The study of efficacy and safety of chemotherapy plus bevacizumab with oxaliplatin stop-and-go strategy in first-line treatment for metastatic colorectal cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 761-761
Author(s):  
Nao Takano ◽  
Goro Nakayama ◽  
Yasuhiro Kodera
Keyword(s):  
Colorectal Cancer ◽  
Maintenance Therapy ◽  
Metastatic Colorectal Cancer ◽  
Dose Intensity ◽  
Sensory Neuropathy ◽  
Efficacy And Safety ◽  
First Line ◽  
Peripheral Sensory Neuropathy ◽  
Stop And Go ◽  
Peripheral Sensory

761 Background: In metastatic colorectal cancer (mCRC), the benefit of the molecular targeted drugs added to chemotherapy has been reported and a combination therapy of capecitabine (CAP) and oxaliplatin (CapeOX) plus bevacizumab (BEV) is an established first-line therapy for mCRC. However, the management of the cumlateve neurotoxicity of oxaliplatin still remains. We evaluated the efficacy and safety of CapeOX plus BEV with oxaliplatin stop and go strategy. Methods: Two prospective clinical trials of previously untreated unresectable mCRC were analyzed. Fifty four patients were treated with CapeOX plus BEV with oxaliplatin stop and go strategy (CCOG-0902). They were treated 4 cycles of CapeOX plus BV therapy followed by maintenance therapy of 8 cycles of Capecitabine plus BV and oxaliplatin reintroduction was scheduled after maintenance therapy or upon tumor progression. On the other group, forty seven patients were treated with mFOLFOX6 plus BEV (CCOG-0801). Progression free survival (PFS), overall survival (OS), response rate (RR), disease control rate (DCR), relative dose intensity (RDI), and frequency of peripheral sensory neuropathy (PSN) were evaluated. Results: Patient characteristics were balanced between the two groups. The median RDI of oxaliplatin in CCOG-0902 group was significantly higher, 92% than in CCOG-0801 group, 80%. RR and DCR were 61.5% and 96.3% respectively, in CCOG-0902 group, compared with 61.7% and 89.4% respectively, in CCOG-0801 group. Median PFS was 13.6 and 30.5 months, respectively, compared with 11.7 and 31.6 months, respectively, in CCOG-0801 group (p=not significant). The frequency of peripheral sensory neuropathy (PSN) was 19.0% (>Grade3: 1.9%) of patients in CCOG-0902 group compared with 72.3% (>grade 3: 17.0%) in CCOG-0801 group. Conclusions: CapeOX plus BV with oxaliplatin stop and go strategy could have same efficacy as continuing oxaliplatin with avoiding PSN. Clinical trial information: UMIN000006478.

The efficacy and safety of XELOX plus bevacizumab with oxaliplatin stop-and-go strategy in first-line treatment for metastatic colorectal cancer: Final report of CCOG-0902 study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14552-e14552
Author(s):  
Naomi Hayashi ◽  
Goro Nakayama ◽  
Kiyoshi Ishigure ◽  
Hiroyuki Yokoyama ◽  
Toyohisa Yaguchi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Maintenance Therapy ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Final Report ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
Stop And Go ◽  
First Line Treatment

e14552 Background: XELOX plus bevacizumab (BEV) is an established first line therapy for metastatic colorectal cancer (mCRC). However, the cumulative neurotoxicity of oxaliplatin often requires therapy to be discontinued while the patient is still responding. The aim of this study was to evaluate efficacy and safety of XELOX plus BEV with oxaliplatin stop and go strategy. Methods: Fifty four patients with unresectable mCRC were enrolled as first line treatment. They were treated with four cycles of XELOX plus BEV, followed by maintenance therapy with capecitabine (Cape) plus BEV. Reintroduction of oxaliplatin was scheduled after eight cycles of Cape plus BEV or upon tumor progression. The primary endpoint was progression free survival (PFS). Results: Forty nine patients (90%) achieved to the maintenance therapy and thirty two patients (59%) were reintroduced oxaliplatin. After a median follow-up time of 24.2 months, median PFS was 13.4 months (95%CI: 11.7-15.1), median duration of disease control was 13.8 months (95%CI: 11.6-16.0) and median overall survival was 29.0 months (95%CI: 23.1-34.9). The response rate and disease control rate were 57.4% and 96.3% in the initial XELOX plus BEV therapy, 6.1% and 73.5% in Cape plus BEV maintenance therapy, and 0% and 72.4% in reintroduced XELOX plus BEV therapy. The incidence of neuropathy was 38% in initial therapy, 33% in maintenance therapy and 43% in reintroduced therapy. Conclusions: XELOX plus bevacizumab therapy with oxaliplatin stop-and-go strategy was feasible to maintain long disease control without increasing severe neurotoxicity in first-line treatment for mCRC. Clinical trial information: UMIN000006478.

