Retrospective cohort study on the safety and efficacy of panitumumab (Pmab) for patients with metastatic colorectal cancer (mCRC): The HGCSG1002 study—Analysis of clinical early predictor for the efficacy.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 593-593
Author(s):  
Susumu Sogabe ◽  
Hiraku Fukushima ◽  
Satoshi Yuki ◽  
Yoshimitsu Kobayashi ◽  
Takuto Miyagishima ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Plasma Level ◽  
Serum Level ◽  
Clinical Outcome ◽  
Progression Free Survival ◽  
Rank Test ◽  
Test Results ◽  
Ecog Ps ◽  
Level Reduction ◽  
Early Predictor

593 Background: Inhibition of the EGFR pathway has become a key part in the treatment of colorectal cancer. There were few studies for clinical early predictive markers. To investigate the early magnesium (Mg2+), calcium (Ca2+), albumin (Alb), CEA and CA 19-9 plasma level reductions as a predictor for clinical outcome in terms of progression free survival (PFS) and overall survival (OS). Methods: 200 patients (pts) with mCRC treated by Pmab contained chemotherapy were retrospectively registered from 20 centers in Japan (HGCSG 1002 study). Of these, the pts that were refractory to or intolerant for 5-FU/ irinotecan/ oxaliplatin, and were never administered anti-EGFR-antibody, were included in this analysis. Mg2+, Ca2+, Alb, CEA and CA19-9 plasma levels were obtained from medical records. The differences in terms of PFS and OS according to the presence of Mg2+, Ca2+, Alb, CEA and CA19-9 reductions were evaluated by the log-rank test. Results: Of 67 pts were able to evaluate for this analysis. Pts’ characteristics were as follows: male/female 38/29, median age 64 (range 45-81), ECOG PS (0/1/2- ) 45/17/5. Response rate and disease control rate were 16.4% and 65.7%, PFS and OS were 4.3 m and 12.4 m, respectively. There were no correlations between Ca/Alb plasma level reductions and PFS/OS. Mg2+ reduction of at least 50% respect to the basal value during the course of treatment was significantly correlated with improved OS and PFS (OS, P=0.03; PFS, P=0.01), but the early reduction (until the 4th week or the 8th week after start of chemotherapy) was not correlated with OS and PFS. An early CEA serum level reduction of at least 40% until the 8th week was significantly correlated with improved OS and PFS (OS, P=0.04; PFS, P=0.07), moreover of at least 30% until the 4th week was correlated to longer PFS (P=0.053). Similar results were seen in CA19-9. Conclusions: An early CEA plasma level reduction of at least 30% or 40% was suggested to be a predictor for PFS in Pmab containing chemotherapy for mCRC pts. Although Mg2+ serum level reduction was correlated to clinical outcome, but could not show that is an early predictor for PFS and OS in our study.

Intratumoral mRNA levels predict clinical outcome in patients with metastatic colorectal cancer treated in a prospective clinical trial with 5-FU and oxaliplatin

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10010-10010
Author(s):  
D. Yang ◽  
D. Vallböhmer ◽  
W. Zhang ◽  
S. Iqbal ◽  
A. El-Khoueiry ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Repair ◽  
Clinical Outcome ◽  
Prospective Trial ◽  
Progression Free Survival ◽  
Rank Test ◽  
Mrna Levels ◽  
Second Line ◽  
Tissue Samples ◽  
Cox 2

