scholarly journals Irinotecan eluting beads-transarterial chemoembolization using Callispheres® microspheres is an effective and safe approach in treating unresectable colorectal cancer liver metastases

2021 ◽  
Author(s):  
Guangsheng Zhao ◽  
Song Liu ◽  
Yuewei Zhang ◽  
Tong Zhao ◽  
Ruoyu Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Liver Metastases ◽  
Treatment Response ◽  
Survival Data ◽  
Transarterial Chemoembolization ◽  
Response Rate ◽  
Objective Response ◽  
Postoperative Treatment ◽  
Colorectal Cancer Liver Metastases

Abstract Background Callispheres® microspheres (CSM) are the first drug-eluting bead (DEB) product developed in China; meanwhile, DEB-transarterial chemoembolization (TACE) with CSM is effective and safe in the treatment of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. However, the data regarding the role of irinotecan-eluting beads-TACE (DEBIRI-TACE) using CSM for colorectal cancer liver metastases (CRLM) treatment is limited. Therefore, the present study aimed to investigate the efficacy and safety of DEBIRI-TACE using CSM in the patients with unresectable CRLM. Methods Totally, 42 unresectable CRLM patients treated with DEBIRI-TACE using CSM were continuously enrolled in this study. Postoperative treatment response (including complete response rate (CR), objective response rate (ORR), and disease control rate (DCR)), survival data (overall survival (OS)), liver function, and adverse events were documented during the follow-up. Results CR, ORR, and DCR were 19.0%, 92.9%, and 100.0%, respectively, at month (M) 1; were 23.8%, 92.9%, and 97.6%, respectively, at M3; then were 14.3%, 78.6%, and 90.5%, respectively at M6. Regarding survival profiles, 1-year OS was 81.0%; 2-year OS was 58.5%; median OS was 25.0 months (95%CI: 19.3–30.7 months). Additionally, ALT and AST experienced an obviously increased trend at 4 days, but a declined trend at 7 days, while ALB and TBIL had no obvious change. No grade 3 or grade 4 adverse event was observed, and main adverse events included fever (95.3%), pain (57.1%), fatigue (50.0%), and nausea/vomiting (42.8%). Conclusion DEBIRI-TACE with CSM achieves high treatment response, acceptable survival benefits, and good toleration in unresectable CRLM treatment.

LM02-trial perioperative treatment with panitumumab and FOLFIRI in patients with wild-type RAS, potentially resectable colorectal cancer liver metastases.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16046-e16046
Author(s):  
Gudrun Piringer ◽  
Thomas Gruenberger ◽  
Irene Kuehrer ◽  
Dietmar Oefner ◽  
Klaus Kaczirek ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Liver Metastases ◽  
Objective Response ◽  
Progression Free Survival ◽  
Preoperative Therapy ◽  
Wild Type ◽  
Colorectal Cancer Liver Metastases ◽  
Common Grade ◽  
Grade 3

e16046 Background: Nearly half of patients with colorectal cancer develop liver metastases and only 20% are initially resectable. Surgical resection of liver metastases results in five-year survival rates of 24-48%. Perioperative FOLFOX therapy increases progression free survival. In advanced disease the addition of targeting therapies to chemotherapy results in an overall survival advantage. In this study the efficacy and safety of perioperative panitumumab and FOLFIRI therapy were investigated. Methods: Patients with previously untreated, wild-type RAS, potentially resectable colorectal cancer liver metastases were included. Chemotherapy consisted of irinotecan 180mg/m2 intravenously over 120 minutes and fluorouracil bolus 400mg/m2 intravenously, followed by a 46 h infusion of fluorouracil 2400mg/m2 repeated every 2 weeks. Panitumumab was given as an intravenous dose of 6mg/kg every 2 weeks. Preoperative 4 cycles and postoperative 8 cycles were administered. Primary objectives were the evaluation of efficacy and safety. Results: We enrolled 36 patients in 7 centers in Austria. ITT-analyses included 35 patients. There were 28 men and 7 women, the median age was 66 years. 91.4% completed the planned 4 cycles of preoperative therapy and 82.9% underwent liver resection. R0 resection rate was 82.7%. 20 patients started postoperative chemotherapy and 12 patients completed the planned 8 cycles. Objective response rate after preoperative therapy was 65.7% with one radiological complete remission and 22 partial remissions. In 20% and 5.7% of patients stable disease and progressive disease were documented, respectively. Three patients discontinued preoperative treatment due to adverse events without response evaluation. The most common grade 3 adverse events were diarrhea (n = 4), rash (n = 3) and leukopenia (n = 3) during preoperative therapy. One patient died due to sepsis and one had a pulmonary embolism grade 4. After surgery two patients died due to hepatic failure and one patient had a suture related complication grade 3. Most common grade 3/4 adverse events during postoperative therapy were rash (n = 2), stroke (n = 1) and intestinal obstruction (n = 1). Conclusions: Panitumumab in combination with FOLFIRI as preoperative therapy for operable colorectal liver metastases in RAS wild-type patients results in a radiological objective response rate in 65.7% of patients with a manageable grade 3 diarrhea rate of 14.3%. Progression-free survival and overall survival are still monitored. Clinical trial information: 2012_000265-20 .

