scholarly journals Clinical utility of PEG-G-CSF for preventing severe neutropenia in metastatic colorectal cancer patients treated with FOLFOXIRI plus bevacizumab: A single centor retrospective study

2019 ◽  
Author(s):  
Kitagawa Yusuke ◽  
Hiroki Osumi ◽  
Eiji Shinozaki ◽  
Yumiko Ota ◽  
Izuma Nakayama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Severe Neutropenia ◽  
Free Survival ◽  
The Common ◽  
Grade 3 ◽  
Colorectal Cancer Patients

Abstract Background: This study aimed to evaluate in clinical practice the efficacy and safety of polyethylene glycol conjugated granulocyte colony-stimulating factor (PEG-G-CSF) for preventing neutropenia in metastatic colorectal cancer (mCRC) patients that received fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab (Bev). Methods: We retrospectively analyzed mCRC patients who received FOLFOXIRI plus Bev between December 2015 and December 2017. We evaluated the efficacy of PEG-G-CSF for treating neutropenia, the overall response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors version 1.1, progression free survival (PFS), overall survival (OS), and adverse events of FOLFOXIRI plus Bev based on the Common Terminology Criteria for Adverse Events version 4.0. Results: A total of 26 patients (median age 53.5 years) were included. The ORR rate was 65.3%, the median PFS was 9.6 months (7.2–16.9), and the median OS was 24.2 months (13.6–NA). Grade 3 or 4 neutropenia occurred in 53.8% of the patients and febrile neutropenia occurred in 7.7%. PEG-G-CSF was given to 77.0% of the patients, including prophylactically (n = 9) and after the development of grade 3 or 4 neutropenia (n = 11). No patients experienced grade 3 or higher neutropenia after the administration of PEG-G-CSF. In seven of the nine patients who received PEG-G-CSF prophylactically (77.7%), no dose adjustment was required.Conclusions: PEG-G-CSF was useful in preventing severe neutropenia in mCRC patients treated with FOLFOXIRI plus Bev.

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 Clinical utility of polyethylene glycol conjugated granulocyte colony-stimulating factor (PEG-G-CSF) for preventing severe neutropenia in metastatic colorectal cancer patients treated with FOLFOXIRI plus bevacizumab: A single-center retrospective study

2020 ◽  
Author(s):  
Kitagawa Yusuke ◽  
Hiroki Osumi ◽  
Eiji Shinozaki ◽  
Yumiko Ota ◽  
Izuma Nakayama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Polyethylene Glycol ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Severe Neutropenia ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Grade 3 ◽  
Stimulating Factor

Abstract Background: This study aimed to evaluate the efficacy and safety of polyethylene glycol conjugated granulocyte colony-stimulating factor (PEG-G-CSF) for preventing neutropenia in metastatic colorectal cancer (mCRC) patients that received fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab (Bev) in clinical practice. Methods: We retrospectively analyzed mCRC patients who received FOLFOXIRI plus Bev between December 2015 and December 2017. We evaluated the efficacy of PEG-G-CSF as preventing or treating grade 3/4 neutropenia, the overall response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors version 1.1, progression-free survival (PFS), overall survival (OS), and adverse events of FOLFOXIRI plus Bev based on the Common Terminology Criteria for Adverse Events version 4.0. Results A total of 26 patients (median age 53.5 years) were included. The ORR rate was 65.3%, the median PFS was 9.6 months (7.2–16.9), and the median OS was 24.2 months (13.6–NA). Grade 3 or 4 neutropenia occurred in 53.8% of the patients, and febrile neutropenia occurred in 7.7%. PEG-G-CSF was given to 77.0% of the patients, including prophylactically (n = 9) and after the development of grade 3 or 4 neutropenia (n = 11). No patients experienced grade 3 or higher neutropenia after the administration of PEG-G-CSF. In seven of the nine patients who received PEG-G-CSF prophylactically (77.8%), no dose adjustment was required. Conclusions PEG-G-CSF is useful in preventing severe neutropenia in mCRC patients treated with FOLFOXIRI plus Bev.

