Making the case for adjuvant chemotherapy for older patients with colon cancer

Hy Muss, MD, and Debra Bynum, MD, co-authored an editorial in the July 20, 2012 issue of the Journal of Clinical Oncology.

Dr. Muss is leader of the UNC Lineberger Geriatric Oncology Program. Dr. Bynum is the director of the UNC Geriatric Fellowship Program in the UNC Center for Aging and Health.

The editorial, titled “Adjuvant Chemotherapy in Older Patients with Stage III Colon Cancer: An Underused Lifesaving Treatment,“ accompanies an article titled “Effect of Adjuvant Chemotherapy on Survival of Patients with Stage III Colon Cancer Diagnosed after Age 75 Years.”  

Hanna Sanoff, MD, assistant professor of medicine at UNC and first author of the paper, says, “Our findings about the effectiveness of chemotherapy in older patients treated in usual care settings reinforce the notion that patients in their seventies and eighties, and perhaps some in their nineties, should be given the opportunity to discuss adjuvant chemotherapy with a medical oncologist.“

In their editorial, Drs. Muss and Bynum cite the “aging tsunami” that is upon is and the effect it will have on aging Americans with cancer. Right now, 55 percent of all new cancer diagnoses are in patients 65 years or older, and 37 percent are in patients 75 years or older.

In colon cancer, of the 130,000 estimated new patients with colon cancer in 2012, approximately 40 percent will be 75 years of age or older, and approximately 40 percent will present with a Stage III tumor.

They explain that Sanoff et al examined four data sets to get a better idea in the real-world setting of the potential benefits of adjuvant chemotherapy in patients age 75 years or older with Stage III colon cancer: Surveillance, Epidemiology, and End Results (SEER); Medicare and Medicaid programs; Cancer Care Outcomes Research and Surveillance (CanCORS); and the National Comprehensive Cancer Network (NCCN).  

The analysis confirms previous clinical trials data that show adjuvant chemotherapy saves lives in Stage III patients and indicates that the benefits of adjuvant treatment in older patients are similar in magnitude to those reported in clinical trials for benefit of chemotherapy versus none.  No relationship between age and chemotherapy toxicity was noted, including nausea and vomiting, stomatis (oral inflammation), and diarrhea; however leucopenia (low white blood cell count) was more common in older adults in two of the trials.

A key goal of the Sanoff et al analysis was to determine the value of oxaliplatin when added to fluoropyrimidine (fluorouracil [FU] or capecitabine) therapy, citing a trend among studies for improved survival with oxaliplatin. The study authors discuss three trials: the Multicenter International Study of Oxaliplatin/FU/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC), the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the Adjuvant Colon Cancer End Points Group (ACCENT).  While the MOSAIC and NSABP trials show survival trends similar to the meta-analysis in terms of improved survival with oxaliplatin, the ACCENT trial showed improved survival with oxaliplatin only in patients younger than age 65.

Drs. Muss and Bynum offer conclusions about how physicians can decide what to do for their older patients with Stage III colon cancer. First, physicians must accurately estimate life expectancy of the patient in front of them. The offer online assessment tools to assist physicians: http://www.eprognosis.com and Adjuvant! Online (http://www.adjuvantonline.com)

Second, good evidence suggests that the standard geriatric assessment can predict outcomes for patients with cancer.

Third, physicians need to be aware that 80 percent of recurrences in patients with Stage III colon cancer are seen in the first three years after diagnosis, and approximately 90 percent of the patients die within five years.  This means that except in patients with short life spans, adjuvant chemotherapy should be strongly considered.

The editorialists state that the Sanoff et al article raises many provocative questions.

Do older patients with colon cancer do as well with adjuvant chemotherapy as younger patients? Probably yes. Should physicians be more aggressive in providing adjuvant therapy in older patients with Stage III colon cancer?  Probably yes, but certainly not in all such patients. They say that the Sanoff et al study clearly points out what physicians know to be true—older patients are less likely to receive adjuvant chemotherapy.

Drs. Muss and Bynum summarize that seminal clinical trials continue to show poor accrual of older patients, with less than five percent of patients included over the age of 75 years.  They cite the example of the Medical Research Council (Fluorouracil, Oxaliplatin, CPT11 [irinotecan] trial (FOCUS2) in metastatic colon cancer, that incorporated a geriatric assessment into the protocol, urging that such trials should be developed for sicker or frail elders to explore the use of less toxic but potentially effective therapies in the adjuvant setting.

They conclude by recommending that the model for geriatric care should be based on the functional assessment of the patient- not the age of the patient- and the ability of a person to function well in their daily routines. They suggest that physicians caring for elders who are uncertain about how to mange their treatment team up with geriatricians to make the best treatment decisions.

