Phase III Multicenter Randomized Trial of Oxaliplatin Added to Chronomodulated Fluorouracil–Leucovorin as First-Line Treatment of Metastatic Colorectal Cancer

2000 ◽  
Vol 18 (1) ◽  
pp. 136-136 ◽  
Author(s):  
S. Giacchetti ◽  
B. Perpoint ◽  
R. Zidani ◽  
N. Le Bail ◽  
R. Faggiuolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Phase Iii ◽  
Line Treatment ◽  
Survival Times ◽  
First Line ◽  
Grade 3 ◽  
First Line Treatment

PURPOSE: To study how adding oxaliplatin (l-OHP) to chronomodulated fluorouracil (5-FU)–leucovorin (LV) affected the objective response rate, as first-line treatment of metastatic colorectal cancer. PATIENTS AND METHODS: Two hundred patients from 15 institutions in four countries were randomly assigned to receive a 5-day course of chronomodulated 5-FU and LV (700 and 300 mg/m2/d, respectively; peak delivery rate at 0400 hours) with or without l-OHP on the first day of each course (125 mg/m2, as a 6-hour infusion). Each course was repeated every 21 days. Response was assessed by extramural review of computed tomography scans. RESULTS: Grade 3 to 4 toxicity from 5-FU–LV occurred in ≤ 5% of the patients (≤ 1% of the courses). Grade 3 to 4 diarrhea occurred in 43% of the patients given l-OHP (10% of the courses), and less than 2% of the patients had severe hematotoxicity. Thirteen percent of the patients had moderate functional impairment from peripheral sensory neuropathy. Sixteen percent of the patients receiving 5-FU–LV had an objective response (95% confidence interval [CI], 9% to 24%), compared with 53% of those receiving additional l-OHP (95% CI, 42% to 63%) (P < .001). The median progression-free survival time was 6.1 months with 5-FU–LV (range, 4.1 to 7.4 months) and 8.7 months (7.4 to 9.2 months) with l-OHP and 5-FU–LV (P = .048). Median survival times were 19.9 and 19.4 months, respectively. CONCLUSION: By chronomodulating 5-FU–LV, we were able to add l-OHP without compromising dose-intensities. l-OHP significantly improved the antitumor efficacy of this regimen.

Cetuximab metastatic colorectal cancer strategy (ERMES) study: A phase III randomized two arm study with FOLFIRI + cetuximab until disease progression compared to FOLFIRI + cetuximab for 8 cycles followed by cetuximab alone until disease progression in first-line treatment of patients with RAS and BRAF wild type metastatic colorectal cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS810-TPS810 ◽  
Author(s):  
Carmine Pinto ◽  
Nicola Normanno ◽  
Armando Orlandi ◽  
Evaristo Maiello ◽  
Domenico Bilancia ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Disease Progression ◽  
Objective Response ◽  
Phase Iii ◽  
Type I ◽  
Line Treatment ◽  
First Line ◽  
Primary Endpoints ◽  
First Line Treatment

TPS810 Background: The optimal duration and content of first-line therapy in mCRC pts once they have achieved objective response is controversial. In the FIRE-3 trial, ETS was significantly associated with PFS and OS. Based on this evidence it can be hypothesized that once this goal has been achieved, further exposure to combined antineoplastic treatment may not result in improvement or preservation of such result but only in an increase of toxicity. We designed a strategy study to compare FOLFIRI + cetuximab until PD to FOLFIRI + cetuximab for 8 cycles followed by cetuximab alone until PD in first line treatment of RAS/BRAF WT mCRC pts. Methods: This is a multicenter, open-label, randomized phase III trial. Untreated and unresecteble RAS/BRAF WT mCRC pts were randomized 1:1 to receive Cetuximab (400 mg/mq w1 and then 250 mg/mq weekly) + FOLFIRI until PD (standard arm) or Cetuximab (400 mg/mq week 1 and then 250 mg/mq weekly) + FOLFIRI for 8 cycles followed by Cetuximab monotherapy until PD (experimental arm). Tumor assessment is planned every 8 weeks. The objective of the study is to demonstrate a not inferior efficacy and a better toxicity profile for the experimental treatment compared to the standard treatment. The co-primary endpoints are PFS and incidence of G 3-4 AEs. Secondary endpoints are OS, ORR, ETS (8 weeks) and safety. A prospective multiple gene mutation analysis by NGS of both tumor tissue and blood will be performed to find potential predictive factors and surrogate markers of treatment efficacy. The two co-primary endpoints will be compared between the two arms using a fixed-sequence testing procedure to control for the family-wise type I error rate of 0.05 in a strong sense. This sequence considers that a reduction of grade 3-4 AEs is only of relevance, if non-inferiority is shown regarding PFS. 600 evaluable pts will be enrolled and randomized. Study recruitment started on January 2015, currently 139 pts have been randomized. Clinical trial information: NCT02484833.

