Phase 1a/1b and pharmacogenetic study of docetaxel, oxaliplatin and capecitabine in patients with advanced cancer of the stomach or the gastroesophageal junction.


PURPOSE:The prognosis of gastroesophageal cancer is poor, and current regimens are associated with limited efficacy. The purpose of this study was to explore the safety and preliminary efficacy of docetaxel, oxaliplatin plus capecitabine for advanced cancer of the stomach or the gastroesophageal junction (GEJ). Secondary objectives included pharmacokinetic and pharmacogenetic analyses. METHODS:Patients were treated in escalating dose levels with docetaxel and oxaliplatin (both on day 1), plus capecitabine b.i.d. on days 1-14 every 3 weeks, to determine the dose-limiting toxicity and maximum tolerated dose (MTD). An expansion cohort was treated at the MTD. A total of ten polymorphisms in pharmacokinetic and pharmacodynamic candidate genes were analyzed and tested for association with treatment outcome. RESULTS:A total of 34 evaluable patients were enrolled. The MTD was docetaxel 50 mg/m(2), oxaliplatin 100 mg/m(2) plus capecitabine 850 mg/m(2) b.i.d. The median number of treatment cycles was 6 (range 2-8). Grade ≥ 3 toxicities included neutropenia (24 %), leukocytopenia (15 %), febrile neutropenia (12 %), fatigue (9 %) and diarrhea (6 %). The overall response rate was 45 %; two patients achieved a complete response. Median progression-free survival and overall survival were 6.5 months (95 % CI 5.4-7.6) and 11.0 months (95 % CI 7.9-14.1), respectively. The polymorphisms ERCC1 354C>T, TYMS 1053C>T and rs2612091 in ENOSF1 were associated with severe toxicity; ERCC1 354C>T and ERCC2 2251A>C were associated with poor progression-free survival. CONCLUSION:Docetaxel, oxaliplatin plus capecitabine are a well-tolerable, safe and effective treatment regimen for patients with advanced cancer of the stomach or GEJ. Pharmacogenetic markers in pharmacokinetic and pharmacodynamic candidate genes may be predictive for treatment outcome.


Deenen MJ,Meulendijks D,Boot H,Legdeur MC,Beijnen JH,Schellens JH,Cats A




Has Abstract


2015-12-01 00:00:00














  • Targeting cisplatin-resistant human tumor cells with metabolic inhibitors.

    abstract:PURPOSE:Although cisplatin is the drug of choice in treating lung cancer patients, relapse and resistance is a common drawback to its clinical effectiveness. Based on cisplatin's reported ability to interfere with numerous cellular components, including mitochondria, we probed alterations in metabolism in cisplatin-res...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Sullivan EJ,Kurtoglu M,Brenneman R,Liu H,Lampidis TJ

    更新日期:2014-02-01 00:00:00

  • Cancer chemotherapy in the elderly: a series of 51 patients aged greater than 70 years.

    abstract::A total of 2,238 new cancer patients were treated in our institution in 1988; among the 423 (18.9%) who were greater than 70 years old, 51 underwent chemotherapy. The median age was 75.8 years, and the Karnofsky performance status (KPS) was greater than or equal to 70% for 40 patients. Malignancies were hematopoietic ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Bécouarn Y,Bui BN,Brunet R,Ravaud A

    更新日期:1991-01-01 00:00:00

  • Combination of topotecan and etoposide as a salvage treatment for patients with recurrent small cell lung cancer following irinotecan and platinum first-line chemotherapy.

    abstract:PURPOSE:The efficacy and safety of a combined regimen of topotecan and etoposide was tested in patients with relapsed or refractory small-cell lung cancer. PATIENTS AND METHODS:From October 2003 to May 2005, 23 patients who have failed to the previous irinotecan and platinum chemotherapy received intravenous topotecan...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Choi HJ,Cho BC,Shin SJ,Cheon SH,Jung JY,Chang J,Kim SK,Sohn JH,Kim JH

    更新日期:2008-02-01 00:00:00

  • IPI-504, a novel and soluble HSP-90 inhibitor, blocks the unfolded protein response in multiple myeloma cells.

