Management of colorectal cancer - Defining the role of raltitrexed

In Europe and the US > 300 000 cases of advanced colorectal cancer are diag nosed each year, and it is the third most common type of cancer after breas t/prostate and lung cancers, The lifetime risk of developing colorectal can cer increases with genetic predisposition or a family history of colorectal cancer. The 5-year survival rate varies depending on the stage at which co lorectal cancer is diagnosed. Advanced colorectal cancer (stage IV, Duke's D) has a 5-year survival rate of <5%. Screening and early detection can significantly increase the likelihood of survival. Treatment of early colorectal cancer relies on surgery and/or che motherapy. Patients with stage I to II (Duke's A to B) colorectal cancer ha ve a good prognosis, with a > 70% survival rate at 5 years. While the manag ement of advanced colorectal cancer also encompasses these options, treatme nt is largely palliative. Fluorouracil is currently the gold standard for t reatment of advanced colorectal cancer. However, despite its widespread use it is associated with a relatively low tumor response rate (< 15%), drug r egimens are complex and toxicities are significant. Raltitrexed, a specific thymidylate synthase inhibitor, has been approved f or the treatment of advanced colorectal cancer. As first-line therapy it ha s similar efficacy to fluorouracil in terms of tumor response rates (approx imately 14 to 19%) and overall survival duration (approximately 10 to 11 mo nths), although disease progression may be sooner with raltitrexed. However , in an effort to further increase survival duration, raltitrexed has been administered concomitantly with fluorouracil or oxaliplatin therapy as firs t- or second-line therapy with promising preliminary results. In comparative clinical trials, leukopenia and mucositis were more commonly associated with fluorouracil than with raltitrexed monotherapy. In contras t, elevated transaminase levels. which were not clinically significant, and anemia were more common with the raltitrexed regimen. Higher drug acquisition costs for raltitrexed than for fluorouracil are par tially offset by reduced pharmacy resource utilization, lower drug administ ration costs and reduced costs relating to the management of chemotherapy-i nduced adverse events. Overall treatment-related costs were slightly higher for raltitrexed than for fluorouracil administered according to the Mayo r egimen, but lower than either the Lokich or De Gramont regimens. Early comparative quality-of-life assessments favoured raltitrexed over flu orouracil: however, comparisons at 15 weeks failed to show any clear prefer ence in favor of either treatment. Palliative improvements occurred in pati ents who responded to treatment or those who had disease stabilization in b oth treatment groups. Conclusions: Raltitrexed is a first-line treatment option for the managemen t of advanced colorectal cancer and offers a more convenient administration regimen than traditional fluorouracil infusion regimens. Available data su ggest that it may have lower overall treatment costs than some but not all fluorouracil regimens: however, formal cost-effectiveness comparisons (in t erms of cost per clinical outcome) are not available. Preliminary results f rom trials of combination therapy with raltitrexed and either fluorouracil or oxaliplatin are promising, however, further data on raltitrexed combinat ion therapy are necessary to better determine its place in the management o f advanced colorectal cancer.