Improved time to treatment failure with an intermittent oxaliplatin strategy: results of CONcePT.

Abstract

BACKGROUND:

Oxaliplatin is an integral component of colorectal cancer treatment, but its use is limited by neurotoxicity. The Combined Oxaliplatin Neurotoxicity Prevention Trial (CONcePT) tested intermittent oxaliplatin (IO) administration and the use of concurrent calcium and magnesium salts (Ca/Mg), two modifications intended to reduce neurotoxicity and extend the duration of treatment.

PATIENTS AND METHODS:

In this trial involving double randomization, 140 patients were randomized to receive modified FOLFOX7 plus bevacizumab with IO (eight-cycle blocks of oxaliplatin treatment) versus continuous oxaliplatin (CO); and Ca/Mg versus placebo (pre- and postoxaliplatin infusion). The primary end point was time-to-treatment failure (TTF).

RESULTS:

One hundred thirty-nine patients were entered and treated up to the point of early study termination due to concerns by the data-monitoring committee (DMC) that Ca/Mg adversely affected tumor response. Tumor response was not a study end point. Given DMC concerns, an additional independent, blinded radiology review of all images showed no adverse effect of treatment schedule or Ca/Mg on response by Response Evaluation Criteria In Solid Tumors. The IO schedule was superior to CO [hazard ratio (HR) = 0.581, P = 0.0026] for both TTF and time-to-tumor progression (TTP) (HR = 0.533, P = 0.047).

CONCLUSIONS:

An IO dosing schedule had a significant benefit on both TTF and TTP versus CO dosing in this trial despite the very attenuated sample. There was no effect of Ca/Mg on response.

• Authors: H S Hochster, A Grothey, L Hart, K Rowland, R Ansari, S Alberts, N Chowhan, R K Ramanathan, M Keaton, J D Hainsworth, B H Childs
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 25 Issue 6 Pg. 1172-8 (Jun 2014) ISSN: 1569-8041 [Electronic] England
• PMID: 24608198 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Antibodies, Monoclonal, Humanized
• Organoplatinum Compounds
• Oxaliplatin
• Bevacizumab
• Magnesium Sulfate
• Leucovorin
• Calcium Gluconate
• Fluorouracil

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Bevacizumab
• Calcium Gluconate (administration & dosage)
• Colorectal Neoplasms (drug therapy, mortality)
• Double-Blind Method
• Female
• Fluorouracil
• Humans
• Kaplan-Meier Estimate
• Leucovorin
• Magnesium Sulfate (administration & dosage)
• Male
• Middle Aged
• Organoplatinum Compounds (administration & dosage, adverse effects)
• Oxaliplatin
• Proportional Hazards Models