Intermittent versus continuous chemotherapy in advanced colorectal cancer: a randomised ‘GISCAD’ trial

Labianca, Roberto; Sobrero, Alberto F.; Isa, L.; Cortesi, Enrico; Barni, Sandro; Nicolella, Dario; Aglietta, Massimo; Lonardi, Sara; Corsi, Domenico; Turci, D.; Beretta, Giordano Domenico; Fornarini, Giuseppe; Dapretto, E.; Floriani, Irene; Zaniboni, Alberto

doi:10.1093/annonc/mdq580

Cited by 102 publications

(51 citation statements)

References 21 publications

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“…Such prognostic biomarkers might enable the appropriate selection of patients eligible to intermittent chemotherapy or sequential therapeutic strategies dedicated to the optimization of patient's quality of life and chemotherapy cost-effectiveness (5,6,34).…”

Section: Cancer Epidemiol Biomarkers Prev; 24(3) March 2015mentioning

confidence: 99%

Prognostic Value of Angiopoietin-2 for Death Risk Stratification in Patients with Metastatic Colorectal Carcinoma

Jary

Vernerey

Lecomte

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Baseline prognostic biomarkers stratifying treatment strategies in first-line metastatic colorectal cancer (mCRC) are lacking. Angiopoietin-2 (Ang-2) is proposed as a potential biomarker in several cancers. We therefore decided to establish the additional prognostic value of Ang-2 for overall survival (OS) in patients with first-line mCRC.Methods: We enrolled 177 patients treated with a bevacizumab containing chemotherapy in two prospective phase II clinical trials. Patient plasma samples were collected at baseline. ELISAs were used to measure Ang-2.Results: The multivariable Cox model identified increased lactate dehydrogenase [HR, 1.60; 95% confidence interval (CI), 1.04-2.45; P ¼ 0.03] and Ang-2 log-transformation level (HR, 1.59; 95% CI, 1.14-2.21; P ¼ 0.0065) as two significant independent OS prognostic factors. It exhibited good calibration (P ¼ 0.8) and discrimination (C-index: 0.64; 95% CI, 0.58-0.68). Ang-2 parameter inclusion in the GERCOR reference model signifi-

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Section: Cancer Epidemiol Biomarkers Prev; 24(3) March 2015mentioning

confidence: 99%

Prognostic Value of Angiopoietin-2 for Death Risk Stratification in Patients with Metastatic Colorectal Carcinoma

Jary

Vernerey

Lecomte

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Возможность предоставления «химиотерапевтических каникул» пациентам с метастатическим колоректальным раком была изучена в рандомизированном мультицентро-вом исследовании GISCAD [43], в которое было включено 337 пациентов. Все пациенты получали в качестве первой линии химиотерапию в режиме FOLFIRI.…”

Section: длительность первой линии химиотерапииunclassified

Chemotherapy in the Management of Localized and Metastatic Colon Cancer: New and Yet Unforgotten Approaches

Доброва¹,

Гордеева²,

Черноглазова³

et al. 2017

Medicinskij sovet

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За последние пару десятков лет мы стали свидетелями существенного прогресса в лечении метастатического колоректального рака: появление новых таргетных препаратов и дифференцированного подхода к их назначению, расширение показаний к резекции метастазов в печени и легких привели к увеличению продолжительности жизни пациентов этой группы. Тем не менее химиотерапия остается основой лекарственного лечения рака толстой кишки. В данной работе мы рассматриваем ряд новых подходов, касающихся применения химиотерапии при III и IV стадиях заболевания.Ключевые слова: метастатический колоректальный рак, рак толстой кишки, химиотерапия, оксалиплатин, 5-фторурацил, иринотекан. CHEMOTHERAPY IN THE MANAGEMENT OF LOCALIZED AND METASTATIC COLON CANCER: NEW AND YET UNFORGOTTEN APPROACHESOver the course of the past couple of decades, we have witnessed some significant improvements in the treatment of metastatic colorectal cancer: the emergence of novel targeted drugs and a differentiated approach to their administration, the extension of indications for surgical resection for liver and lungs metastases has resulted in the increased life expectancy among patients in this group. Nevertheless, chemotherapy remains the treatment of choice for colon cancer. In this paper, we discuss new approaches to the use of chemotherapy on stages III and IV of colorectal cancer.