Alternating Hepatic Arterial Infusion and Systemic Chemotherapy for Liver Metastases From Colorectal Cancer: A Phase II Trial Using Intermittent Percutaneous Hepatic Arterial Access

2001 ◽  
Vol 19 (9) ◽  
pp. 2404-2412 ◽  
Author(s):  
M. Sitki Copur ◽  
Mary Capadano ◽  
James Lynch ◽  
Timothy Goertzen ◽  
Timothy McCowan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Objective Response Rate ◽  
Response Rate ◽  
Group Performance ◽  
Objective Response ◽  
Hepatic Arterial Infusion ◽  
Fixed Dose ◽  
Arterial Infusion ◽  
Complete Cycle

PURPOSE: To evaluate the objective response to a short course of hepatic arterial infusion (HAI) using temporary, percutaneously placed catheters alternating with systemic prolonged continuous infusion fluorouracil (ci 5-FU) and daily oral leucovorin (L). PATIENTS AND METHODS: Eligible patients were previously untreated (except for adjuvant therapy) adults with liver-predominant metastases, with Eastern Cooperative Oncology Group performance status of 0 to 2. Treatment regimen included HAI with fluorodeoxyuridine (FUDR) 60 mg/m2/d and L 15 mg/m2/d continuously infused daily for 4 days. After a 1-week rest, ci 5-FU was administered through a central venous access device using a dose of 180 mg/m2/d with a fixed dose of oral L at 5 mg/m2/d for 21 out of 28 days. Cycles were repeated every 6 weeks. After four cycles of therapy, patients were maintained on ci 5-FU and daily oral L until evidence of progression. RESULTS: Forty-three patients were enrolled onto this trial. One patient was ineligible. The objective response rate for all patients (17 partial, zero complete) was 41% (95% confidence interval [CI], 26% to 56%). Five patients were not able to receive at least one complete cycle of HAI. Among patients who received at least one complete cycle of HAI, the response rate was 46% (95% CI, 30% to 62%). Five patients underwent a liver resection after enrolling onto the protocol. At the time of analysis, estimated median time to progression was 6 months, and estimated median overall survival was 13 months. CONCLUSION: The objective response rate was comparable to that achieved with more prolonged and more frequent HAI using FUDR. This approach should be studied as an acceptable alternative to surgically placed hepatic arterial catheters/pumps and may have a role as neoadjuvant therapy for liver metastases that are unresectable, as well as an adjuvant role for patients with resected hepatic metastatic colorectal cancer.

Phase II study of irinotecan in the treatment of advanced colorectal cancer in chemotherapy-naive patients and patients pretreated with fluorouracil-based chemotherapy.

1997 ◽  
Vol 15 (1) ◽  
pp. 251-260 ◽  
Author(s):  
P Rougier ◽  
R Bugat ◽  
J Y Douillard ◽  
S Culine ◽  
E Suc ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Response Rate ◽  
Objective Response ◽  
World Health ◽  
Who Grade ◽  
Pretreated Patients ◽  
Grade 3

