Chemotherapy for metastatic colon cancer: No effect on survival when the dose is reduced due to side effects

Abstract

Background5-Fluorouracil (5FU), Folinic acid (FA), and Oxaliplatin (FOLFOX) or 5FU, FA, and Irinotecan (FOLFIRI) are standard regimens for palliative chemotherapy of metastatic colon cancer. Since data showing the influence of dose reduction in palliative treatment are rare, the objective of this single center, retrospective study was to further characterize the influence of dose reduction on efficacy of these therapeutic regimens.MethodsOne hundred nine patients, diagnosed with stage IV colon cancer between 2004 and 2012 and receiving palliative first-line chemotherapy with either FOLFOX or FOLFIRI regimens in our outpatient clinic were analyzed for treatment efficacy. Patients who received dose reductions due to side effects usually received doses of 80% or lower of per protocol dose. Survival data were obtained from the Regensburg Tumor Registry. Survival analysis was performed using Kaplan-Meier statistical analysis and multivariable analysis.ResultsA dose reduction due to side effects was necessary in 46 (42%) patients. Dose reduction was independent of age. Major reasons for dose reduction were neutropenia (30%) followed by polyneuropathy (16%) and diarrhea (14%). Dosage was more often reduced in patients receiving FOLFOX based therapy. Comparison of patients with dose reduction versus patients with full dosage showed no significant difference on overall survival (p = 0.430). Subgroup analysis revealed dose reduction in patients with N2 stage disease was associated with improved survival. Patients who underwent dose reduction received more cycles of chemotherapy (13.7 vs. 10.8 cycles) and cumulative dosage was similar in both groups.ConclusionContrary to our expectations, the need to reduce chemotherapy dosage due to side effects does not indicate a worse prognosis in our retrospective analysis. We believe this can in part be explained by better adaption to interindividual pharmacokinetics and longer time of treatment.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4380-z) contains supplementary material, which is available to authorized users.

DSTYK Promotes Metastasis and Chemoresistance via EMT in Colorectal Cancer

“…Without DSTYK, TGF-β induces cell apoptosis instead of EMT. Furthermore, chemotherapy is the standard first-line treatment option for CRC patients with metastatic unresectable disease ( Van Cutsem et al, 2016 ; Munker et al, 2018 ). OXA has been considered as the first‐line chemotherapeutic drug in colorectal cancer treatment ( Hsu et al, 2018 ).…”

Combining Correlated Outcomes and Surrogate Endpoints in a Network Meta-Analysis of Colorectal Cancer Treatments

“…We also combined the treatments based on the components of the regimens, regardless of the schedule (sequentially or continuously, doses, and orders) and drug administration routes (bolus or infusion). Although the dose reduction due to side effects was reported to not have an effect on survival for chemotherapy treatments of colon cancer, we were unable to investigate the impact of these parameters [ 86 ]. Furthermore, the types or choices of chemotherapy can depend on the site or a regional preference of the hospital when standard cares show no differences.…”

A retrospective analysis of plasma concentration monitoring of fluorouracil in patients with advanced colorectal cancer

“…When severe adverse reactions occur, 5-FU plasma concentration monitoring results should be considered, and chemotherapy dose may be adjusted to reduce the risk of severe adverse reactions and ensure antitumour efficacy. 23 In conclusion, 5-FU plasma concentration monitoring may improve the safety and efficacy of treating patients with advanced colorectal cancer in China. It is expected to become important for clinical individualised 5-FU use.…”

“…[3][4][5] RDI is related to DI and TI numerically, and from a clinical view it is associated with the efficacy of anti-tumour therapy, and is related to drug resistance of cancer cells. Munker et al 23 studied the effect of RDI on chemotherapy efficacy, and it was agreed that a relatively high RDI should be applied if adverse reactions are tolerable. [3][4][5] In this study, the proportion of AUC <20 mg*h/L was 40.5%, which may be due to the relative low DI and RDI.…”