Phase II Trial of Cetuximab in Combination With Fluorouracil, Leucovorin, and Oxaliplatin in the First-Line Treatment of Metastatic Colorectal Cancer

2007 ◽  
Vol 25 (33) ◽  
pp. 5225-5232 ◽  
Author(s):  
Josep Tabernero ◽  
Eric Van Cutsem ◽  
Eduardo Díaz-Rubio ◽  
Andrés Cervantes ◽  
Yves Humblet ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Study ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Curative Intent ◽  
First Line Treatment

PurposeThis phase II study investigated the efficacy and safety of cetuximab combined with standard oxaliplatin-based chemotherapy (infusional fluorouracil, leucovorin, and oxaliplatin [FOLFOX-4]) in the first-line treatment of epidermal growth factor receptor–expressing metastatic colorectal cancer (mCRC).Patients and MethodsThe activity of cetuximab plus oxaliplatin was investigated in colon cancer cell lines and xenograft models. In the clinical study, patients with mCRC received on day 1 of a 14 day cycle, cetuximab (initial dose 400 mg/m2during week 1, then 250 mg/m2weekly) followed by FOLFOX-4 (oxaliplatin 85 mg/m2on day 1; leucovorin 200 mg/m2on days 1 and 2, followed by fluorouracil 400 mg/m2bolus then 600 mg/m2intravenous infusion during 22 hours on days 1 and 2).ResultsThe preclinical studies confirmed the supra-additive activity of cetuximab to oxaliplatin. In the clinical study, 43 patients were included, with a median age of 65 years (range, 43 to 78 years). Response rates (RRs) were 79% (unconfirmed) and 72% (confirmed), with 95% disease control. Median progression-free survival (mPFS) and median duration of response were 12.3 and 10.8 months, respectively. Ten patients (23%) underwent resection with curative intent of previously unresectable metastases. After a median follow-up of 30.5 months, median overall survival (mOS) was 30.0 months. Cetuximab did not increase the characteristic toxicity of FOLFOX-4 and was generally well tolerated.ConclusionCetuximab in combination with FOLFOX-4 is a highly active first-line treatment for mCRC, showing encouraging RR, mPFS, and mOS values. The treatment resulted in a high resectability rate, which could potentially result in an improved cure rate. This combination is under phase III development.

Randomized, Controlled Trial of Irinotecan Plus Infusional, Bolus, or Oral Fluoropyrimidines in First-Line Treatment of Metastatic Colorectal Cancer: Results From the BICC-C Study

2007 ◽  
Vol 25 (30) ◽  
pp. 4779-4786 ◽  
Author(s):  
Charles S. Fuchs ◽  
John Marshall ◽  
Edith Mitchell ◽  
Rafal Wierzbicki ◽  
Vinod Ganju ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Controlled Trial ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Primary Study ◽  
Line Treatment ◽  
First Line ◽  
Double Blind ◽  
First Line Treatment

PurposeThis phase III study compared the safety and efficacy of the following three different irinotecan-containing regimens in the first-line treatment of metastatic colorectal cancer: irinotecan plus infusional fluorouracil (FU)/leucovorin (LV) (FOLFIRI), irinotecan plus bolus FU/LV (mIFL), and irinotecan plus oral capecitabine (CapeIRI).Patients and MethodsA total of 430 previously untreated metastatic colorectal cancer patients were randomly assigned to receive FOLFIRI (n = 144), mIFL (n = 141), or CapeIRI (n = 145). Patients were concurrently randomly assigned to a double-blind treatment with celecoxib or placebo. After a protocol amendment, an additional 117 patients were randomly assigned to either FOLFIRI plus bevacizumab (FOLFIRI+Bev; n = 57) or mILF plus bevacizumab (mIFL+Bev; n = 60), whereas the CapeIRI arm was discontinued. The primary study end point was progression-free survival (PFS), with secondary end points of overall survival (OS), response rate, and toxicity.ResultsMedian PFS was 7.6 months for FOLFIRI, 5.9 months for mIFL (P = .004 for the comparison with FOLFIRI), and 5.8 months for CapeIRI (P = .015). Median OS was 23.1 months for FOLFIRI, 17.6 months for mIFL (P = .09), and 18.9 months for CapeIRI (P = .27). CapeIRI was associated with higher rates of severe vomiting, diarrhea, and dehydration. After the amendment to add bevacizumab, the median survival time has not yet been reached for FOLFIRI+Bev and was 19.2 months for mIFL+Bev (P = .007). FOLFIRI+Bev was associated with a higher rate of ≥ grade 3 hypertension than mIFL+Bev.ConclusionFOLFIRI and FOLFIRI+Bev offered superior activity to their comparators and were comparably safe. An infusional schedule of FU should be the preferred irinotecan-based regimen in first-line metastatic colorectal cancer.

