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Impact of Pre-Treatment Lactate Dehydrogenase Levels on Prognosis and Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer.

Passardi A, Scarpi E, Tamberi S, Cavanna L, Tassinari D, Fontana A, Pini S, Bernardini I, Accettura C, Ulivi P, Frassineti GL, Amadori D - PLoS ONE (2015)

Bottom Line: High LDH levels were predictive of a lower median PFS (8.1 months vs. 9.2 months, p< 0.0001) and median OS (16.1 months vs. 25.2 months, p< 0.0001) in the overall population.A high LDH value was confirmed as a marker of poor prognosis.Bevacizumab reduced the progressive disease rate and improved PFS in the high-LDH subgroup, making serum LDH a potentially effective an easily available and marker to select patients who benefit from bevacizumab.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

ABSTRACT

Background: To investigate the impact of pre-treatment lactate dehydrogenase (LDH) levels on the outcome of patients with metastatic colorectal cancer treated with first-line chemotherapy with or without the anti-VEGF monoclonal antibody, bevacizumab, in a phase III prospective multicentre randomized ITACa (Italian Trial in Advanced Colorectal Cancer) trial.

Methods: Three hundred and seventy patients enrolled onto the ITACa first-line trial were considered for this study, 176 receiving chemotherapy (either FOLFIRI or FOLFOX) plus bevacizumab and 194 receiving chemotherapy only. Pre-treatment LDH levels were evaluated to identify a potential correlation with progression-free survival (PFS), overall survival (OS) and objective response rate.

Results: Information on pre-treatment LDH levels was available for 344 patients. High LDH levels were predictive of a lower median PFS (8.1 months vs. 9.2 months, p< 0.0001) and median OS (16.1 months vs. 25.2 months, p< 0.0001) in the overall population. In the chemotherapy plus bevacizumab group, median PFS was 9.1 and 9.8 months in patients with high LDH and low LDH, respectively (p= 0.073), whereas in the chemotherapy-only arm it was 6.9 and 9.1 months, respectively (p < 0.0001). In patients with high LDH, the addition of bevacizumab to chemotherapy led to a reduction in the rate of progressive disease (16.4 vs. 30.5%, p= 0.081) and to a prolonged PFS (p= 0.028).

Conclusion: A high LDH value was confirmed as a marker of poor prognosis. Bevacizumab reduced the progressive disease rate and improved PFS in the high-LDH subgroup, making serum LDH a potentially effective an easily available and marker to select patients who benefit from bevacizumab.

Trial registration: NCT01878422 ClinicalTrials.gov.

No MeSH data available.


Related in: MedlinePlus

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Mentions: The ITACa trial was approved by the local ethics committee (Comitato Etico Area Vasta Romagna) on September 19th, 2007 and was registered in our National Clinical Trials Observatory (Osservatorio delle Sperimentazioni Cliniche) and in the European Clinical Trials Database (EudraCT no. 2007-004539-44) before patient recruitment began. Registration on ClinicalTrials.gov (NCT01878422) was not mandated but was carried out at a later date. The authors confirm that all ongoing and related trials for this drug/intervention are registered. The study design and key eligibility and exclusion criteria have been previously described in detail (S1 CONSORT Checklist and S1 Protocol) [5]. Three hundred and seventy patients enrolled onto the ITACa first-line trial from 14/11/2007 to 06/03/2012 were considered for this study. All patients provided written informed consent and the studies were carried out in accordance with the Declaration of Helsinki under good clinical practice conditions and after full ethics committee approval of all participating centers (Comitato Etico Area Vasta Romagna e I.R.S.T., Comitato Etico Provinciale di Modena, Comitato Etico A.USL di Piacenza, Comitato Etico Interaziendale A.O.U. "Maggiore della Carità" di Novara, Comitato Etico Interaziendale dell'A.S.O. Santa Croce e Carle di Cuneo, Comitato Etico della Provincia di Modena, Comitato Etico della Provincia di Ferrara, Comitato Etico Unico per la Provincia di Parma, Comitato Etico Indipendente Azienda USL di Bologna, Comitato Etico della ASL LE di Lecce, Comitato Etico Provinciale di Belluno per la Sperimentazione Clinica). Patients were recruited from 14th November 2007 to 6th March 2012 and followed up until 31st December 2013. After randomization, 176 patients underwent CT (either FOLFIRI or FOLFOX4) plus B, while 194 patients received CT only (Fig 1). Patients were treated until disease progression or unacceptable toxicity occurred. Tumor response was radiologically evaluated every 8 weeks according to the Response Evaluation Criteria in Solid Tumors (RECIST) until disease progression or withdrawal. The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR) and safety.


