Multicenter, randomized phase II trial of bevacizumab plus folinic acid, fluorouracil, gemcitabine (FFG) versus bevacizumab plus folinic acid, fluorouracil, oxaliplatin (FOLFOX4) as first-line therapy for patients with advanced colorectal cancer.

Abstract:

PURPOSE:To assess safety and efficacy of folinic acid, 5-fluorouracil, gemcitabine (FFG) and folinic acid, fluorouracil, oxaliplatin (FOLFOX4) regimens with added bevacizumab as first-line treatment in patients with advanced colorectal cancer (CRC). PATIENTS AND METHODS:Patients with Stage III unresectable or Stage IV adenocarcinoma of the colon or rectum were randomly assigned to either FFG weekly for 6 weeks of an 8-week cycle or FOLFOX4 every 2 weeks. After FDA approval, bevacizumab 5 mg/kg was added every 2 weeks. Treatment continued until disease progression. Planned enrollment was 190 patients. Primary endpoint was overall response rate (ORR); secondary endpoints included evaluation of adverse events, time to progression (TTP), and overall survival (OS). Disease Control Rate (DCR; % of patients with complete or partial responses or stable disease) was a post hoc analysis. RESULTS:The trial was stopped prematurely due to low enrollment. Of 84 enrolled patients (42 to each arm), 36 patients (18 in each arm) received bevacizumab. ORR was greater (P = .002) for FOLFOX4 (17/42; 40.5%) than for FFG (4/42; 9.5%); however, TTP, OS, and DCR results were not statistically different comparing FOLFOX4 and FFG. Peripheral neuropathy was more frequent (P = <.001) with FOLFOX4 (18/42; 42.9%) than with FFG (1/42; 2.4%). CONCLUSIONS:FFG and FOLFOX4 were generally well tolerated. Based on ORR, FOLFOX4 was superior to FFG. However, differences in TTP and OS comparing regimens were inconclusive. General use of gemcitabine as a biomodulator of 5-fluorouracil in CRC cannot be recommended at this time and the regimen remains investigational.

journal_name

Invest New Drugs

authors

Madajewicz S,Waterhouse DM,Ritch PS,Khan MQ,Higby DJ,Leichman CG,Malik SK,Hentschel P,Gill JF,Zhao L,Nicol SJ

doi

10.1007/s10637-010-9598-9

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

772-8

issue

2

eissn

0167-6997

issn

1573-0646

journal_volume

30

pub_type

杂志文章,多中心研究,随机对照试验
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    doi:10.1007/s10637-019-00840-1

    authors: Gluck WL,Gounder MM,Frank R,Eskens F,Blay JY,Cassier PA,Soria JC,Chawla S,de Weger V,Wagner AJ,Siegel D,De Vos F,Rasmussen E,Henary HA

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  • A phase I evaluation of the combination of vinflunine and erlotinib in patients with refractory solid tumors.

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    doi:10.1007/s10637-010-9427-1

    authors: Sanoff HK,Davies JM,Walko C,Irvin W,Buie L,Keller K,Ivanova A,Chiu WK,O'Neil BH,Stinchcombe TE,Dees EC

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    doi:10.1007/s10637-005-4540-2

    authors: van Laarhoven HW,Gambarota G,Heerschap A,Lok J,Verhagen I,Corti A,Toma S,Gallo Stampino C,van der Kogel A,Punt CJ

    更新日期:2006-01-01 00:00:00

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    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1007/s10637-006-5937-2

    authors: Sawa T,Yana T,Takada M,Sugiura T,Kudoh S,Kamei T,Isobe T,Yamamoto H,Yokota S,Katakami N,Tohda Y,Kawakami A,Nakanishi Y,Ariyoshi Y

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    pub_type: 临床试验,杂志文章

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    更新日期:1992-08-01 00:00:00

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    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-010-9614-0

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    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-017-0470-z

    authors: Mori M,Kaneko N,Ueno Y,Yamada M,Tanaka R,Saito R,Shimada I,Mori K,Kuromitsu S

    更新日期:2017-10-01 00:00:00

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    journal_title:Investigational new drugs

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    doi:10.1007/s10637-008-9122-7

    authors: Panneer Selvam J,Aranganathan S,Nalini N

    更新日期:2008-12-01 00:00:00

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    abstract::Bombesin/gastrin-releasing peptides (BN/GRP) were shown to bind selectively to cell surface receptors, stimulating the growth of various types of malignancies in murine and human models. The novel BN/GRP synthetic receptor antagonist, RC-3095, was able to produce long-lasting tumor regressions in murine and human tumo...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-006-6886-5

    authors: Schwartsmann G,DiLeone LP,Horowitz M,Schunemann D,Cancella A,Pereira AS,Richter M,Souza F,da Rocha AB,Souza FH,Pohlmann P,De Nucci G

