mFOLFOXIRI with or without cetuximab as conversion therapy in patients with RAS/BRAF wild-type unresectable liver metastases colorectal cancer: The FOCULM study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 99-99
Author(s):  
Huabin Hu ◽  
Kun Wang ◽  
Wei Wang ◽  
Meng Qiu ◽  
Rongbo Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Wild Type ◽  
Conversion Therapy ◽  
Treatment Groups ◽  
Significant Survival ◽  
Secondary Endpoints ◽  
Group A ◽  
Unresectable Colorectal Liver Metastases ◽  
Group B

99 Background: Conversion therapy for unresectable colorectal liver metastases (LM) can downsize tumours and create a situation where the patient has no evidence of disease (NED). We assessed the effectiveness of cetuximab plus mFOLFOXIRI or mFOLFOXIRI in this setting. Methods: FOCULM was a prospective 2:1 controlled, multicenter, phase II trial. Given no free drugs offered and the patients' affordability for cetuximab, the study design has been amended from randomization to non-randomization since September, 2016. Patients with unresectable LM were assigned to receive cetuximab (500mg/m2) plus mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 165 mg/m2, folinic acid 400 mg/m2, 5-fluorouracil 2800mg/m2 46h infusion, every 2 weeks) (group A) or mFOLFOXIRI (group B). Primary endpoint was the rate of NED achieved, secondary endpoints were ORR, resection rate, the rate of local and ablative treatment (LAT), OS, PFS and DpR. Results: From February 2014 to July 2019, 114 patients were enrolled at 6 centers in China and 101 patients were in the ITT population (67 group A, 34 group B). Treatment groups were generally well balanced, although more patients with ≥5 LM were in group A. The rate of NED achieved was 62.7% in group A and 38.2% in group B (P = 0.020). At a median follow-up of 19.4 months, patients in group A had significantly prolonged the mOS, increased ORR, the rate of LAT and DpR compared with those in group B (Table). Patients with NED achieved yielded a significant survival benefit, whether in group A (Not reached vs. 49.4 months; P = 0.001) or group B (Not reached vs. 25.1 months; P = 0.007). Conclusions: The addition of cetuximab to a mFOLFOXIRI in patients with RAS/BRAF wild-type unresectable LM colorectal cancer significantly improved the rate of NED achieved, ORR and OS. Clinical trial information: NCT02063529. [Table: see text]

Identification of patients who most benefit from hepatic arterial infusion (HAI) combined or not with systemic chemotherapy for the treatment of unresectable colorectal liver metastases

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14565-14565
Author(s):  
P. Pilati ◽  
S. Mocellin ◽  
M. Lise ◽  
D. Nitti
Keyword(s):  
Liver Metastases ◽  
Colorectal Liver Metastases ◽  
Systemic Chemotherapy ◽  
Tumor Response ◽  
Hepatic Arterial Infusion ◽  
Arterial Infusion ◽  
Tumor Load ◽  
Group A ◽  
Unresectable Colorectal Liver Metastases ◽  
Group B

