scholarly journals The Role of Serum CEA and CA19-9 in Efficacy Evaluations and Progression-Free Survival Predictions for Patients Treated with Cetuximab Combined with FOLFOX4 or FOLFIRI as a First-Line Treatment for Advanced Colorectal Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Jun Jia ◽  
Pengfei Zhang ◽  
Miaomiao Gou ◽  
Fan Yang ◽  
Niansong Qian ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Baseline Level ◽  
Advanced Colorectal Cancer ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Effective Rate ◽  
First Line ◽  
Free Survival ◽  
Early Predictors ◽  
First Line Treatment

Background. Previously, it was demonstrated that serum levels of tumor markers, CEA and CA19-9, correlated with chemotherapy. Consequently, it has been hypothesized that dynamic monitoring of changes in these markers may predict the shrinkage or growth of colorectal cancers. To test this hypothesis, we analyzed CEA and CA19-9 serum levels in patients with advanced colorectal cancer who received cetuximab in combination with chemotherapy. These levels were evaluated at various time points to identify their potential to serve as early efficacy predictors during treatment and early predictors of disease progression. Patients and Methods. Measurements of tumor markers, CEA and CA 19-9, in patients with metastatic colorectal cancer (n=73) who received cetuximab plus folinic acid, fluorouracil, and oxaliplatin or irinotecan (FOLFOX4/FOLFIRI) as a first-line treatment at our center were retrospectively analyzed. These levels were also compared with objective responses according to the World Health Organization criteria. Initially, 65 patients had elevated CEA levels (>5 ng/ml), and 59 patients had elevated levels of CA19-9 (>37 U/ml). A total of 172 cycles and 165 cycles of computed tomography/magnetic resonance imaging observations were available for review from these two patient groups. Results. After completing three cycles of treatment, the best diagnosis of cetuximab resistance was achieved when CEA increased by 35% (efficacy, 83.33%; sensitivity, 75.41%) and when CA19-9 increased by 28% (efficacy, 80.00%; sensitivity, 84.31%). Next, the efficacy of cetuximab at the time of diagnosis (at the first imaging examination/after three cycles of treatment) was evaluated after the first cycle of chemotherapy. When CEA decreased by 60% from its baseline level, the best effective rate and sensitivity were observed (63.64% and 80.95%, respectively). Similarly, when CA19-9 was 45% lower than its baseline level, the best effective rate and sensitivity were observed (84.21% and 93.18%, respectively). To evaluate progression-free survival (PFS), levels of both CEA and CA19-9 were evaluated after the third cycle of chemotherapy. Increases of 35% and 28%, respectively, resulted in a shorter PFS period compared with the other patients (3.15 months vs. 9.10 months, respectively; P<0.0001). Conversely, when the evaluation was performed after the first cycle of chemotherapy, patients exhibiting a 60% decrease in CEA and a 45% decrease in CA19-9 had a longer PFS period (11.13 months vs. 8.10 months, respectively; P=0.0395). Conclusions. CEA and CA19-9 are useful indicators of therapeutic curative effect from cetuximab combined with first-line chemotherapy. These markers also helped assess cetuximab resistance and served as early predictors of initial treatment effectiveness. Furthermore, a simultaneous increase or decrease in the levels of both indicators was consistent with the observed differences in PFS.

Effect of the addition of bevacizumab to first-line FOLFOX on efficacy, including response rate, progression-free survival, and overall survival, in patients with metastatic colorectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 588-588
Author(s):  
M. Suenaga ◽  
N. Mizunuma ◽  
S. Matsusaka ◽  
E. Shinozaki ◽  
M. Ogura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Survival Benefit ◽  
Response Rate ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

