Elderly Patients with Colorectal Cancer Benefit from Chemotherapy

Elderly patients with colorectal cancer can gain as much benefit from chemotherapy after surgery as younger patients with the disease, according to a study presented at the American Society of Clinical Oncology (ASCO) meeting. This means that patients with stages II and III colorectal cancer over age 70- with otherwise good health-should not be denied chemotherapy following surgery, explained lead author Daniel Sargent, PhD, Mayo Clinic Cancer Center, Rochester, Minnesota.

Dr. Sargent and colleagues performed a large meta-analysis of patients who received chemotherapy, and 15 percent of the 3,351 patients analyzed were older than 70 years. The patients in the older age group had a significant and positive effect from their chemotherapy for both overall survival and disease- free survival (p < 0.0001). The meta-analysis included seven Phase III clinical trials conducted in the US, Canada, Italy, and other countries. The studies compared the effectiveness of 5-FU-containing chemotherapy following surgery versus observation alone after surgery. Patients were judged as well enough overall in physical status to enable them to receive chemotherapy and to tolerate side effects.

Benefits of chemotherapy were seen across the board in all age groups, including those under age 50, those ages 50-60, 60-70, and those over age 70. After eight years of follow-up, chemotherapy reduced the risk of death by 24 percent compared to observation alone. Overall survival at five years for patients who had chemotherapy following surgery was 71 percent versus 64 percent for those who did not receive adjuvant therapy.

In the seven trials, major toxicities included nausea/vomiting, diarrhea, stomatitis, and leukopenia. A similar incidence of toxicity was found in younger and older patients.

"There has been controversy over whether elderly patients are resilient enough to withstand chemotherapy. This study should provide reassurance to physicians and patients that chemotherapy can be as beneficial and tolerable in patients over age 70 as it is for younger patients," said Dr. Sargent.

CPT-11 Extends Life for Patients with Colorectal Cancer

Two studies showed that triple-drug chemotherapy with CPT- 11/fluorouracil/leucovorin (CFL) was superior to standard chemotherapy with FL in patients with previously untreated metastatic colorectal cancer. The addition of CPT-11 extended life by about 3.5 months. These results suggest that CPT-11 added to FL should be the new standard of care, said Leonard B. Saltz, MD, Memorial Sloan Kettering Cancer Center, New York.

Donald Haller, MD, University of Pennsylvania Cancer Center, Philadelphia, discussed Dr. Saltz's presentation and said, "This study gives us an unambiguous message about the value of CFL. Both trials demonstrated a statistically significant two- to three-month improvement in survival. These results raise the bar for clinical trials and provide a new standard of care for patients with metastatic colorectal cancer in the US."

Two studies were analyzed, one of which was conducted primarily in North America, Australia, and New Zealand (study 038), and the second was conducted primarily in Europe (study 303). The studies had slight differences in the methods of delivering fluorouracil-either by bolus or continuous infusion. Response rates for trial 038 were 39 percent for CFL versus 21 percent for FL. Response rates for study 303 were 35 percent versus 22 percent, respectively. Pooled results from both studies showed that 37 percent responded in the first study versus 21 percent in the second study. Patients treated with CFL had about 2.5 more months until their disease progressed, compared to those treated with FL.

Sophisticated analysis showed the only factor that predicted response and survival was the addition of CPT-11 to chemotherapy with FL. Combined overall survival for both studies was a median of 16.9 months for CFL versus 13.3 months for FL.

A substudy of trial 038 showed that all subgroups of patients benefitted from the addition of CPT-11 to 5-FU/LV. "Response rates and time to disease progression were universally higher with the three-drug combination no matter which subgroup a patient was in. This included older and younger patients; those with good or poor physical performance status; those with extensive disease, liver, or intra-abdominal metastases; those who received prior chemotherapy following surgery; and those with abnormal baseline lab values," stated R.D. Knight, MD, Pharmacia Corporation, Peapack, NJ.