Impact of omitting fluorouracil from FOLFIRI plus bevacizumab as second-line chemotherapy for metastatic colorectal cancer patients.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 76-76
Author(s):  
Yuki Matsubara ◽  
Toshiki Masuishi ◽  
Takatsugu Ogata ◽  
Taiko Nakazawa ◽  
Kyoko Kato ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Metastatic Colorectal Cancer ◽  
Second Line ◽  
First Line ◽  
Second Line Chemotherapy ◽  
Prior Use ◽  
Metastatic Sites ◽  
Ecog Ps ◽  
Line Chemotherapy

76 Background: FOLFIRI + bevacizumab (FOLFIRI + BEV) is a standard second-line chemotherapy (Cx) for metastatic colorectal cancer (mCRC) patients (pts) who are refractory or intolerant to fluoropyrimidines (FPs) and oxaliplatin (OX). However, the efficacy of continuing FPs as second-line Cx for pts who are refractory to FPs in first-line Cx remains unclear. Methods: We retrospectively evaluated mCRC pts who received irinotecan (IRI) + BEV or FOLFIRI + BEV as second-line Cx at a single institution from Jan 2010 to Apr 2020. The main eligibility criteria were ECOG performance status (PS) of 0-2, known KRAS status, a standard initial dose of fluorouracil (5-FU) (bolus 400 mg/m2, infusional 2400 mg/m2) in FOLFIRI + BEV and IRI (150 mg/m2), refractory to FPs, no prior use of IRI, and prior use of OX. We compared the efficacy and safety of IRI + BEV with those of FOLFIRI + BEV. The adjusted hazard ratios (aHRs) for progression-free survival (PFS) and overall survival (OS) were calculated using a multivariate Cox model that contained variables with p < 0.05 in the univariate analysis to reduce the imbalance between both the treatments. Results: Among the 261 pts, 107 were eligible (IRI + BEV/FOLFIRI + BEV, 31/76 pts). Pt characteristics were as follows (IRI + BEV/FOLFIRI + BEV): median age, 67/62; ECOG PS, 1–2, 55/46%; KRAS mutant, 45/50%; BRAF V600E mutant, 6/11%; right-sided tumor, 19/43%; lactate dehydrogenase (LDH) ≥ 400 U/L, 13/12%; PFS of first-line Cx < 6 month (m), 39/30%; prior use of BEV, 84/63%. Relative dose intensity (RDI) (IRI + BEV/FOLFIRI + BEV) of IRI and BEV was similar in the groups; median RDI (range) of IRI, 80 (44–100) /83 (49–100) %; p = 0.560; median RDI of BEV, 86 (35–100) /83 (20–100) %; p = 0.681. Efficacies (IRI + BEV/FOLFIRI + BEV) after a median follow-up of 13.1/14.3 m were as follows: median PFS, 6.4/5.8 m (HR, 0.90; 95% CI, 0.57–1.38; p = 0.64; aHR, 0.82; 95% CI, 0.50-1.34; p = 0.44); median OS, 16.6/16.5 m (HR, 0.83; 95% CI, 0.51-1.32; p = 0.44; aHR, 1.01; 95% CI, 0.59-1.69; p = 0.97); objective response rate, 25.9/11.3%. Adjustment factors for PFS were prior colorectomy, number of metastatic sites, ECOG PS, liver metastasis, and the level of LDH, while those for OS were prior colorectomy, number of metastatic sites, liver metastasis, peritoneal metastasis, and the level of LDH. All subgroup analyses for PFS and OS according to the pt characteristics also showed no significant differences in the groups. All grade nausea (32/58%) and stomatitis (13/36%) and grade 3–4 neutropenia (23/58%) and febrile neutropenia (0/3%) were less common in the IRI + BEV than in the FOLFIRI + BEV group. Conclusions: Our study suggests that omitting 5-FU from FOLFIRI + BEV as second-line Cx for mCRC pts who are refractory to FPs may lower the occurrence of adverse events without impairing the treatment efficacy.