Durvalumab and tremelimumab in combination with FOLFOX in patients with RAS-mutated, microsatellite-stable, previously untreated metastatic colorectal cancer (MCRC): Results of the first intermediate analysis of the phase Ib/II MEDETREME trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3006-3006 ◽  
Author(s):  
François Ghiringhelli ◽  
Benoist Chibaudel ◽  
Julien Taieb ◽  
Jaafar Bennouna ◽  
Jerome Martin-Babau ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Single Agent ◽  
Suppressor Cells ◽  
Progression Free Survival ◽  
Free Survival ◽  
Efficacy Analysis ◽  
Grade 3 ◽  
Chemotherapy Patients

3006 Background: Single agent PD-1/L1 inhibition are not effective in metastatic colorectal cancer (MCRC) with microsatellite stable tumors. However, signal of efficacy was shown using combo therapy of anti-PD-L1 and anti CTLA-4 in multitreated patients. FOLFOX regimen could induced immunogenic cell death and elimination of myeloid derived suppressor cells (MDSCs) thus leading to a potential positive effect on antitumor immune response. Methods: This is a single arm exploratory investigator-initiated trial planned to include 57 pts to receive mFOLFOX6 (6cycles) in combination with durvalumab (150mg/q2W) and tremelimumab (75mg/q4W). After 6 cycles of chemotherapy, patients are treated with durvalumab untils progression. Primary endpoint is 6 months’ progression-free survival rate. Secondary endpoints are response rate, tolerability and translational research evaluating tissue and blood immune parameter. Upon Simon’s design an efficacy intermediate analysis was planned after the 16th patient has passed 6 months. Results: As of 1st of January 2020 the 55/57 pts were enrolled and treated with the MEDETREME regimen at 8 French sites. The intermediate efficacy analysis was conducted on the 1st of January after a median of 13.4 months of treatment. The following adverse events were noted: asthenia (81.25%), neuropathy (87.5%), diarrhea (56.25%) and neutropenia (62.5%). Notable grade 3/4 (CTC AE 4.03) include asthenia (18.75%) diarrhea (12.5%) neutropenia (50%) and elevated blood pressure (25%). Most of adverse events were related to chemotherapy. It has been noted one cytolysis grade 3, one thyroid dysfunction grade 3 and one hypophysitis grade 3 related to immunotherapy. Median PFS was not reached. Progression free survival at 6 months was observed in 10/16 pts (62,5%) given 5 CR, 5 PR and 4 SD. Updated translational data will be presented at the meeting. Conclusions: The interim safety analysis has supported safety and efficacy of the MEDITREME regimen in first- line MCRC. Finally, results will be presented after maturation of follow up. Clinical trial information: NCT03202758 .

Real-world safety and effectiveness of regorafenib in metastatic colorectal cancer: the French CORRELATE cohort

2021 ◽  
Author(s):  
Jean-Philippe Metges ◽  
Dominique Genet ◽  
David Tougeron ◽  
Catherine Ligeza ◽  
Michel Ducreux ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Phase Iii Clinical Trials ◽  
Grade 3

Aim: We report real-world evidence with regorafenib in previously treated metastatic colorectal cancer from the French cohort of the international, prospective, observational CORRELATE study. Patients & methods: Patients receiving regorafenib according to French health authority approval were included. The primary end point was treatment-emergent adverse events. Overall survival and progression-free survival were secondary end points. Results: Two hundred and forty-two patients (61% male, median age: 66 years) were enrolled. The most common grade ≥3 drug-related treatment-emergent adverse events were hand–foot skin reaction (10.3%), asthenia/fatigue (9.9/1.2%) and hypertension (6.2%). Median overall survival and progression-free survival were 6.8 (95% CI: 6.3–7.6) and 2.8 months (95% CI: 2.6–3.0), respectively. Conclusion: The real-world safety and effectiveness data of regorafenib in metastatic colorectal cancer in France align with findings from Phase III clinical trials and the global CORRELATE population.

The combination of TAS-102 and bevacizumab as the third-line chemotherapy for metastatic colorectal cancer (TAS-CC3 Study).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 614-614
Author(s):  
Chihiro Kosugi ◽  
Hirohiko Kamiyama ◽  
Yoichiro Yoshida ◽  
Hiroshi Yoshida ◽  
Keiichiro Ishibashi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Primary Endpoint ◽  
Task Force ◽  
Progression Free Survival ◽  
Free Survival ◽  
Grade 3 ◽  
Line Chemotherapy

