SAN FRANCISCO—The notion of "lines" of therapy for treatment of patients with colorectal cancer appears to be blurred, with the actual sequence of treatment becoming less important than making sure patients have access to all active agents, Axel Grothey, MD, of the Mayo Clinic, said at the Third Annual Oncology Congress. Rather than using either single-agent sequencing or upfront combinations in all patients, he noted, "the goal of therapy, whether curative or palliative, defines the overall strategy and treatment algorithm."

Dr. Grothey cited the FOCUS trial, which brought into question the assumption that in the palliative setting, combination therapy is the only first-line option. In FOCUS (Lancet 370:143-152, 2007), 2,135 patients were randomized to receive single-agent fluorouracil(Drug information on fluorouracil)/leucovorin until treatment failure, then irinotecan(Drug information on irinotecan) (Camptosar); single-agent fluorouracil, then combination chemotherapy with either FOLFIRI or FOLFOX; or combination chemotherapy with either FOLFIRI or FOLFOX as first-line treatment.

The results showed that fluorouracil followed by either combination therapy was not inferior to using combination therapy upfront, but that any regimen containing a combination was superior to sequential fluorouracil/irinotecan.

Only 20% received all 3 agents

Dr. Grothey pointed out that overall survival rates in FOCUS were somewhat lower than seen in other similar phase III trials, probably because of the limited use of second- and third-line therapies. Only about 20% of FOCUS patients received all three active agents.

So, in palliative therapy for metastatic colorectal cancer, he said, "the actual sequence of treatment regimens does not matter as much as the ultimate goal, which is to expose all patients to all active agents."

Dr. Grothey is also concerned over the notion of "piling up" therapies, pointing out that combining multiple therapies upfront in unselected patients is not an appropriate treatment strategy.

He pointed to the CAIRO study (Lancet 370:135-142, 2007) in which 820 patients with advanced colorectal cancer were randomized to either sequential treatment with first-line capecitabine(Drug information on capecitabine) (Xeloda), second-line irinotecan, and third-line capecitabine/oxaliplatin (Eloxatin) or combination treatment with capecitabine/irinotecan followed by capecitabine/oxaliplatin.