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    journal_title:Investigational new drugs

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    doi:10.1007/BF00203541

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    pub_type: 杂志文章

    doi:10.1007/s10637-019-00881-6

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    pub_type: 杂志文章,评审

    doi:10.1007/BF00173788

    authors: Bradley EC,Issell BF,Hellman R

    更新日期:1984-01-01 00:00:00

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    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-011-9640-6

    authors: Burkholder TP,Clayton JR,Rempala ME,Henry JR,Knobeloch JM,Mendel D,McLean JA,Hao Y,Barda DA,Considine EL,Uhlik MT,Chen Y,Ma L,Bloem LJ,Akunda JK,McCann DJ,Sanchez-Felix M,Clawson DK,Lahn MM,Starling JJ

    更新日期:2012-06-01 00:00:00

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    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-019-00784-6

    authors: Rodrigues-Junior DM,de Almeida Pontes NM,de Albuquerque GE,Carlin V,Perecim GP,Raminelli C,Vettore AL

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    journal_title:Investigational new drugs

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s10637-006-9014-7

    authors: Kefford R,Beith JM,Van Hazel GA,Millward M,Trotter JM,Wyld DK,Kusic R,Shreeniwas R,Morganti A,Ballmer A,Segal E,Nayler O,Clozel M

    更新日期:2007-06-01 00:00:00

  • Activity of the polyamine-vectorized anti-cancer drug F14512 against pediatric glioma and neuroblastoma cell lines.

    abstract::The poor prognosis of children with high-grade glioma (HGG) and high-risk neuroblastoma, despite multidisciplinary therapeutic approaches, demands new treatments for these indications. F14512 is a topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells via the Polyamine...

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    pub_type: 杂志文章

    doi:10.1007/s10637-014-0132-3

    authors: Leblond P,Boulet E,Bal-Mahieu C,Pillon A,Kruczynski A,Guilbaud N,Bailly C,Sarrazin T,Lartigau E,Lansiaux A,Meignan S

    更新日期:2014-10-01 00:00:00

  • New trial designs to assess antitumor and antiproliferative agents in prostate cancer.

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    journal_title:Investigational new drugs

    pub_type: 杂志文章,评审

    doi:10.1023/a:1015618108456

    authors: Stadler W

    更新日期:2002-05-01 00:00:00

  • Recombinant gamma interferon in advanced breast cancer: a phase II trial.

    abstract::Fifteen patients with advanced carcinoma of the breast who had failed prior chemotherapy, were treated with recombinant gamma interferon at a dose of 2mg/m2 (1mg = 2.4 X 10(7) international units) intravenously for five consecutive days every other week. The median patient age was 51 and all patients had a performance...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00173511

    authors: Muss HB,Caponera M,Zekan PJ,Jackson DV Jr,Stuart JJ,Richards F,Cooper MR,Levin EA,Reich SD,Capizzi RL

    更新日期:1986-01-01 00:00:00

  • Preclinical antitumor activity of XK469 (NSC 656889).

    abstract::XK469 (NSC 656889) is a water-soluble member of the novel quinoxaline family of antitumor agents. In vitro, XK469 demonstrated selective cytotoxicity for several murine solid tumors including colorectal and mammary adenocarcinoma cell lines, when compared to both leukemia and normal epithelial cells. In vivo, XK469 wa...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1023/a:1006206814025

    authors: LoRusso PM,Parchment R,Demchik L,Knight J,Polin L,Dzubow J,Behrens C,Harrison B,Trainor G,Corbett TH

    更新日期:1998-01-01 00:00:00

  • Artemisinin reduces human melanoma cell migration by down-regulating alpha V beta 3 integrin and reducing metalloproteinase 2 production.

    abstract::Artemisinin and its derivatives are well known antimalarial drugs, particularly useful after resistance to traditional antimalarial pharmaceuticals has started to occur in Plasmodium falciparum. In recent years, anticancer activity of artemisinin has been reported both in vitro and in vivo. Artemisinin has inhibitory ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-008-9188-2

    authors: Buommino E,Baroni A,Canozo N,Petrazzuolo M,Nicoletti R,Vozza A,Tufano MA

    更新日期:2009-10-01 00:00:00

  • Early depth of tumor shrinkage and treatment outcomes in non-small cell lung cancer treated using Nivolumab.

