gms | German Medical Science

In metastatic colorectal cancer chemotherapy with 5-FU and FA effects increases quality of and overall survival [Ref. 1]. Combination regimes includingcontinuous-infusion (ci)5-FU/FA with oxaliplatin (L-OHP) or irinotecan (CPT-11) yields a greater remission rate of about 50% and a gain in overall survival between 1,5 and 3,5 months, toxicity is increased however [Ref. 2], [Ref. 3]. In patients with progressive disease after receiving oxaliplatin-based regimens there exist no standard treatment. Cross over to Irinotecan/ci5-FU/FA results in a remission rate of only 4% and a progression free survival of 2,5 months [Ref. 4]. Limiting toxicity of this therapy is diarrhoea and bone marrow suppression. Mitomycin/ci 5-FU-infusion is a further drug-combination active in advanced colorectal cancer. A remission rate of 35% was described in 46 patients, 20 of whom were pretreated with FU/FA [Ref. 5]. Mitomycin in combination with the 5-FU prodrug capecitabine resulted in an objective remission rate of 15% and median 5,4 months time to treatment failure [Ref. 6]. There are no data on mitomycin-based combinations after oxaliplatin failure.

In an retrospective analysis we analysed data of 19 patients with metastatic colorectal cancer treated with the combination mitomycin / ci5-FU/FA(FUMI). All patients where pretreated with 1 to 3 regimens, 17/19 had received oxaliplatin-based chemotherapy (Folfox-4). All patients where progressive during or after pretreatment. Mitomycin 10mg abs. was given as i.v.bolus on day 1, followed by 500mg FA as short infusion, followed by 2.600mg/m² 5-FU 24-hours-continuous-infusion. Treatment was repeated weekly for 6 applications, the 2nd cycle was started day 50. 16/19 were assessable for toxicity and response. The median number of cycles was 1,7 (range 0,3 to 3). 4 patients (21%) (all pretreated with FOLFOX-4) reached a partial remission for 20 to 25 weeks, 2 patients (16%) had objective stabilization for 16 to 21 weeks, 10 patients (52%) where progressive. 3 Patients (11%) were ineligible. Limiting toxicity was myelosuppression, necessitating mitomycin-dose-reduction in 18/19 patients. Toxicity was usually mild, however no toxic death occurred.

Our results indicate that FUMI is an active treatment in advanced colorectal cancer even after pretreatment with an oxaliplatin-based regimen. In our view this qualifies as a second line treatment after oxaliplatin failure.

Figure 1 [Fig. 1].