10010 Background: 5-flurouracil (5-FU) and Oxaliplatin-based therapy is one of the most frequently used combinations in the treatment of advanced colorectal cancer (CRC). There are no validated and established predictive factors for clinical outcome following 5-FU/Oxaliplatin treatment. We had shown an association between intratumoral mRNA levels of TS and ERCC1 involved in 5-FU metabolism and DNA repair, respectively, and survival to 5-FU/Oxaliplatin chemotherapy in advanced CRC in a retrospective study. Now we investigated whether intratumoral mRNA levels of these two genes and others involved in 5-FU metabolism (DPD, TP, dUTPase), DNA repair (ERCC2, XRCC1), angiogenesis (COX-2, EGFR, IL-8, PLA2), and drug detoxification (GSTP-1) predict the clinical outcome of patients with CRC in a prospectively designed biomarker study. Methods: 85 patients with metastatic CRC treated with second-line 5-FU/Oxaliplatin from the prospective trial were included. mRNA levels of 12 genes were assessed from paraffin- embedded tissue samples using laser capture microdissection and quantitative Real-time PCR. Overall survival (OS) was the primary endpoint. Progression-free survival (PFS), response, and toxicity were the secondary endpoints. Results: There were 40 women and 45 men (median age 60 years; range 29–87), median survival of 9.7 ms, median PFS of 4.2 ms, CR in 1 (1%) patient, PR in 15 (18%), SD in 36 (43%) and PD in 32 (38%) patients. High intratumoral mRNA levels of PLA2, TP, GSPTP-1 and low mRNA levels of COX-2 were each significantly associated with shorter OS (P≤0.05, log-rank test). There was a trend in the association between high mRNA levels of PLA2 and shorter PFS (P=0.08). In addition, high mRNA levels of XRCC1 and IL-8 were each significantly associated with high risk of cumulative grade 3+ toxicity (P≤0.05). No significant association was found between mRNA levels and response to 5-FU/Oxaliplatin. Conclusions: This study suggests that mRNA levels of PLA2, TP, GSTP-1, COX-2, XRCC1, and IL-8 may be useful to predict the outcome of patients with metastatic CRC with second-line 5-FU/Oxaliplatin chemotherapy. These findings should be validated with future basic sciences studies and prospective clinical trials. [Table: see text]

scholarly journals Angiogenesis genotyping and clinical outcome during regorafenib treatment in metastatic colorectal cancer patients.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 595-595 ◽  
Author(s):  
Riccardo Giampieri ◽  
Lisa Salvatore ◽  
Michela Del Prete ◽  
Tiziana Prochilo ◽  
Marco D'Anzeo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Progression Free Survival ◽  
Therapeutic Index ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Colorectal Cancer Patients ◽  
Ecog Ps

595 Background: The introduction of regorafenib for the treatment of colorectal cancer represented a sure medical achievement though at a cost of relevant toxicity. As a consequence the lack of predictive factors made the use of regorafenib in the clinical practice challenging. Previous observations suggested that polymorphisms of VEGF and its receptor (VEGFR) genes may regulate angiogenesis and lymphangiogenesis and potentially influence outcome during anti-angiogenesis treatment. Aim of our study was to evaluate the role of VEGF and VEGFR genotyping in determining clinical outcome for colorectal cancer patients receiving regorafenib. Methods: From a multicentre experience 138 samples (tumour or blood samples) of colorectal cancer patients receiving regorafenib were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). Patients’ progression-free survival (PFS) and overall survival (OS) were analysed. Results: Results from angiogenesis genotyping showed that only VEGF-A rs2010963 maintained an independent correlation with PFS and OS (respectively HR: 0.49, 95% CI: 0.33-0.81, p=0.003 and HR: 0.52, 95% CI: 0.34-0.99, p=0.04). A correlation with disease control rate (DCR) was also observed (DCR 55% vs. 26%, p=0.02). Among clinical factors only ECOG PS was independently correlated with OS (HR: 0.52, 95% CI: 0.21-0.81, p=0.009), whereas no correlation with PFS was evident. Grouping together observations from angiogenesis genotyping and ECOG PS allowed further patients stratification into 3 prognostic groups: favourable, intermediate and unfavourable. Median OS resulted progressively decreased across these groups (OS not reached, 7.8 and 3.9 months respectively in the favourable, intermediate and unfavourable group, p<0.0001). Conclusions: VEGF-A rs2010963 genotyping may represent an important tool for a more accurate selection of candidates for regorafenib. This selection opportunity will ultimately improve the therapeutic index of such a treatment approach by limiting treatment to potentially responding patients and sparing unnecessary toxicity to those unlikely to benefit.

