemotherapy in elderly patients.

To account for the potential selection bias, patients who met inclusion criteria were analyzed in one of two samples.

- Overall Sample: (Externally Valid Analysis)

- Propensity Score Matched Sample: (Internally Valid analysis)

The PSM sample was used to eliminate selection bias due to treatment selection in a survival model.

 

The overall sample and PSM sample were then adjusted for multiple clinical variables:

Variables:

  • Sociodemographic variables : (sex, age, race, marital status,etc)
  • Clinical Variables : (hematologist, oncologist follow up)
  • Dichotomous variable : (tumor stage, T3/T4 vs T1/T2)
  • Catergorical Variables (# of positive LN)
  • Charlson comorbidity index- (used to predict 1 year mortality in patients with a rang of co-morbid conditions)
Outcome Measures: 

Primary Outcome: Colon cancer-specific death during the follow-up period.

Secondary Outcomes: none

   
Conclusion
Results: 

A maximum likelihood method using a binary regression model was used. Four separate regression models were created to analyze the effect of age on the survival benefit of adjuvant chemotherapy. The overall sample was reflected in Model 1 and Model 2, while the PSM sample was reflected in Model 3 and Model 4. Each sample had a model that reflected multivariable analysis that adjusted for confounding variables and one that did not. Hazard ratios and 95% confidence intervals were obtained for all regressions to help measure survival benefit. Hazard ratio and confidence intervals were then plotted against five age categories for the sample adjusted models in the overall and PSM samples.

- Elderly patients > 65 who receive adjuvant chemotherapy have a higher probability of survival that those who do not receive standard adjuvant chemotherapy.

- Survival benefit associated with treatment was not identical across all age catergories.

- Treatment associated survival benefit declines with age.

 

HR for unadjusted and Multivariable adjusted Survival models

Age

Model 1-Overall Sample Unadjusted

Model 2 – Overall Sample Adjusted

Model 3-PSM Sample Unadjusted

Model 4- PSM Sample Adjusted

66-69

0.45

0.47

0.62

0.54

70-74

0.31

0.32

0.38

0.36

75-79

0.40

0.41

0.40

0.36

80-84

0.57

0.59

0.65

0.65

>85

0.56

0.54

0.55

0.51
Concerns Regarding Methodology, Applicability to Older Adults, etc.: 
  1. This was not a well generalized study. While the focus of the study were older adults from over 65 to over 85, the patient population reflected only male patients, and had a poor demographic breakdown in terms of ethnic diversity.
  2. The primary outcome was colon cancer specific related death. The study does not give any details as to how long patients were treated with adjuvant therapy before time of death.
  3. A comparison of the outcomes from the untreated cohort could add strength to the study design.
  4. In any study using propensity score matching, while this may help reduce large biases, significant biases may remain.
Funding Source and Role: 
Sanofi-Aventis, Pfizer: The sponsor provided financial support for the study.
Created By: 
Martine Sanon MD, Geriatric Fellow Brookdale Department of Geriatrics, Mount Sinai School of Medicine
This is a review of the validity of a single study; the ‘bottom lines’ do not reflect comparison with the rest of the literature on this subject.