Comparison of Oral Capecitabine Versus Intravenous Fluorouracil Plus Leucovorin as First-Line Treatment in 605 Patients With Metastatic Colorectal Cancer: Results of a Randomized Phase III Study

2001 ◽  
Vol 19 (8) ◽  
pp. 2282-2292 ◽  
Author(s):  
Paulo M. Hoff ◽  
Rafat Ansari ◽  
Gerald Batist ◽  
John Cox ◽  
Walter Kocha ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Disease Progression ◽  
Response Rate ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Oral Capecitabine ◽  
Grade 3 ◽  
First Line Treatment

PURPOSE: To compare the response rate, efficacy parameters, and toxicity profile of oral capecitabine with bolus intravenous (IV) fluorouracil plus leucovorin (5-FU/LV) as first-line treatment in patients with metastatic colorectal cancer. PATIENTS AND METHODS: We prospectively randomized 605 patients to treatment with oral capecitabine for 14 days every 3 weeks or 5-FU/LV by rapid IV injection daily for 5 days in 4-week cycles. RESULTS: The overall objective tumor response rate among all randomized patients was significantly higher in the capecitabine group (24.8%) than in the 5-FU/LV group (15.5%; P = .005). In the capecitabine and 5-FU/LV groups, median times to disease progression were 4.3 and 4.7 months (log-rank P = .72), median times to treatment failure were 4.1 and 3.1 months (P = .19), and median overall survival times were 12.5 and 13.3 months (P = .974), respectively. Capecitabine, compared with bolus 5-FU/LV treatment, produced a significantly lower incidence (P < .0002) of diarrhea, stomatitis, nausea, and alopecia. Patients treated with capecitabine also displayed lower incidences of grade 3/4 stomatitis and grade 3/4 neutropenia (P < .0001) leading to significantly less neutropenic fever/sepsis. Grade 3 hand-foot syndrome (P < .00001) and grade 3/4 hyperbilirubinemia were the only toxicities more frequently associated with capecitabine than with 5-FU/LV treatment. CONCLUSION: Oral capecitabine was more active than 5-FU/LV in the induction of objective tumor responses. Time to disease progression and survival were at least equivalent for capecitabine compared with the 5-FU/LV arm. Capecitabine also demonstrated clinically meaningful benefits over bolus 5-FU/LV in terms of tolerability.

XELOX (Capecitabine Plus Oxaliplatin): Active First-Line Therapy for Patients With Metastatic Colorectal Cancer

2004 ◽  
Vol 22 (11) ◽  
pp. 2084-2091 ◽  
Author(s):  
Jim Cassidy ◽  
Josep Tabernero ◽  
Chris Twelves ◽  
René Brunet ◽  
Charles Butts ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Xenograft Model ◽  
Sensory Neuropathy ◽  
Dose Finding ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