588 Background: Bevacizumab (BV) is a recombinant, humanized monoclonal antibody against vascular endothelial growth factor. Used in combination with chemotherapy, BV has been shown to improve survival in both first- and second-line treatment for metastatic colorectal cancer (mCRC). However, it was reported that addition of BV to FOLFOX conferred only little survival benefit (Saltz et al. JCO2008). The aim of this study was to assess the efficacy of addition of BV to FOLFOX in first-line treatment for patients with mCRC. Methods: Bevacizumab was approved for mCRC in July 2007 in Japan. This study was conducted at a single institution and comprised 217 consecutive patients receiving first-line treatment for mCRC between 2005 and 2009. The primary objective was to compare survival benefit in patients treated with FOLFOX4 (FF) between 2005 and 2007 with that in patients receiving FOLFOX4+BV 5 mg/kg (FF+BV) between 2007 and 2009. Results: Total number of patients in the FF and FF+BV groups was 132 and 85, respectively. Characteristics of patients were as follows (FF vs. FF+B): median age, 62 yrs (range 28-76 yrs) vs. 60 yrs (range16-74 yrs); ECOG PS0, 98.8% vs. 81.8%; and median follow-up time, 20.8 months vs. 24.4 months. Median progression-free survival (PFS) in the FF and FF+BV groups was 10 months (95% CI, 8.7-11.3) and 17 months (95% CI, 10.2-14.1), while median overall survival (OS) was 21 months (95% CI, 17.9-24.1) and not reached, respectively. Response rate was 46% (95% CI, 37- 54) in FF, and 62% (95% CI, 51-73) in FF+BV. Addition of BV to FOLFOX4 significantly improved PFS (p=0.002) and OS (p<0.001). Conclusions: The additive effect of BV for first-line FOLFOX was reconfirmed. These data indicate potential survival benefits from the addition of BV to FOLFOX in first-line treatment of mCRC. In addition, PFS may be a sensitive indicator of outcome prior to post-treatment. No significant financial relationships to disclose.

Phase II trial of combined chemotherapy with irinotecan, S-1, and bevacizumab (IRIS/Bev) in patients with metastatic colorectal cancer: Update analysis—Hokkaido Gastrointestinal Cancer Study Group (HGCSG) trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3593-3593
Author(s):  
Satoshi Yuki ◽  
Yoshito Komatsu ◽  
Takuto Miyagishima ◽  
Takashi Kato ◽  
Kazuteru Hatanaka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Primary Endpoint ◽  
Performance Status ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Grade 3 ◽  
First Line Treatment

3593 Background: The FIRIS study (Muro K et al. Lancet Oncol 2010;11:853–860) previously demonstrated the non-inferiority of Irinotecan plus S-1(IRIS) to FOLFIRI for metastatic colorectal cancer(mCRC), with progression-free survival (PFS) as the primary endpoint. We previously reported that IRIS plus bevacizumab(IRIS/bev) is very effective as first-line treatment (Komatsu Y et al. ESMO 2010). We now report the updated results of this study. Methods: Eligible patients had to have mCRC with a confirmed diagnosis of adenocarcinoma, an age of >20 years, ECOG performance status (PS) of 0-1, and no history of prior chemotherapy. S-1 40-60 mg twice daily p.o. was given on days 1-14 and irinotecan 100 mg/m2 and bevacizumab 5 mg/kg i.v. were given on days 1 and 15 of a 28-day cycle. The primary endpoint was safety. The secondary endpoints included overall response (OR), progression-free survival (PFS), and overall survival (OS). Results: The target number of 53 patients was enrolled as of March 2009. The results are reported for 52 patients with evaluable lesions. The clinical characteristics of the patients were as follows. The median age was 63.5 years (range, 48 to 82). The male:female ratio was 3:2. The performance status on the Eastern Cooperative Oncology Group scale was 0. In January 2012, on safety analysis, the incidence of grade 3 or 4 neutropenia was 27%. The incidences of other grade 3 or 4 adverse reactions were as follows: diarrhea, 17%; anorexia, 4%; stomatitis, 2%; hypertension, 21%; and gastrointestinal perforation, 0%. The overall response rate was 63.5%. Three patients had complete response. Thirty patients had partial response, 16 had stable disease, none had progressive disease, and 3 were not evaluable. Median progression-free survival was 17.0 months and median survival time was 39.6 months. Conclusions: IRIS/Bev is a remarkably active and generally well-tolerated first-line treatment for patients with mCRC. Randomized control trial comparing this regimen with oxaliplatin containing regimen(XELOX or mFOLFOX6 plus bevacizumab) is being planned.

Addition of bevacizumab to first-line FOLFOX4 and overall survival in patients with metastatic colorectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 610-610 ◽  
Author(s):  
Mitsukuni Suenaga ◽  
Satoshi Matsusaka ◽  
Nobuyuki Mizunuma ◽  
Eiji Shinozaki ◽  
Mariko Ogura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