    abstract:BACKGROUND:Inhibitors of heat shock protein (Hsp) 90 induce apoptosis in multiple myeloma (MM) cells, but the molecular mechanisms underlying this cytotoxic outcome are not clear. Here, we investigate the effect of IPI-504, a novel and highly soluble inhibitor of the Hsp90 ATPase activity, on the unfolded protein respo...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Patterson J,Palombella VJ,Fritz C,Normant E

    更新日期:2008-05-01 00:00:00

  • A pilot study of cyclical chemotherapy with high-dose methotrexate and CHOP (MTX-CHOP) in poor-prognosis non-Hodgkin's lymphoma (NHL).

    abstract::In a pilot study of cyclical chemotherapy in patients with poor-prognosis non-Hodgkin's lymphoma (NHL), high-dose methotrexate (MTX) 1 g/m2 with folinic acid rescue was given as initial treatment and then between cycles of a single-arm CHOP combination administered every 4 weeks. Of 21 patients with previously untreat...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Child JA,Barnard DL,Cartwright SC,Lauder I,Simmons AV,Stone J,Thorogood J

    更新日期:1983-01-01 00:00:00

  • Effect of front-line chemotherapy on circulating CK-19 mRNA-positive cells in patients with metastatic breast cancer.

    abstract:PURPOSE:To evaluate the effect of front-line chemotherapy on CK-19mRNA+ circulating tumor cells (CTCs) and their relevance in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS:The presence of CK-19mRNA+ CTCs was assessed using a real-time RT-PCR assay in 298 previously untreated patients with MBC befo...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章


    authors: Georgoulias V,Apostolaki S,Bozionelou V,Politaki E,Perraki M,Georgoulia N,Kalbakis K,Kotsakis A,Xyrafas A,Agelaki S,Mavroudis D

    更新日期:2014-12-01 00:00:00

  • A new liposomal formulation of Gemcitabine is active in an orthotopic mouse model of pancreatic cancer accessible to bioluminescence imaging.

    abstract::Despite its rapid enzymatic inactivation and therefore limited activity in vivo, Gemcitabine is the standard drug for pancreatic cancer treatment. To protect the drug, and achieve passive tumor targeting, we developed a liposomal formulation of Gemcitabine, GemLip (Ø: 36 nm: 47% entrapment). Its anti-tumoral activity ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Bornmann C,Graeser R,Esser N,Ziroli V,Jantscheff P,Keck T,Unger C,Hopt UT,Adam U,Schaechtele C,Massing U,von Dobschuetz E

    更新日期:2008-03-01 00:00:00

  • Potentiation of the antitumour effect of cyclophosphamide in mice by thalidomide.

    abstract:PURPOSE:Thalidomide has recently shown significant promise in the treatment of some types of cancer, and trials in combination with conventional chemotherapy are being undertaken. We wished to determine whether thalidomide potentiated the effect of cyclophosphamide, a commonly used cytotoxic drug, in a murine tumour mo...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Ding Q,Kestell P,Baguley BC,Palmer BD,Paxton JW,Muller G,Ching LM

    更新日期:2002-09-01 00:00:00

  • Interactions of human leukocyte interferon with vinca alkaloids and other chemotherapeutic agents against human tumors in clonogenic assay.

    abstract::Purified human leukocyte interferon produced by recombinant techniques (IFN-alpha A) was tested in vitro with chemotherapeutic drugs, vinblastine (VLB), vincristine (VCR), vindesine (VDS), vinzolidine (VZL), cis-platinum (PLAT), doxorubicin (DOXO), etoposide (VP-16), and melphalan (MEL). The activity of these agents a...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Aapro MS,Alberts DS,Salmon SE

    更新日期:1983-01-01 00:00:00

  • Primary breast tumor levels of suspected molecular determinants of cellular sensitivity to cyclophosphamide, ifosfamide, and certain other anticancer agents as predictors of paired metastatic tumor levels of these determinants. Rational individualization

    abstract:PURPOSE:Cyclophosphamide is one of the most frequently used agents in the neoadjuvant, adjuvant, and high-dose chemotherapeutic treatment of breast cancers. Preclinical models indicate that cellular sensitivity to cyclophosphamide and other oxazaphosphorines, e.g., ifosfamide, is inversely related to the cellular conte...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Sreerama L,Sládek NE

    更新日期:2001-03-01 00:00:00

  • A phase II study of capecitabine in the treatment of ovarian cancer resistant or refractory to platinum therapy: a multicentre Italian trial in ovarian cancer (MITO-6) trial.