Polymorphisms correlated with the clinical outcome of locally advanced or metastatic colorectal cancer patients treated with ALIRI vs. FOLFIRI

Pteridines ◽  
2013 ◽  
Vol 24 (1) ◽  
pp. 69-79 ◽  
Author(s):  
Ana Barcelos ◽  
Elisa Giovannetti ◽  
Robert de Jonge ◽  
Mina Maftouh ◽  
Pieter Griffioen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Metastatic Colorectal Cancer ◽  
Topoisomerase I ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Copy Number Variations ◽  
Rank Test ◽  
Functional Polymorphisms

AbstractLeucovorin-modulated 5-fluorouracil (5-FU) plus irinotecan (FOLFIRI) is the most common treatment of metastatic colorectal cancer (CRC). 5-FU inhibits thymidylate synthase (TS) and irinotecan topoisomerase I, leading to inhibition of DNA replication and repair. FOLFIRI efficacy suggested that other TS inhibitors might synergize with irinotecan, and Phase I/II studies for second-line treatment showed promising results of combinations with the multitargeted antifolate pemetrexed (PMX), which exerts its effects primarily via TS inhibition. However, a randomized Phase II trial of PMX + irinotecan (ALIRI) showed similar efficacy and safety, but significantly shorter progression-free survival (PFS) compared with FOLFIRI in locally advanced or metastatic CRC. In our previous aCGH study, we evaluated genome-wide copy number variations, whereas in the current study we evaluated relationships between functional polymorphisms and PFS. Candidate polymorphisms were studied by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) (TSER-2R/3R) or Taqman-PCR (MTHFR-1958G>A, MTR-2756A>G, MTHFR-1298A>C, SHMT1-1420C>T, ATIC-347C>G, AMPD-134C>T, MTRR-66A>G and SLC-19A180G>A) in 84 patients (40 FOLFIRI, 44 ALIRI). The Kaplan-Meier method was used to plot PFS, and the log-rank test to compare curves. At univariate analysis the homozygous variants of both MTR-2756A>G and SHMT1-1420C>T were associated with significantly shorter PFS. Conversely, a significantly longer PFS (7.3 months) was observed when ATIC-347C>G CC+CG genotypes were grouped vs. GG. At multivariate analysis the genotypes MTR-2756A>G AA+AG, SHMT1-1420C>T TT+CT and ATIC-347C>G CC+CG emerged as significant predictors for PFS. Because MTR, SHMT1 and ATIC are all involved in folate pathways, we further explored the effect of a combination of their risk genotypes on PFS, showing that patients carrying two risk genotypes had a significantly shorter PFS (3.9 months, p<0.001). The correlations of polymorphisms in genes with clinical outcome underscore the importance of a candidate gene-based approach. Ultimately, the validation of the role of these polymorphisms in prospective multicenter trials might optimize currently available treatments in selected CRC patients (e.g., FOLFIRI) or PMX-based treatments in other tumor types.

Early assessment of MCV to predict clinical outcome in patients with advanced gastrointestinal stromal tumors (GIST) receiving imatinib.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10086-10086
Author(s):  
Anastasia Constantinidou ◽  
Dimitrios Krikelis ◽  
David Olmos ◽  
Michelle R. Scurr ◽  
Robin Lewis Jones ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Primary Tumour ◽  
Progression Free Survival ◽  
Percentage Change ◽  
Lower Percentage ◽  
Rank Test ◽  
Test Results ◽  
Early Assessment ◽  
Kaplan Meier ◽  
Two Parameters

