Chronomodulated chemotherapy in metastatic gastrointestinal cancer combining 5-FU and sodium folinate with oxaliplatin, irinotecan or gemcitabine: the Jena experience in 79 patients.

Purpose: To study efficacy and tolerability of chronomodulated (CM)-chemotherapy in patients with metastatic or locally advanced tumors of the GI tract. Furthermore, calcium folinate was replaced by sodium folinate due to better feasibility. Patients and methods: We treated 79 patients with metastatic or locally advanced colorectal cancer (n = 52), cancer of the pancreas/biliary tract (n = 14), and other malignancies (n = 14) with a total of 592 courses of CM-therapy. Out of the total study population 53/79, i.e., 67.1% had received prior chemotherapy. Most of the patients (77.2%) received sodium-folinate-5-FU-oxaliplatin-CM (SOFOX-CM) as first-line chronomodulated therapy, 20.3% received sodium-folinate-5-FU-irinotecan-CM (SOFIRI-CM), and 2.5% (n=1) received sodium-folinate-5-FU-gemcitabine-CM (SOFGEM-CM). Results: We found a moderate overall toxicity with grade 3-4 neuropathy in 7.46% of patients during a total of 433 courses of SOFOX-CM and grade 3-4 diarrhea in 10.26% of patients after 154 courses of SOFIRI-CM. SOFOX-CM had to be stopped only in one patient due to grade 3-4 sensory neuropathy. CM-therapy led to complete response (CR) in 1.3%, partial response (PR) in 15.2%, stable disease (SD) in 32.9%, and progressive disease (PD) in 44.3% of all patients. For the 26 chemonaive patients remission data were as follows: CR one patient (3.8%), PR four patients (15.4%), SD seven patients (26.9%), PD 12 patients (46.3%), lost to follow-up one patient (3.8%), and too-early-for-analysis one patient (3.8%). The median progression-free-survival (PFS) was 4 months (range, 0-24 months). The median PFS was also 4 months (range, 0-21 months) for those patients receiving SOFOX-CM as first CM-therapy (n=61), while it was found to be 0 months (range, 0-10 months) for patients (n = 16) receiving SOFIRI-CM as first chronomodulated therapy. Conclusions: We found CM-therapy to be effective and safe in the treatment of advanced malignancies of the GI tract. Sodium folinate offers superior feasibility and compatibility with cytostatic drugs without drawbacks.