Impact of Pre-Treatment Lactate Dehydrogenase Levels on Prognosis and Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer.

Passardi A, Scarpi E, Tamberi S, Cavanna L, Tassinari D, Fontana A, Pini S, Bernardini I, Accettura C, Ulivi P, Frassineti GL, Amadori D - PLoS ONE (2015)

Consort flowchart.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526665&req=5

pone.0134732.g001: Consort flowchart.
Mentions: The ITACa trial was approved by the local ethics committee (Comitato Etico Area Vasta Romagna) on September 19th, 2007 and was registered in our National Clinical Trials Observatory (Osservatorio delle Sperimentazioni Cliniche) and in the European Clinical Trials Database (EudraCT no. 2007-004539-44) before patient recruitment began. Registration on ClinicalTrials.gov (NCT01878422) was not mandated but was carried out at a later date. The authors confirm that all ongoing and related trials for this drug/intervention are registered. The study design and key eligibility and exclusion criteria have been previously described in detail (S1 CONSORT Checklist and S1 Protocol) [5]. Three hundred and seventy patients enrolled onto the ITACa first-line trial from 14/11/2007 to 06/03/2012 were considered for this study. All patients provided written informed consent and the studies were carried out in accordance with the Declaration of Helsinki under good clinical practice conditions and after full ethics committee approval of all participating centers (Comitato Etico Area Vasta Romagna e I.R.S.T., Comitato Etico Provinciale di Modena, Comitato Etico A.USL di Piacenza, Comitato Etico Interaziendale A.O.U. "Maggiore della Carità" di Novara, Comitato Etico Interaziendale dell'A.S.O. Santa Croce e Carle di Cuneo, Comitato Etico della Provincia di Modena, Comitato Etico della Provincia di Ferrara, Comitato Etico Unico per la Provincia di Parma, Comitato Etico Indipendente Azienda USL di Bologna, Comitato Etico della ASL LE di Lecce, Comitato Etico Provinciale di Belluno per la Sperimentazione Clinica). Patients were recruited from 14th November 2007 to 6th March 2012 and followed up until 31st December 2013. After randomization, 176 patients underwent CT (either FOLFIRI or FOLFOX4) plus B, while 194 patients received CT only (Fig 1). Patients were treated until disease progression or unacceptable toxicity occurred. Tumor response was radiologically evaluated every 8 weeks according to the Response Evaluation Criteria in Solid Tumors (RECIST) until disease progression or withdrawal. The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR) and safety.

Bottom Line: High LDH levels were predictive of a lower median PFS (8.1 months vs. 9.2 months, p< 0.0001) and median OS (16.1 months vs. 25.2 months, p< 0.0001) in the overall population.A high LDH value was confirmed as a marker of poor prognosis.Bevacizumab reduced the progressive disease rate and improved PFS in the high-LDH subgroup, making serum LDH a potentially effective an easily available and marker to select patients who benefit from bevacizumab.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

ABSTRACT

Background: To investigate the impact of pre-treatment lactate dehydrogenase (LDH) levels on the outcome of patients with metastatic colorectal cancer treated with first-line chemotherapy with or without the anti-VEGF monoclonal antibody, bevacizumab, in a phase III prospective multicentre randomized ITACa (Italian Trial in Advanced Colorectal Cancer) trial.

Methods: Three hundred and seventy patients enrolled onto the ITACa first-line trial were considered for this study, 176 receiving chemotherapy (either FOLFIRI or FOLFOX) plus bevacizumab and 194 receiving chemotherapy only. Pre-treatment LDH levels were evaluated to identify a potential correlation with progression-free survival (PFS), overall survival (OS) and objective response rate.

Results: Information on pre-treatment LDH levels was available for 344 patients. High LDH levels were predictive of a lower median PFS (8.1 months vs. 9.2 months, p< 0.0001) and median OS (16.1 months vs. 25.2 months, p< 0.0001) in the overall population. In the chemotherapy plus bevacizumab group, median PFS was 9.1 and 9.8 months in patients with high LDH and low LDH, respectively (p= 0.073), whereas in the chemotherapy-only arm it was 6.9 and 9.1 months, respectively (p < 0.0001). In patients with high LDH, the addition of bevacizumab to chemotherapy led to a reduction in the rate of progressive disease (16.4 vs. 30.5%, p= 0.081) and to a prolonged PFS (p= 0.028).

Conclusion: A high LDH value was confirmed as a marker of poor prognosis. Bevacizumab reduced the progressive disease rate and improved PFS in the high-LDH subgroup, making serum LDH a potentially effective an easily available and marker to select patients who benefit from bevacizumab.

Trial registration: NCT01878422 ClinicalTrials.gov.

No MeSH data available.


Related in: MedlinePlus