Dose escalating study of 5-FU/folinic acid (FA)/oxaliplatin/irinotecan (FOLFOXIRI) and cetuximab in first-line therapy of patients with metastatic colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15025-e15025
Author(s):  
T. Trarbach ◽  
K. Schuette ◽  
J. Stoehlmacher ◽  
E. Goekkurt ◽  
H. Guenther ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Folinic Acid ◽  
Performance Status ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Complete Response ◽  
First Line Therapy ◽  
Highly Active ◽  
Grade 3

e15025 Background: Highly active chemotherapy schedules are necessary in several clinical situations, i.e. for conversional chemotherapy in order to resect liver metastases. Adding oxaliplatin or cetuximab to 5-FU / FA / irinotecan was shown to increase the efficacy of chemotherapy in patients with metastatic colorectal cancer (Falcone et al, JCO 2007, Van Cutsem et al, ASCO 2008). Methods: We performed a phase I study in patients (pts) with metastatic colorectal cancer, WHO PS 0–1 who had not been pretreated for metastatic disease. They received cetuximab (500 mg/m2, 2h), oxaliplatin (85 mg/m2, 2h), folinic acid (400 mg/m2, 2h), irinotecan (95, 125, or 165 mg/m2, 1h), 5-FU (3200 mg/m2, 46 h), each on day 1 in biweekly cycles. Dose was escalated if dose limiting toxicities (DLT) were absent in the first three pts per cohort, or if <2 DLTs in six pts. Non-evaluable pts were replaced. Pts were not selected for EGFR IHC or KRAS status. Results: Twenty-one pts were enrolled into the study between Jan 2007 and June 2008, six evaluable pts per each cohort. Two pts who had adverse events deemed unrelated to study during the first cycle (morphine overdosing, mechanical ileus) were replaced, one patient (port dysfunction during first dose) was excluded from analysis. Patient characteristics were as follows: median age 59 (33–72) years, 16 pts WHO PS 0, 15 pts male, 10 pts rectal cancer primary, 3 pts previous adjuvant chemotherapy. In the first two cohorts, 95 and 125 mg/m2 irinotecan, one DLT occurred per dose level (neutropenia gr. 4 and diarrhea gr. 3). In the 165 mg/m2 cohort, 2 DLTs were observed (neutropenia grade 4). Most common grade ≥ 3 toxicities were neutropenia (40%), diarrhea (25%), skin toxicities (15%), thrombopenia (10%) and infections (15%). One patient had a confirmed complete response, 14 pts had confirmed partial response (ORR 75%, 95% CI: 51–91%), 5 pts stable disease. Median progression free survival has not yet been reached. Conclusions: With the combination of FOLFOXIRI/cetuximab, the recommended dose of irinotecan is 125 mg/m2 for further investigation in clinical trials in patients with good performance status. The observed response rate of 75% is very promising. [Table: see text]

Randomized Phase III Study of Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid Plus Oxaliplatin As First-Line Therapy for Metastatic Colorectal Cancer

2008 ◽  
Vol 26 (12) ◽  
pp. 2006-2012 ◽  
Author(s):  
Jim Cassidy ◽  
Stephen Clarke ◽  
Eduardo Díaz-Rubio ◽  
Werner Scheithauer ◽  
Arie Figer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Folinic Acid ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Hand Foot Syndrome ◽  
Grade 3

PurposeTo evaluate whether capecitabine plus oxaliplatin (XELOX) is noninferior to fluorouracil. folinic acid, and oxaliplatin (FOLFOX-4) as first-line therapy in metastatic colorectal cancer (MCRC).Patients and MethodsThe initial design of this trial was a randomized, two-arm, noninferiority, phase III comparison of XELOX versus FOLFOX-4. After patient accrual had begun, the trial design was amended in 2003 after bevacizumab phase III data became available. The resulting 2 × 2 factorial design randomly assigned patients to XELOX versus FOLFOX-4, and then to also receive either bevacizumab or placebo. We report here the results of the analysis of the XELOX versus FOLFOX-4 arms. The analysis of bevacizumab versus placebo with oxaliplatin-based chemotherapy is reported separately. The prespecified primary end point for the noninferiority analysis was progression-free survival.ResultsThe intent-to-treat population comprised 634 patients from the original two-arm portion of the study, plus an additional 1,400 patients after the start of the amended 2 × 2 design, for a total of 2,034 patients. The median PFS was 8.0 months in the pooled XELOX-containing arms versus 8.5 months in the FOLFOX-4–containing arms (hazard ratio [HR], 1.04; 97.5% CI, 0.93 to 1.16). The median overall survival was 19.8 months with XELOX versus 19.6 months with FOLFOX-4 (HR, 0.99; 97.5% CI, 0.88 to 1.12). FOLFOX-4 was associated with more grade 3/4 neutropenia/granulocytopenia and febrile neutropenia than XELOX, and XELOX with more grade 3 diarrhea and grade 3 hand-foot syndrome than FOLFOX-4.ConclusionXELOX is noninferior to FOLFOX-4 as a first-line treatment for MCRC, and may be considered as a routine treatment option for appropriate patients.