10086 Background: In patients with advanced GIST, imatinib trough levels have been associated with a lower rate of clinical benefit. Anecdotal observations have suggested that commencing treatment with imatinib may be associated with an increase in red blood cell size as measured by MCV and MCH, indicating the effect of imatinib on KIT signalling in the bone marrow. Methods: In this retrospective review we examined a possible connection between changes in MCV and MCH after the first 3 months (mo) of treatment with imatinib and progression-free survival (PFS). Data for patients with inoperable advanced or metastatic GIST treated between 2000 and 2011 were available for analysis. Patients were categorised in quartiles according to the distribution of the percentage of change of MCV and MCH between start of imatinib (baseline) and 3 (+/- 0.5) mo (ratio %=MCV change at 3 mo/MCV at baseline). PFS curves were plotted using the Kaplan-Meier method and compared using the log rank test. Results: One hundred and thirty patients were eligible for analysis and the demographics were: male:female 84:46, median age at presentation: 60.5 (23.5-86.5) years, commonest primary tumour sites: stomach (72/130) and small bowel (44/130), commonest metastatic site: liver (76/130). In the patients with a 10% or over increase in MCV (p75-p100) at the 3 mo (+/-0.5) time point a significantly longer PFS was observed compared to those with a smaller magnitude of change (PFS of 37.1 mo vs 24.3 mo, p=0.032). A similar trend although not statistically significant was observed in patients with MCH of 15% or over (p75-p100) with PFS of 34.0 mo vs 25.8 (p=0.125). The two parameters (MCV and MCH) showed a high correlation of percentage change (r2=0.85). The patients with a 10% MCV increase and /or 15% MCH increase (total=40) showed a significantly longer PFS (34.0 mo) compared to those with lower percentage change (PFS= 24.3) p=0.035. Conclusions: Simple laboratory parameters may be indicators of imatinib pharmacokinetics and may therefore be used as surrogate markers of clinical outcome. Larger prospective studies are required to confirm the results of this study.

P14.90 Survival outcomes and prognostic factors in glioblastoma patients treated with radiotherapy plus concomitant and adjuvant temozolomide - real-world study

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii55-ii55
Author(s):  
M J Sousa ◽  
J Magalhães ◽  
R Basto ◽  
C Costa ◽  
A Pego ◽  
...  
Keyword(s):  
Survival Rate ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Rank Test ◽  
Survival Outcomes ◽  
Hematologic Toxicity ◽  
Current Standard ◽  
Adjuvant Temozolomide ◽  
Standard Of Care Treatment ◽  
Ecog Ps

Abstract BACKGROUND Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumour in adults. The current standard of care for newly diagnosed GBM is maximal surgical resection, followed by radiotherapy plus concomitant and adjuvant temozolomide (TMZ). This study aimed to evaluate the survival outcomes and identify predictors of survival among these patients. MATERIAL AND METHODS We performed a single-centre retrospective analysis of GBM patients treated with radiotherapy plus concomitant and adjuvant TMZ from 2013 to 2020. The analyses of progression-free survival (PFS) and overall survival (OS), each one evaluated starting from initial diagnosis, were performed. Survival curves were estimated with the Kaplan- Meier method and compared using the log-rank test. RESULTS Fifty-eight patients were identified. The median age was 61 years (range 18- 80), 51 (88%) patients were in ECOG-PS 0–1, 6 (10%) patients had isocitrate dehydrogenase (IDH) mutation and 53 (91%) of patients had undergone debulking surgery. At a median follow-up of 21 months, median OS was 12.8 months (95% confidence interval [CI] 9.7–15.9), whereas median PFS was 9.5 months (95% CI 8.5–10.5). The 1-year survival rate was 42% and the 2-year survival rate was 10%. Grade 3 or 4 hematologic toxicity occurred in 11 (19%) patients. Twenty-five (42%) patients completed at least 6 cycles of TMZ monotherapy with statistically significant differences between this sub-group and those who weren’t able to continue TMZ monotherapy [median OS 19.3 months (95% CI 14.4–24.2) vs 10.6 months (95% CI 7.8–13.4) p&lt;0.001]. ECOG-PS = 0 [median OS 16.7 months (95% CI 13.4–20.0, p=0.001)] and patients under 65 years of age [median OS 15.6 months (95% CI 12.3–18.9, p=0.02) were associated with significantly better median OS. CONCLUSION The current standard of care treatment for GBM remains poor. An important factor predictor of survival is the completion of the 6 maintenance cycles of TMZ. At baseline, ECOG PS and the patient’s age could be used to define patient prognosis.