    abstract:PURPOSE:Capecitabine is an oral chemotherapeutic agent, already used in breast and colon cancer. Previous data showed encouraging results in the treatment of recurrent ovarian cancer. The aim of this study was to describe activity and toxicity of capecitabine in patients with platinum resistant or refractory ovarian ca...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究


    authors: Pisano C,Morabito A,Sorio R,Breda E,Lauria R,Gebbia V,Scaltriti L,Scalone S,Zagonel V,Greggi S,Beneduce G,Losito S,Gallo C,Di Maio M,Forestieri V,Pignata S

    更新日期:2009-10-01 00:00:00

  • Preclinical pharmacology of 2-methoxyantimycin A compounds as novel antitumor agents.

    abstract:PURPOSE:The present study was designed to determine pharmacological and biochemical properties of 2-methoxyantimycin A analogs (OMe-A1, OMe-A2, OMe-A3, and OMe-A5), which are novel antitumor compounds, and provide a basis for future pharmaceutical development, preclinical evaluation, and clinical trials. METHODS:A hig...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Wang H,Li M,Rhie JK,Hockenbery DM,Covey JM,Zhang R,Hill DL

    更新日期:2005-09-01 00:00:00

  • Pharmacokinetic study of fludarabine phosphate (NSC 312887).

    abstract::Characterization of the pharmacokinetics of 2-FLAA has been completed in seven patients receiving 18 or 25 mg/m2 daily X 5 of 2-FLAMP over 30 min. Assuming 2-FLAMP was instantaneously converted to 2-FLAA, the plasma levels of 2-FLAA declined in a biexponential fashion. Computer fitting of the plasma concentration-time...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Hersh MR,Kuhn JG,Phillips JL,Clark G,Ludden TM,Von Hoff DD

    更新日期:1986-01-01 00:00:00

  • CYP17A1 polymorphism c.-362T>C predicts clinical outcome in metastatic castration-resistance prostate cancer patients treated with abiraterone.

    abstract:BACKGROUND:Abiraterone became a standard hormonal therapy for patients with metastatic castration-resistance prostate cancer (mCRPC). However, patients may experience primary resistance to treatment. To date, few predictive biomarkers of efficacy have been identified. Our aim was to investigate the association between ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Crucitta S,Del Re M,Paolieri F,Bloise F,Sbrana A,Sammarco E,Mercinelli C,Cucchiara F,Fontanelli L,Galli L,Danesi R

    更新日期:2020-10-01 00:00:00

  • Inhibition of cellular esterases by the antitumour imidazotetrazines mitozolomide and temozolomide: demonstration by flow cytometry and conventional spectrofluorimetry.

    abstract::Using flow cytometry and conventional spectrofluorimetry we have previously shown that chloroethylnitrosoureas (CNUs) can exhibit marked inhibition of cellular enzymes catalysing hydrolysis of fluorescein diacetate (FDA). More potent inhibition was seen for the carbamoylating CNUs, whereas alkylating agents were large...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Dive C,Workman P,Watson JV

    更新日期:1989-01-01 00:00:00

  • Evaluation of anticancer drug schedule dependency using an in vitro human tumor clonogenic assay.

    abstract::A human tumor clonogenic assay (HTCA) has been used to evaluate standard and experimental anticancer drugs with respect to their inhibition of clonogenicity of both fresh human cancers and human tumor cell lines. By comparing the inhibitory effect on tumor colony-forming unit (TCFU) growth of 1-h and continuous drug e...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Ludwig R,Alberts DS,Miller TP,Salmon SE

    更新日期:1984-01-01 00:00:00

  • Dihydrodiol dehydrogenases regulate the generation of reactive oxygen species and the development of cisplatin resistance in human ovarian carcinoma cells.

    abstract::We have previously demonstrated that overexpression of dihydrodiol dehydrogenase isoform 1 (DDH1) or DDH2 leads to the induction of drug resistance to platinum based drugs in human ovarian, lung, cervical and germ cell tumor cell lines. DDH belongs to a family of aldoketo reductases that are involved in the detoxifica...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Chen J,Adikari M,Pallai R,Parekh HK,Simpkins H