Oxaliplatin rechallenge in patients with metastatic colorectal cancer prior treatment with oxaliplatin.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 785-785
Author(s):  
Jeong-Eun Kim ◽  
Yong Sang Hong ◽  
Kyu-Pyo Kim ◽  
Seong Joon Park ◽  
Jae-Lyun Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Hypersensitivity Reaction ◽  
Metastatic Colorectal Cancer ◽  
Treatment Option ◽  
Performance Status ◽  
Progression Free Survival ◽  
Complete Response ◽  
Cytotoxic Agents ◽  
Free Survival ◽  
Disease Free

785 Background: With limited number of available cytotoxic agents for the treatment of metastatic colorectal cancer (mCRC) patients (pts), rechallenge of chemotherapy can be considered for continuum of treatment. We investigated the efficacy and feasibility of oxaliplatin rechallenge in mCRC pts who have been already exposed to prior oxaliplatin-based chemotherapy. Methods: mCRC pts, who were re-treated with oxaliplatin-based chemotherapy as second or later line treatment in the presence of evaluable disease, were retrospectively accrued. Only those who remained disease-free or progression-free at least 6 months after the last dose of prior oxaliplatin were included. Results: Between January 2009 and May 2014, 110 pts were retreated with oxaliplatin-based regimen; 42 (38.2%) patients received prior oxaliplatin as adjuvant chemotherapy and 68 (61.8%) as palliative chemotherapy. Median disease-free or progression-free duration after prior oxaliplatin was 15.4 months (range, 12.9-17.6 months). All of them received oxaliplatin rechallenge in combination with fluoropyrimidines. The overall response rate to the oxaliplatin rechallenge was 30.9% (34/110), and the disease-control rate was 68.2% (75/110) with 1 complete response, 33 partial responses, and 41 stable diseases. Median progression-free survival and overall survival with rechallenge of oxaliplatin-based therapy were 5.9 months (95% CI, 4.6-7.2 months) and 19.7 months (95% CI, 11.9-27.5 months), respectively. Grade 2 or 3 neuropathy was observed in 16 patients. Any grade hypersensitivity reaction was observed in 10 patients within 4 cycle of treatment. Among them, 6 patients stopped treatment due to grade 3 or 4 hypersensitivity reaction. Conclusions: Rechallenge of oxaliplatin-based therapy could be a treatment option in patients who achieved at least 6 months of disease-free or progression-free survival with prior oxaliplatin-based chemotherapy, especially in those who have lack of further treatment option with good performance status. However, neurotoxicity and hypersensitivity reaction should be cautiously monitored in this setting.

scholarly journals A comparison of FOLFIRI (Folinic Acid, Fluorouracil and Irinotecan) Plus Bevacizumab and FLOLFIRI Plus Aflibercept as Second-Line Treatment for Metastatic Colorectal Cancer

2020 ◽  
Author(s):  
Min-Sang Lee ◽  
Yong-Pyo Lee ◽  
Hongsik Kim ◽  
Jung Yong Hong ◽  
Jeeyun Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Folinic Acid ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
Free Survival ◽  
Treatment Groups ◽  
Grade 3 ◽  
Colorectal Cancer Patients

