Abstract 346: Tumoral expression of folate-associated genes is associated with progression-free survival of patients with advanced colorectal cancer

2021 ◽  
Author(s):  
Yvonne Wettergren ◽  
Elisabeth Odin ◽  
Göran Carlsson ◽  
Pushpa Saksena ◽  
Anders Edsjö ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Progression Free Survival ◽  
Free Survival

scholarly journals Efficacy and Safety of Regorafenib Combined with Toripalimab in the Third-Line and beyond Treatment of Advanced Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Wei Yu ◽  
Qiaomeng Tao ◽  
Yufeng Zhang ◽  
Fengming Yi ◽  
Long Feng
Keyword(s):  
Colorectal Cancer ◽  
Adverse Reactions ◽  
Advanced Colorectal Cancer ◽  
Cox Regression ◽  
Combined Therapy ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Free Survival ◽  
The Third ◽  
Third Line

Background. The most effective treatment of immune checkpoint inhibitors (ICIs) is restricted in microsatellite instability (MSI-H) subsets of advanced colorectal cancer, but MSI-H only accounts for 4-5% among them. ICIs are completely ineffective in advanced colorectal cancer patients with microsatellite stable (MSS), according to literatures published. Regorafenib is a novel tyrosine kinase inhibitor (TKIs) that could normalize tumor blood vessels by inhibiting vascular endothelial growth factor receptor and its downstream, thus improving cytotoxic T cell infiltration in tumor microenvironment, which has a synergistic effect with ICIs. Toripalimab is a type of anti-PD-1 monoclonal antibody produced by Junshi Biosciences in China. Herein, we aimed to explore the efficacy and safety of regorafenib combined with toripalimab in the third-line and beyond treatment of advanced colorectal cancer. Methods. We evaluated the outcomes of MSS patients with advanced colorectal cancer who received regorafenib combined with toripalimab in the Second Affiliated Hospital of Nanchang University from June 2019 to January 2021. These patients had previously received at least second-line treatment; the regimens were oxaliplatin and irinotecan-based chemotherapy and/or accompanied with bevacizumab or cetuximab. Thirty-three patients were treated orally with regorafenib 80 mg or 120 mg once daily for 21 days, 28 days as a cycle, combined with intravenous toripalimab until disease progression or intolerant to adverse reactions. We used the Kaplan–Meier method to estimate the rate of progression-free survival (PFS) and log-rank method to do a statistical test of the survival curve. The Cox regression model was used to analyze the influence of multiple factors on PFS. The primary endpoints were objective remission rate (ORR) and disease control rate (DCR). The secondary endpoints were the incidence of adverse reactions and median progression-free survival (mPFS). Results. The evaluation of treatment effects was assessed according to RECIST 1.1. Four patients (12.12%) got partial response, twelve patients (36.36%) experienced stable disease, and seventeen patients (51.52%) suffered progressive disease. ORR was 12.12% and DCR was 48.48%. mPFS was 113 days (95% CI: 0–272.1). In univariate analysis, patients who had previously received second-line treatment were significantly better than those who had received third-line or more treatment ( p = 0.005 ). Lung metastasis was a negative factor in combined therapy ( p = 0.032 ). Five patients without previous treatment of bevacizumab were effective. Previous treatment without bevacizumab showed a trend of effective when combination therapy ( p = 0.034 ). It was also a positive factor that the Eastern Cooperative Oncology Group performance status (ECOG) score was 0 ( p = 0.034 ). Multivariable Cox regression analysis showed the number of previous chemotherapy lines and excision of primary lesions were independent prognostic factors. The most common treatment-related adverse reactions were hand-foot syndrome (33.33%), liver dysfunction (27.27), hypothyroidism (24.24%), fever (24.24%), fatigue (21.21%), leukopenia (15.15%), hypertension (12.12%), platelet count decreased (6.06%), diarrhea (3.03%), and myocarditis (3.03%); one patient stopped treatment as myocarditis. The incidence of grade 3/4 adverse reactions was 9.09%. Conclusions. Regorafenib combined with toripalimab has a promising effect in the third-line and beyond treatment of advanced colorectal cancer. In the early use of combination therapy, excision of primary lesions can have a positive impact in regorafenib and toripalimab combination. This treatment-related adverse reactions are tolerant in combined therapy.