PURPOSE To assess the efficacy of irinotecan (CPT-11) in the treatment of advanced colorectal cancer in both chemotherapy-naive and pretreated patients. PATIENTS AND METHODS Two hundred thirteen patients (aged 18 to 75 years) with metastatic colorectal cancer, World Health Organization (WHO) performance status < or = 2, and life expectancy > or = 3 months were treated with CPT-11 350 mg/m2 every 3 weeks. All 178 patients eligible for efficacy analysis had not received more than one prior fluorouracil (5-FU)-based chemotherapy regimen (adjuvant or palliative) and had adequate hematologic, renal, and hepatic function. RESULTS Primary tumor sites were the colon (71%) and rectum (28%). Sixty-six percent of the patients had > or = two metastatic sites. Ninety-eight percent of the patients had undergone previous surgery, and 77.5% had received prior chemotherapy. Thirty-two of 178 eligible patients achieved on objective response (four complete responses [CRs] and 28 partial responses [PRs]; response rate, 18%; 95% confidence interval, 12.6% to 24.4%), 65 were stable, and 59 progressed. The response rate was 17.7% in the pretreated group and 18.8% in the chemotherapy-naive group. Within the former subgroup, response rates of 16.1% were reported in patients who were progressive on prior 5-FU chemotherapy and 19.1% in patients who were progressive off such treatment. The median duration of objective response (9.1 months) and median time to achievement of a response (9.3 weeks) did not differ between chemotherapy-naive and pretreated patients. The most frequent adverse events were neutropenia, which developed in 80% of the patients, delayed diarrhea (87%), alopecia (88%), fatigue (81%), and nausea/vomiting (77%). All these adverse events were manageable. Severe (WHO grade 3 or 4) neutropenia was only observed in 18% of the cycles, leukopenia in 11%, delayed diarrhea in 11%, and nausea and vomiting in 3%. Development of simultaneous grade 3 or 4 neutropenia and delayed diarrhea during 4% of the cycles was the safety issue of greatest concern. CONCLUSION CPT-11 has definite activity in the treatment of advanced metastatic colorectal cancer both in chemotherapy-naive and in pretreated patients who experienced disease progression on 5-FU, which suggests a lack of cross-resistance between CPT-11 and 5-FU. Diarrhea and neutropenia, the major toxicities of CPT-11, contribute to the risk to develop febrile neutropenic sepsis.

Overall survival analysis of the FOXFIRE prospective randomized studies of first-line selective internal radiotherapy (SIRT) in patients with liver metastases from colorectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3507-3507 ◽  
Author(s):  
Ricky A. Sharma ◽  
Harpreet Singh Wasan ◽  
Guy A. Van Hazel ◽  
Volker Heinemann ◽  
Navesh K. Sharma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Liver Metastases ◽  
Response Rate ◽  
Objective Response ◽  
Hepatic Metastases ◽  
First Line ◽  
Selective Internal Radiotherapy ◽  
Internal Radiotherapy ◽  
Randomized Studies

3507 Background: The FOXFIRE, SIRFLOX and FOXFIRE-Global (FF-SF-FFG) randomized studies evaluated the efficacy of combining first-line chemotherapy for metastatic colorectal cancer (mCRC) with selective internal radiotherapy (SIRT) using yttrium-90 resin microspheres in patients with liver metastases. The studies were designed for prospective, combined analysis of overall survival (OS). Methods: FF-SF-FFG randomized (1:1) chemotherapy-naïve mCRC patients (performance status 0/1) with liver metastases not suitable for curative resection/ablation. Arm A was oxaliplatin-based chemotherapy (mFOLFOX6/ OxMdG) ± investigator-chosen biologically targeted agent. Arm B was the same systemic therapy (oxaliplatin dose modification) + single treatment SIRT with cycle 1/2 of chemotherapy. Primary tumor in situ and/or limited extra-hepatic metastases were permitted. Minimum sample size was 1075 patients (HR 0.8, 80% power, two-sided 5% significance). Secondary outcomes included PFS, liver-specific PFS and response rate. Apart from safety, outcomes were analysed on intention-to-treat population using meta-analytic methods of pooled individual patient data. Results: Between 2006 and 2014, 1103 patients were randomized in 14 countries. Median age was 63 years (range 23-89); median follow-up 43.3 months. There were 844 deaths. There was no difference in OS (HR 1.04; 95% CI 0.90-1.19, p= 0.609) or PFS (HR 0.90, CI 0.79-1.02, p= 0.108) between Arms. Objective response rate ( p= 0.001) and liver-specific progression (HR 0.51, CI 0.43-0.62, p< 0.001) were significantly more favorable in Arm B. Patients in Arm B had higher risk of non-liver progression as first event (HR 1.98, CI 1.53-2.58, p< 0.001). Grade 3-5 adverse events were more common in Arm B (74.0%) than A (66.5%), p= 0.009. In health status questionnaires, EQ-5D utility scores were not significantly different between Arms at 6, 12 or 24 months. Conclusion: Despite higher response rates and improved liver-specific PFS, the addition of SIRT to first-line oxaliplatin-fluorouracil chemotherapy for patients with liver-only and liver-dominant mCRC did not improve OS or PFS. Clinical trial information: 83867919.