scholarly journals Prognostic and clinicopathological significance of systemic immune-inflammation index in colorectal cancer: a meta-analysis

2020 ◽  
Vol 12 ◽  
pp. 175883592093742 ◽  
Author(s):  
Meilian Dong ◽  
Yonggang Shi ◽  
Jing Yang ◽  
Quanbo Zhou ◽  
Yugui Lian ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Cochrane Library ◽  
Hazard Ratios ◽  
Clinicopathological Significance ◽  
Immune Inflammation ◽  
Ecog Ps ◽  
The Cochrane Library

Background: Previous studies on the systemic immune-inflammation index (SII), which is based on platelet, neutrophil and lymphocyte counts, as a prognostic marker in patients with colorectal cancer (CRC) yielded inconsistent results. The aim of this study was to evaluate the prognostic and clinicopathological role of SII in CRC via meta-analysis. Methods: A comprehensive literature survey was performed on PubMed, Web of Science, Embase and the Cochrane Library databases to include studies published up to 6 April 2020. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were computed to estimate the prognostic and clinicopathological value of SII in CRC. Results: A total of 12 studies published between 2016 and 2019 were included in our meta-analysis. The combined analysis showed that high SII levels were significantly associated with worse overall survival (OS; HR = 1.61, 95% CI = 1.21–2.13, p = 0.001) and progression-free survival (HR = 1.74, 95% CI = 1.26–2.39, p = 0.001) in CRC. Moreover, elevated SII was also correlated with poor tumor differentiation (OR = 1.60, 95% CI = 1.27–2.02, p < 0.001), presence of distant metastasis (OR = 2.27, 95% CI = 1.10–4.67, p = 0.026), ECOG PS of 1–2 (OR = 1.98, 95% CI = 1.39–2.84, p < 0.001) and tumor size ⩾5 cm (OR = 1.49, 95% CI = 1.18–1.88, p = 0.001). However, high SII was not significantly associated with sex, tumor location, lymph node metastasis, or age in patients with CRC. Conclusion: Our meta-analysis indicated that high SII levels predicted poor prognosis in CRC. In addition, an elevated SII was also associated with clinical factors, implying higher malignancy of the disease.

scholarly journals Association of Interleukin 6 Promoter Polymorphism (-174G/C) with IL-6 Level and Outcome in Severe Sepsis

2008 ◽  
Vol 62 (4-5) ◽  
pp. 162-164 ◽  
Author(s):  
Oļegs Sabeļnikovs ◽  
Liene Ñikitina-Zaķe ◽  
Indulis Vanags
Keyword(s):  
Severe Sepsis ◽  
Plasma Level ◽  
Serum Level ◽  
Clinical Outcome ◽  
Interleukin 6 ◽  
Promoter Polymorphism ◽  
University Hospital ◽  
Genotype Distribution ◽  
Promoter Polymorphisms ◽  
Regulatory Polymorphism

Association of Interleukin 6 Promoter Polymorphism (-174G/C) with IL-6 Level and Outcome in Severe SepsisInterleukin (IL-6) is a key cytokine in the pathogenesis of severe sepsis. The importance of a regulatory polymorphism within the IL-6 promoter remains unclear in these patients. The aim of the study was to determine if IL-6 (-174 G/C) promoter polymorphism has an effect on IL-6 plasma level and outcome of severe sepsis. The study was conducted in general ICU of Stradiñš Clinical University Hospital. A total of 103 critically ill patients with confirmed severe sepsis were prospectively included. Association analysis of the IL-6 (-174C) allele with serum level and clinical outcome was performed. We found no differences in genotype distribution between survivors and nonsurvivors. The serum IL-6 level was significantly higher in nonsurvivors compared with survivors. We found an association of genotype with the IL-6 level in nonsurvivors, but not in survivors. Our findings show a functional significance of IL-6 promoter polymorphisms in nonsurviving severe sepsis patients.