Randomized Multicenter Phase II Trial of Two Different Schedules of Capecitabine Plus Oxaliplatin as First-Line Treatment in Advanced Colorectal Cancer

2003 ◽  
Vol 21 (7) ◽  
pp. 1307-1312 ◽  
Author(s):  
Werner Scheithauer ◽  
Gabriela V. Kornek ◽  
Markus Raderer ◽  
Birgit Schüll ◽  
Katharina Schmid ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Time ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
Response Rate ◽  
Progression Free Survival ◽  
Synergistic Activity ◽  
Free Survival ◽  
Multicenter Phase ◽  
To Receive

Purpose: Capecitabine and oxaliplatin, two new agents with potential synergistic activity, have demonstrated promising antitumor efficacy in advanced colorectal cancer (ACC). Preclinical and clinical evidence indicating that dose intensification of the oral fluorouracil prodrug might result in improved therapeutic results led us to the present randomized multicenter phase II study. Patients and Methods: Eighty-nine patients with bidimensionally measurable ACC previously untreated for metastatic disease were randomly allocated to receive oxaliplatin 130 mg/m2 day 1 plus capecitabine 2,000 mg/m2/d days 1 to 14 every 3 weeks (arm A) or to receive oxaliplatin 85 mg/m2 days 1 and 14 combined with capecitabine 3,500 mg/m2 days 1 to 7 and 14 to 21 every 4 weeks (arm B). In both treatment arms, chemotherapy was continued for a total of 6 months unless there was prior evidence of progression of disease. Results: Patients allocated to the high-dose capecitabine combination arm B had a higher radiologically confirmed response rate (54.5% v 42.2%) and a significantly longer median progression-free survival time than those allocated to control arm A (10.5 v 6.0 months; P = .0013). Median overall survival times cannot be calculated for either treatment arm at this point. Despite a 34% higher dose intensity of capecitabine in arm B, there was no difference in hematologic toxicity between treatment arms (neutropenia/thrombocytopenia: 60%/43% in arm B v 56%/33% in arm A). Similarly, the incidence rate and degree of nonhematologic adverse events were comparable: The most commonly encountered symptoms (all grades, arm A and arm B) included nausea/emesis (A: 58%; B: 62%), diarrhea (A: 44%; B: 31%), peripheral sensory neuropathy (A: 80%; B: 83%), and fatigue (A: 40%; B: 50%). Conclusion: Results of this study indicate that both combination regimens are feasible, tolerable, and clinically active. The dose-intensified bimonthly capecitabine arm, however, seems to be more effective in increasing both response rate and progression-free survival time.

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.

Correlation of immunological effects of anti-VEGF therapy with progression-free survival of advanced colorectal cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14559-e14559
Author(s):  
M. Manzoni ◽  
B. Rovati ◽  
S. Delfanti ◽  
K. Bencardino ◽  
S. Chatzileontiadou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Efficacy ◽  
Advanced Colorectal Cancer ◽  
Immune Surveillance ◽  
Flow Cytometric Analysis ◽  
Progression Free Survival ◽  
Absolute Number ◽  
Biological Data ◽  
Free Survival ◽  
Colorectal Cancer Patients

e14559 Background: The clinical efficacy of Bevacizumab (BEV) in advanced colorectal cancer (mCRC) could be related not only to its well-established effect on tumor neoangiogenesis but also to a counteraction of VEGF-mediated dendritic cell (DC) abnormalities. The addition of BEV to chemotherapy (CT) may improve the number and function of blood DCs in cancer pts. We have focused on the correlation between this effect and the clinical efficacy of a BEV-based, 1st-line treatment for mCRC. Methods: Starting from January 2007 we performed a flow cytometric analysis of PB lymphocytes and DC subsets in 53 mCRC pts who had not received prior CT for metastatic disease or for whom 6 months had elapsed since adjuvant CT (M/F: 31/22, median age: 59yrs; range 32–75; ECOG PS <2), before and every 3 courses of a BEV+CT (5-FU± CPT11± Oxaliplatin) program. Biological data of the 42 evaluable pts that received all the planned treatment were correlated to both tumor response (OR) and progression free survival (PFS). Results: During treatment, DCs and their subsets showed a progressive, significant increase in absolute number, with respect to baseline, both in responder (CR,PR,SD) (67%) and in non responder pts. This effect on the DC profile was evidenced in responder pts up to 4 weeks since the last treatment course. After therapy completion, pts with PFS > 15 months (58%) showed DC and DC1 absolute number significantly higher with respect to pts with shorter PFS (p< .02). Conclusions: The recovery of blood DCs induced by 1st- line, BEV-based therapy in mCRC pts indicates a potential additional anticancer mechanism of this drug. The improvement of DC number does not influence OR but correlates with longer PFS. This suggests that BEV can influence tumor regrowth by contributing to overcome the impairement of the host immune surveillance induced by VEGF. No significant financial relationships to disclose.