Abstract Background: To date, there are few clinical studies comparing the efficacy and safety of FOLFIRI (folinic acid, fluorouracil and irinotecan) plus bevacizumab or aflibercept in metastatic colorectal cancer patients (mCRC) pretreated with oxaliplatin-based chemotherapy. Methods: We analyzed the treatment outcomes of patients receiving FOLFIRI in combination with bevacizumab or aflibercept as second-line treatment for mCRC between October 2017 and March 2020. This analysis included 67 patients receiving FOLFIRI plus aflibercept and 83 receiving FOLFIRI plus bevacizumab. Results: The overall response rate (ORR) was 13.6% (95% CI: 4.85-22.34) in the FOLFIRI-aflibercept group and 14.7% (95% CI: 6.68-22.71) in the FOLFIRI-bevacizumab group. This difference in ORR was not statistically significant. The median progression free survival (PFS) was 8.6 months in the FOLFIRI-bevacizumab group and 8.5 months in the FOLFIRI-aflibercept group (P = 0.752) (Fig. 1). Patients in the FOLFIRI-bevacizumab group showed a median overall survival (OS) of 12.4 months, while patients in the FOLFIRI-aflibercept group had a median OS of 13.7 months (P = 0.276). There were no significant differences in survival between the two treatment groups. The adverse events were also largely similar between the two groups. However, hypertension of grade 3 or more was more frequent in the FOLFIRI-aflibercept group. Conclusion: FOLFIRI plus bevacizumab and FOLFIRI plus aflibercept had similar anti-tumor activities and toxicity profiles when used as second-line therapy in mCRC patients. Based on these data, both aflibercept and bevacizumab are suitable anti-angiogenic agents when used in combination with FOLFIRI for mCRC.

scholarly journals Safety, efficacy and patient-reported outcomes with trifluridine/tipiracil in pretreated metastatic colorectal cancer: results of the PRECONNECT study

ESMO Open ◽  
2020 ◽  
Vol 5 (3) ◽  
pp. e000698
Author(s):  
Jean-Baptiste Bachet ◽  
Lucjan Wyrwicz ◽  
Timothy Price ◽  
Chiara Cremolini ◽  
Jean-Marc Phelip ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Open Label ◽  
Patient Reported ◽  
Registration Number ◽  
Grade 3

BackgroundIn RECOURSE (, trifluridine/tipiracil significantly improved overall survival and progression-free survival (PFS) versus placebo in patients with pretreated metastatic colorectal cancer (mCRC). PRECONNECT was designed to further characterise safety and clinical use of trifluridine/tipiracil.MethodsIn this ongoing, international, multicentre, open-label trial, patients with pretreated mCRC received oral trifluridine/tipiracil 35 mg/m2 twice daily on days 1–5 and 8–12 of each 28-day cycle. The primary endpoint was safety; secondary endpoints included PFS and quality of life (QoL).Results793 patients (median age 62 years) from 13 countries received trifluridine/tipiracil for a median of 2.84 months (IQR 2.64). Adverse events (AEs) were experienced by 96.7%; the most common (≥20% of patients) were neutropaenia, asthenia/fatigue, nausea, anaemia and diarrhoea. Grade ≥3 AEs occurred in 73.9% of patients, with the most common being neutropaenia (39.1% of patients), anaemia (9.8%) and asthenia/fatigue (5.0%). Median PFS was 2.8 months (95% CI 2.7 to 2.9). Median time to Eastern Cooperative Oncology Group performance status deterioration (≥2) was 8.9 months (range 0.03–14.72). There was no clinically relevant change from baseline in QoL.ConclusionsPRECONNECT showed consistent results with the previously demonstrated safety and efficacy profile of trifluridine/tipiracil, with no new safety concerns identified. QoL was maintained during treatment.Trial registration numberNCT03306394.

Phase II trial of combined chemotherapy with irinotecan, S-1, and bevacizumab (IRIS/Bev) in patients with metastatic colorectal cancer: Update analysis—Hokkaido Gastrointestinal Cancer Study Group (HGCSG) trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3593-3593
Author(s):  
Satoshi Yuki ◽  
Yoshito Komatsu ◽  
Takuto Miyagishima ◽  
Takashi Kato ◽  
Kazuteru Hatanaka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Primary Endpoint ◽  
Performance Status ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Grade 3 ◽  
First Line Treatment