614 Background: TAS-102 improved overall survival of metastatic colorectal cancer (mCRC) patients with median progression free survival (PFS) of 2.0 months (RECOURSE trial). Subsequently, the combination of TAS-102 and bevacizumab has been shown to extend median PFS with 3.7 months (C-TASK FORCE). However, this study included patients with 2nd line and 3rd line chemotherapy. Our study was planned exclusively for patients receiving this combination as a 3rd line chemotherapy to investigate clinical impact of this combination beyond cytotoxic doublet. Methods: This phase II study was conducted in investigator-initiated, open-label, single-arm, multicentered manner in Japan. Eligible patients were 20-80 years old, and had to have an ECOG performance status of 0 or 1; had confirmed unresectable mCRC with histologically diagnosed adenocarcinoma; were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in the 1st and the 2nd line chemotherapy. TAS-102 (35 mg/ m²) was given orally twice daily on days 1–5 and 8–12 in a 4-weeks cycle, and bevacizumab (5 mg/ kg) was administered by intravenous infusion for 30 minutes in every 2 weeks. The primary endpoint was progression free survival (PFS), and the secondary endpoints were time to treatment failure (TTF), response rate (RR), overall survival (OS), and safety. Results: Between June 2016 and August 2017, 32 pts were enrolled. The median PFS was 4.5 months, and the median OS was 9.3 months. Partial response was observed in 2 patients. The most common adverse events above grade 3 were neutropenia (15 patients) followed by thrombocytopenia (4 patients). Treatment-related serious adverse events were reported in 1 patient. There were no non-hematologic adverse events above grade 3. No treatment-related deaths occurred. Conclusions: This is the first study which involves the combination TAS-102 and bevacizumab as the 3rd line chemotherapy in the setting beyond cytotoxic doublet for the patients with mCRC. This study met its primary endpoint PFS, which is comparable to the results of C-TASK FORCE study. This combination has a potential to be one of therapeutic options of the 3rd line chemotherapy for mCRC. Clinical trial information: 000022438.

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.

Bevacizumab Pharmacokinetics Influence Overall and Progression-Free Survival in Metastatic Colorectal Cancer Patients

2016 ◽  
Vol 55 (11) ◽  
pp. 1381-1394 ◽  
Author(s):  
Morgane Caulet ◽  
Thierry Lecomte ◽  
Olivier Bouché ◽  
Jérôme Rollin ◽  
Valérie Gouilleux-Gruart ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Progression Free Survival ◽  
Free Survival ◽  
Colorectal Cancer Patients

Phase III Trial of Infusional Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan (FOLFOXIRI) Compared With Infusional Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) As First-Line Treatment for Metastatic Colorectal Cancer: The Gruppo Oncologico Nord Ovest

2007 ◽  
Vol 25 (13) ◽  
pp. 1670-1676 ◽  
Author(s):  
Alfredo Falcone ◽  
Sergio Ricci ◽  
Isa Brunetti ◽  
Elisabetta Pfanner ◽  
Giacomo Allegrini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Peripheral Neurotoxicity ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Secondary Resection ◽  
Phase Iii Study ◽  
Grade 3

Purpose The Gruppo Oncologico Nord Ovest (GONO) conducted a phase III study comparing fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI [irinotecan 165 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 200 mg/m2 day 1, fluorouracil 3,200 mg/m2 48-hour continuous infusion starting on day 1, every 2 weeks]) with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI). Methods Selection criteria included unresectable metastatic colorectal cancer, age 18 to 75 years, and no prior chemotherapy for advanced disease. The primary end point was response rate (RR). Results A total of 244 patients were randomly assigned. An increase of grade 2 to 3 peripheral neurotoxicity (0% v 19%; P < .001), and grade 3 to 4 neutropenia (28% v 50%; P < .001) were observed in the FOLFOXIRI arm. The incidence of febrile neutropenia (3% v 5%) and grade 3 to 4 diarrhea (12% v 20%) were not significantly different. Responses, as assessed by investigators, were, for FOLFIRI and FOLFOXIRI, respectively, complete, 6% and 8%; and partial, 35% and 58%, (RR, 41% v 66%; P = .0002). RR confirmed by an external panel was 34% versus 60% (P < .0001). The R0 secondary resection rate of metastases was greater in the FOLFOXIRI arm (6% v 15%; P = .033, among all 244 patients; and 12% v 36%; P = .017 among patients with liver metastases only). Progression-free survival (PFS) and overall survival (OS) were both significantly improved in the FOLFOXIRI arm (median PFS, 6.9 v 9.8 months; hazard ratio [HR], 0.63; P = .0006; median OS, 16.7 v 22.6 months; HR, 0.70; P = .032). Conclusion The FOLFOXIRI regimen improves RR, PFS, and OS compared with FOLFIRI, with an increased, but manageable, toxicity in patients with metastatic colorectal cancer with favorable prognostic characteristics. Further studies of FOLFOXIRI in combination with targeted agents and in the neoadjuvant setting are warranted.

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