Prognostic factors in metastatic gastric cancer patients (pts) treated with second-line chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15169-15169
Author(s):  
V. Catalano ◽  
F. Graziano ◽  
D. Santini ◽  
A. M. Baldelli ◽  
P. Giordani ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Weight Loss ◽  
Prognostic Factors ◽  
Performance Status ◽  
Second Line ◽  
First Line ◽  
Second Line Chemotherapy ◽  
Metastatic Sites ◽  
Ecog Ps ◽  
Line Chemotherapy

15169 Background: Currently, there is no established second-line chemotherapy for pts with advanced gastric cancer who failed to respond or progressed after a first-line chemotherapy. Many of these pts still have a good performance status or have symptoms to be palliated at the time of first-line failure and are candidates for second-line chemotherapy. However, phase II trials demonstrate divergent results about pts more likely to benefit from second-line chemotherapy. We retrospectively analyzed the influence of various clinicopathologic factors on the survival of pts treated with second-line chemotherapy. Methods: Analysis is based on the data of 169 pts consecutively treated at 3 oncology department with a second-line chemotherapy. Univariate and multivariate analyses were performed to determine prognostic factors of survival. The variable used for analysis were: sex, age, ECOG performance status, a weight loss > 5 Kg in the last month; site of primary tumor, histopathology; hemoglobin, serum albumin, and CEA levels, number and site of metastatic disease, response to and time-to-progression (TTP) with the first- line chemotherapy. Results: The variables predictive of better survival were: ECOG PS 0–1 (p<0.001), no weight loss (p=0.001), hemoglobin level > 10 g/dl (p=0.01), CEA level <50 U/ml (p<0.02), number of metastatic sites = 2 (p=0.002), TTP of the first-line chemotherapy > 4 months (p=0.008). Peritoneal carcinomatosis was predictive of poor survival only when associated with one or more signs or symptoms as vomiting, anorexia, abdominal pain, ascites(p=0.03). Four factors were independently associated with better overall survival: ECOG PS 0–1 (p=0.002; HR 0.46; CI 95%, 0.29–0.75), CEA level <50 U/ml (p=0.008; HR 0.54; CI 95%, 0.35–0.85), one or two metastatic sites of disease (p=0.01; HR 0.58; CI 95%, 0.39–0.88), and TTP of the first-line chemotherapy > 4 months (p=0.02; HR 0.66; CI 95%, 0.45–0.95). Conclusions: In the absence of data deriving from randomized, controlled, clinical trials, this analysis suggests that some clinical factors may help clinicians to better select groups of pts with gastric cancer more likely to benefit from a second-line chemotherapy. No significant financial relationships to disclose.

Continued cetuximab in second-line treatment for patients with unresectable metastatic wild-type KRAS, NRAS, and BRAF colorectal cancer after disease progression during first-line cetuximab-based therapy.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 127-127
Author(s):  
Ying Liu ◽  
Feng Wang ◽  
Ning Ma ◽  
Shuning Xu ◽  
Lei Qiao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Second Line Therapy ◽  
Second Line Chemotherapy ◽  
Line Therapy ◽  
Ecog Ps ◽  
Line Chemotherapy

127 Background: Cetuximab plus chemotherapy is a first-line treatment option for metastatic RAS wild type colorectal cancer patients. Currently, no data are available on continuing cetuximab or changing bevacizumab as second-line therapy beyond first-line cetuximab-based chemotherapy. Methods: Patients (aged ≥18 years) with metastatic, histologically and genetically confirmed wild-type KRAS, NRAS and BRAF colorectal cancer progressing after first-line cetuximab plus chemotherapy were randomly assigned (1:1 ratio) to second-line chemotherapy with cetuximab (arm A) or with bevacizumab (arm B) 2·5 mg/kg per week equivalently. The choice between oxaliplatin-based or irinotecan-based second-line chemotherapy depended on the first-line regimen (switch of chemotherapy). The primary endpoints were progression-free survival (PFS) and objective response rate (ORR). The second endpoint was overall survival (OS). Results: 77 Patients (from July 1, 2016 to Sept 20, 2019, 77) were randomized (41 in arm A and 36 in arm B). ORR was 29.3% and 19.4% in Arm A and Arm B ( p= 0.31). PFS was 7.2 months (95% CI 5.2–9.2) for Arm A and 5.9 months (95% CI 5.1–6.7) for Arm B ( p= 0.677). OS was 18.5 months (95% CI 15.1–21.8) for Arm A and 17.5 months (95% CI 15.4–19·7) for Arm B ( p= 0.444). Patients with ECOG PS 0 had significantly longer PFS and OS than ECOG PS 1 in second-line therapy whether cetuximab or bevacizumab combined with chemotherapy. ECOG 0 group vs ECOG 1 group, PFS was 8.7 months vs 4.6 months (p = 0.00) and OS was 21.2 months vs 12.3 months (p = 0.00). Moreover, ETS may predict efficacy of second-line continued cetuximab. The most frequently grade 3–4 adverse events in both arms were neutropenia (19.4% VS 16.7%), diarrhea (7.5% vs 11.1%), and nausea(10% vs 13.9%). Conclusions: Continuing cetuximab or changing bevacizumab plus standard second-line chemotherapy in patients with metastatic wild-type KRAS, NRAS and BRAF colorectal cancer after first-line cetuximab plus chemotherapy have similar clinical benefits. ECOG score is an independent predictor of prognosis and second-line treatment efficacy for colorectal cancer.