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“…In addition to the intermittent treatment approach applied in the GISCAD trial, the effect of a de-escalation strategy after an irinotecan-based first-line regimen combined with monoclonal antibodies compared with continuation of full-dose treatment remains unclear. 7 In addition, the endpoint of PFS was considered to have a high potential for bias owing to the open-label design of all 3 studies and the assessment of the radiologic images at the study sites and not centrally. Also, the indirect comparison had some limitations.…”

Section: Alexander Stein Et Almentioning

confidence: 99%

“…Although intermittent treatment with preplanned maintenance or full-stop intervals was evaluated in several trials, this approach has not been widely adopted. [7][8][9] Recent trials allocated patients after 3 to 6 months of induction treatment to different maintenance strategies and/or observation alone. [10][11][12][13][14][15][16] These trials all showed an effect on progression-free survival (PFS) or the respective alternate endpoints eg, time to failure of strategy or time to second progression; however, the effect on OS has remained unclear.…”

Section: Introductionmentioning

confidence: 99%

Effect of Application and Intensity of Bevacizumab-based Maintenance After Induction Chemotherapy With Bevacizumab for Metastatic Colorectal Cancer: A Meta-analysis

Stein

Schwenke²,

Folprecht

et al. 2016

Clinical Colorectal Cancer

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The role of bevacizumab-based maintenance after first-line bevacizumab-based induction treatment of metastatic colorectal cancer was evaluated in a meta-analysis of 3 randomized trials. Maintenance treatment with bevacizumab with or without fluoropyrimidines improved progression-free survival and showed a trend toward improved overall survival. Background: The administration and intensity of bevacizumab-based maintenance therapy after induction treatment with bevacizumab is still a matter of debate. Thus, the present meta-analysis and an indirect comparison were performed to clarify these issues. Patients and Methods: Trials evaluating a separately defined "maintenance phase," with randomization after the induction phase, were selected. Three trials of maintenance with bevacizumab with or without a fluoropyrimidine (CAIRO3, SAKK 41/06, and AIO KRK 0207) were analyzed regarding the effect on progression-free survival (PFS) and overall survival (OS) of any maintenance therapy compared with observation alone and different maintenance intensities (bevacizumab with or without fluoropyrimidine) compared with observation alone and between each other. Results: Maintenance with bevacizumab with or without fluoropyrimidine after bevacizumabbased induction treatment for 4 to 6 months significantly improved PFS (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.43-0.75; P ¼ .0004) and showed a trend toward prolonged OS (HR, 0.89; 95% CI, 0.78-1.02; P ¼ .09) compared with observation alone. The effect on PFS increased with the intensity of the maintenance regimen (HR, 0.72; 95% CI, 0.60-0.85 for single-agent bevacizumab vs. HR, 0.45; 95%, CI 0.39-0.51 for combination therapy, both compared to observation alone). In contrast, the HRs for OS remained in the same range. A similarly improved PFS (HR, 0.63; 95% CI, 0.50-0.79) was shown for the more intensive maintenance therapy (bevacizumab and fluoropyrimidine) compared with bevacizumab alone. Conclusion: Bevacizumab-based maintenance therapy after induction chemotherapy with bevacizumab significantly improves PFS and showed a trend toward prolonged OS and should thus be considered, in particular, in patients with a response to induction treatment.

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Intermittent versus continuous chemotherapy in advanced colorectal cancer: a randomised ‘GISCAD’ trial

Abstract: Reducing the charge of therapy in this population did not diminish the efficacy of treatment. Further studies with this strategy, including biologicals, are warranted.

Cited by 102 publications

References 21 publications

Prognostic Value of Angiopoietin-2 for Death Risk Stratification in Patients with Metastatic Colorectal Carcinoma

Prognostic Value of Angiopoietin-2 for Death Risk Stratification in Patients with Metastatic Colorectal Carcinoma

Chemotherapy in the Management of Localized and Metastatic Colon Cancer: New and Yet Unforgotten Approaches

Effect of Application and Intensity of Bevacizumab-based Maintenance After Induction Chemotherapy With Bevacizumab for Metastatic Colorectal Cancer: A Meta-analysis

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