610 Background: In our previous report, addition of bevacizumab (BV) to the FOLFOX4 regimen appeared to significantly improve response rate, progression-free survival and overall survival in first-line treatment for patients with metastatic colorectal cancer (mCRC) (Suenaga M, et al. ASCO-GI 2011 [abstr 588]). Update results met median overall survival, and statistical analysis of survival was performed. Methods: An observational cohort study was carried out on all eligible patients scheduled to receive FOLFOX4 (n = 128) or FOLFOX4+BV (n = 85) between 2005 and 2007, 2007 and 2009, with a median follow-up time of 20.4 months vs. 30.2 months, respectively. Predefined efficacy endpoints were treatment characteristics, response rates, progression-free survival, and overall survival in the periods of time observed. Results: Median progression-free survival was 9.9 months (95% CI, 8.4-11.4) in the FOLFOX4- and 17 months (95% CI, 11.8-22.3) in the FOLFOX4+BV-treated patients (p=0.002). Median overall survival times were 20.5 months (95% CI, 16.9-24) and 38.8 months (95% CI, 32.9-44.8) in the two groups, respectively (p<0.001). In the ECOG PS 0 population, progression-free survival in the FOLFOX4 and FOLFOX4+BV groups was 11 months and 17 months with a hazard ratio of 0.63 (95% CI, 0.44-0.89) in favour of FOLFOX4+BV, similarly in OS with a hazard ratio of 0.53 (95% CI, 0.36-0.77). Subgroup population received 5-FU plus leucovorin (FL) as maintenance during oxaliplatin discontinuation due to adverse events had longer PFS or OS in both groups, though no significance. PFS were 14.7 and 21.6 months, and OS were 29 and 45.9 months, respectively. Secondary resection was performed more in FOLFOX4+BV (11.8%) than FOLFOX4 (3.9%) patients. Conclusions: These data indicate potential survival benefits from the addition of BV to the FOLFOX4 regimen as first-line treatment for mCRC. Maintenance using FL after discontinuation of oxaliplatin due to adverse events appeared to be an essential factor for better survival.

Phase II study alternating mFOLFOX 6 and FOLFIRI (FIREFOX) plus bevacizumab (bev) regimen in first-line treatment of advanced colorectal cancer in Japanese patients (KSCC 0801).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 602-602
Author(s):  
Yutaka Ogata ◽  
Yoshito Akagi ◽  
Yoshihiro Kakeji ◽  
Yasunori Emi ◽  
Eiji Oki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
Response Rate ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
First Line ◽  
Eligibility Criteria ◽  
Free Survival ◽  
Ecog Ps

602 Background: The Kyushu Study group of Clinical Cancer conducted a phase II study that evaluated the FIREFOX regimen. (KSCC0701, Akagi et al, J Clin Oncol 28:15s, 2010). This study demonstrated the efficacy and mild neurotoxicity of this regimen. The present study evaluated the efficacy and safety of the FIREFOX plus bevacizumab (bev). Methods: Eligibility criteria included histologically confirmed advanced colorectal cancer, ECOG PS 0-2 and adequate bone marrow, renal and hepatic function. Patients (pts) received an alternating regimen of 4 cycles of mFOLFOX-6 plus bev (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, bev 5 mg/kg d1 followed by 400 mg/m2 bolus 5-FU and a 46-hr 2,400 mg/m2 5-FU infusion every 2 weeks) followed by 4 cycles of FOLFIRI plus bev (oxaliplatin replaced with irinotecan 150 mg/m2 d1). This schedule was repeated until unacceptable toxicity or disease progression occurred. The primary endpoint is progression-free survival. (UMIN000001312) Results: Of the 52 pts enrolled from May 2008 to July 2009. Two of the patients did not fulfill the eligibility criteria. M/F, 30/20; median age, 59.5 years (range 37 - 75); ECOG PS 0/1/2, 46/4/0. The median number of administration cycles was 14 (range, 2 - 44). Response rate (RECIST criteria) for CR, PR, SD, PD and NE were 2 (4%), 28 (56%), 14 (28%), 4 (8%) and 2 (4%), respectively. An overall response rate was 60% (95% CI: 45 - 74%). Median progression-free survival was14.2 M (95% CI: 10.6 M-16.3 M) and median overall survival was 27.5 M (95% CI; 22.4 M – not determined). The 2-year survival rate was 56.8%. Of the 52 pts evaluated for toxicity. The most common grade 3-4 adverse events were leukopenia (7.7%), neutropenia (32.7%), anemia (1.9%), fatigue (9.6%), anorexia (13.5%), stomatitis (3.8%), neurotoxicity (3.8%), hypertension (1.9%), diarrhea (7.7%), febrile neutropenia (3.8%), nausea (9.6%), vomiting (5.8%), hypersensitivity (3.8%), and thromboembolism (1.9%). Conclusions: The results of this phase II study show that the FIREFOX plus bev regimen is effective and well tolerated in the first-line treatment of advanced colorectal cancer. The low rate of neurotoxicity is also promising.

