New Chemotherapy Drugs for Colon and Rectal Cancer

The identification of KRAS as the most predictive marker in colon cancer for benefit of cetuximab (Erbitux) was a critical development. Increasingly, we have seen that most targeted agents appear to benefit only a relatively small number of patients. Targeted agents are expensive and they have associated toxicities, so there is an increasing focus on personalizing therapy. KRAS turned out not only to be an accurate predictor, but also to be a very commonly occurring marker. If you identify a marker in 5% of patients, it is not likely to be clinically relevant. KRAS mutations are present in about 40% of patients with colon cancer, and it is clear from phase-2 and phase-3 trials that if a patient has KRAS mutation that cetuximab adds no benefit, either as a single agent or in combination with chemotherapy. Only patients with KRAS wild-type status should be eligible for cetuximab as a single agent or in combination with chemotherapy in first-, second- or third-line treatment. Data also support the same approach with panitumumab (Vectibix) The FDA has approved revisions to the prescribing information for cetuximab and panitumumab, indicating that the use of these drugs is not recommended for treatment of advanced colorectal cancer in patients whose tumors have a K-ras mutation in codon 12 or 13.

see NCCN Chemo Guidelines, and the editorial by Mayer.  Recent NEJM review of new durgs (figure 1) the studies showing better response (figure 2 and figure 3) and increasing survival (figure 4.) FDA recently approved Camptosar (irinotecan) combined with 5FU/leucovorin as first line therapy to treat metastatic colon cancer, when two studies showed the three drug combination had better survival than 5FU/LV ( 17.4 mos versus 14.1 mos and 14.8 months versus 12.6 months) JAMA 2000;284:33 . the combination of weekly camptosar and bolus 5-FU and LV (Saltz regimen)10 was approved as first-line treatment of metastatic colorectal carcinoma. The response rate of this combination was 39%, the median duration of response was 9.2 months, the median time to disease progression was 7.0 months, and the median survival time was 14.8 months . the three-drug combination of camptosar, oxaliplatin, and 5-FU/LV produced a high response rate (58.1%) with a median duration of response of 11 months and a median time to disease progression of 13 months,  four other phase I or II studies with the same four-drug combination, but different treatment schedules, have been reported.The response rates ranged from 39% to 69%. The reported median time to disease progression ranged from 11.8 to 14 months (JCO Jun 1 2002: 2651-2657)