Randomized phase II trial of CapOX plus bevacizumab versus CapIRI plus bevacizumab as first-line treatment in Japanese patients with metastatic colorectal cancer (CCOG-1201).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 781-781
Author(s):  
Masahiro Sasahara ◽  
Goro Nakayama ◽  
Kiyoshi Ishigure ◽  
Hiroyuki Yokoyama ◽  
Keisuke Uehara ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Line Treatment ◽  
First Line ◽  
Intent To Treat ◽  
First Line Treatment

781 Background: The aim of this randomized, multicenter, non-comparative phase II trial was to investigate the efficacy and safety of capecitabine/oxaliplatin (CapOX) plus bevacizumab (BEV) and capecitabine/irinotecan (CapIRI) plus BEV as a first-line treatment in Japanese patients with metastatic colorectal cancer (mCRC). Methods: Patients with untreated mCRC were randomly assigned to the following treatment arms; CapOX/BEV arm (bevacizumab 7.5mg/kg and oxaliplatin 130 mg/m2 on day 1, and oral capecitabine 1000 mg/m2 bid on day 1-14, every 3 weeks) and CapIRI/BEV arm (bevacizumab 7.5mg/kg and irinotecan 200 mg/m2 on day 1, and capecitabine 800 mg/m2 bid on day 1-14, every 3 weeks). The primary endpoint was overall response rate (ORR), and secondary end points included progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 107 patients were enrolled. The intent-to-treat population comprised 52 patients in CapOX/BEV arm and 51 patients in CapIRI/BEV arm. The ORR was 58% in CapOX/BEV arm and 57% in CapIRI/BEV arm ( p= 0.545). The median tumor shrinkage rate (DpR) was 36.0% (range, -24.0 to 100%) and 36.7% (range, -26.0 to 100%), respectively (p = 0.399). Median PFS was 12.4 months (95% confidence interval [CI], 10.6–14.3 months) in CapOX/BEV arm and 11.5 months (95% CI, 9.6–13.4 months) in CapIRI/BEV arm (hazard ratio [HR], 1.145; 95% CI, 0.760–1.725; p= 0.517). The median OS was 26.6 months (95% CI, 21.5–31.8 months) and 28.7 months (95% CI, 19.6–37.9), respectively (HR, 1.206; 95% CI, 0.0.733–1.907; p= 0.461). The frequency of hematological and non-hematological adverse events (≥grade3) were 10% and 27% in CapOX/BEV arm, and 16% and 27% in CapIRI/BEV arm, respectively. Conclusions: Both regimens, CapOX plus BEV and CapIRI plus BEV, could be equally feasible first-line treatment for Japanese patients with mCRC. Clinical trial information: UMIN_000007545.

Cediranib With mFOLFOX6 Versus Bevacizumab With mFOLFOX6 As First-Line Treatment for Patients With Advanced Colorectal Cancer: A Double-Blind, Randomized Phase III Study (HORIZON III)

2012 ◽  
Vol 30 (29) ◽  
pp. 3588-3595 ◽  
Author(s):  
Hans-Joachim Schmoll ◽  
David Cunningham ◽  
Alberto Sobrero ◽  
Christos S. Karapetis ◽  
Philippe Rougier ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Significant Difference ◽  
Patient Reported ◽  
First Line Treatment

