Weekly High-dose 5-Fluorouracil as 24-hour Infusion Combined with Sodium Folinic Acid (AIO regimen) Plus Irinotecan in Second-line and Sequential Therapy of Metastatic Colorectal Cancer (CRC).

Abstract

BACKGROUND/AIM:

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.) combined with sodium folinic acid (FA) (AIO-regimen) plus irinotecan (Iri.) after pretreatment with AIO-regimen plus oxaliplatin (L-OHP).

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 progression of first-line treatment in accordance with the AIO-regimen plus oxaliplatin. On an outpatient basis, the patients received a treatment regimen comprising of weekly 80 mg/m2 irinotecan in the form of a 1-hour i.v. infusion and 2,000 mg/m2 5-FU combined with 500 mg/m2 sodium folinic acid administered as a 24-h infusion i.v. once weekly.

RESULTS:

During second-line treatment, a total of 59 patients received 520 chemotherapy applications. As the main higher-grade symptom of toxicity, diarrhea (NCI-CTC-toxicity grade 3) presented in 8 patients (13.6%, 95%CI=5.1-23.7), followed by leukocytopenia (CTC grade 3) in 3 patients (5.1%, 95%CI=0-11.9), followed by thrombocytopenia (CTC grade 3) in 1 patient (1.7%, 95%CI=0-5.1). Fifty-nine patients were evaluable for treatment response. The remission data can be summarized as follows: complete remission (CR); n=0; partial remission (PR); n=6 (10%; 95%CI=3.4-18.6); stable disease (SD); n=31 (53%; 95%CI=39.0-64.4); progressive disease (PD); n=19 (33%; 95%CI=20.3-44.1). The median progression-free survival (PFS) rate (n=59) was 4.2 months (range=3.8-5.8 months). The median survival time counted from the start of second-line treatment (n=59) 14.2 months (range 8.2-17.3 months) and the median survival time counted from the start of first-line therapy (n=59) 25 months (range 19-27 months).

CONCLUSION:

Palliative second-line treatment according to the AIO regimen plus irinotecan offers both a favourable toxicity profile and promising efficacy in second-line and palliative sequential therapy.

• Authors: Axel Wein, Juergen Siebler, Kerstin Wolff, Nicola Ostermeier, Dagmar Busse, Alexander Hagel, Franz Koch, Kirsten Merx, Markus Friedrich Neurath, Ralf-Dieter Hofheinz
• Journal: Anticancer research (Anticancer Res) Vol. 37 Issue 7 Pg. 3771-3779 (07 2017) ISSN: 1791-7530 [Electronic] Greece
• PMID: 28668873 (Publication Type: Clinical Trial, Phase II, Journal Article)
• Copyright: Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Antineoplastic Agents
• Irinotecan
• Leucovorin
• Fluorouracil
• Camptothecin

Topics

• Adult
• Aged
• Antineoplastic Agents (adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Camptothecin (adverse effects, analogs & derivatives, therapeutic use)
• Colorectal Neoplasms (drug therapy)
• Disease-Free Survival
• Female
• Fluorouracil (adverse effects, therapeutic use)
• Humans
• Infusions, Intravenous
• Irinotecan
• Kaplan-Meier Estimate
• Leucovorin (adverse effects, therapeutic use)
• Male
• Middle Aged
• Palliative Care
• Remission Induction