Pharmacogenomic analysis of the triplet combination of gemcitabine, oxaliplatin, and cetuximab as salvage therapy for metastatic colorectal cancer (mCRC) patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14531-e14531
Author(s):  
A. Hernandez ◽  
E. Bandres ◽  
J. Rodriguez ◽  
N. Bitarte ◽  
N. Ramirez ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Germ Line ◽  
Univariate Analysis ◽  
Genomic Analysis ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Median Number ◽  
Rank Test ◽  
Exact Test ◽  
Combination Methods

e14531 Background: We have previously reported that biweekly gemcitabine-based therapy was active in pretreated mCRC pts (De la Cruz et al, ASCO GI 2008, abstr 377). We aimed to investigate whether germ line polymorphisms may be predictors of clinical outcome in mCRC pts treated with this combination. Methods: We evaluated SNPs of genes involved in gemcitabine metabolism (CDA, dCDK, RRM1, DCTD, SLC28A1), DNA repair (XRCC1, XRCC 3, ERCC1, XPD) and two IgG Fcγ R polymorphisms (Fcγ RIIa- H131R and Fcγ RIIIa-V158F), reported to be predictive of cetuximab-based therapy, even in K-ras mutated pts. Whole blood was collected and DNA extracted from peripheral lymphocytes using a DNA isolation Kit (Qiagen, CA). Polymorphisms were detected using the TaqMan genotyping assays (Applied Biosystems, CA). Clinical response was evaluated according to RECIST criteria. Univariate analysis (Fisher´s exact test for response; log-rank test for TTP and OS) was performed to examine associations between polymorphisms and clinical outcome. Results: Blood samples of 35 out of 39 enrolled pts were tested for genomic analysis. Patient‘s characteristics are as follows; M/F: 26/13, median age: 59 years, median number of prior chemotherapy lines: 2 (1–4), Köhne risk groups; low: 8 pts, intermediate: 18 pts, high: 13 pts. After a median follow-up of 20 months, median progression-free survival (PFS) is 6.7 months (95% CI; 5.2–8.3) and median overall survival 15.4 m (95% CI; 14.7–16.1). Overall response rate (ORR) was 53.8%. RRM1 R284R SNPs (p=0.06), T741T (p=0.02) and RRM1–524CT (p=0.04) were linked to clinical responsiveness. All pts possessing 2 or 3 favourable RRM1 SNPs responded. ORR was 53.3% for pts with no favourable SNPs versus 85% for pts with any favourable SNP (p=0.04). ORR was also significantly higher in pts with any histidine allele in the Fcγ RIIa polymorphism (93% vs. 60%, p=0.034). Median PFS was adversely affected in pts harbouring no favourable RRM1 SNPs (4.2m versus 6.7 months, p=0.019) and in those pts with homozygous Fcγ RIIa-131R allele (4.4 vs. 7.5 months, p=0.007). Conclusions: Polymorphic variants of RRM1 and Fcγ RIIa may play a key role in the efficacy of gemcitabine and cetuximab-based therapy for mCRC pts. No significant financial relationships to disclose.

Safety, efficacy, and time to clinical response with bevacizumab plus FOLFIRI regimen in metastatic colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15138-e15138
Author(s):  
S. Tomao ◽  
G. Spinelli ◽  
L. Rossi ◽  
G. Pasciuti ◽  
G. Arcangeli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Clinical Response ◽  
Median Time ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Clinical Activity ◽  
Efficacy And Safety ◽  
First Line ◽  
Ecog Ps

