A phase I trial of intermittent high-dose gefitinib and fixed-dose docetaxel in patients with advanced solid tumors.

Abstract:

PURPOSE:Based on our mouse xenograft model demonstrating that intermittent high-dose gefitinib sensitizes tumors to subsequent treatment with taxanes, we initiated this phase I trial to explore docetaxel in combination with escalating doses of intermittent gefitinib (Iressa) given prior to docetaxel. METHODS:This was a phase I study where patients with advanced cancer were treated with escalating doses of gefitinib (1,000, 1,500, 2,250, 3,000 mg) on days 1 and 2 followed by docetaxel (75 mg/m2) on day 3 of a 21 day cycle. Gefitinib pharmacokinetic data were obtained on days 1, 2, and 3 of cycles 1 and 2 at each dose level. RESULTS:18 patients were enrolled in this study with the most frequent tumor types being non-small cell lung cancer and head and neck squamous cell cancer. The dose-limiting toxicity was neutropenia (n=1 at dose level 2, n=2 at dose level 4). Rash, diarrhea, and fatigue were the most common grade 1-2 toxicities. Pharmacokinetic data indicated no accumulation of gefitinib between cycles 1 and 2 and no clear correlation between gefitinib plasma levels and toxicity. Partial responses were observed in one patient with head and neck squamous cell carcinoma and one patient with anaplastic thyroid cancer. CONCLUSION:The recommended dose for phase II studies is gefitinib 2,250 mg on days 1 and 2, followed by docetaxel 75 mg/m2 on day 3.

authors

Fury MG,Solit DB,Su YB,Rosen N,Sirotnak FM,Smith RP,Azzoli CG,Gomez JE,Miller VA,Kris MG,Pizzo BA,Henry R,Pfister DG,Rizvi NA

doi

10.1007/s00280-006-0286-6

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

467-75

issue

4

eissn

0344-5704

issn

1432-0843

journal_volume

59

pub_type

杂志文章
  • Midostaurin does not prolong cardiac repolarization defined in a thorough electrocardiogram trial in healthy volunteers.

    abstract:PURPOSE:Midostaurin (PKC412) is a multitargeted tyrosine kinase inhibitor of FMS-like tyrosine kinase 3 receptor (FLT3), c-KIT, and other receptors. Midostaurin is active in patients with acute myeloid leukemia and systemic mastocytosis. Although no substantive risk for cardiac abnormalities has been observed with mido...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1007/s00280-012-1825-y

    authors: del Corral A,Dutreix C,Huntsman-Labed A,Lorenzo S,Morganroth J,Harrell R,Wang Y

    更新日期:2012-05-01 00:00:00

  • Pharmacokinetics of temozolomide administered in combination with O6-benzylguanine in children and adolescents with refractory solid tumors.

    abstract:PURPOSE:Temozolomide pharmacokinetics were evaluated in children receiving concurrent O(6)-benzylguanine (O(6)BG), which enhanced the hematological toxicity of temozolomide. METHODS:Temozolomide was administered orally, daily for 5 days starting at 28 mg/m(2) per day with escalations to 40, 55, 75 and 100 mg/m(2) per ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-009-1015-8

    authors: Meany HJ,Warren KE,Fox E,Cole DE,Aikin AA,Balis FM

    更新日期:2009-12-01 00:00:00

  • Novel small molecule drugs inhibit tumor cell metabolism and show potent anti-tumorigenic potential.

    abstract:BACKGROUND:Rapidly dividing tumor cells have an increased demand for nutrients to support their characteristic unabated growth; this demand is met by an increased availability of nutrients such as amino acids through vasculogenesis and by the enhanced cellular entry of nutrients through the upregulation of specific tra...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-010-1453-3

    authors: Trojel-Hansen C,Erichsen KD,Christensen MK,Jensen PB,Sehested M,Nielsen SJ

    更新日期:2011-07-01 00:00:00

  • Phase 1 study to evaluate the effect of the MEK inhibitor trametinib on cardiac repolarization in patients with solid tumours.