Gemcitabine and capecitabine as third-line treatment in patients with metastatic colorectal cancer after failure of irinotecan and oxaliplatin.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 620-620 ◽  
Author(s):  
M. Qiu ◽  
F. Bi ◽  
J. Liu ◽  
Q. Li ◽  
C. Yi
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Performance Status ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Disease Stabilization ◽  
Third Line ◽  
Third Line Treatment

620 Background: There is no standard chemotherapeutic regimen for patients with advanced colorectal cancer (CRC) progressing after combination regimens including irinotecan and oxaliplatin and having good performance status. 5-FU and gemcitabine are synergistic in preclinical studies of colon cancer cells. And gemcitabine also increases intracellular release of 5-FU from capecitabine. The aim of this study is to evaluate the efficacy and tolerance of the gemcitabine/capecitabine combination as third-line treatment for patients with advanced colorectal cancer. Methods: Between May 2007 and September 2009, the data on 12 patients with metastatic colorectal cancer after failure of irinotecan- and oxaliplatin-containing regimens reviewed retrospectively. The median patient age was 54.0 years (range 37-77). The ECOG performance status was 0, 1 or 2. All patients has 2 or more previous chemotherapy. Patients received GemCap regimen (oral capecitabine 1,000 mg/m2 twice daily on days 1 to 14 plus Gem 1,000 mg/m2 on days 1 and 8 every 3 weeks). Eleven patients were evaluable for the response and all patients were evaluable for toxicity. Results: No partial response was achieved and disease stabilization in 4 (36.4.3%) cases. Median progression-free survival and median overall survival were 9.1 weeks (range 3.0-18.0) and 22.3 weeks (range 10.5- 53.0). Four patients with disease stabilization had longer median progression-free survival than those with disease progression (13 weeks vs. 6.2 weeks). No toxic deaths occurred. Grade 3 toxicities were thrombocytopenia (in 2 patients), neutropenia (in 2 patients) and mucositis (in 1 patient), hand-foot syndrome (in 1 patient) and GI toxicity (in 2 patients). Conclusions: The combination of gemcitabine and capecitabine was found to be a safe palliative regimen for heavily pretreated patients with metastatic CRC. Despite no patients had radiologic response, patients with disease stabilization achieved better progression-free survival. This regimen seems to be potentially effective regimen in the treatment of CRC. No significant financial relationships to disclose.

Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study.

1997 ◽  
Vol 15 (2) ◽  
pp. 808-815 ◽  
Author(s):  
A de Gramont ◽  
J F Bosset ◽  
C Milan ◽  
P Rougier ◽  
O Bouché ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Continuous Infusion ◽  
Low Dose ◽  
Advanced Colorectal Cancer ◽  
Progression Free Survival ◽  
High Dose ◽  
Survival Times ◽  
Free Survival ◽  
Therapeutic Ratio ◽  
Grade 3

PURPOSE This multicenter study compared the therapeutic ratio of a monthly schedule of low-dose leucovorin (LV) and fluorouracil (5-FU) bolus with a bimonthly schedule of high-dose LV and 5-FU bolus plus continuous infusion in patients with advanced colorectal cancer. PATIENTS AND METHODS Of the 448 patients randomly assigned to treatment, 433 were assessable. Treatment A was a monthly regimen of intravenous (IV) LV 20 mg/m2 plus bolus 5-FU 425 mg/m2 for 5 days every 4 weeks. Treatment B was a bimonthly regimen of IV LV 200 mg/m2 as a 2-hour infusion followed by bolus 5-FU 400 mg/m2 and 22-hour infusion 5-FU 600 mg/m2 for 2 consecutive days every 2 weeks. Therapy was continued until disease progression. Second-line chemotherapy, which included 5-FU continuous infusion, was allowed in both arms. RESULTS The response rates in 348 patients with measurable lesions were 14.4% (monthly regimen) and 32.6% (bimonthly regimen) (P = .0004). The median progression-free survival times were 22 weeks (monthly regimen) and 27.6 weeks (bimonthly regimen) (P = .0012). The median survival times were 56.8 weeks (monthly regimen) and 62 weeks (bimonthly regimen) (P = .067). Grade 3-4 toxicities occurred in 23.9% of patients in the monthly arm compared with 11.1% of those in the bimonthly arm (P = .0004). Patients in arm A more frequently experienced severe granulocytopenia (7.3% v 1.9%), diarrhea (7.3% v 2.9%), and mucositis (7.3% v 1.9%) than patients in arm B. CONCLUSION The bimonthly regimen was more effective and less toxic than the monthly regimen and definitely increased the therapeutic ratio. However, there was no evidence of increased 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.

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