Effectiveness of neoadjuvant chemotherapy including bevacizumab in patients with resectable colorectal cancer liver metastases

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4060-4060 ◽  
Author(s):  
B. Gruenberger ◽  
W. Scheithauer ◽  
D. Tamandl ◽  
C. Zielinski ◽  
J. Schueller ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Response Rate ◽  
Objective Response ◽  
Neoadjuvant Treatment ◽  
High Response Rate ◽  
Curative Surgery ◽  
Colorectal Cancer Liver Metastases ◽  
End Points ◽  
Response To Chemotherapy

4060 Background: Chemotherapy including bevacizumab has become the new standard in the first line treatment of patients with metastatic colorectal cancer (mCRC). Response to chemotherapy has been assessed as major prognostic factor for RFS in resectable mCRC patients, but safety concerns have been raised. We conducted a phase II trial to evaluate the safety of neoadjuvant chemotherapy including bevacizumab (Bev). Methods: Patients with resectable mCRC received six cycles (3 months) of neoadjuvant XELOX (capecitabine 3,500mg/m2/day days 1–7 plus oxaliplatin 85mg/m2 day 1) with bevacizumab (5mg/kg) every 2 weeks. The sixth cycle did not include Bev resulting in a gap of 5 weeks between last Bev and surgery. Primary end points were feasibility of neoadjuvant treatment with this regimen and response rate; secondary end points were feasibility of curative liver resection and perioperative morbidity of the surgical procedure. Results: 54 patients (32 male, 22 female) with a median age of 61 years (SD ± 10.6) were included. The median number of preoperative cycles was 6 (SD ± 2). Grade 3/4 side effects were PNP in 13%, H&F in 3%, diarrhea in 38%, anaemia in 3% and neutropenia in 12% of our patients. Thromboembolic events occurred in 4 patients (7%), hypertension grade III in 2 (4%) and perforation in 1 (2%) patients. A dose reduction of chemotherapy was required in 43%. There were no treatment related deaths. The overall objective response rate for all 54 patients was 74% (40 patients) including 11% pCR. 11 additional patients (20%) had stable disease and only 3 (6%) progressed. Potential curative surgery was performed in all but 5 patients (91%). 2 patients were not resected due to PD, 2 because of pulmonary embolism during chemotherapy and 1 patient because of positive hilar lymph nodes. Conclusions: These data provide evidence that neoadjuvant chemotherapy including bevacizumab can be safely administered in patients with resectable mCRC. A high response rate and a disease control rate of 94% suggest that XELOX + Bev is an effective regimen in this treatment setting. No significant financial relationships to disclose.

First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study

2021 ◽  
Author(s):  
Heinz-Josef Lenz ◽  
Eric Van Cutsem ◽  
Maria Luisa Limon ◽  
Ka Yeung Mark Wong ◽  
Alain Hendlisz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Mismatch Repair ◽  
Clinical Benefit ◽  
Objective Response Rate ◽  
Low Dose ◽  
Response Rate ◽  
Objective Response ◽  
First Line

PURPOSE Nivolumab received US Food and Drug Administration approval as a single agent or in combination with ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) that progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan based on CheckMate 142. Presented are results of nivolumab plus low-dose ipilimumab in the first-line therapy cohort from the phase II CheckMate 142 study. PATIENTS AND METHODS Patients with no prior treatment in the metastatic setting for MSI-H/dMMR CRC were treated with nivolumab every 2 weeks plus low-dose ipilimumab every 6 weeks until disease progression. The primary end point was objective response rate (investigator assessment; RECIST v1.1). RESULTS Median age of treated patients was 66 years (N = 45). Median follow-up was 29.0 months. Objective response rate and disease control rate were 69% (95% CI, 53 to 82) and 84% (95% CI, 70.5 to 93.5), respectively, with 13% complete response rate. Median duration of response was not reached; 74% of responders had ongoing responses at data cutoff. Median progression-free survival and median overall survival were not reached with minimum follow-up of 24.2 months (24-month rates, 74% and 79%, respectively). Clinical benefit was observed regardless of baseline demographic and tumor characteristics, including BRAF or KRAS mutation status. In a post hoc analysis, of 14 patients who discontinued treatment and did not receive subsequent therapy, 10 remained progression-free. Patient-reported outcomes were stable over the treatment period. Grade 3-4 treatment-related adverse events occurred in 22% of patients; 13% discontinued because of any-grade treatment-related adverse events. CONCLUSION Nivolumab plus low-dose ipilimumab demonstrated robust and durable clinical benefit and was well tolerated as a first-line treatment for MSI-H/dMMR mCRC. Based on these promising data, randomized studies are warranted.

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