Treatment Strategies Needed for Subpopulations of Colorectal Cancer Patients

CRYSTAL CITY, Virginia—Clinicians need to develop treatment strategies for subpopulations of patients with colorectal cancer, according to Richard Goldberg, MD, professor of medicine and division chief of hematology-oncology, University of North Carolina School of Medicine, Chapel Hill. He spoke at the 2006 Gastrointestinal Oncology Conference, sponsored by the International Society of Gastrointestinal Oncology.

Race and gender may play some role in response to therapy, but age is irrelevant, Dr. Goldberg said. "It is very important for us to understand the underlying genetic changes that trigger colorectal cancer so that we can exploit them therapeutically," he said. "We have to understand the biology of the disease; that's the key." He noted that "although genetic analysis of tumor tissue is an enticing research tool, it is not one that has practical value in routine clinical practice at this time."

Role of Race

Dr. Goldberg reviewed data showing that African Americans have lower response rates than Caucasians when given standard colorectal chemotherapy for metastatic colorectal cancer. Originally presented at the 2006 ASCO Annual Meeting (abstract 3503), the analysis of data from clinical trial N9741 showed a 30% response rate to chemotherapy among 117 African Americans, compared with a 41% response rate among 1,297 Caucasians (P = .015). There was no difference in time to progression.

In this study, fewer African Americans experienced severe toxicity, 34% vs 48% of Caucasians, suggesting that dose escalation may be possible in some African-American patients. The largest disparity in toxicities was with severe diarrhea: 5% of African Americans vs 17% of Caucasians.

Preliminary data from the study suggest that different frequencies of polymorphisms in drug metabolism genes between the two groups may explain the clinical differences. "It bears further looking into," Dr. Goldberg said.

Age Has No Impact

Dr. Goldberg is convinced that age does not impact response to chemotherapy in colorectal cancer patients. In a pooled analysis of four clinical trials of adjuvant chemotherapy, Dr. Goldberg and his colleagues found that the efficacy of oxaliplatin (Eloxatin) plus fluorouracil/leucovorin administered bimonthly did not differ between patients younger or older than 70 years of age. Response rate, disease progression, recurrence-free survival, and overall survival were similar in older and younger patients, according to the report published recently in the Journal of Clinical Oncology (24:4085-4091, 2006). The researchers analyzed data from 3,742 colorectal cancer patients, including 614 age 70 or older.

Dr. Goldberg noted that other data examining irinotecan (Camptosar)-based chemotherapy regimens showed the same result. "Combination chemotherapy has a benefit that is not age dependent," he said. "We believe that elderly patients are not a separate population and do not need to be treated differently as long as they're fit." However, clinicians should keep a closer eye on adverse events in older patients, he said. In his pooled analysis, toxicities were more frequent in patients older than age 70: 49% experienced neutropenia vs 43% of younger patients, and 5% experienced thrombocytopenia vs 2% in younger patients.

Microsatellite Instability

Early data also suggest that tumors with microsatellite instability respond to chemotherapy "differently" than tumors with more common chromosomal instability, Dr. Goldberg said. "We need large, prospective trials with robust specimen collection to move forward" on the question of how microsatellite instability in tumor cells impacts response to chemotherapy, he said.

Retreatment Possible

In his presentation at the 2006 Gastrointestinal Oncology Conference, Dr. Richard Goldberg said that the "concept of lines of therapy" in advanced colorectal cancer is rapidly breaking down.

"We spent years trying to establish which was the best first, second, third line of therapy," he said. "But patients often go off therapy for reasons other than progression, and clinicians need to keep in mind that they can go back to drugs they've already used in these patients. You can reintroduce those drugs." He added that in his practice, "these patients are living 3 to 4 years, and some of them will respond to retreatment with a regimen on which they previously had disease progression."