    更新日期:2008-05-01 00:00:00

  • Isolated molecular relapse in FIP1L1-PDGFRalpha hypereosinophilic syndrome after discontinuation and single weekly dose of imatinib: need of quantitative molecular procedures to modulate imatinib dose.

    abstract::Imatinib is the treatment of choice for FIP1L1-PDGFRalpha (F/P+) positive myeloproliferative neoplasms, but little is known about optimal dose and duration of treatment to maintain complete molecular remission once achieved. We describe a case of F/P+ patients who started imatinib and reached a molecular remission, bu...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Breccia M,Cilloni D,Cannella L,Stefanizzi C,Tafuri A,Fama A,Santopietro M,Saglio G,Alimena G

    更新日期:2009-05-01 00:00:00

  • The minimal impact of food on the pharmacokinetics of ridaforolimus.

    abstract:PURPOSE:Ridaforolimus, a potent inhibitor of the mammalian target of rapamycin (mTOR), is under development for the treatment for solid tumors. This open-label, randomized, 3-period crossover study investigated the effect of food on the pharmacokinetics of ridaforolimus 40 mg as well as safety and tolerability of the s...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,随机对照试验


    authors: Stroh M,Li X,Marsilio S,Panebianco D,Johnson-Levonas A,Juan A,Orford K,Agrawal N,Trucksis M,Wagner JA,Murphy G,Iwamoto M

    更新日期:2012-07-01 00:00:00

  • Population pharmacokinetic analysis of phase 1 bemarituzumab data to support phase 2 gastroesophageal adenocarcinoma FIGHT trial.

    abstract:PURPOSE:To report population pharmacokinetic (PK) analysis of the phase 1 study (FPA144-001, NCT02318329) and to select a clinical dose and schedule that will achieve an empirical target trough concentration (Ctrough) for an anti-fibroblast growth factor receptor 2b antibody, bemarituzumab. METHODS:Nonlinear mixed-eff...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Xiang H,Liu L,Gao Y,Ahene A,Macal M,Hsu AW,Dreiling L,Collins H

    更新日期:2020-11-01 00:00:00

  • ERCC1 predicts outcome in patients with gastric cancer treated with adjuvant cisplatin-based chemotherapy.

    abstract:BACKGROUND:Adjuvant chemotherapy is gaining an increasing role in resectable gastric cancer. Customizing chemotherapy on the basis of chemosensitivity may improve outcome, and putative predictive molecular markers have been mostly evaluated in Asian patients. We profiled key DNA and damage signaling factors and correla...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: De Dosso S,Zanellato E,Nucifora M,Boldorini R,Sonzogni A,Biffi R,Fazio N,Bucci E,Beretta O,Crippa S,Saletti P,Frattini M

    更新日期:2013-07-01 00:00:00

  • Pharmacokinetic studies of 9-nitrocamptothecin on intermittent and continuous schedules of administration in patients with solid tumors.

    abstract:PURPOSE:Oral administration of 9-nitrocamptothecin (9NC), and the formation of its metabolite 9-aminocamptothecin (9AC), may be associated with high interpatient and intrapatient variability. Therefore, we evaluated the plasma pharmacokinetics and urine recovery of 9NC administered on three different schedules as part ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章


    authors: Jung LL,Ramanathan RK,Egorin MJ,Jin R,Belani CP,Potter DM,Strychor S,Trump DL,Walko C,Fakih M,Zamboni WC

    更新日期:2004-12-01 00:00:00

  • Radioenhancement by cisplatin with accelerated fractionated radiotherapy in a human tumour xenograft.

    abstract::The aim of the present study was to investigate whether cisplatin would enhance the radioresponse of a human tumour xenograft when given in different schedules combined with accelerated fractionated radiation therapy. A human squamous carcinoma of the hypopharynx, FaDu, was grown in the thigh of athymic nude mice. Tum...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Joschko MA,Webster LK,Bishop JF,Groves J,Yuen K,Olver IN,Narayan KN,Ball DL

    更新日期:1997-01-01 00:00:00

  • Reduced activity of topoisomerase II in an Adriamycin-resistant human stomach-adenocarcinoma cell line.