14565 Background: Although locoregional treatments such as hepatic arterial infusion (HAI) claim the advantage of delivering higher doses of anticancer agents directly into the affected organ, there is substantial lack of evidence for benefit in terms of overall survival (OS). To test the hypothesis that systemic chemotherapy affects OS of patients with unresectable colorectal liver metastases treated with HAI. Furthermore, we investigated patient- and tumor-related predictive factors that might identify patients who most benefit from HAI regimen. Methods: In this retrospective study, 153 consecutive patients treated at our institution were considered. In group-A (n=72), patients were treated with HAI alone (floxuridine (FUDR) 0.2 mg/Kg + leucovorin (LV) 4 mg/m2 + desamethasone 20 mg 14 days/month) between 1994 and 1999. In group-B (n=81), patients were treated with the same HAI regimen combined with systemic chemotherapy (5-fluorouracil (5FU) 450 mg/m2 + LV 20 mg/m2) between 1999 and 2003. Results: No difference in OS was observed between group-A and group-B (median OS: 18.0 and 19.1 months, respectively). Considering all patients (group A + group B), low tumor load was associated with a better tumor response rate, but none of the traditional clinico-pathological prognostic factors correlated with OS. Median OS was better in patients with less than 50% of liver parenchyma involvement (21.3 vs 13.2 months; P<0.0001) as well as in responders (complete or partial response) versus non-responders (24.4 vs 13.4 months; P<0.0001). The combination of low tumor load with good tumor response to HAI was the only variable retained at multivariate analysis, and identified a subgroup of patients with a very favorable clinical outcome (median survival: 34.2 months; hazard ratio: 0.347, CI: 0.249–0.564, P< 0.0001). Conclusions: Combination with 5FU+LV systemic chemotherapy did not lead to an OS benefit over FUDR-based HAI alone. The identification of tumor response predictors is urgently needed, as it would lead to the tailored treatment of patients with low load but unresectable metastatic liver disease who most benefit from HAI therapy. No significant financial relationships to disclose.

Surgical management of synchronous colorectal liver metastases: Simultaneous versus staged resections.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 616-616
Author(s):  
Igor Shchepotin ◽  
Andrii Lukashenko ◽  
Olena Kolesnik ◽  
Anton Burlaka
Keyword(s):  
Colorectal Cancer ◽  
Surgical Treatment ◽  
Postoperative Complications ◽  
Liver Metastases ◽  
Metastatic Cancer ◽  
Economic Effect ◽  
Hepatic Metastases ◽  
Group A ◽  
Bed Days ◽  
Group B

616 Background: Surgical treatment of metastatic colorectal cancer remains the only method that improves overall 5-year survival. This study aimed to compare the surgical outcome and survival benefit between synchronous and staged resection of liver metastases from colorectal cancer. Methods: Clinicopathologic data, treatments, and postoperative outcomes from 110 patients who underwent simultaneous (48 patients, group A) or staged (62 patients, group B) colorectal and hepatic resections at clinic of National cancer institute in period of 2008-2013 were reviewed. Results: Postoperative complications in patients with simultaneous resections (group A) were observed in 13 cases (27.1%), including 5, 1, 4, 2, 0, and 1 of grades I, II, IIIa, IIIb, IV, and V, respectively. Similar results have been reported in group B after staged resections, where overall postoperative complications registered in 16 patients (25.8 %), including 4, 3, 6, 3, 0 of grades I, II, IIIa, IIIb, and IV respectively. Overall level of post-operative complications in the groups A and B after surgical stages finishing did not differ statistically (p=0.96). Shorter operative intervention duration was registered in the group A – (311±10.1) min, whereas in the group B it was (496.6±16.2) min (р<0.001). Patients after staged resection stayed in clinic for a longer time – 23.9±0.8 bed-days, when simultaneous resections provided with shorter recovery terms in post-operative period – 9.8±0.5 bed-days (p<0.001). Overall 3-year survival in the group of patients with simultaneous resections (group А) was 42 % and in the group B 55 % (р=0.22). Conclusions: Analysis of our research indicated necessity of the development of differentiated approach in management of synchronous colorectal liver metastatic cancer. Simultaneous resections of colorectal cancer primary lesions and hepatic metastases were safe and could serve as a primary option for selected patients. Subsequent research should be directed towards study of prognosis factors and criteria for patients’ selection for surgical treatment groups, assessment of economic effect, and patients life quality.

