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A systematic review of salvage therapy to patients with metastatic colorectal cancer previously treated with fluorouracil, oxaliplatin and irinotecan +/- targeted therapy.

Cancer treatment reviews (2014-04-16)
Dorte Lisbet Nielsen, Jesper Andreas Palshof, Finn Ole Larsen, Benny Vittrup Jensen, Per Pfeiffer
ABSTRACT

Oxaliplatin, irinotecan and 5-fluorouracil in combination with or without targeted therapies are well-documented treatment options for first- and second-line treatments of metastatic colorectal cancer. However, there are much less data on the beneficial effect on systemic therapy in the third-line setting. We therefore performed a systematic review of the current literature on third or later lines of treatment to patients with metastatic colorectal cancer after the use of approved drugs or combinations. A computer-based literature search was carried out using Pubmed and data reported at international meetings. Original studies reporting ≥15 patients who had previously received 5-fluorouracil, oxaliplatin and irinotecan were included. Furthermore, patients with KRAS wild type tumours should had received EGFR-directed therapy. Conventional chemotherapeutic agents as capecitabine, mitomycin C, and gemcitabine have limited or no activity. Retreatment with oxaliplatin might be an option in selected patients. In addition, rechallenge with EGFR-directed therapy might be a valuable strategy. Data also suggest that angiogenetic drugs may postpone further progression and prolong survival. Lately, regorafinib has been approved. In conclusion, our current knowledge is based on many retrospective studies, some phase II studies and very few randomized clinical trials. Further prospective phase III trials comparing an investigational drug or combination with best supportive care in third- or later lines of treatment in metastatic colorectal cancer are highly warranted. Identification of predictive biomarkers and improvement of our understanding of molecular mechanisms is crucial.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
5-Fluorouracil, ≥99% (HPLC), powder
Supelco
L-Alanine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
L-Alanine, from non-animal source, meets EP, USP testing specifications, suitable for cell culture, 98.5-101.0%
Sigma-Aldrich
L-Alanine, ≥98% (TLC)
Sigma-Aldrich
L-Alanine, ≥99%
Sigma-Aldrich
L-Alanine, ≥99.0% (NT)
Sigma-Aldrich
L-Alanine, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
Fluorouracil, meets USP testing specifications
Sigma-Aldrich
Irinotecan hydrochloride, topoisomerase inhibitor
Supelco
L-Alanine, certified reference material, TraceCERT®
Supelco
5-Fluorouracil, analytical standard
Alanine, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
5-Fluorouracil, Vetec, reagent grade, ≥99%
Fluorouracil, European Pharmacopoeia (EP) Reference Standard
Supelco
Fluorouracil, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
7-Ethyl-10-hydroxycamptothecin, ≥98% (HPLC), powder
Sigma-Aldrich
L-Alanine-12C3, 99.9 atom % 12C
Sigma-Aldrich
Oxaliplatin, powder
Oxaliplatin, European Pharmacopoeia (EP) Reference Standard