scholarly journals Efficacy of second-line chemotherapy after a first-line triplet in patients with metastatic colorectal cancer

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
S. Bazarbashi ◽  
A. M. Hakoun ◽  
A. M. Gad ◽  
M. A. Elshenawy ◽  
A. Aljubran ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Group Performance ◽  
Chemotherapeutic Agents ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Second Line Chemotherapy ◽  
Line Therapy ◽  
Line Chemotherapy

Background Exposing patients with metastatic colorectal cancer (mcrc) to all three active chemotherapeutic agents (oxaliplatin, irinotecan, fluorouracil) has improved survival. The benefit of second-line chemotherapy after a first-line triplet is not clearly defined. We evaluated the efficacy of second-line chemotherapy in patients who had received first-line triplet therapy.Methods The medical records of patients treated on a prospective trial of first-line triplet therapy were reviewed for second-line treatment. Univariate and multivariate analyses were performed to establish factors of prognostic significance.Results Of the 53 patients who received first-line triplet therapy, 28 (53%) received second-line chemotherapy [13 men; 8 with a colon primary; mutant KRAS in 10, wild-type in 15, and unknown status in 3; Eastern Cooperative Oncology Group performance status (ps) of 1 in 16 patients, ps 2 in 3, ps 3 in 2, and unknown in 7; involved organs: liver in 17 patients, lung in 16, and peritoneum in 8]. Second-line chemotherapy consisted of xelox or folfox in 13 patients, xeliri or folfiri in 12, and single-agent irinotecan in 3. Concurrent bevacizumab was given in 16 patients (57%), and cetuximab, in 2 (7%). Median survival was 28.0 months [95% confidence interval (ci): 22.8 months to 33.2 months] for patients receiving second-line therapy and 23.0 months (95% ci: 13.2 months to 32.8 months) for those not receiving it. Best response was partial in 6 patients (21%), stable disease in 11 (39%), and progressive disease in 11 (39%). Median progression-free survival was 4.8 months (95% ci: 2.4 months to 9.6 months), and overall survival was 15 months (95% ci: 9.6 months to 20.4 months).Conclusions Second-line chemotherapy after first-line triplet therapy in mcrc is feasible and suggests efficacy comparable to that reported for second-line therapy after a doublet, regardless of the agent used.by research evidence.

Secondary treatment and predictive factors for second-line chemotherapy after first-line oxaliplatin-based therapy in metastatic colorectal cancer

2007 ◽  
Vol 46 (7) ◽  
pp. 982-988 ◽  
Author(s):  
Halfdan Sørbye ◽  
Åke Berglund ◽  
Kjell Magne Tveit ◽  
Dagfinn Øgreid ◽  
Eva Hoff Wanderås ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Predictive Factors ◽  
Secondary Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy

scholarly journals Second-line chemotherapy after early disease progression during first-line chemotherapy containing bevacizumab for patients with metastatic colorectal cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shun Yamamoto ◽  
Kengo Nagashima ◽  
Takeshi Kawakami ◽  
Seiichiro Mitani ◽  
Masato Komoda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Disease Progression ◽  
Performance Status ◽  
Progression Free Survival ◽  
Second Line ◽  
First Line ◽  
Early Disease ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy

Abstract Background The ML18174 study, which showed benefits of bevacizumab (BEV) continuation beyond progression (BBP) for metastatic colorectal cancer (mCRC), excluded patients with first-line progression-free survival (PFS) shorter than 3 months. The present study was conducted to evaluate the efficacy of second-line chemotherapy after early disease progression during first-line chemotherapy containing bevacizumab. Methods The subjects of this study were mCRC patients who experienced disease progression < 100 days from commencement of first-line chemotherapy containing BEV initiated between Apr 2007 and Dec 2016. Second-line chemotherapy regimens were classified into two groups with and without BEV/other anti-angiogenic agents (BBP and non-BBP) and efficacy and safety were compared using univariate and multivariate analysis. Results Sixty-one patients were identified as subjects of this study. Baseline characteristics were numerically different between BBP (n = 37) and non-BBP (n = 25) groups, such as performance status (0–1/> 2/unknown: 89/8/3 and 56/40/4%), RAS status (wild/mutant/unknown: 32/54/16 and 76/16/8%). Response rate was 8.6% in BBP group and 9.1% in non-BBP group (p = 1.00). Median PFS was 3.9 months in BBP group and 2.8 months in non-BBP group (HR [95%CI]: 0.79 [0.46–1.34], p = 0.373, adjusted HR: 0.87 [0.41–1.82], p = 0.707). Median overall survival was 8.5 months in BBP group and 5.4 months in non-BBP group (HR 0.66 [0.38–1.12], p = 0.125, adjusted HR 0.53 [0.27–1.07], p = 0.078). Conclusion In mCRC patients who experienced early progression in first-line chemotherapy, second-line chemotherapy showed poor clinical outcomes regardless use of anti-angiogenic agents.