Purpose To compare the efficacy of cediranib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor [VEGFR TKI]) with that of bevacizumab (anti–VEGF-A monoclonal antibody) in combination with chemotherapy as first-line treatment for advanced metastatic colorectal cancer (mCRC). Patients and Methods HORIZON III [Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients With Untreated Metastatic Colorectal Cancer] had an adaptive phase II/III design. Patients randomly assigned 1:1:1 received mFOLFOX6 [oxaliplatin 85 mg/m2 and leucovorin 400 mg/m2 intravenously followed by fluorouracil 400 mg/m2 intravenously on day 1 and then continuous infusion of 2,400 mg/m2 over the next 46 hours every 2 weeks] with cediranib (20 or 30 mg per day) or bevacizumab (5 mg/kg every 14 days). An independent end-of-phase II analysis concluded that mFOLFOX6/cediranib 20 mg met predefined criteria for continuation; subsequent patients received mFOLFOX6/cediranib 20 mg or mFOLFOX6/bevacizumab (randomly assigned 1:1). The primary objective was to compare progression-free survival (PFS). Results In all, 1,422 patients received mFOLFOX6/cediranib 20 mg (n = 709) or mFOLFOX6/bevacizumab (n = 713). Primary analysis revealed no significant difference between arms for PFS (hazard ratio [HR], 1.10; 95% CI, 0.97 to 1.25; P = .119), overall survival (OS; HR, 0.95; 95% CI, 0.82 to 1.10; P = .541), or overall response rate (46.3% v 47.3%). Median PFS and OS were 9.9 and 22.8 months for mFOLFOX6/cediranib and 10.3 and 21.3 months for mFOLFOX6/bevacizumab. The PFS upper 95% CI was outside the predefined noninferiority limit (HR < 1.2). Common adverse events with more than 5% incidence in the cediranib arm included diarrhea, neutropenia, and hypertension. Cediranib-treated patients completed fewer chemotherapy cycles than bevacizumab-treated patients (median 10 v 12 cycles). Patient-reported outcomes (PROs) were significantly less favorable in cediranib-treated versus bevacizumab-treated patients (P < .001). Conclusion Cediranib activity, in terms of PFS and OS, was comparable to that of bevacizumab when added to mFOLFOX6; however, the predefined boundary for PFS noninferiority was not met. The cediranib safety profile was consistent with previous studies but led to less favorable PROs compared with bevacizumab. Investigation of oral TKIs in CRC continues.

Randomized phase III study of 5-fluorouracil/folinate/oxaliplatin given continuously or intermittently with or without cetuximab, as first-line treatment of metastatic colorectal cancer: The NORDIC VII study (NCT00145314), by the Nordic Colorectal Cancer Biomodulation Group.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 365-365 ◽  
Author(s):  
K. Tveit ◽  
T. Guren ◽  
B. Glimelius ◽  
P. Pfeiffer ◽  
H. Sorbye ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Braf Mutation ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Intention To Treat ◽  
Negative Prognostic Factor ◽  
First Line Treatment

365 Background: The role of anti-EGFR therapy in first-line treatment of metastatic colorectal cancer (mCRC) is not established. In the present study pts were randomized to FLOX or FLOX + cetuximab until progression or FLOX intermittently + cetuximab continuously. Methods: Treatment arm A: Nordic FLOX (q2w): oxaliplatin 85 mg/m2day 1, 5-FU bolus 500 mg/m2 and FA 60 mg/m2 day 1-2; B: FLOX + cetuximab, initial dose 400 mg/m2, then 250 mg/m2/week; C: FLOX for 16 weeks + cetuximab continuously, with FLOX added at progression. Primary endpoint was progression-free survival (PFS). Results: Between May 05-Oct 07, 571 pts were randomized, 566 pts evaluable in intention to treat (ITT) analyses. Median age was 61 (24-74). ECOG status: 0=67%, 1=29%, 2=4%. KRAS and BRAF mutation (mut) analyses were obtained in 498 (87%) and 457 pts (81%), respectively. 40% of tumors had KRAS mut, 12% had BRAF mut. Cetuximab combined with Nordic FLOX did not significantly improve RR, PFS or OS compared to FLOX. KRAS mutation was not predictive for cetuximab effect. OS was similar for patients treated with FLOX intermittently and cetuximab continuously as for patients treated until progression. BRAF mutation was a strong negative prognostic factor (median OS 7.6 vs. 20.4 mo). Conclusions: Cetuximab did not add significant benefit to the Nordic FLOX regimen in first-line treatment of mCRC, irrespective of KRAS-mut. [Table: see text] [Table: see text]

scholarly journals Randomized phase III trial of S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer: SALTO study by the Dutch Colorectal Cancer Group