3593 Background: The FIRIS study (Muro K et al. Lancet Oncol 2010;11:853–860) previously demonstrated the non-inferiority of Irinotecan plus S-1(IRIS) to FOLFIRI for metastatic colorectal cancer(mCRC), with progression-free survival (PFS) as the primary endpoint. We previously reported that IRIS plus bevacizumab(IRIS/bev) is very effective as first-line treatment (Komatsu Y et al. ESMO 2010). We now report the updated results of this study. Methods: Eligible patients had to have mCRC with a confirmed diagnosis of adenocarcinoma, an age of >20 years, ECOG performance status (PS) of 0-1, and no history of prior chemotherapy. S-1 40-60 mg twice daily p.o. was given on days 1-14 and irinotecan 100 mg/m2 and bevacizumab 5 mg/kg i.v. were given on days 1 and 15 of a 28-day cycle. The primary endpoint was safety. The secondary endpoints included overall response (OR), progression-free survival (PFS), and overall survival (OS). Results: The target number of 53 patients was enrolled as of March 2009. The results are reported for 52 patients with evaluable lesions. The clinical characteristics of the patients were as follows. The median age was 63.5 years (range, 48 to 82). The male:female ratio was 3:2. The performance status on the Eastern Cooperative Oncology Group scale was 0. In January 2012, on safety analysis, the incidence of grade 3 or 4 neutropenia was 27%. The incidences of other grade 3 or 4 adverse reactions were as follows: diarrhea, 17%; anorexia, 4%; stomatitis, 2%; hypertension, 21%; and gastrointestinal perforation, 0%. The overall response rate was 63.5%. Three patients had complete response. Thirty patients had partial response, 16 had stable disease, none had progressive disease, and 3 were not evaluable. Median progression-free survival was 17.0 months and median survival time was 39.6 months. Conclusions: IRIS/Bev is a remarkably active and generally well-tolerated first-line treatment for patients with mCRC. Randomized control trial comparing this regimen with oxaliplatin containing regimen(XELOX or mFOLFOX6 plus bevacizumab) is being planned.

Weekly bolus 5-fluorouracil and bevacizumab in the palliative treatment of metastatic colorectal cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 736-736
Author(s):  
Michelle Jane Cook ◽  
Carole Connor ◽  
Mohammed Mojid Khan ◽  
Peter Denzil Correa
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Palliative Treatment ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Response To Treatment ◽  
Uncontrolled Hypertension ◽  
Weekly Bolus

736 Background: Patients with metastatic colorectal cancer (mCRC) are often elderly with multiple co-morbidities making them poor candidates for combination chemotherapy. Evidence suggests significant benefit from the addition of Bevacizumab (Bev) to single agent fluoropyrimidine chemotherapy in the palliative treatment of mCRC. There is no current trial data to support use of weekly bolus 5-fluorouracil (5-FU) chemotherapy combined with Bev. We present details of our experience with this treatment regimen. Methods: Patients with mCRC treated with weekly bolus 5-FU 370 mg/m2and Bev 5mg/kg every 2 weeks (Weekly-5FU-Bev) as a new line of palliative treatment were reviewed. All were deemed unsuitable for Capecitabine. Data were collected retrospectively from patient records. Survival statistics were calculated from date of treatment initiation using Kaplan-Meier methods. Results: From 2012-2015, 21 patients were treated with Weekly-5FU-Bev. Median age was 80 years (range 56-90 years), 57.1% were performance status (PS) 0, 19% PS 1 and 23.8% PS 2. 61.9% patients were Ras wild-type. Median treatment duration to date is 20 weeks (range 4-117 weeks). Treatment was stopped in 8 due to progressive disease, 1 due to toxicity and 4 for other reasons. Treatment was generally well tolerated with significant fatigue the most commonly reported side effect in 24%. 3 patients experienced venous thrombo-embolic events, 1 developed uncontrolled hypertension and 1 suffered a non-fatal tumour perforation. There were no treatment related deaths. Clinical benefit rate determined by best response to treatment was impressive at 66.7% with 1 complete response, 1 partial response, 1 biochemical response (non-measurable disease) and 12 patients with stable disease. Median progression free survival was 9.3 months (95% CI 2.8-15.8 months). Median overall survival has not been reached with 15 patients still alive. Conclusions: Acknowledging the limitations of this retrospective analysis of a carefully selected patient group, Weekly-5FU-Bev appears to be well tolerated and efficacious in the treatment of elderly patients with mCRC and can be considered an option in patients unsuitable for or intolerant of Capecitabine.

scholarly journals The Efficacy and Safety of Fruquintinib Plus PD-1 Inhibitor in ≥3 line MSS Metastatic Colorectal Cancer Patients