    abstract:PURPOSE:Trametinib is a reversible, selective inhibitor of the mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and 2 (MEK2). Cardiotoxicity (congestive heart failure, decreased heart rate, left ventricular dysfunction, and hypertension) related to trametinib is an infrequent, but serious, adverse event...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s00280-016-3090-y

    authors: Patnaik A,Tolcher A,Papadopoulos KP,Beeram M,Rasco D,Werner TL,Bauman JW,Scheuber A,Cox DS,Patel BR,Zhou Y,Hamid M,Schramek D,Sharma S

    更新日期:2016-09-01 00:00:00

  • Biweekly oxaliplatin plus 1-day infusional fluorouracil/leucovorin followed by metronomic chemotherapy with tegafur/uracil in pretreated metastatic colorectal cancer.

    abstract:PURPOSE:Metronomic chemotherapy, at a minimally toxic dose and with a frequent schedule, is a potentially novel approach to the control of advanced cancer disease via a different mechanism from maximum tolerable doses chemotherapy. Taking advantage of the potential effectiveness of metronomic therapy, tegafur/uracil (U...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1007/s00280-006-0377-4

    authors: Lin PC,Chen WS,Chao TC,Yang SH,Tiu CM,Liu JH

    更新日期:2007-08-01 00:00:00

  • Etoposide sensitivity of radioresistant human glioma cell lines.

    abstract:PURPOSE:Malignant gliomas display aggressive local behavior and are not cured by existing therapy. Etoposide, a topoisomerase-II-inhibitor agent, is one of the most active and useful antineoplastic agents. However, etoposide is not usually used on these tumors. We undertook an in vitro study to prove that etoposide is ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800050713

    authors: Beauchesne P,Bertrand S,N'guyen MJ,Christianson T,Dore JF,Mornex F,Bonner JA

    更新日期:1998-01-01 00:00:00

  • Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine.

    abstract:PURPOSE:Curcumin, a major constituent of the spice turmeric, suppresses expression of the enzyme cyclooxygenase 2 (Cox-2) and has cancer chemopreventive properties in rodents. It possesses poor systemic availability. We explored whether formulation with phosphatidylcholine increases the oral bioavailability or affects ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-006-0355-x

    authors: Marczylo TH,Verschoyle RD,Cooke DN,Morazzoni P,Steward WP,Gescher AJ

    更新日期:2007-07-01 00:00:00

  • Incorporation of OSI-7836 into DNA of Calu-6 and H460 xenograft tumors.

    abstract::OSI-7836 (4'-thio-beta-D-arabinofuranosylcytosine) is a novel nucleoside analog in phase I clinical development for the treatment of cancer. As with other nucleoside analogs, the proposed mechanism of action involves phosphorylation to the triphosphate form followed by incorporation into cellular DNA, leading to cell ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-004-0844-8

    authors: Richardson F,Black C,Richardson K,Franks A,Wells E,Karimi S,Sennello G,Hart K,Meyer D,Emerson D,Brown E,LeRay J,Nilsson C,Tomkinson B,Bendele R

    更新日期:2005-03-01 00:00:00

  • Effect of etoposide (VP16-213) on lipid peroxidation and antioxidant status in a high-dose radiochemotherapy regimen.

    abstract::A total of 13 patients receiving bone marrow transplants (BMT) for treatment of different haematological diseases were investigated. Conditioning therapy preceding BMT consisted of fractionated total-body irradiation (12 Gy) and high-dose chemotherapy with cyclophosphamide (2 +/- 60 mg/kg). Patients stratified to be a...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00689585

    authors: Ladner C,Ehninger G,Gey KF,Clemens MR

    更新日期:1989-01-01 00:00:00

  • Irinotecan induces enterocyte cell death and changes to muc2 and muc4 composition during mucositis in a tumour-bearing DA rat model.

    abstract::Irinotecan-induced mucositis is a major oncological problem. Goblet cells secrete mucus, protecting the intestinal mucosa, with secretion altered during mucositis. The enteric nervous system is involved in regulating gut motility and secretion. The aim of this study was to determine whether enteric neural cells and go...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-019-03787-5

    authors: Thorpe D,Sultani M,Stringer A

    更新日期:2019-05-01 00:00:00

  • A phase I study to investigate the metabolism, excretion, and pharmacokinetics of [14C]fruquintinib, a novel oral selective VEGFR inhibitor, in healthy Chinese male volunteers.

    abstract:PURPOSE:Fruquintinib (HMPL-013) is a novel, potent, and highly selective tyrosine kinase inhibitor targeting the vascular endothelial growth factor receptors (1, 2 and 3). This study was conducted to investigate the metabolism, excretion, and pharmacokinetics of HMPL-013 after a single oral dose to healthy Chinese men....