EXPERT study: Randomized phase III trial of radical surgery and postoperative mFOLFOX6 versus perioperative mFOLFOX6 plus cetuximab in patients with KRAS wild-type resectable colorectal liver metastases (CLMs).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 652-652 ◽  
Author(s):  
Yoshihiro Mise ◽  
Kiyoshi Hasegawa ◽  
Masaru Oba ◽  
Kensei Yamaguchi ◽  
Hiroyuki Uetake ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Medical Information ◽  
Radical Surgery ◽  
University Hospital ◽  
Phase Iii ◽  
Wild Type ◽  
Phase Iii Trial ◽  
Significant Difference ◽  
Group A ◽  
Group B

652 Background: Up-front radical surgery and adjuvant chemotherapy were regarded as one of the standard-of-care (SOC) in patients with resectablecolorectal liver metastases (CLMs), while perioperative chemotherapy plus surgery is also accepted. We conducted a multicenter randomized phase III trial to compare radical surgery and post-operative mFOLFOX6 with peri-operative mFOLFOX6 plus cetuximab in patients with KRAS wild-type resectable CLMs. Methods: Patients who had KRAS wild-type resectable CLMs having one to eight liver nodules without extrahepatic disease, were randomly assigned to groups: Group A (reference), hepatectomy and 12 cycles of post-operative mFOLFOX6: Group B (experimental), six cycles of preoperative mFOLFOX6 plus cetuximab (loading dose with 400mg/m2and thereafter 250mg/m2weekly), hepatectomy and six cycles of postoperative mFOLFOX6 plus cetuximab. Primary endpoint was progression-free survival (PFS). We hypothesized that 3-year PFS in Group B would be 25% with the hazard ratio (HR) being 0.75. Considering 3 year follow-up period with 5% of two-sided alpha error and 80% of power, target number were set as 500 (250 each). Study was registered in the University Hospital Medical Information Network (UMIN000007787). Results: This study was initiated since June 2012. However, the enrollment was terminated according to the recommendation from the monitoring committee on 2015 due to a slow accrual. A total of 77 patients (Group A 37 vs. Group B 40) were analyzed. Baseline characteristics were well-balanced between groups. Median numbers of liver mets were two each, ranging from one to eight. The HRs for PFS and overall survival (OS) showed no significant difference (PFS, HR = 1.18 [0.69-2.01], p = 0.54: OS, HR = 1.03 [0.46 – 2.29], p = 0.95). There were 3-year PFS of 35% in Group A vs. 30% in Group B, and 3-year OS: 86% vs. 74%, respectively. Conclusions: No additional survival benefits adding on peri-operative cetuximab were indicated, of which findings is consistent with the previous clinical studies, although there were small number of enrolled patients. Clinical trial information: UMIN000007787.

Phase I Trial of Systemic Oxaliplatin Combination Chemotherapy With Hepatic Arterial Infusion in Patients With Unresectable Liver Metastases From Colorectal Cancer

2005 ◽  
Vol 23 (22) ◽  
pp. 4888-4896 ◽  
Author(s):  
Nancy Kemeny ◽  
William Jarnagin ◽  
Philip Paty ◽  
Mithat Gönen ◽  
Lawrence Schwartz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Response Rate ◽  
Hepatic Metastases ◽  
Hepatic Arterial Infusion ◽  
Arterial Infusion ◽  
Pump Flow Rate ◽  
Group A ◽  
Unresectable Liver Metastases ◽  
Group B

