Introduction Colorectal cancer is the second most common cancer in developed nations. Despite surgery and adjuvant treatments, about 40% of patients develop metastases during the course of the disease 1 . Fluorouracil (5-FU) has been the main cytotoxic drug used in the treatment of colorectal cancer. Among the numerous schedules tested in the last decades, protract- ed venous infusion 5-FU has demonstrated higher re- sponse rates than bolus 5-FU, with a different toxicity profile and a small increase in overall survival 2 . A significant step forward has been achieved in re- cent years with new chemotherapeutic drugs such as irinotecan and oxaliplatin 3-6 and biological agents such as cetuximab and bevacizumab 7,8 . These have improved the outcomes of patients with advanced colorectal can- cer. By optimizing the use of these new, active drugs, a median survival of 21.5 months has been reported 9 . Third- and fourth-line treatments are still often used for patients who have progressed to the most active reg- imens and still have good performance status and good to intermediate chemosensitive disease. Due to the lack of standard regimens after failure of irinotecan and ox- aliplatin, protracted venous infusion 5-FU remains the most widely used drug in this group of patients, despite central venous catheter-related complications such as thrombosis and sepsis and their negative impact on quality of life. Capecitabine is an oral fluoropyrimidine primarily metabolized in the liver and converted to 5-FU by thymidine phosphorylase in tumor tissue 10 . In terms of disease progression and overall survival, this drug has shown results equivalent to those of bolus 5-FU and leucovorin, with a more favorable toxicity profile 11,12 . Moreover, it has been suggested that patients prefer oral chemotherapy to intravenous regimens 13 . Mitomycin C (MMC) has been widely used in the treatment of colorectal cancer over the last 30 years, with a wide range of response rates 14 . Based on in vit- ro data showing synergistic or at least additive effects for the two drugs when MMC is administered before 5-FU 15 , the combination of protracted venous infusion 5-FU and MMC has been widely used in advanced colorectal carcinoma. Given as first-line treatment, this regimen has been reported to be active and to of- fer higher response rates than 5-FU alone 16 . Moreover, MMC has been shown to upregulate intra- tumor thymidine phosphorylase activity, with the possi- bility of an increased synergism with capecitabine. This suggests a rationale for combining these two drugs 17 . Based on these data, the combination of MMC and capecitabine has been evaluated in several phase II studies in patients with advanced colorectal cancer. In- teresting results in terms of activity and tolerability have been achieved in patients untreated for metastatic disease 18 . However, there is no agreement on the role of this combination as a third-line treatment 19,20 . Tumori, 92: 285-289, 2006 CHEMOTHERAPYWITH MITOMYCIN C AND CAPECITABINE IN PATIENTS WITH ADVANCED COLORECTALCANCER PRETREATED WITH IRINOTECAN AND OXALIPLATIN Lorenza Rimassa, Giuseppe Gullo, Carlo Carnaghi, Giovanni Abbadessa, Monica Zuradelli, Maria Chiara Tronconi,Tiziana Pressiani, and Armando Santoro Medical Oncology and Haematology Department, Istituto Clinico Humanitas, Rozzano (MI), Italy Key words: advanced colorectal cancer, capecitabine, mitomycin C. Aims and background: To assess the activity and tolerability of the combination of mitomycin C and capecitabine in patients with metastatic colorectal cancer after failure of irinotecan- and oxaliplatin-containing regimens. Methods: We retrospectively reviewed 28 patients with pretreat- ed advanced colorectal cancer who had been treated with mit- omycin C, 6 mg/m 2 on day 1, and capecitabine, 1,900 mg/m 2 on days 1-14, every 3 weeks. Tumor assessment was performed every 3 cycles, toxicity assessed at each cycle. Results: Main patient characteristics were median age, 61 years (range, 35-73); male/female ratio, 16/12; single metastatic site involvement, 5/28 (18%); > 3 metastatic sites, 10/28 (36%). Ninety-six courses of therapy were given (me- dian number, 3; range, 1-9). Twenty-six patients were as- sessable for response, and all were assessable for toxicity. There was 1 partial response (4%) and 12 had stable dis- ease (43%). Median time to progression was 2 months (range, 1-9) and median overall survival was 6 months (range, 1-29+), with a 1-year overall survival rate of 25%. The regimen was very well tolerated without significant hemato- logical toxicity. Conclusions: Our results are disappointing. Despite the good safety profile, they do not support further investigation or the routine use of this regimen in this setting. Correspondence to: Lorenza Rimassa, Medical Oncology and Hematology Department, Istituto Clinico Humanitas, Via Manzoni 56, 20089 Rozzano (MI), Italy. Tel +39-02-82244573; fax +39-02-82244591; e-mail lorenza.rimassa@humanitas.it Received March 10, 2006; accepted April 18, 2006.