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-017-3394-6

    authors: Zhou S,Shao F,Xu Z,Wang L,Jin K,Xie L,Chen J,Liu Y,Zhang H,Ou N

    更新日期:2017-09-01 00:00:00

  • Phase II study of a new alkylating agent (PTT-119) in resistant-relapsed non-Hodgkin's lymphomas.

    abstract::In a phase II study we evaluated the effect and toxicity of a new alkylating agent, PTT-119, in 26 patients with non-Hodgkin's lymphomas (NHL) resistant to or relapsed after other chemotherapy. PTT was scheduled by escalating the dose from 2.0 to 3.3 mg/kg every 3 weeks. Among 21 evaluable patients with NHL, 12 (57%) ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00273532

    authors: Tura S,Mazza P,Gherlinzoni F,Zinzani PL,Poletti G,Visani G,Lemoli RM,Cavo M,Galieni P,Tassi C

    更新日期:1989-01-01 00:00:00

  • Analysis of age, estimated creatinine clearance and pretreatment hematologic parameters as predictors of fludarabine toxicity in patients treated for chronic lymphocytic leukemia: a CALGB (9011) coordinated intergroup study.

    abstract:PURPOSE:Fludarabine is a renally excreted agent that is an effective treatment for chronic lymphocytic leukemia (CLL), a disease predominantly of the elderly. We sought to determine whether age, renal function or pretreatment hematologic status predicted toxicity of fludarabine treatment for CLL. METHODS:We evaluated ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1007/s00280-002-0443-5

    authors: Martell RE,Peterson BL,Cohen HJ,Petros WP,Rai KR,Morrison VA,Elias L,Shepherd L,Hines J,Larson RA,Schiffer CA,Hurwitz HI

    更新日期:2002-07-01 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

    doi:10.1007/s00280-007-0554-0

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

    更新日期:2008-05-01 00:00:00

  • High-dose dexamethasone for prevention of cis-platin-induced vomiting.

    abstract::Severe, debilitating nausea and vomiting are seen in almost 100% of patients treated with cis-platinum. These side-effects can be so severe and prolonged as to preclude therapy in a large number of patients. Commonly used antiemetics have had only limited success in controlling cis-platinum-induced nausea and vomiting...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00258206

    authors: Aapro MS,Alberts DS

    更新日期:1981-01-01 00:00:00

  • Safety and activity of temsirolimus and bevacizumab in patients with advanced renal cell carcinoma previously treated with tyrosine kinase inhibitors: a phase 2 consortium study.

    abstract:PURPOSE:Bevacizumab or temsirolimus regimens have clinical activity in the first-line treatment of advanced renal cell carcinoma (RCC). This phase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior anti-VEGF receptor tyrosine k...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-014-2668-5

    authors: Merchan JR,Qin R,Pitot H,Picus J,Liu G,Fitch T,Maples WJ,Flynn PJ,Fruth BF,Erlichman C

    更新日期:2015-03-01 00:00:00

  • Pegylated liposomal doxorubicin in combination with vinorelbine as salvage treatment in pretreated patients with advanced breast cancer: a multicentre phase II study.

    abstract:PURPOSE:To investigate the activity and tolerance of pegylated liposomal doxorubicin in combination with vinorelbine in pretreated patients with metastatic breast cancer. PATIENTS AND TREATMENT:Thirty-six women with metastatic breast cancer were enrolled. The median age was 64 years, 80% of the patients had a performa...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s00280-006-0236-3

    authors: Ardavanis A,Mavroudis D,Kalbakis K,Malamos N,Syrigos K,Vamvakas L,Kotsakis A,Kentepozidis N,Kouroussis C,Agelaki S,Georgoulias V,Breast Cancer Committee of the Hellenic Oncology Research Group.