The efficacy and safety of CapeOX plus bevacizumab therapy with a planned oxaliplatin stop-and-go strategy in patients with metastatic colorectal cancer: A multi-center, single-arm, phase II study (CCOG-0902 study).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 795-795
Author(s):  
Yuuki Sunakawa ◽  
Goro Nakayama ◽  
Kiyoshi Ishigure ◽  
Hiroyuki Yokoyama ◽  
Keisuke Uehara ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Maintenance Therapy ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Efficacy And Safety ◽  
Stop And Go ◽  
Grade 3

795 Background: The aim of this study was to evaluate the efficacy and safety of CapeOX plus bevacizumab with a planned oxaliplatin stop-and-go strategy in Japanese patients with metastatic colorectal cancer (mCRC). Methods: Patients with untreated mCRC were treated with 4 cycles of CapeOX plus bevacizumab therapy, followed by capecitabine plus bevacizumab maintenance therapy. Reintroduction of oxaliplatin was scheduled after 8 cycles of maintenance therapy or upon tumor progression. The primary endpoint was progression-free survival (PFS), and secondary end points included overall survival (OS), objective response rate to each treatment, reintroduction rate of oxaliplatin, frequency of peripheral sensory neuropathy (PSN), and safety. Results: The 52 patients who received the protocol treatment were included in the evaluation of efficacy and safety. Median PFS and OS were 12.4 months (95% confidence interval [CI], 10.0–14.8) and 30.6 months (95% CI, 27.6–33.5), respectively. The objective response rates were 55.8% for the initial CapeOX plus bevacizumab therapy, 17.8% for capecitabine plus bevacizumab maintenance therapy, and 31.0% for reintroduced CapeOX plus bevacizumab therapy. The frequency of PSN was 63.5%, including 3.8% of patients with grade 3 PSN. No patients required treatment discontinuation because of PSN during the induction or maintenance therapy. Conclusions: CapeOX plus bevacizumab therapy with a planned oxaliplatin stop-and-go strategy is a feasible first-line treatment for Japanese patients with mCRC. Clinical trial information: UMIN000006478.

scholarly journals Multicenter phase II clinical study of the efficiency and safety of capecitabine plus intermittent oxaliplatin with bevacizumab as first-line therapy in patients with metastatic colorectal cancer: the VOICE trial

2021 ◽  
Author(s):  
Chihiro Kosugi ◽  
Keiji Koda ◽  
Tadamichi Denda ◽  
Keiichiro Ishibashi ◽  
Hideyuki Ishida ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Maintenance Therapy ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Induction Therapy ◽  
Maintenance Treatment ◽  
Dose Intensity ◽  
University Hospital ◽  
Efficacy And Safety ◽  
First Line

Abstract Background: In the first-line treatment of metastatic colorectal cancer (mCRC) patients with CAPOX plus bevacizumab, the optimal duration of maintenance treatment without oxaliplatin to avoid discontinuation of therapy due to peripheral sensory neuropathy (PSN) remains unknown. The aim of this phase II study was to evaluate the efficacy and safety of combination therapy with five-cycle CAPOX (capecitabine plus oxaliplatin) plus bevacizumab, followed by five-cycle maintenance therapy with capecitabine plus bevacizumab and reintroduction of CAPOX plus bevacizumab for five cycles, with a preplanned oxaliplatin intermittent strategy in mCRC.Methods: Patients with untreated mCRC were administered CAPOX [oxaliplatin 130 mg/m2 and capecitabine (2000 mg/m2 daily) as intermittent treatment for 14 days, followed by a 7-day treatment-free interval, every 3 weeks] + bevacizumab (7.5 mg/kg) every 3 weeks for five cycles, maintenance treatment without oxaliplatin for five cycles, and CAPOX + bevacizumab reintroduction for five cycles or upon tumor progression. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the time to treatment failure (TTF), overall survival, response rate (RR), and safety.Results: Forty-seven patients who fulfilled the inclusion criteria were enrolled in the evaluation of efficacy and safety. The relative dose intensity and the cumulative dose of oxaliplatin during the overall treatment period were 649.1 mg/m2 and 1132.5 mg, respectively. Median PFS was 14.1 months (95% confidence interval [CI], 8.6–19.5), and median TTF was 12.3 months (95% CI, 10.3–14.3). The objective RRs were 51.1% (24/47) during induction therapy, 58.3% (21/36) during maintenance therapy, and 63.6% (14/22) during reintroduction therapy. The frequency of patients with neutropenia, diarrhea, PSN, venous thromboembolism, or grade ≥ 3 allergic reactions was 2.1%.Conclusion: CAPOX plus bevacizumab therapy with a preplanned intermittent oxaliplatin strategy consisting of brief five-cycle induction therapy, five-cycle maintenance therapy with capecitabine plus bevacizumab, and five-cycle reintroduction therapy consisting of CAPOX plus bevacizumab is safe and effective for mCRC patients.Trial registration: This trial was registered with the University Hospital Medical Information Network on 7 June 2011 (UMIN ID: 000005732).