    abstract::A human stomach-adenocarcinoma cell line (MKN-45) was selected for resistance to Adriamycin by stepwise exposure to increasing concentrations of this agent. The resulting cell line (MKN/ADR) exhibited a high level of cross-resistance to topoisomerase II (topo II)-targeted drugs such as Adriamycin, mitoxantrone, and et...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Son YS,Suh JM,Ahn SH,Kim JC,Yi JY,Hur KC,Hong WS,Muller MT,Chung IK

    更新日期:1998-01-01 00:00:00

  • Fluoropyrimidine therapy: hyperbilirubinemia as a consequence of hemolysis.

    abstract:BACKGROUND:Hemolytic anemia has been noted during treatment with a variety of chemotherapeutic agents. We observed mild compensated hemolytic anemia in a patient receiving capecitabine during a randomized, controlled trial of adjuvant therapy. In order to investigate the hypothesis that hemolysis is the underlying caus...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,随机对照试验


    authors: Nikolic-Tomasevic Z,Jelic S,Cassidy J,Filipovic-Ljeskovic I,Tomasevic Z

    更新日期:2005-12-01 00:00:00

  • Antitumor alkylating agents: in vitro cross-resistance and collateral sensitivity studies.

    abstract::Cell lines resistant to five antitumor alkylating agents (CDDP, PAM, 4-HC, HN2, and BCNU) were developed from five parental human tumor lines representative of solid tumors with a range of sensitivities to antitumor alkylating agents. The parental cell lines were SCC-25 squamous carcinoma of the head and neck, MCF-7 b...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Frei E 3rd,Holden SA,Gonin R,Waxman DJ,Teicher BA

    更新日期:1993-01-01 00:00:00

  • A phase I trial of amsalog (CI-921) administered by intravenous infusion using a 5-day schedule.

    abstract:PURPOSE:Amsalog, a derivative of 9-aminoacridine, is an inhibitor of topoisomerase II. Early studies of intravenous amsalog administered either once weekly, or daily for 3 days repeated every 3 weeks, showed that myelosuppression is the dose-limiting toxicity (DLT). Phase II studies showed only limited activity in brea...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章


    authors: Fyfe D,Price C,Langley RE,Pagonis C,Houghton J,Osborne L,Woll PJ,Gardner C,Baguley BC,Carmichael J,Cancer Research Campaing Phase I\/II Trials Committee.

    更新日期:2001-04-01 00:00:00

  • Multicenter phase II study of combination therapy with cetuximab and S-1 in patients with KRAS exon 2 wild-type unresectable colorectal cancer previously treated with irinotecan, oxaliplatin, and fluoropyrimidines (KSCC 0901 study).

    abstract:PURPOSE:Anti-epidermal growth factor receptor antibody therapy alone or in combination with irinotecan is recognized as a standard third-line treatment for KRAS wild-type unresectable metastatic colorectal cancer. However, in some cases, it is difficult to administer irinotecan after third-line treatment. Therefore, we...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究


    authors: Takahashi T,Emi Y,Oki E,Kobayashi K,Tsuji A,Shimokawa M,Tanaka T,Akagi Y,Ogata Y,Baba H,Yoshida K,Natsugoe S,Maehara Y,Kyushu Study Group of Clinical Cancer (KSCC).

    更新日期:2016-09-01 00:00:00

  • Lapatinib in combination with paclitaxel plays synergistic antitumor effects on esophageal squamous cancer.

    abstract:PURPOSE:Paclitaxel-based chemoradiotherapy was proven to be efficacious in treating patients with advanced esophageal cancer. However, the toxicity and the development of resistance limited its anticancer efficiency. The present study was to evaluate the antitumor effects of lapatinib, a dual tyrosine inhibitor of both...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Guo XF,Li SS,Zhu XF,Dou QH,Liu D

    更新日期:2018-09-01 00:00:00

  • Comparison of the sulforhodamine B assay and the clonogenic assay for in vitro chemoradiation studies.

    abstract:PURPOSE:Since there is a growing interest in preclinical research on interactions between radiation and cytotoxic agents, this study focused on the development of an alternative to the very laborious clonogenic assay (CA). METHODS:The colorimetric sulforhodamine B (SRB) assay was compared to the clonogenic assay for r...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Pauwels B,Korst AE,de Pooter CM,Pattyn GG,Lambrechts HA,Baay MF,Lardon F,Vermorken JB

    更新日期:2003-03-01 00:00:00