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    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-019-00770-y

    authors: Kawachi H,Fujimoto D,Morimoto T,Hosoya K,Sato Y,Kogo M,Nagata K,Nakagawa A,Tachikawa R,Tomii K

    更新日期:2019-12-01 00:00:00

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    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-014-0173-7

    authors: Falchook GS,Moulder S,Naing A,Wheler JJ,Hong DS,Piha-Paul SA,Tsimberidou AM,Fu S,Zinner R,Janku F,Jiang Y,Huang M,Parkhurst KL,Kurzrock R

    更新日期:2015-02-01 00:00:00

  • Pharmacokinetics and metabolism of the staurosporine analogue CGP 41 251 in mice.

    abstract::Studies with CGP 41 251 (I), an N-benzoylstaurosporine derivative and PKC-alpha inhibitor, revealed that oral administration of 400 microg/day of the compound to wild type mice on four successive days reversed multi drug resistance (Killion et al. Oncology Research 7: 453-459, 1995). In our study, the same regimen of ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1023/a:1006260217400

    authors: van Gijn R,van Tellingen O,Haverkate E,Kettenes-van den Bosch JJ,Bult A,Beijnen JH

    更新日期:1999-01-01 00:00:00

  • Cyclosporine and alpha-difluoromethylornithine exhibit differential effects on colon and pancreatic cancer in vitro.

    abstract::alpha-Difluoromethylornithine (DFMO) is a known irreversible inhibitor of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. Cyclosporine (CsA) has been reported to inhibit ODC activity in vitro. In the present study, we compared the effects of DFMO and CsA on growth, survival, and poly...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00175295

    authors: Saydjari R,Townsend CM Jr,Barranco SC,Thompson JC

    更新日期:1987-01-01 00:00:00

  • Eugenol inhibits cell proliferation via NF-κB suppression in a rat model of gastric carcinogenesis induced by MNNG.

    abstract::The modulation of intracellular nuclear factor-kappaB (NF-κB) signaling pathway involved in the deregulated expression of cell proliferation and cell cycle regulatory molecules is a pragmatic approach for chemoprevention. Eugenol (4-allyl-1-hydroxy-2-methoxybenzene), a natural phenolic constituent of oils of cloves is...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-009-9345-2

    authors: Manikandan P,Vinothini G,Vidya Priyadarsini R,Prathiba D,Nagini S

    更新日期:2011-02-01 00:00:00

  • A phase II trial of diaziquone (AZQ) in mixed mesodermal sarcomas of the uterus. A Gynecologic Oncology Group study.

    abstract::AZQ was given intravenously to 23 patients with mixed mesodermal sarcoma of the uterus refractory to conventional treatment at a dose of 22.5-30 mg/m2 q three weeks. There was one partial response lasting seven weeks and one drug-related death. Based upon the activity observed in this trial, there does not appear to b...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1007/BF00194555

    authors: Slayton RE,Blessing JA,Clarke-Pearson D

    更新日期:1991-02-01 00:00:00

  • VM-26 in colorectal carcinoma: a Southwest Oncology Group study.

    abstract::In this multi-institutional phase II study, VM-26 or Teniposide was administered to forty-two patients with advanced colorectal cancer. Patients were initially treated at 60 mg/M2 daily for 5 days with dose adjustments depending on toxicity. One complete response and one partial response were observed lasting six and ...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1007/BF00216931

    authors: Oishi N,Fleming TR,Laufman L,Ungerleider JS,Natale RB,Einstein AB Jr,Von Hoff DD,Macdonald JS

    更新日期:1990-02-01 00:00:00

  • The novel kinase inhibitor ponatinib is an effective anti-angiogenic agent against neuroblastoma.

    abstract::Background High-risk neuroblastoma has poor outcomes with high rates of relapse despite aggressive treatment, and novel therapies are needed to improve these outcomes. Ponatinib is a multi-tyrosine kinase inhibitor that targets many pathways implicated in neuroblastoma pathogenesis. We hypothesized that ponatinib woul...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-016-0387-y

    authors: Whittle SB,Patel K,Zhang L,Woodfield SE,Du M,Smith V,Zage PE

    更新日期:2016-12-01 00:00:00

  • Phase II trial of intravenous melphalan for metastatic colorectal carcinoma. A Southwest Oncology Group study.

    abstract::Based on the high response rates seen among patients with colon cancer receiving high dose Melphalan with autologous marrow infusion, the Southwest Oncology Group conducted a Phase II trial of the compound at a conventional dose. The initial starting dose of 40 mg/m2 was reduced to 30 mg/m2 after severe myelotoxicity ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00171991

    authors: Knight WA 3rd,Goodman P,Taylor SA,Macdonald JS,Coltman CA Jr,Constanzi JJ,Baker LH

    更新日期:1990-01-01 00:00:00