The efficacy and safety of XELOX plus bevacizumab with oxaliplatin stop-and-go strategy in first-line treatment for metastatic colorectal cancer: CCOG 0902 study.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 564-564
Author(s):  
Takuya Watanabe ◽  
Goro Nakayama ◽  
Kiyoshi Ishigure ◽  
Naomi Hayashi ◽  
Toyohisa Yaguchi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Maintenance Therapy ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
Stop And Go ◽  
First Line Treatment

564 Background: XELOX plus bevacizumab (BEV) is an established first-line therapy for metastatic colorectal cancer (mCRC). However, the cumulative neurotoxicity of oxaliplatin often requires therapy to be discontinued while the patient is still responding. The aim of this study was to evaluate efficacy and safety of XELOX plus BEV with oxaliplatin stop and go strategy. Methods: Fifty four patients with unresectable mCRC were enrolled as first-line treatment. They were treated with four cycles of XELOX plus BEV, followed by maintenance therapy with capecitabine (Cape) plus BEV. Reintroduction of oxaliplatin was scheduled after eight cycles of Cape plus BEV or upon tumor progression. The primary endpoint was progression free survival (PFS). Results: Forty nine patients (90%) achieved to the maintenance therapy and thirty one patients (59%) were reintroducted oxaliplatin. The response rates and disease control rates were 57% and 96% in the initial XELOX plus BEV, 6.1% and 73% in Cape plus BEV maintenance therapy. Median PFS in initial XELOX plus BEV was 11.0 months (95%CI: 7.8-14.1). One year survival rate was 86%. Conclusions: XELOX plus BEV was feasible as a first line treatment with mCRC. The most cases achieved disease control during Cape plus BEV maintenance therapy. Clinical trial information: UMIN000006478.

VOICE trial: Final results from multicenter phaseII study of assessment of clinical efficiency and safety in capecitabine plus intermittent oxaliplatin together with bevacizumab as first-line therapy for patients with advanced colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 740-740 ◽  
Author(s):  
Chihiro Kosugi ◽  
Keiji Koda ◽  
Tadamichi Denda ◽  
Keiichiro Ishibashi ◽  
Hideyuki Ishida ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Peripheral Neuropathy ◽  
Primary Endpoint ◽  
Sensory Neuropathy ◽  
Severe Neutropenia ◽  
First Line ◽  
Peripheral Sensory Neuropathy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Peripheral Sensory

740 Background: The FOLFOX with bevacizumab (B-mab) has been established as a standard first-line therapy for metastatic colorectal cancer (mCRC), and OPTIMOX1 study suggested that stop and go strategy for oxaliplatin reduced peripheral sensory neuropathy. The CapeOx is one of the standard treatments for mCRC that has been proven to be as effective as the FOLFOX regimen. Thus we accessed the efficacy and safety of the combination of intermittent CapeOx + B-mab as a first-line therapy in patients with mCRC in this trial. Methods: Eligibility criteria included ECOG PS: 0–1, No Peripheral neuropathy ( < Grade 1). Patients received CapeOX (oxaliplatin 130mg/m2, capecitabine 2000mg/m2 + B-mab 7.5mg/kg) q3 weeks for 5 cycles, maintenance without oxaliplatin for 5 cycles, and reintroduction CapeOX + B-mab for 5 cycles until progression. Primary endpoint was Progression Free Survival (PFS). Results: Between March 2011 and August 2013, 55 pts were enrolled. Baseline characteristics were median age of 67 years (range, 20–83); PS 0/1 (49/6 pts); male/female (33/22 pts), colon/rectum (28/27pts) and metastatic lesion liver/lung/lymph nodes (32/18/21 pts). A total of 47 pts were evaluated as Par Protocol Set population. 38 pts moved from initial CapeOX to maintenance Capecitabine. 20 pts moved to CapeOx reintroduction. Median PFS was 14.7months (95%CI, 8.6–19.5) and Median TTF was 12.3 months (95%CI, 10.3–14.3). Best overall response rate was 48.0%. Oxaliplatin reintroduction rate was 57.4%. Main grade 3/4 toxicity were: neutropenia (1 pt), anemia (1 pt), peripheral neuropathy (1 pt), allergic reaction of oxaliplatin (1 pt), deep vein thrombosis (1 pt), nausea (1 pt), hand-foot syndrome (1 pt), and hypertension (1 pt). Conclusions: This study met its primary endpoint PFS. CapeOx intermittent oxaliplatin indicated to reduce incidence of severe neutropenia and peripheral sensory neuropathy. The results suggested that our treatment strategy was well tolerate and effective for first line therapy in mCRC, and maintenance duration for 5 cycles, was reasonable. Clinical trial information: UMIN000005732.

