Less intense therapy yields comparable survival for some colorectal cancer patients

The preliminary results of a new study of advanced colorectal cancer appear to challenge the current combination drug regimen that has become standard in the US over the last 4 years. The new data suggest that starting patients who present with advanced disease on 5-fluorouracil (5-FU) leads to comparable survival compared with starting with a more toxic combination regimen.

In 1999, Dr. Leonard Saltz, of Memorial Sloan Kettering Cancer Center in New York and Dr. Jean-Yves Douillard, of Centre Ren-Gauducheau, Nantes, France, independently reported study results supporting the addition of irinotecan to standard first-line 5-FU. Since then, irinotecan plus 5- FU has been adopted as the new standard first-line approach in the US.’What they haven’t proven is whether those patients may have done equally well had the extra drugs been delivered in a sequenced way,’ said Professor Matthew Seymour, principal investigator of the Cancer Research UK Cancer Medicine and Pathology Programme. He is based at the University of Leeds and the Leeds Teaching Hospitals NHS Trust.Professor Seymour said the results of the FOCUS trial provide convincing evidence that such a sequenced approach — starting a patient on 5-FU alone and adding other drugs later as needed — can provide the same survival benefit with less toxicity when compared with starting patients on two drugs. He presented his group’s new data this week at the 29th European Society for Medical Oncology Congress.In fact, he said, ‘giving first-line combination therapy didn’t give any better survival results than giving patients first-line 5-FU therapy followed by a combination introduced by adding a second drug.’However, he emphasized the results do not apply to patients who are diagnosed with disease that can be cured. For them, intensive combination chemotherapy may be warranted from the start, even if it exposes patients to a more toxic regimen.The Medical Research Council’s FOCUS trial, involving 2135 patients and spanning more than 3.5 years, aimed to optimize the use of fluorouracil, irinotecan and oxaliplatin. The subjects had inoperable, advanced colorectal cancer that had not been treated.The patients were randomized to one of three regimens: 5-FU alone until treatment failure, then a switch to irinotecan alone; 5-FU until treatment failure, then the addition of oxaliplatin or irinotecan; or 5-FU plus irinotecan or oxaliplatin.Professor Seymour reported that the second and third protocols produced identical overall survival, while patients who received the first treatment protocol did a little less well. However, the differences were not statistically significant.Additionally, survival and response to treatment results in the FOCUS trial, he reported, were superior to what was reported by the last national survey in the UK National Trial.Median survival in the second and third protocols was 15.2 months, with 63% of patients alive at 1 year and 23% at 2 years, versus 10 months median survival, and 40% survival at 1 year in the last UK National Trial, CR06.He attributes the difference to a new schedule developed by FOCUS trial researchers called ‘Modified de Gramont,’ in which folinic acid was administered to enhance the efficacy of 5-FU. ‘It performed well, with more patients having a response, and for longer periods, than in our previous trials, but with minimal side effects.'(Source: Reuters Health: Larry Schuster: Oncolink: November 2004.)