2021 ◽  
Author(s):  
Xiangyi Wang ◽  
li lin ◽  
jun liang
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Complete Response ◽  
Efficacy And Safety ◽  
Once Daily ◽  
Grade 5 ◽  
Grade 3 ◽  
Vegfr Inhibitor ◽  
Colorectal Cancer Patients

Abstract Purpose: Based on the suggestion of REGONIVO study, we reviewed the data of 26 MSS mCRC patients to elaborate the efficacy and safety of fruquintinib (a VEGFR inhibitor) plus PD-1 inhibitor and explore the potential predictors for survival in 3+ line microsatellite stable (MSS) metastatic colorectal cancer (mCRC) patients.Patients and methods: This retrospective study enrolled 26 MSS mCRC patients who progressed after at least 2 lines of systematic chemotherapy but didn’t receive PD-1 inhibitors. Fruquintinib of 3mg was administered once daily with 21 days on/7 days off plus PD-1 inhibitor 200mg every 3 weeks until intolerable toxicity or disease progression. Results: Median overall survival (mOS) was 6.1m (ranged 1.8m-NR 95%CI: 2.60-9.60); median progression free survival (mPFS) was 2.3m (ranged 1.5m-NR 95%CI: 0.93-3.67). There was one complete response (CR) and no partial response (PR). Stable disease was observed in 11 patients (42%) and progression disease (PD) was observed in 14 patients (54%). The object response rate (ORR) was 4% (1/26) and disease control rate (DCR) was 46 %( 12/26). Grade ≥3 AEs were observed in 5 patients (19.2%). Grade 5 AEs (immune related encephalitis and cardiotoxicity) were observed in 2 patients. Additionally, there was a significant correlation between NLR < 3.06 and longer survival (P=0.000) for MSS mCRC patients treated with fruquintinib plus PD-1 inhibitor. Conclusions: Fruquintinib plus PD-1 inhibitor may be a choice for 3+ line MSS mCRC patients，especially with pretreatment NLR<3.06.

A phase II study of oxaliplatin (OX), capecitabine (CAP), and bevacizumab (BV) in the treatment of metastatic colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3541-3541 ◽  
Author(s):  
J. C. Bendell ◽  
N. Fernando ◽  
M. Morse ◽  
G. Blobe ◽  
D. Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Infusion Pump ◽  
Progression Free Survival ◽  
First Line ◽  
Intention To Treat ◽  
First Line Therapy ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
Endothelial Growth Factor

3541 Background: BV, a monoclonal antibody against vascular endothelial growth factor, provides a survival advantage when added to first line therapy for metastatic colorectal cancer. CAP allows for fluoropyrimide treatment without the inconvenience of an infusion pump. We aimed to investigate the combination of OX, CAP, and BV (XeloxA) as a more convenient and active regimen. Methods: Pts with untreated metastatic colorectal cancer received OX 85 mg/m2 d1, CAP 1000 mg/m2 BID d1–5 and 8–12, and BV 10 mg/kg d1. Cycles were repeated every two weeks. The starting dose of CAP was changed to 850 mg/m2 BID due to toxicity in the first 28 patients. Data were analyzed under an intention to treat method. Results: 50 pts received therapy (28M, 22F), median age 55 (range 24–81). Data were available on 49 pts. The most common toxicity was diarrhea, with 12/49 (24%) having grade 3 diarrhea, and 22% with grade 2. After the dose reduction of CAP, 3/21 (14%) pts had grade 3 diarrhea and 2/21 (10%) with grade 2 as compared to 32% grade 3 and 32% grade 2 at the higher dose. At the higher dose of CAP 4% of pts had grade 3 hand-foot syndrome (HFS) and 39% had grade 2. At the lower dose, 10% had grade 3 and 5% had grade 2. Other grade 3 toxicities were minimal, including neurotoxicity (8%), vomiting (6%), and neutropenia (4%). There were 23 responses, 1 CR and 22 PR (RR=47%; 95% CI: 33%-62%). 21 pts had stable disease (43%). Median progression free survival (PFS) was 10.7 months (95% CI: 8.6–13.6). Conclusions: XeloxA is a well tolerated, active regimen in the first line treatment of metastatic colorectal cancer. RR and PFS data approximate that of infusional 5-FU regimens in combination with BV without the necessity of an infusion pump. [Table: see text]

FOLFIRI Followed by FOLFOX6 or the Reverse Sequence in Advanced Colorectal Cancer: A Randomized GERCOR Study