    更新日期:2006-12-01 00:00:00

  • Arsenic compounds induce cytotoxicity and apoptosis in cisplatin-sensitive and -resistant gynecological cancer cell lines.

    abstract:PURPOSE:Arsenic compounds have been found to be effective in the treatment of acute promyelocytic leukemia through the downregulation of bcl-2 expression. Resistant ovarian cancer cells often overexpress bcl-2 or p53 proteins or both. We hypothesized that arsenic compounds, such as As2O3 and As2S3, could also be active...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800100278

    authors: Du YH,Ho PC

    更新日期:2001-06-01 00:00:00

  • Effect of cyclosporine coadministration on the pharmacokinetics of eltrombopag in healthy volunteers.

    abstract:PURPOSE:Eltrombopag is indicated in patients with severe aplastic anemia (SAA) refractory to prior immunosuppressive therapy. The combination of eltrombopag and immunosuppressive therapy (such as cyclosporine) is currently being evaluated in patients with treatment-naive SAA. Cyclosporine is a human breast cancer resis...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1007/s00280-018-3677-6

    authors: Aslanis V,Zhang J,Lomeli B,Grosch K,Ouatas T

    更新日期:2018-11-01 00:00:00

  • Population pharmacokinetics and exposure-response assessment of veliparib co-administered with temozolomide in patients with myeloid leukemias.

    abstract:PURPOSE:Veliparib is an oral inhibitor of poly(ADP-ribose) polymerase enzyme. Combination of veliparib and temozolomide was well-tolerated and demonstrated clinical activity in older patients with relapsed or refractory acute myeloid leukemia (AML) or AML arising from pre-existing myeloid malignancies. We aimed to perf...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s00280-018-3731-4

    authors: Singh R,Mehrotra S,Gopalakrishnan M,Gojo I,Karp JE,Greer JM,Chen A,Piekarz R,Kiesel BF,Gobburu J,Rudek MA,Beumer JH,ETCTN-6745 study team.

    更新日期:2019-02-01 00:00:00

  • Clinical and laboratory studies of the novel cyclin-dependent kinase inhibitor dinaciclib (SCH 727965) in acute leukemias.

    abstract:PURPOSE:Dinaciclib inhibits cyclin-dependent kinases 1, 2, 5, and 9 with a better therapeutic index than flavopiridol in preclinical studies. This study assessed the activity of dinaciclib in acute leukemia both in the clinic and in vitro. METHODS:Adults with relapsed/refractory acute myeloid leukemia (n = 14) and acu...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1007/s00280-013-2249-z

    authors: Gojo I,Sadowska M,Walker A,Feldman EJ,Iyer SP,Baer MR,Sausville EA,Lapidus RG,Zhang D,Zhu Y,Jou YM,Poon J,Small K,Bannerji R

    更新日期:2013-10-01 00:00:00

  • Autophagy, a novel target for chemotherapeutic intervention of thyroid cancer.

    abstract:PURPOSE:Thyroid cancers with unsatisfactory curative effect nowadays are the most common malignant tumors of the endocrine system. Apoptosis evasion, a hallmark of cancer, has driven the search of stimulating novel cell death way in cancer therapy. This review aims to explore the relationship between autophagy and thyr...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,评审

    doi:10.1007/s00280-013-2363-y

    authors: Li LC,Liu GD,Zhang XJ,Li YB

    更新日期:2014-03-01 00:00:00

  • High-dose adriamycin (ADM) and cis-platinum (DDP) in advanced soft-tissue sarcomas and invasive thymomas. A pilot study.

    abstract::Eighteen previously untreated patients with advanced unresectable or metastatic soft-tissue sarcomas (STS) and two patients with locally invasive thymoma were treated with a combination of adriamycin (ADM) 80 mg/m2 on day 1 and cis-platinum (DDP) 120 mg/m2 on day 1. The regimen was repeated at 4-weeks intervals. In ST...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00257118

    authors: Klippstein TH,Mitrou PS,Kochendörfer KJ,Bergmann L

    更新日期:1984-01-01 00:00:00

  • Phase-I dose escalation and sequencing study of docetaxel and continuous infusion topotecan in patients with advanced malignancies.