Irinotecan in the Treatment of Colorectal Cancer: Clinical Overview

2001 ◽  
Vol 19 (5) ◽  
pp. 1501-1518 ◽  
Author(s):  
Udo Vanhoefer ◽  
Andreas Harstrick ◽  
Wolf Achterrath ◽  
Shousong Cao ◽  
Siegfried Seeber ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Topoisomerase I ◽  
Clinical Status ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Phase Iii Trials ◽  
Line Chemotherapy

PURPOSE AND METHODS: For more than three decades, the therapeutic options for patients with advanced colorectal cancer have almost exclusively been based on fluoropyrimidines. With the recognition that topoisomerase-I (TOP-I) is an important therapeutic target in cancer therapy, irinotecan, a semisynthetic TOP-I–interactive camptothecin derivative, has been clinically established in the treatment of colorectal cancer. RESULTS: Irinotecan was investigated as second-line chemotherapy after prior treatment with fluorouracil (FU)-based regimens in two large randomized phase III trials comparing irinotecan with either best supportive care or an infusional FU/leucovorin (LV) regimen. The outcomes of these trials established irinotecan as the standard therapy in the second-line treatment of colorectal cancer. The therapeutic value of irinotecan in the first-line treatment of metastatic colorectal cancer was investigated in two large randomized phase III trials comparing the combination of irinotecan and FU/LV with FU/LV alone. Both trials demonstrated significant superior efficacy for the combination of irinotecan and FU/LV in terms of response rate, median time to disease progression, and median survival time. Consequently, the combination of irinotecan and FU/LV has been approved as first-line chemotherapy for patients with metastatic colorectal cancer and constitutes the reference therapy against which other treatment options must be tested in the future. CONCLUSION: In this review, the clinical rationale and update of the present clinical status of irinotecan in the treatment of colorectal cancer and future prospects of irinotecan-based combinations are discussed.

Metastatic Colorectal Cancer Treatment to progression or Not?

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13511-13511
Author(s):  
B. Melosky ◽  
C. Lohrisch ◽  
C. Kollmansberger ◽  
S. Gill ◽  
H. Kennecke ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Hazard Ratio ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Number Of Cycles ◽  
Line Chemotherapy

13511 Background: Treatment until progression or planned interruption of first line chemotherapy is common in the therapy for metastatic colorectal cancer and are upon the discretion of the oncologist. A retrospective analysis was performed to determine the impact of these differing therapeutic strategies on overall survival. Methods: Eligible patients were treated between 2002 to 2004 in British Columbia. All patients received chemotherapy with both FOLFOX and FOLFIRI, either first or second line. Records were retrospectively reviewed for treatment interruption, efficacy and toxicity. Overall survival was the primary endpoint. Results: 101 patients were identified. Twenty-three patients who progressed before receiving 8 cycles of chemotherapy and 9 patients who stopped their chemotherapy due to toxicity were excluded. The remaining patients were analyzed for survival. Twenty-three patients were treated to progression of whom 6 received first line FOLFIRI and 17 received first line FOLFOX. The mean number of cycles of first line therapy was was 11.5. Forty six patients received a planned break. Of these, 21pateints received first line FOLFIRI and 25 patients received first line FOLFOX. Mean number of cycles of first line therapy was 9.7. Median survival of patients treated to progression was 16 months compared to 22 months for patients with planned break of therapy (p=0.003). The Hazard ratio was 2.3 (p=0.01) in favor of patients who had a planned break. Uni-variate and multivariate analysis showed no significance of sex, age, site (colon versus rectal), sequence and ECOG status as predictive factors. Conclusion: In this study, patients who were treated until progression with first line chemotherapy with either FOLFOX or FOLFIRI had an inferior survival. Possible explanations for the detrimental hazard ratio for patients treated to progression are decreasing reserve for second line therapy when first line therapy is prolonged and increasing resistance to 5-FU based therapy with prolonged exposure. As this is a retrospective, observational study, other variables not captured by the modeled covariates that may have influenced results. This data suggests that treating to best response and then allowing a break does not detrimentally affect survival. No significant financial relationships to disclose.

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