Purpose To determine the maximum-tolerated dose (MTD) of concurrent systemic oxaliplatin (Oxal) combinations plus hepatic arterial infusion (HAI) in patients with unresectable hepatic metastases from colorectal cancer. Patients and Methods Thirty-six patients (89% previously treated) with unresectable liver metastases were treated with concurrent HAI and systemic Oxal plus irinotecan (CPT-11; group A) or Oxal, fluorouracil (FU), and leucovorin (LV; group B). Systemic chemotherapy was administered every 2 weeks concurrent with 2 weeks of HAI floxuridine (FUDR) and dexamethasone (Dex) every 28 days. Results The MTD for patients in group A was Oxal 100 mg/m2, CPT-11 150 mg/m2, and FUDR 0.12 mg/kg × 30 mL divided by pump flow rate. The MTD for group B was Oxal 100 mg/m2, LV 400 mg/m2, and FU 1,400 mg/m2 by continuous infusion over 48 hours, with the same FUDR dose as in group A. Grade 3 or 4 toxicities in groups A and B included diarrhea (24% and 20%), neutropenia (10% and 7%), neurotoxicity (24% and 20%), and bilirubin more than 3 mg/mL (5% and 7%, respectively). The complete and partial response rate totaled 90% for group A and 87% for group B. Median survival time was 36 and 22 months for groups A and B, respectively. Seven patients in group A were ultimately able to undergo liver resection. Conclusion Combination therapy with HAI FUDR and Dex plus systemic Oxal combinations may be safely administered to patients with colorectal cancer. The high response rate (88%) and the possibility of conversion to resectability, despite disease progression on prior systemic regimens, suggest that these combinations should be evaluated in larger studies as first- or second-line therapy in patients with hepatic metastases from colorectal cancer.

Cetuximab/irinotecan/5-FU +/-oxaliplatin or FOLFOXIRI +/- bevacizumab in patients with colorectal cancer and nonresectable liver metastases (AIO CELIM2-study).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4024-4024 ◽  
Author(s):  
Gunnar Folprecht ◽  
Marika Mende ◽  
Torsten Liersch ◽  
Wolf Otto Bechstein ◽  
Claus-Henning Kohne ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Liver Metastases ◽  
Objective Response ◽  
Response Rates ◽  
Wild Type ◽  
Secondary Endpoints ◽  
Poor Recruitment ◽  
Grade 3 ◽  
Braf Mutant

4024 Background: EGFR based combinations and the triplet combination FOLFOXIRI are known to increase response rates compared to doublet combinations. Methods: Patients with colorectal cancer and non-resectable liver metastases were enrolled into the trial. RAS wild type patients were randomised to cetuximab/FOLFIRI or cetuximab/FOLFOXIRI, RAS/BRAF mutant patients were randomised to FOLFOXIRI with or without bevacizumab. The primary endpoint was response. Secondary endpoints included progression free and overall survival. The trial was closed early due to poor recruitment. Results: Between 2014 and 2018, ninety-two pts were enrolled into the study. 54 wild type pts were randomised into cetuximab based treatment with (28 pts) or without (26 pts) oxaliplatin, 38 RAS/BRAF mutant pts were randomised to receive FOLFOXIRI alone (18 pts) or plus bevacizumab (16 pts). Objective response was achieved in 21/26 pts (81 % [95 CI: 61 – 93 %]) with cet/FOLFIRI, 24/28 pts (86 % [95 CI: 67 – 96 %]) with cet / FOLFOXIRI, 13/1 8 pts (72 % [95 CI: 46 – 90 %]) with FOLFOXIRI and 14/20 pts (70 % [95 CI: 46 – 88 %]) with bev/FOLFOXIRI. Two pts with cet/FOLFOXIRI and one pat with FOLFOXIRI achieved CR according to imaging. The median PFS was 12.7 [95 % CI: 7.2 – 18.2], 15.0 [95 % CI: 11.3 – 18.7], 17.5 [95 % CI: 8.0 – 27.1] and 15.0 [95 % CI: 11.4 – 18.5] months with cet/FOLFIRI, cet/FOLFOXIRI, FOLFOXIRI and bev/FOLFOXIRI. The median overall survival was 42 mo. [95 % CI: 28 – 55], 55 [95 % CI:41 – 68], 28 [95 % CI: 22 – 36] and 44 [95 % CI: 0 – 94] months with cet/FOLFIRI, cet/FOLFOXIRI, FOLFOXIRI and bev/FOLFOXIRI. The frequency of grade ≥ 3 toxicity per arm (cet/FOLFIRI, cet/FOLFOXIRI, FOLFOXIRI and bev/FOLFOXIRI) was 29 %, 46 %, 56 %. 45 % for neutropenia/leukopenia, 11 %, 12 %, 28 %, 25 % for diarrhea and 29 %, 19 %, 6 % and 5 % for skin toxicities. Conclusions: High response rates were observed in patients with colorectal liver metastases with all regimens. The numerically highest response rate was observed in RAS wild type patients treated with cetuximab/FOLFOXIRI. Clinical trial information: NCT01802645 .