Predictive value of baseline CD66e/CEA serum levels on efficacy of bevacizumab-based treatment in advanced colorectal cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 388-388
Author(s):  
Gerald W. Prager ◽  
Kira H. Bramswig ◽  
Christoph Zielinski
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Response ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Serum Levels ◽  
First Line ◽  
Chi Square ◽  
Free Survival ◽  
Group I ◽  
Group Ii

388 Background: CD66e (Carcinoembryonic antigen, CEA) affects tumorigenesis by enhancing tumor cell survival and by inducing tumor-angiogenesis. This study aimed to evaluate baseline CD66e serum levels as response predictor to bevacizumab-based therapies in patients with metastatic colorectal cancer (mCRC). Methods: 298 patients with mCRC and first-line treatment were analyzed. 169 mCRC received bevacizumab plus chemotherapy and 129 patients with mCRC treated with cetuximab (KRAS w.t.) and identical chemotherapy (FOLFOX6 or FOLFIRI). Disease control (DC), progression-free survival (PFS) as well as overall survival (OS) were assessed and related to baseline CD66e-serum levels. Patients with basal CD66e-serum levels below the statistical median of 26.8 ng/ml (group I) were compared with patients with higher CD66e levels (group II). Results: Baseline CD66e serum levels inversely correlated with therapeutic response in patients receiving bevacizumab-based treatment (chi square i<0.005: OR=0.579, 95% C.I. 0.422, 0.795; p<0.001), inversely correlated with median PFS leading to a median PFS benefit of 2.1 month for patients in group I when compared with group II (p<0.05), as well as inversely correlated with median OS (37.5 month vs. 21.4 month, p<0.05). In an independent cohort of 129 patients treated with cetuximab-based therapy, no association of therapeutic response or PFS with CD66e serum levels was found (p>0.05). Conclusions: These data give first evidence of CD66e as a predictive biomarker for the efficacy of first-line bevacizumab-based therapy in patients with mCRC.

A phase III study of comparing FOLFOX+/-bevacizumab with FOLFOX+/-bevacizumab+ high-dose intravenous vitamin C as first-line therapy in patients with advanced colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS4115-TPS4115
Author(s):  
Feng Wang ◽  
Jian Xiao ◽  
Yan-Qiao Zhang ◽  
Xianglin Yuan ◽  
Weijia Fang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin C ◽  
Advanced Colorectal Cancer ◽  
Progression Free Survival ◽  
High Dose ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Intravenous Vitamin ◽  
High Dose Vitamin

TPS4115 Background: Previous studies showed that high dose vitamin C especially when administered intravenously might have anti-cancer effect. A recent preclinical study found that human colorectal cancer cells harboring KRAS or BRAF mutations are selectively killed by high dose vitamin C. Our phase I dose-escalation and expansion study has shown that high dose (up to 1.5g/kg) intravenous vitamin C with FOLFOX or FOLFIRI is well tolerated in patients with colorectal or gastric cancer. This trial is a randomized, multicenter, phase Ⅲ study of high dose vitamin C infusion combined with FOLFOX +/- bevacizumab versus FOLFOX +/- bevacizumab as first-line therapy in patients with advanced colorectal cancer. Methods: This study has enrolled patients with histologically confirmed metastatic adenocarcinoma of colorectum, normal G6PD status and no prior treatment for metastatic disease. 432 patients are randomized 1:1 into one of two groups. Patients in the control group are treated with mFOLFOX6 (oxaliplatin 85 mg/m² d1 concurrent with leucovorin 400 mg/m², followed by bolus 5FU 400 mg/m² d1, followed by infusional 5FU 2400 mg/m² over 46 hours) with or without bevacizumab (5mg/kg, d1) every 2 weeks. Patients in the experimental group are treated with vitamin C intravenously (1.5g/kg/day, d1-3) in combination with mFOLFOX6 with or without bevacizumab every 2 weeks. Randomization is stratified by the location of primary site (left-sided or right-sided) and treatment with bevacizumab (with or without). The primary endpoint is progression free survival (assessed by investigator per RECIST v1.1). Secondary endpoints are overall survival, response rate, assessment of treatment-related adverse events, progression free survival and overall survival in RAS or BRAF mutant patients. Genome, microbiome and metabolome are also assessed. Clinical trial information: NCT02969681 .

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