scholarly journals Colorectal Cancer Biomarkers in the Era of Personalized Medicine

2019 ◽  
Vol 9 (1) ◽  
pp. 3 ◽  
Author(s):  
Jai Patel ◽  
Mei Fong ◽  
Megan Jagosky
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Therapy Response ◽  
Dose Intensity ◽  
Cancer Biomarkers ◽  
Clinical Implications ◽  
Test Results ◽  
First Line ◽  
Genomic Markers ◽  
Generation Sequencing

The 5-year survival probability for patients with metastatic colorectal cancer has not drastically changed over the last several years, nor has the backbone chemotherapy in first-line disease. Nevertheless, newer targeted therapies and immunotherapies have been approved primarily in the refractory setting, which appears to benefit a small proportion of patients. Until recently, rat sarcoma (RAS) mutations remained the only genomic biomarker to assist with therapy selection in metastatic colorectal cancer. Next generation sequencing has unveiled many more potentially powerful predictive genomic markers of therapy response. Importantly, there are also clinical and physiologic predictive or prognostic biomarkers, such as tumor sidedness. Variations in germline pharmacogenomic biomarkers have demonstrated usefulness in determining response or risk of toxicity, which can be critical in defining dose intensity. This review outlines such biomarkers and summarizes their clinical implications on the treatment of colorectal cancer. It is critical that clinicians understand which biomarkers are clinically validated for use in practice and how to act on such test results.

scholarly journals Retrospective analysis of the effect of CAPOX and mFOLFOX6 dose intensity on survival in colorectal patients in the adjuvant setting

2016 ◽  
Vol 23 (3) ◽  
pp. 171 ◽  
Author(s):  
A. Mamo ◽  
J. Easaw ◽  
F. Ibnshamsah ◽  
A. Baig ◽  
Y.S. Rho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dose Reduction ◽  
Real Life ◽  
Disease Free Survival ◽  
Dose Intensity ◽  
Sensory Neuropathy ◽  
Stage Iii ◽  
Cancer Centre ◽  
Peripheral Sensory ◽  
Disease Free

Background Despite lack of a true comparative study, the FOLFOX (5-fluorouracil–leucovorin–oxaliplatin) and CAPOX (capecitabine–oxaliplatin) regimens are believed to be similar in their efficacy and tolerability in the treatment of stage III colorectal cancer. However, that belief has been disputed, because real-life data suggest that the CAPOX regimen is more toxic, leading to more frequent reductions in the delivered dose intensity—thus raising questions about the effect of dose intensity on clinical outcomes.Methods A retrospective data review for two Canadian institutions, the Segal Cancer Centre and the Tom Baker Cancer Centre, considered patients diagnosed with stage III colorectal cancer during 2006–2013. Primary endpoints were dose intensity and toxicity, with a secondary endpoint of disease-free survival.Results The study enrolled 180 eligible patients (80 at the Segal Cancer Centre, 100 at the Tom Baker Cancer Centre). Of those 180 patients, 75 received CAPOX, and 105 received mFOLFOX6. In the CAPOX group, a significant dose reduction was identified for capecitabine compared with 5-fluorouracil in mFOLFOX6 group (p = 0.0014). Similarly, a significant dose reduction was observed for oxaliplatin in mFOLFOX6 compared with oxaliplatin in CAPOX (p = 0.0001). Compared with the patients receiving CAPOX, those receiving mFOLFOX6 were twice as likely to experience a treatment delay of more than 1 cycle-length (p = 0.03855). Toxicity was more frequent in patients receiving mFOLFOX6 (nausea: 30% vs. 18%; diarrhea: 47% vs. 24%; peripheral sensory neuropathy: 32% vs. 3%). At a median follow-up of 40 months, preliminary data showed no difference in disease-free survival (p = 0.598). Pooled data from both institutions were also separately analyzed, and no significant differences were found.Conclusions Our results support the use of CAPOX despite a lack of head-to-head randomized trial data.

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