Survival of classic swine fever virus in hams made from the meat of pigs vaccinated with the PAV-250 strain and unvaccinated pigs

2019 ◽  
Vol 10 (3) ◽  
pp. 536-551
Author(s):  
Heidi Amezcua Hempel ◽  
María Salud Rubio Lozano ◽  
Eliseo Manuel Hernández Baumgarten ◽  
Pablo Correa Girón † ◽  
Oscar Torres Ángeles ◽  
...  
Keyword(s):  
Reference Strain ◽  
Clinical Signs ◽  
Classical Swine Fever ◽  
Fever Virus ◽  
Direct Immunofluorescence ◽  
Biometric Analysis ◽  
Treatment Groups ◽  
Group A ◽  
Group B ◽  
Group D

The study was to determine the presence of Classical Swine Fever virus (CSFv), in the meat of vaccinated pigs with the PAV-250 strain and then challenged using the same strain. Five treatment groups were established (each with four pigs). Group A: Pigs thatwere fed with processed hams from negative animals; Group B: Pigs that were fed with processed hams from commercial pigs inoculated with the ALD (reference strain) (titre of 104.0/ml); Group C: Pigs fed with processed hams from pigs infected with the virulent ALD strain (titre of 102.5/ml); Group D: Pigs fed with processed hams from pigs vaccinated with the PAV-250 strain and challenged with the ALD strain (titre of 101.1/ml); and Group E: Pigs fed with processed hams from pigs vaccinated with two doses of the PAV-250 strain and challenged with the ALD strain (negative). Blood samples were taken at d 1, 5, 10, 15 and 20 for biometric analysis. Groups B, C and D manifested clinical signs of CSFv: 40 °C temperature, anorexia, paralysis, vomiting, diarrhea, tremor, hirsute hair and cyanosis. Pigs were slaughtered and necropsies performed to identify lesions in tissues. Results of direct immunofluorescence testing of tissues were positive and the virus was recovered. Under these study conditions, it was found that CSFv resisted the cooking method at 68 °C for 40 min in hams from unvaccinated pigs, and that the virus was able to transmit the disease to healthy unvaccinated pigs, whereas the hams from the vaccinated animals did not transmit the virus.

scholarly journals Yttrium-90 radioembolization for colorectal cancer liver metastases in KRAS wild-type and mutant patients: Clinical and ccfDNA studies

2016 ◽  
Vol 37 (1) ◽  
pp. 57-65 ◽  
Author(s):  
E. Janowski ◽  
O. Timofeeva ◽  
S. Chasovskikh ◽  
M. Goldberg ◽  
A. Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Wild Type ◽  
Colorectal Cancer Liver Metastases ◽  
Yttrium 90

A Comparative Study of Epidemiology, Clinicopathologic Features and Outcome of Colorectal Cancer Patients between Ain Shams University Hospitals and Luxor International Hospital

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Tarek Hussein Kamel ◽  
Amr Lotfy Farag ◽  
Dr/Sherif Hassanin Ahmed ◽  
Chresteen Talaat Samy Hanna
Keyword(s):  
Colorectal Cancer ◽  
Comparative Study ◽  
Disease Free Survival ◽  
University Hospital ◽  
Treatment Modalities ◽  
Clinicopathologic Features ◽  
Free Survival ◽  
Significant Difference ◽  
Group A ◽  
Group B

