Palliative second-line treatment with weekly high-dose 5-fluorouracil as 24-hour infusion and folinic acid (AIO) plus oxaliplatin after pre-treatment with the AIO-regimen in colorectal cancer (CRC)

Background and Aims: The aim of this work was to evaluate the efficacy and safety of second-line treatment with weekly high-dose 5-Fluorouracil (5-FU) as a 24-hour infusion (24-h inf) and folinic acid (FA) (AIO-regimen) plus Oxaliplatin (L-OHP) after pre-treatment with the AIO regimen, focusing in particular on the efficacy of palliative first- and second-line treatment in colorectal carcinoma (CRC). Patients and Methods: Patients with non-resectable distant CRC metastases were enrolled in a prospective phase II study for palliative second-line treatment after previous palliative first-line treatment in accordance with the AIO regimen. On an outpatient basis, the patients received a treatment regimen comprising biweekly 85 mg/m(2) L-OHP in the form of a 2-hour intravenous (i.v.) infusion and 500 mg/m(2) FA as a 1 to 2-hour i.v. infusion, followed by 2,600 mg/m(2) 5-FU administered as a 24-h inf i.v. once weekly. A single treatment cycle comprised 6 weekly infusions followed by 2 weeks of rest. Results: During second-line treatment, a total of 26 patients received 340 chemotherapy applications. As the main symptom of toxicity, diarrhoea (NCI-CTC toxicity grade 3+4) presented in 5 patients (19%; 95% CI: 4-34), followed by nausea (CTC grade 3) in one patient (4%; 95% CI: 0-11). Twenty-three patients were evaluable for treatment response. The remission data can be summarised as follows: Complete remission (CR): n=l (4%; 95% CI: 0-13); partial remission (PR): n=3 (13%; 95% CI: 0-27); stable disease (SD): n=11 (48%; 95% CI: 27-68) and progressive disease (PD): n=8 (35%; 95% CI: 15-54). The median progression-free survival (PFS) rate (n=26) was 3.3 months (range 0-11.5), the median survival time counted from the start of second-line treatment (n=26) 11.6 months (range 2.1-33.0) and the median survival time counted from the start of first-line treatment (n=26) 19.9 months (range 7.7-49.8). Conclusion: Palliative second-line treatment according to the AIO regimen plus L-OHP is feasible in an outpatient setting and well tolerated by the patients. Tumour control (CR + PR + SD) was achieved in 65% of the patients, the median survival time being 11.6 months. The AIO regimen followed by the AIO regimen plus L-OHP' therapy sequence led to a promising median survival time of 19.9 months (range 7.7-49.8).