    abstract:PURPOSE:Anti-tumor activity can often be enhanced with combination therapy in managing patients with metastatic cancer. However, dose sequence and schedule of delivery can alter the pharmacokinetics, toxicity, and anti-tumor response. Therefore, attention to drug-drug interactions which may be sequence or schedule-depe...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1007/s00280-004-0925-8

    authors: Posey JA,Wang H,Hamilton J,Delgrosso A,Zhang R,Freda T,Zamboni WC

    更新日期:2005-08-01 00:00:00

  • Analysis of gastric cancer with cDNA microarray.

    abstract::Recent advances in cDNA microarray techniques have enabled us to study the expression of many genes simultaneously. As gastric cancer remains one of the most common cancers in Japan, we studied gene expression profiles in gastric cancer by cDNA microarray analysis to determine if it would be clinically useful. We demo...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-004-0882-2

    authors: Haraguchi N,Inoue H,Mimori K,Tanaka F,Utsunomiya T,Yoshikawa K,Mori M

    更新日期:2004-09-01 00:00:00

  • The role of deoxycytidine-metabolizing enzymes in the cytotoxicity induced by 3'-amino-2',3'-dideoxycytidine and cytosine arabinoside.

    abstract::The cellular metabolism of 3'-amino-2',3'-dideoxycytidine (3'-NH2-dCyd), a cytotoxic agent previously reported to be a poor substrate for purified Cyd/dCyd deaminase (dCydD), was compared with that of cytosine arabinoside (ara-C) in cells that displayed dCydD activity (HeLa) and in cells that did not (L1210). Growth i...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00686406

    authors: Mancini WR

    更新日期:1992-01-01 00:00:00

  • Phase II study of capecitabine and the oral mTOR inhibitor everolimus in patients with advanced pancreatic cancer.

    abstract:PURPOSE:The combination of an mTOR inhibitor with 5-fluorouracil-based anticancer therapy is attractive because of preclinical evidence of synergy between these drugs. According to our phase I study, the combination of capecitabine and everolimus is safe and feasible, with potential activity in pancreatic cancer patien...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-015-2730-y

    authors: Kordes S,Klümpen HJ,Weterman MJ,Schellens JH,Richel DJ,Wilmink JW

    更新日期:2015-06-01 00:00:00

  • Schedule dependence, activity against natural metastases, and cross-resistance of pyrazine diazohydroxide (sodium salt, NSC 361456) in preclinical models in vivo.

    abstract::Pyrazine diazohydroxide (sodium salt, NSC 361456; PZDH) is a new antitumor drug with relatively broad activity in initial evaluations against murine leukemias, solid tumors, and two human tumor xenografts in vivo. The present studies were designed to address questions about PZDH activity on different treatment schedul...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00686053

    authors: Harrison SD Jr,Plowman J,Dykes DJ,Waud WR,Griswold DP Jr

    更新日期:1990-01-01 00:00:00

  • Adriamycin, bleomycin, vinblastine and imidazole carboxamide (ABVD) therapy for advanced Hodgkin's disease resistant to mustine, vinblastine, procarbazine and prednisolone (MVPP).

    abstract::Forty-one previously treated patients with advanced Hodgkin's disease were treated with a combination chemotherapy regimen -- ABVD (adriamycin, bleomycin, velbe/vincristine, imidazole carboxamide). Complete remission was achieved in three patients (7%), partial remission in 23 (56%), and no response in 15 patients (37...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00258297

    authors: Sutcliffe SB,Wrigley PF,Stansfeld AG,Malpas JS

    更新日期:1979-01-01 00:00:00

  • Synthesis of short retinoidal amides related to fenretinide: antioxidant activities and differentiation-inducing ability.

    abstract:PURPOSE:By a scaffold shortening strategy, a small series of retinoidal amides fenretinide (4-HPR) analogs have been synthesized from α, β-ionones and tested for their antiproliferative and differentiating activities, and antioxidant effect. METHODS:The antiproliferative activity and triggering of apoptosis of our sho...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-017-3265-1

    authors: Anzaldi M,Viale M,Macciò C,Castagnola P,Oliveri V,Rosano C,Balbi A

    更新日期:2017-04-01 00:00:00