Can Chemotherapy Be Discontinued in Unresectable Metastatic Colorectal Cancer? The GERCOR OPTIMOX2 Study

Chibaudel, Benoist; Maindrault-Gœbel, F.; Lledo, Gérard; Mineur, Laurent; André, Thierry; Bennamoun, M.; Mabro, May; Artru, Pascal; Carola, Élisabeth; Flesch, M.; Dupuis, Olivier; Colin, Philippe; Larsen, Annette K.; Afchain, Pauline; Tournigand, Christophe; Louvet, Christophe; Gramont, Aimery de

doi:10.1200/jco.2009.23.4344

Cited by 362 publications

(259 citation statements)

References 22 publications

Supporting

Mentioning

225

Contrasting

Unclassified

Order By: Relevance

“…11,12,17,18 The results from the present analysis do not allow for conclusions regarding the comparative value of bevacizumab versus fluoropyrimidines or the effect of EGFR antibodies in this setting. The discussed maintenance approach has generally been limited to an oxaliplatin-based regimen, although a small number of patients receiving an irinotecan-based induction regimen were included in the SAKK 41/06 (about 30%) and the OPTIMOX 3/DREAM trials.…”

Section: Alexander Stein Et Almentioning

confidence: 61%

“…[10][11][12]14,15,[17][18][19] Of these, 5 trials were selected for additional analysis, because these trials evaluated a separately defined "maintenance phase," with randomization after the induction phase ( . The selected studies were assessed for potential bias with regard to the randomization approach, timely parallel enrollment, similarity of treatment groups, data-driven reporting, analysis population (intent-to-treat [ITT] vs. other), and other aspects.…”

Section: Definition Of Analysis and Trial Selectionmentioning

confidence: 99%

“…[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. The current meta-analysis was performed to compare observation alone with bevacizumab or bevacizumab and chemotherapy maintenance after induction chemotherapy in terms of PFS and OS.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

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.

show abstract

Section: Alexander Stein Et Almentioning

confidence: 61%

Section: Definition Of Analysis and Trial Selectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

show abstract

“…An every-other-week schedule of leucovorin-modulated 5-FU has been widely tested, and is reported to be well tolerated. [21][22][23] FOLFOX-6 involves oxaliplatin given with leucovorin at a dose of 400 mg/m 2 and bolus 5-FU at a dose of 400 mg/m 2 , followed by a 46-hour infusion of 5-FU at a dose of 2600 mg/m 2 . 21 Modified FOLFOX-7 uses oxaliplatin with leucovorin at a dose of 400 mg/m 2 followed by a 46-hour infusion of 5-FU at a dose of 3000 mg/m 2 .…”

mentioning

confidence: 99%

“…21 Modified FOLFOX-7 uses oxaliplatin with leucovorin at a dose of 400 mg/m 2 followed by a 46-hour infusion of 5-FU at a dose of 3000 mg/m 2 . 22 The results of a phase 1 trial of sequential irinotecan given with leucovorin at a dose of 500 mg/m 2 and 5-FU given as a 48-hour infusion recommended a 5-FU dose of 3125 mg/m 2 . 23 The current trial was designed to determine the recommended dose of PDX given in combination with infusional 5-FU.…”

mentioning

confidence: 99%

A phase 1 clinical trial of sequential pralatrexate followed by a 48‐hour infusion of 5‐fluorouracil given every other week in adult patients with solid tumors

Grem

Kos

Evande

et al. 2015

Cancer

View full text Add to dashboard Cite

BACKGROUND: Pralatrexate (PDX) is an inhibitor of dihydrofolate reductase that was rationally designed to improve cellular uptake and retention of the drug. Preclinical data have shown synergy with the sequential administration of a dihydrofolate reductase inhibitor followed 24 hours later by 5-fluorouracil (5-FU). METHODS: Twenty-seven patients were enrolled at 1 of 5 PDX dose levels from 75 to 185 mg/m 2 on day 1 followed 24 hours later by 5-FU at a dose of 3000 mg/m 2 /48 hours every 2 weeks with folic acid and vitamin B12 supplementation. Baseline blood was collected for pharmacogenetic analysis of polymorphisms of methylenetetrahydrofolate reductase and thymidylate synthase. RESULTS: Mucositis was the most common dose-limiting toxicity. When the worst toxicities across all cycles were considered, grade 3 to 4 neutropenia, anemia, and thrombocytopenia were found to have occurred in 14.8%, 14.8%, and 0% of patients, respectively. Grade 2 to 3 toxicities included mucositis (66.6%), dehydration (33.3%), fatigue (25.9%), and diarrhea (22.2%). Version 3.0 of the National Cancer Institute Common Toxicity Criteria was used to grade toxicities The median progression-free survival (PFS) was 112 days (range, 28-588 days). Seven patients (26%) had a PFS of >180 days (5 patients with colorectal cancer, 1 patient with pancreatic cancer, and 1 patient with non-small cell lung cancer). Polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase did not correlate with toxicity. CONCLUSIONS: The recommended dose of PDX was 148 mg/m 2 . A subset of heavily pretreated patients had PFS durations of 6 months with this regimen. Cancer 2015;121:3862-8. INTRODUCTION 5-fluorouracil (5-FU) and folate inhibitors of dihydrofolate reductase (DHFR), including methotrexate (MTX), are active in a variety of malignancies. There is strong preclinical evidence that the optimal sequence for combining DHFR inhibitors with 5-FU involves pretreatment with the DHFR inhibitor followed by 5-FU. 1-4 Administration of 5-FU followed by MTX is antagonistic in both in vitro and in vivo studies. The antipurine action of MTX is believed to result from 2 factors: 1) partial depletion of 10-formyl-tetrahydrofolate, which is required for purine synthesis; and 2) buildup of dihydrofolate, which is an inhibitor of de novo purine synthesis. Ongoing thymidylate synthesis is required to deplete the cellular reduced-folate pool. Pretreatment with 5-FU inhibits thymidylate synthase (TS) thereby blocking the conversion of reduced folates to dihydrofolate. The reduced-folate pool is thus spared for purine synthesis, and the dihydrofolate pool does not expand. When MTX precedes 5-FU, ongoing thymidylate synthesis depletes reduced folates and dihydrofolate pools accumulate, thus allowing blockade of purine biosynthesis. Inhibition of de novo purine synthesis expands the intracellular pool of phosphoribosyl pyrophosphate, which is then available for the anabolism of 5-FU to fluorouridine monophosphate by orotate phosphoribosyl transferase. Enhancement o...

show abstract

Effect of Reduced-Dose Capecitabine Plus Cetuximab as Maintenance Therapy for RAS Wild-Type Metastatic Colorectal Cancer

et al. 2020

View full text Add to dashboard Cite

show abstract

Can Chemotherapy Be Discontinued in Unresectable Metastatic Colorectal Cancer? The GERCOR OPTIMOX2 Study

Abstract: The planned complete discontinuation of chemotherapy had a negative impact on DDC and PFS compared with the maintenance therapy strategy. These results suggest that chemotherapy discontinuation cannot be decided before therapy is initiated in patients with advanced colorectal cancer.

Cited by 362 publications

References 22 publications

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

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

A phase 1 clinical trial of sequential pralatrexate followed by a 48‐hour infusion of 5‐fluorouracil given every other week in adult patients with solid tumors

Effect of Reduced-Dose Capecitabine Plus Cetuximab as Maintenance Therapy for RAS Wild-Type Metastatic Colorectal Cancer

Contact Info

Product

Resources

About