Abstract Background Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world. It is the third most common malignancy after lung & breast and the fourth leading cause of cancer-related deaths worldwide, accounting for approximately 1,400,000 new cases and about 700,000 deaths worldwide. Objectives The aim of this retrospective study is to compare the epidemiology, clinicopathologic features, different treatment modalities and outcomes regarding disease free survival (DFS), progression free survival (PFS) & overall survival (OS) of colorectal cancer disease between cases presented to Ain shams university hospital & to Luxor international hospital in 3 consecutive years. Patients and Methods The study is retrospective comparative study. Clinical oncology department in Ain Shams University Hospital and Luxor International Hospital. The data Collected from January 2013 to December 2015. This study analyzed hospital records of patients who diagnosed with colorectal cancer (CRC) and allocated into two groups: Group A: CRC patients presented to Ain-Shams University Hospital from January 2013 to December 2015, group B: CRC patients presented to Luxor International Hospital from January 2013 to December 2015. Results There was no statistically significant difference regarding age parameter in LIH when compared to ASU, but the study was consistent with higher incidence in patients who were aged more than forty- accounted about 70.5% in all CRC cases. Cases less than 40 years old, in group A were 35.2%, while in Group B were 23.5%. Even there was no statistically significant difference but it may be attributable to more westernization in Lower Egypt. Other explanation may be due to decreased low socioeconomic status and different lifestyle factors in more developing region what increase risk of colorectal cancer. Among our cases, there is no statistically significant difference regarding gender between the two hospitals. Both sexes almost were affected equally, females appeared to be at a slightly higher risk of developing CRC cancer with current prevalence 1.3:1 in ASU group, and 1.1:1 in LIH group. Conclusion The need to increase awareness about CRC in Egypt especially upper Egypt, is recommended. An awareness campaign should be performed to promote detection of CRC at its earliest and most curable stage by recognizing early symptoms and enabling early referrals for colonoscopy. Those at higher risk should be offered more intensive surveillance. Similarity of the data from different centers suggests that this is the picture of colorectal cancer typical of Egypt.

Feasibility of “Watch-and-Wait” Management before Repeat Hepatectomy for Colorectal Liver Metastases

2018 ◽  
Vol 36 (3) ◽  
pp. 233-240 ◽  
Author(s):  
Yoji Kishi ◽  
Satoshi Nara ◽  
Minoru Esaki ◽  
Kazuaki Shimada
Keyword(s):  
Liver Metastases ◽  
Colorectal Liver Metastases ◽  
Repeat Hepatectomy ◽  
Hepatic Recurrence ◽  
Free Interval ◽  
Tumor Number ◽  
Group A ◽  
Synchronous Colorectal Liver Metastases ◽  
Group B ◽  
Better Than

Background: Whether repeat hepatectomy for colorectal liver metastases should be performed after chemotherapy or observation is unclear. Methods: We selected patients with resectable hepatic recurrence after their first hepatectomies performed between 2000 and 2015. They were classified according to the further treatment: Group A, prompt repeat hepatectomy; Group B, observation; and Group C, ≤6 months of chemotherapy. In Group B/C, patients who later underwent hepatectomy and those who did not due to disease progression were classified as B1/C1 and B2/C2, respectively. Predictors of B2/C2 were evaluated. Results: Groups A, B, and C consisted of 81, 36, and 17 patients, respectively. Recurrence-free interval was longer in Group A (median months; Group A, 10.3; Group B, 5.7; Group C, 3.5; p < 0.01). Group B1/C1 and B2/C2 included 34 and 19 patients, respectively. Five-year survival after recurrence of Group B1/C1 was 56%, which was comparable with Group A (56%, p = 0.77) and better than Group B2/C2 (0%, p < 0.01). Multivariate analysis showed synchronous colorectal liver metastases (OR 7.23) and recurrent hepatic tumor number (OR 4.04) were predictors of tumor progression. Conclusion: Selecting patients optimally either for prompt or delayed repeat hepatectomy following chemotherapy or observation is a feasible strategy.

Sign in / Sign up

Export Citation Format

Share Document