Dr. Muss is leader of the UNC Lineberger Geriatric Oncology Program. Dr. Bynum is the director of the UNC Geriatric Fellowship Program in the UNC Center for Aging and Health.

The editorial, titled “Adjuvant Chemotherapy in Older Patients with Stage III Colon Cancer: An Underused Lifesaving Treatment,“ accompanies an article titled “Effect of Adjuvant Chemotherapy on Survival of Patients with Stage III Colon Cancer Diagnosed after Age 75 Years.”  

Hanna Sanoff, MD, assistant professor of medicine at UNC and first author of the paper, says, “Our findings about the effectiveness of chemotherapy in older patients treated in usual care settings reinforce the notion that patients in their seventies and eighties, and perhaps some in their nineties, should be given the opportunity to discuss adjuvant chemotherapy with a medical oncologist.“

In their editorial, Drs. Muss and Bynum cite the “aging tsunami” that is upon is and the effect it will have on aging Americans with cancer. Right now, 55 percent of all new cancer diagnoses are in patients 65 years or older, and 37 percent are in patients 75 years or older.

In colon cancer, of the 130,000 estimated new patients with colon cancer in 2012, approximately 40 percent will be 75 years of age or older, and approximately 40 percent will present with a Stage III tumor.

They explain that Sanoff et al examined four data sets to get a better idea in the real-world setting of the potential benefits of adjuvant chemotherapy in patients age 75 years or older with Stage III colon cancer: Surveillance, Epidemiology, and End Results (SEER); Medicare and Medicaid programs; Cancer Care Outcomes Research and Surveillance (CanCORS); and the National Comprehensive Cancer Network (NCCN).  

The analysis confirms previous clinical trials data that show adjuvant chemotherapy saves lives in Stage III patients and indicates that the benefits of adjuvant treatment in older patients are similar in magnitude to those reported in clinical trials for benefit of chemotherapy versus none.  No relationship between age and chemotherapy toxicity was noted, including nausea and vomiting, stomatis (oral inflammation), and diarrhea; however leucopenia (low white blood cell count) was more common in older adults in two of the trials.

A key goal of the Sanoff et al analysis was to determine the value of oxaliplatin when added to fluoropyrimidine (fluorouracil [FU] or capecitabine) therapy, citing a trend among studies for improved survival with oxaliplatin. The study authors discuss three trials: the Multicenter International Study of Oxaliplatin/FU/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC), the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the Adjuvant Colon Cancer End Points Group (ACCENT).  While the MOSAIC and NSABP trials show survival trends similar to the meta-analysis in terms of improved survival with oxaliplatin, the ACCENT trial showed improved survival with oxaliplatin only in patients younger than age 65.

Drs. Muss and Bynum offer conclusions about how physicians can decide what to do for their older patients with Stage III colon cancer. First, physicians must accurately estimate life expectancy of the patient in front of them. The offer online assessment tools to assist physicians: http://www.eprognosis.com and Adjuvant! Online (http://www.adjuvantonline.com)

Second, good evidence suggests that the standard geriatric assessment can predict outcomes for patients with cancer.

Third, physicians need to be aware that 80 percent of recurrences in patients with Stage III colon cancer are seen in the first three years after diagnosis, and approximately 90 percent of the patients die within five years.  This means that except in patients with short life spans, adjuvant chemotherapy should be strongly considered.

The editorialists state that the Sanoff et al article raises many provocative questions.

Do older patients with colon cancer do as well with adjuvant chemotherapy as younger patients? Probably yes. Should physicians be more aggressive in providing adjuvant therapy in older patients with Stage III colon cancer?  Probably yes, but certainly not in all such patients. They say that the Sanoff et al study clearly points out what physicians know to be true—older patients are less likely to receive adjuvant chemotherapy.

Drs. Muss and Bynum summarize that seminal clinical trials continue to show poor accrual of older patients, with less than five percent of patients included over the age of 75 years.  They cite the example of the Medical Research Council (Fluorouracil, Oxaliplatin, CPT11 [irinotecan] trial (FOCUS2) in metastatic colon cancer, that incorporated a geriatric assessment into the protocol, urging that such trials should be developed for sicker or frail elders to explore the use of less toxic but potentially effective therapies in the adjuvant setting.

They conclude by recommending that the model for geriatric care should be based on the functional assessment of the patient- not the age of the patient- and the ability of a person to function well in their daily routines. They suggest that physicians caring for elders who are uncertain about how to mange their treatment team up with geriatricians to make the best treatment decisions.

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