Purpose Capecitabine has demonstrated high efficacy as first-line treatment for metastatic colorectal cancer (MCRC). Oxaliplatin shows synergy with fluorouracil (FU), with little toxicity overlap. The XELOX regimen (capecitabine plus oxaliplatin), established in a previous dose-finding study, should improve on infused oxaliplatin with FU and leucovorin (FOLFOX) regimens. The present studies further characterize efficacy and safety of the XELOX regimen. Patients and Methods The antitumor activity of XELOX was investigated in a colon cancer xenograft model. Patients with MCRC received first-line XELOX in 3-week treatment cycles: intravenous oxaliplatin 130 mg/m2 (day 1) followed by oral capecitabine 1,000 mg/m2 twice daily (day 1, evening, to day 15, morning). Results A preclinical study confirmed that capecitabine has supra-additive activity with oxaliplatin. In the clinical study, 53 of 96 patients (55%) achieved an objective response, and 30 (31%) experienced disease stabilization for ≥ 3 months following treatment. After 24 months' minimum follow-up, median time to disease progression (TTP) and median overall survival were 7.7 and 19.5 months, respectively. XELOX safety was predictable and similar to the FOLFOX4 regimen, except that myelosuppression was uncommon with XELOX (grade 3 or 4 neutropenia, 7%). Most adverse events were mild to moderate, the most common being acute sensory neuropathy (85%). Sixty-day, all-cause mortality was 2%. Conclusion XELOX is a highly effective first-line treatment for MCRC. Response rates, TTP, and overall survival are similar to those observed with FU/leucovorin/oxaliplatin combinations. XELOX provides a more convenient regimen, likely to be preferred by both patients and healthcare providers. Capecitabine has the potential to replace FU/LV in combination with oxaliplatin for MCRC.

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

scholarly journals Cost-effectiveness analysis of cetuximab combined with chemotherapy as a first-line treatment for patients with RAS wild-type metastatic colorectal cancer based on the TAILOR trial

BMJ Open ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. e030738 ◽  
Author(s):  
Huijuan Wang ◽  
Lingfei Huang ◽  
Peng Gao ◽  
Zhengyi Zhu ◽  
Weifeng Ye ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cost Effectiveness ◽  
Metastatic Colorectal Cancer ◽  
Survival Benefit ◽  
Cost Effective ◽  
Phase Iii ◽  
Line Treatment ◽  
Wild Type ◽  
First Line ◽  
First Line Treatment

ObjectivesCetuximab plus leucovorin, fluorouracil and oxaliplatin (FOLFOX-4) is superior to FOLFOX-4 alone as a first-line treatment for patients with metastatic colorectal cancer with RAS wild-type (RAS wt mCRC), with significantly improved survival benefit by TAILOR, an open-label, randomised, multicentre, phase III trial. Nevertheless, the cost-effectiveness of these two regimens remains uncertain. The following study aims to determine whether cetuximab combined with FOLFOX-4 is a cost-effective regimen for patients with specific RAS wt mCRC in China.DesignA cost-effectiveness model combined decision tree and Markov model was built to simulate pateints with RAS wt mCRC based on health states of dead, progressive and stable. The health outcomes from the TAILOR trial and utilities from published data were used respectively. Costs were calculated with reference to the Chinese societal perspective. The robustness of the results was evaluated by univariate and probabilistic sensitivity analyses.ParticipantsThe included patients were newly diagnosed Chinese patients with fully RAS wt mCRC.InterventionsFirst-line treatment with either cetuximab plus FOLFOX-4 or FOLFOX-4.Main outcome measuresThe primary outcomes are costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs).ResultsBaseline analysis disclosed that the QALYs was increased by 0.383 caused by additional cetuximab, while an increase of US$62 947 was observed in relation to FOLFOX-4 chemotherapy. The ICER was US$164 044 per QALY, which exceeded the willingness-to-pay threshold of US$28 106 per QALY.ConclusionsDespite the survival benefit, cetuximab combined with FOLFOX-4 is not a cost-effective treatment for the first-line regime of patients with RAS wt mCRC in China.Trial registration numberTAILOR trial (NCT01228734); Post-results.

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.

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