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 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.

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.

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.

Retrospective cohort study on the safety and efficacy of bevacizumab for metastatic colorectal cancer patients: The HGCSG0801 study—Analysis of bevacizumab beyond progression (BBP).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 684-684
Author(s):  
Hiraku Fukushima ◽  
Satoshi Yuki ◽  
Yoshimitsu Kobayashi ◽  
Kazuteru Hatanaka ◽  
Takaya Kusumi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cohort Study ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Line Chemotherapy

684 Background: Bevacizumab (BV) is widely used in first-line chemotherapy for metastatic colorectal cancer in Japan, but the use of beyond bevacizumab first progression (BBP) has been controversial yet. Methods: Of patients treated with first-line BV in our retrospective cohort study (HGCSG0801), patients treated with BBP (n=22) and those without BBP ( n=19) in second-line setting were analyzed. The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used to assess adverse events. The Response Evaluation in Solid Tumors (RECIST) criteria version 1.0 was used to assess tumor response. The Kaplan–Meier method was used to determine PFS and OS. Log-rank test was used to compare each group in terms of PFS and OS. All statistical tests were performed using SPSS. Results: PS (0/1/2) before second line chemotherapy was 18/3/1 in BBP and 10/8/1 in NBBP, respectively. In the safety analysis, five patients in BBP showed a worsening/newer hypertension, which wasn’t a clinical problem. In the efficacy analysis, the response rate was 22.8% in BBP and 0% in NBBP. The median PFS was better in BBP (6.7 months in BBP and 2.7 months in NBBP), but there was no significant difference in median OS from first BV administration between two groups (27.3 months in BBP and 22.2 months in NBBP). Conclusions: We analyzed BBP in daily practice in Japan. Adverse events were well tolerated, but survival advantage of BBP was not suggested. About the efficacy of BBP, we are waiting the results of ongoing Phase III trials.

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