e15138 Background: Bevacizumab (BEV) has shown clinical activity in metastatic colorectal cancer patients (mCRC)and randomised phase III trials have demonstrated that this agent significantly improves overall and/or progression-free survival when added to first-line irinotecan based chemotherapy (CT) regimens. We evaluated the efficacy and safety of BEV plus FOLFIRI (irinotecan, 5- fluorouracil, and leucovorin) as first line treatment in 27 consecutive metastatic colorectal cancer cases, with the primary end point to calculate the median time to clinical response with this chemotherapeutic schedule. Methods: Between October 2007 and January 2008 we collected the data on 27 patients with mCRC treated with first line chemotherapy with BEV plus FOLFIRI. Elegibility criteria had to be: mCRC; no prior CT for metastatic disease; ECOG PS 0/1, adequate organ function; no CNS metastases. The treatment consisted of a minimum of six cycles of irinotecan plus infusional 5-FU/LV according to the classical FOLFIRI schedule; BEV (5mg/kg) was given on day 1 with CT and then every 2 weeks until disease progression. Safety and response were assessed at the time of first CT and every 4 weeks thereafter. Results: 27 pts were evaluable (male 18; median age 61 years (range 45–77), ECOG PS 0: 52%, PS 1: 48%. The sites of metastases were: liver (15 pts), lung (5 pts), liver and lung (5 pts), peritoneal wall (2 pts).Median follow-up was 18 weeks. Two patients had complete response(CR) and 13 pts partial response (PR), with an overall response rate of 57.7%. Five patients had stable disease and 6 patients showed progressive disease. A clinical benefit was demonstrated in 77 % of pts. We observed a median time to clinical response of 11 weeks, evaluated with tumor markers and with CT/NMR/US examinations. A grade 3 or 4 neutropenia was detected in 39% of pts and grade 2 or 3 hypertension in 9%. We did’nt observe cases of thrombosis, bleeding and gastrointestinal perforation, sometimes related to the use of BEV. Conclusions: In this little experience the efficacy and safety of BEV associated with FOLFIRI schedule, a first line therapy in mCRC,is consistent with results from other previous studies, showing moreover a short time to clinical response with this association. No significant financial relationships to disclose.

Randomized, phase II study of bevacizumab with mFOLFOX6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: Resectability and safety in OLIVIA.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3619-3619 ◽  
Author(s):  
Thomas Gruenberger ◽  
John A. Bridgewater ◽  
Ian Chau ◽  
Pilar Garcia Alfonso ◽  
Michel Rivoire ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Progression Free Survival ◽  
Remnant Liver ◽  
Resection Rate ◽  
Open Label ◽  
R1 Resection ◽  
Unresectable Liver Metastases ◽  
Grade 3 ◽  
Hepatic Lesions ◽  
Ecog Ps

3619^ Background: Patients (pts) with unresectable colorectal cancer liver-only metastases (CLMs) may become resectable after downsizing by chemotherapy (CT) and biologic therapy. Although biologics are thought to improve overall response rate (ORR), the optimal combination of a biologic and CT for resectability remains uncertain. Methods: This open-label, multinational study randomized pts with unresectable CLMs to bevacizumab (BEV) plus mFOLFOX6 or FOLFOXIRI q2w. Resectability was assessed by interdisciplinary review. Unresectability was defined as ≥1 of the following: no possibility of upfront R0/R1 resection of all hepatic lesions, <30% estimated residual liver after resection, or disease in contact with major vessels of the remnant liver. The primary end point was overall resection rate (R0/R1/R2). Results: From 10/2008 to 12/2011, 80 pts were randomized to mFOLFOX6-BEV (n=39) or FOLFOXIRI-BEV (n=41). Pt characteristics were male (46% vs 71%), aged ≥60 y (36% vs 63%), ECOG PS of 1 (23% vs 37%), and ≥5 target CLMs (49% vs 49%) in the mFOLFOX6-BEV and FOLFOXIRI-BEV arms, respectively. Resection rate, ORR, and progression-free survival (PFS) data are shown (Table). Grade ≥3 adverse events (AEs) occurred in 84% and 95% of pts receiving mFOLFOX6-BEV and FOLFOXIRI-BEV, respectively, and included neutropenia (35% vs 48%; febrile, 8% vs 13%) and diarrhea (14% vs 28%). Conclusions: The results suggest that FOLFOXIRI-BEV improves resection rates, ORR, and long-term outcomes vs mFOLFOX6-BEV in pts with initially unresectable CLMs. CT- and BEV-related AEs occurred with the expected incidence and were manageable. FOLFOXIRI-BEV should be evaluated further as an effective regimen to downsize CLMs. Clinical trial information: NCT00778102. [Table: see text]

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