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

Howard S. Hochster, Axel F Grothey, L. Hart, K. Rowland, R. Ansari, Steven Robert Alberts, N. Chowhan, Ramesk K Ramanathan, M. Keaton, J. D. Hainsworth, B. H. Childs

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1172-1178
Number of pages7
JournalAnnals of Oncology
Volume25
Issue number6
DOIs
StatePublished - 2014

Fingerprint

oxaliplatin
Treatment Failure
Magnesium
Salts
Calcium
Clinical Trials Data Monitoring Committees
Appointments and Schedules
Neoplasms

Keywords

  • Bevacizumab
  • Calcium and magnesium salts
  • Colorectal cancer
  • Drug-induced neurotoxicity
  • FOLFOX
  • Intermittent

ASJC Scopus subject areas

  • Oncology
  • Hematology
  • Medicine(all)

Cite this

Hochster, H. S., Grothey, A. F., Hart, L., Rowland, K., Ansari, R., Alberts, S. R., ... Childs, B. H. (2014). Improved time to treatment failure with an intermittent oxaliplatin strategy: Results of CONcePT. Annals of Oncology, 25(6), 1172-1178. https://doi.org/10.1093/annonc/mdu107

Improved time to treatment failure with an intermittent oxaliplatin strategy : Results of CONcePT. / Hochster, Howard S.; Grothey, Axel F; Hart, L.; Rowland, K.; Ansari, R.; Alberts, Steven Robert; Chowhan, N.; Ramanathan, Ramesk K; Keaton, M.; Hainsworth, J. D.; Childs, B. H.

In: Annals of Oncology, Vol. 25, No. 6, 2014, p. 1172-1178.

Research output: Contribution to journalArticle

Hochster, HS, Grothey, AF, Hart, L, Rowland, K, Ansari, R, Alberts, SR, Chowhan, N, Ramanathan, RK, Keaton, M, Hainsworth, JD & Childs, BH 2014, 'Improved time to treatment failure with an intermittent oxaliplatin strategy: Results of CONcePT', Annals of Oncology, vol. 25, no. 6, pp. 1172-1178. https://doi.org/10.1093/annonc/mdu107
Hochster, Howard S. ; Grothey, Axel F ; Hart, L. ; Rowland, K. ; Ansari, R. ; Alberts, Steven Robert ; Chowhan, N. ; Ramanathan, Ramesk K ; Keaton, M. ; Hainsworth, J. D. ; Childs, B. H. / Improved time to treatment failure with an intermittent oxaliplatin strategy : Results of CONcePT. In: Annals of Oncology. 2014 ; Vol. 25, No. 6. pp. 1172-1178.
@article{e769c73f030f479db0b6e7137f5359d3,
title = "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.",
keywords = "Bevacizumab, Calcium and magnesium salts, Colorectal cancer, Drug-induced neurotoxicity, FOLFOX, Intermittent",
author = "Hochster, {Howard S.} and Grothey, {Axel F} and L. Hart and K. Rowland and R. Ansari and Alberts, {Steven Robert} and N. Chowhan and Ramanathan, {Ramesk K} and M. Keaton and Hainsworth, {J. D.} and Childs, {B. H.}",
year = "2014",
doi = "10.1093/annonc/mdu107",
language = "English (US)",
volume = "25",
pages = "1172--1178",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "6",

}

TY - JOUR

T1 - Improved time to treatment failure with an intermittent oxaliplatin strategy

T2 - Results of CONcePT

AU - Hochster, Howard S.

AU - Grothey, Axel F

AU - Hart, L.

AU - Rowland, K.

AU - Ansari, R.

AU - Alberts, Steven Robert

AU - Chowhan, N.

AU - Ramanathan, Ramesk K

AU - Keaton, M.

AU - Hainsworth, J. D.

AU - Childs, B. H.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Bevacizumab

KW - Calcium and magnesium salts

KW - Colorectal cancer

KW - Drug-induced neurotoxicity

KW - FOLFOX

KW - Intermittent

UR - http://www.scopus.com/inward/record.url?scp=84903895266&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903895266&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdu107

DO - 10.1093/annonc/mdu107

M3 - Article

C2 - 24608198

AN - SCOPUS:84903895266

VL - 25

SP - 1172

EP - 1178

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 6

ER -