2004 ◽  
Vol 22 (2) ◽  
pp. 229-237 ◽  
Author(s):  
Christophe Tournigand ◽  
Thierry André ◽  
Emmanuel Achille ◽  
Gérard Lledo ◽  
Michel Flesh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Folinic Acid ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Iii Study ◽  
Grade 3

Purpose In metastatic colorectal cancer, phase III studies have demonstrated the superiority of fluorouracil (FU) with leucovorin (LV) in combination with irinotecan or oxaliplatin over FU + LV alone. This phase III study investigated two sequences: folinic acid, FU, and irinotecan (FOLFIRI) followed by folinic acid, FU, and oxaliplatin (FOLFOX6; arm A), and FOLFOX6 followed by FOLFIRI (arm B). Patients and Methods Previously untreated patients with assessable disease were randomly assigned to receive a 2-hour infusion of l-LV 200 mg/m2 or dl-LV 400 mg/m2 followed by a FU bolus 400 mg/m2 and 46-hour infusion 2,400 to 3,000 mg/m2 every 46 hours every 2 weeks, either with irinotecan 180 mg/m2 or with oxaliplatin 100 mg/m2 as a 2-hour infusion on day 1. At progression, irinotecan was replaced by oxaliplatin (arm A), or oxaliplatin by irinotecan (arm B). Results Median survival was 21.5 months in 109 patients allocated to FOLFIRI then FOLFOX6 versus 20.6 months in 111 patients allocated to FOLFOX6 then FOLFIRI (P = .99). Median second progression-free survival (PFS) was 14.2 months in arm A versus 10.9 in arm B (P = .64). In first-line therapy, FOLFIRI achieved 56% response rate (RR) and 8.5 months median PFS, versus FOLFOX6 which achieved 54% RR and 8.0 months median PFS (P = .26). Second-line FOLFIRI achieved 4% RR and 2.5 months median PFS, versus FOLFOX6 which achieved 15% RR and 4.2 months PFS. In first-line therapy, National Cancer Institute Common Toxicity Criteria grade 3/4 mucositis, nausea/vomiting, and grade 2 alopecia were more frequent with FOLFIRI, and grade 3/4 neutropenia and neurosensory toxicity were more frequent with FOLFOX6. Conclusion Both sequences achieved a prolonged survival and similar efficacy. The toxicity profiles were different.

Lonsurf (trifluridine/tipiracil): Assessing the impact of dose related toxicities and progression free survival in (refractory) metastatic colorectal cancer

2021 ◽  
pp. 107815522110179
Author(s):  
Olivia R Court
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Dose Reduction ◽  
Progression Free Survival ◽  
Electronic Patient Records ◽  
Free Survival ◽  
Length Of Treatment ◽  
Common Grade ◽  
Grade 3 ◽  
The Impact

In the RECOURSE trial which lead to its accreditation, Lonsurf (trifluridine/tipiracil) was shown to extend progression free survival (PFS) by 1.8 months in metastatic colorectal cancer. This Trust audit aims to assess the average quantity of cycles of Lonsurf received by participants and the length of time it extends PFS. Similarly, to identify how many participants required a dose-reduction or experienced toxicities which necessitated supportive therapies. Quantitative data was collected retrospectively from all participants who had received ≥1 cycle of Lonsurf from The Clatterbridge Cancer Centre (CCC) from 2016 until June 2020. Participant electronic patient records were accessed to identify toxicity grading, length of treatment received, the date progression was identified, if dose reductions were applied and if supportive therapies were administered. Lonsurf extends PFS in patients with metastatic colorectal cancer at CCC by 3.0 months (95% CI: 2.73–3.27) and average treatment length was 2.4 months. However, 78 participants (41.5%) received a dose reduction due to toxicities. A total of 955 toxicities were recorded by participants; the most commonly reported toxicities irrespective of grade were fatigue (33.8%), diarrhoea (13.8%) and nausea (12.3%). The most common grade ≥3 toxicities were constipation and infection. The most frequently utilised supportive therapies were loperamide (49.6%) and domperidone (49.1%). Granulocyte colony stimulating factor (GCSF) was required by patients on 5 occasions (0.3%) in total. Lonsurf extends median PFS in patients with metastatic colorectal cancer by 3.0 months. The most common grade ≥3 toxicities which necessitated supportive therapies or a dose reduction were gastrointestinal and infection.

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