2017 ◽  
Vol 28 (6) ◽  
pp. 1288-1293 ◽  
Author(s):  
J.J.M. Kwakman ◽  
L.H.J. Simkens ◽  
J.M. van Rooijen ◽  
A.J. van de Wouw ◽  
A.J. ten Tije ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Phase Iii Trial ◽  
Cancer Group ◽  
First Line Treatment

Safety analysis of the randomized phase II study of FOLFOXIRI plus cetuximab versus FOLFOXIRI plus bevacizumab as the first-line treatment in metastatic colorectal cancer with RAS wild-type tumors: The DEEPER trial (JACCRO CC-13).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 86-86
Author(s):  
Takanori Watanabe ◽  
Akihito Tsuji ◽  
Manabu Shiozawa ◽  
Hirofumi Ota ◽  
Hironaga Satake ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Safety Analysis ◽  
Line Treatment ◽  
Wild Type ◽  
First Line ◽  
Randomized Phase Ii ◽  
First Line Treatment ◽  
Triplet Regimen

86 Background: Triplet regimens, FOLFOXIRI, combined with bevacizumab (bev) or panitumumab have been shown to be superior in terms of early tumor shrinkage (ETS) and depth of response (DpR) compared to doublet regimen plus bev or triplet regimen in patients with RAS wild-type metastatic colorectal cancer (mCRC), in the TRIBE trial ( N Engl J Med 2014) or VOLFI trial ( J Clin Oncol 2019), respectively. There have been few studies which directly compared cetuximab (cet) with bev when combined with triplet regimen. Therefore, we investigated the efficacy and safety of bev vs. cet in combination with FOLFOXIRI in previously untreated mCRC patients with RAS wild-type tumors. Methods: This trial was a randomized phase II trial to evaluate modified (m)-FOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, 5-FU 2400 mg/m2) plus cet vs. bev as first-line treatment in terms of the DpR during the entire course as the primary endpoint in 360 patients with RAS wild-type mCRC (ClinicalTrials.gov Identifier: NCT02515734). The experimental arm with cet was considered to be active if the difference of median DpR was over 12.5% compared with the bev arm, under the conditions of significance level of 0.05 and power of 0.85. Secondary endpoints included the ETS at week 8, progression-free survival, overall survival, secondary resection rate, and toxicity. Results: A total of 359 patients were enrolled between July 2015 and June 2019. For the safety analysis set (median age 65y, 64% male, PS0/1:91%/9%, left/right primary:83%/17%), 173 and 175 patients were randomly assigned to the cet and bev arms, respectively, some patients were excluded for the safety analysis due to the violation of inclusion criteria (6 for cet arm and 5 for bev). On the cutoff date of September 2020, median number of cycles administered was 10 (range, 1-51) for the cet arm and 12 (range, 1-51) for the bev arm. The incidence of severe adverse events (AEs) was 25.4% (44/173) for the cet arm and 25.7% (45/175) for the bev arm, respectively. The following AEs of grade 3-4 were observed more frequently in the cet arm compared to the bev arm: oral mucositis (9.2% vs. 2.3%), diarrhea (12.1% vs. 8.0%), dermatitis acneiform (12.1% vs. 0%), and hypomagnesemia (4.0% vs. 0%). The treatment-related death occurred in 2 patients of the cet arm, while no patients in the bev arm. The rate of treatment discontinuation due to AEs of any cause was comparable between the cet and bev arms (7% vs. 9%). Conclusions: This safety analysis indicated that both regimens of m-FOLFOXIRI plus cet or bev were tolerable in RAS wt mCRC patients although some frequent severe AEs were observed. Clinical trial information: UMIN000018217.

Sign in / Sign up

Export Citation Format

Share Document