Abstract:
PURPOSE:The objectives of this phase I dose-finding study of erlotinib were to investigate the toxicity profile, to confirm the acceptable toxicity of doses up to 150 mg/day, and to assess the pharmacokinetic (PK) profile and antitumor activity in Japanese patients with solid tumors. PATIENTS AND METHODS:Patients with solid tumors not amenable to standard forms of treatment were included. Treatment cycle 1 consisted of single-dose administration on day 1, withdrawal on day 2, continuous daily administration from days 3-23, and withdrawal from days 24-30. Subsequent cycles (28 days) used continuous daily administration. The dose of erlotinib was escalated from 50 mg/day to 150 mg/day in 50-mg increments. PK evaluation was performed in all patients during cycle 1. RESULTS:Fifteen patients, aged 38-70 (median; 57) years with non-small-cell lung (n = 11), colorectal (n = 3) or head and neck (n = 1) cancer were enrolled. The major toxicities were rash, diarrhea and liver dysfunctions, which were generally mild and easily manageable. The good tolerability of erlotinib up to the dose of 150 mg/day was confirmed. One patient developed grade 5 treatment-related interstitial pneumonitis. Four of 11 evaluable patients achieved partial responses; all four had non-small-cell lung cancer (NSCLC). The peak plasma concentration of erlotinib, and the area under the concentration-time curve increased proportionally to the dose, suggesting linear PK. CONCLUSION:The recommended dose of erlotinib in Japanese patients is 150 mg/day. Further trials in Japanese NSCLC patients are warranted.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Yamamoto N,Horiike A,Fujisaka Y,Murakami H,Shimoyama T,Yamada Y,Tamura Tdoi
10.1007/s00280-007-0494-8subject
Has Abstractpub_date
2008-03-01 00:00:00pages
489-96issue
3eissn
0344-5704issn
1432-0843journal_volume
61pub_type
杂志文章abstract::The present study was aimed at answering the question of what patients with hepatocellular carcinomas could obtain long-term benefits from resectional therapy. The 239 patients hepatectomized from 1973 through 1986, with 33 tumor-free, 3-year survivors, were the subjects of the study. The following criteria for long-t...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00647247
更新日期:1989-01-01 00:00:00
abstract:OBJECTIVE:To investigate the effects of FSTL1-mediated NF-κB signaling pathway on cisplatin (DDP) sensitivity of EOC cells. METHODS:FSTL1 expression was determined in epithelial ovarian cancer (EOC) tissues and corresponding adjacent tissues using immunohistochemistry. SKOV3 and SKOV3/DDP cells were transfected and gr...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04215-9
更新日期:2021-01-03 00:00:00
abstract:PURPOSE:Based on the promising results of a Phase I study with a combination of gemcitabine and DTIC performed in advanced soft tissue sarcoma (ASTS) patients, and due to the limited efficacy of second or third line therapies in those patients, we designed a Phase II study to determine the activity of this new regimen....
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0263-0
更新日期:2007-02-01 00:00:00
abstract:PURPOSE:This phase II study was performed to evaluate the efficacy and safety of cisplatin/pemetrexed combined with 15 mg/kg of bevacizumab followed by pemetrexed/bevacizumab maintenance therapy as first-line chemotherapy in advanced non-squamous non-small cell lung cancer (NSCLC) limited to epidermal growth factor rec...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-018-3573-0
更新日期:2018-06-01 00:00:00
abstract::Carboxypeptidase G2 (CPG2) is used when unexpected toxicity or renal failure occurs during high-dose methotrexate therapy. Leucovorin is also administered to antagonise the effects of methotrexate on purine anabolism. To investigate the effects of CPG2 on leucovorin rescue, we incubated the enzyme with both stereoisom...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-004-0910-2
更新日期:2005-04-01 00:00:00
abstract:PURPOSE:Although anthracycline is a key agent in breast cancer treatment, its use is associated with the risk of cardiotoxicity. Recently, the value of combination therapy with docetaxel and cyclophosphamide was reported. Because the characteristics of paclitaxel differ on weekly versus tri-weekly administration, such ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-009-1137-z
更新日期:2010-05-01 00:00:00
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
更新日期:1992-01-01 00:00:00
abstract::We studied bioavailability, treatment schedule dependence, and therapeutic efficacy of orally administered MST-16, a novel derivative of bis(2,6-dioxopiperazine), against murine tumors and human tumor xenografts. The rate of its intestinal absorption was about 50%, and it was immediately metabolized to its parent comp...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685528
更新日期:1991-01-01 00:00:00
abstract:PURPOSE:Malignant pleural mesothelioma (MPM) is a highly lethal neoplasm. S-1 has been developed as a novel oral antineoplastic agent based on the modulation of 5-fluorouracil (5-FU) bioactivity. This study was conducted to investigate the preclinical therapeutic effect of S-1 on MPM. METHODS:We used three human MPM c...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1503-x
更新日期:2011-08-01 00:00:00
abstract::A B16 melanoma cell line in which resistance to doxorubicin (Dx) had been induced by in vitro exposure to the drug, was found not to be cross-resistant with 4'-deoxy-4'-iodo-doxorubicin (4'-I-Dx), a new Dx derivative. Dx was 200 times less active in resistant than in sensitive cells, whereas the iodo derivative compou...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00262780
更新日期:1988-01-01 00:00:00
abstract::Schedule dependency of bisantrene was evaluated in refractory metastatic breast cancer. Patients were randomly assigned to receive either a single (S) bolus injection of 300 mg/m2 (37 patients) or an injection of 80 mg/m2 daily for 5 days (D x 5) (35 patients) every 3-4 weeks after stratification by performance status...
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/BF00262287
更新日期:1986-01-01 00:00:00
abstract::Thymidine (dThd) concentrations have been measured in the sera of normal subjects and solid tumor cancer patients by means of a sensitive high-pressure liquid chromatographic assay to determine whether natural and methotrexate (MTX)-induced fluctuations were large enough to alter the toxicity of MTX to marrow. The mea...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00434388
更新日期:1981-01-01 00:00:00
abstract:PURPOSE:To establish the cytochrome P450 (CYP) isozymes involved in the metabolism of the alkylating agent, thiotepa, to the pharmacologically active metabolite, TEPA. METHODS:In vitro chemical inhibition studies were conducted by incubating thiotepa and pooled human hepatic microsomes in the presence of known inhibit...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-002-0453-3
更新日期:2002-06-01 00:00:00
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
更新日期:2014-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The optimal chemotherapeutic protocol for the treatment of esophageal cancer has not yet been established. A dose-escalation study of docetaxel combined with cisplatin and 5-fluorouracil (5-FU) was performed to determine the optimal dose in patients with advanced esophageal squamous cell carcinom...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1447-1
更新日期:2010-11-01 00:00:00
abstract::Saturable elimination of 5-FU is exhibited in rats during constant infusions. Over the range of 3-480 mg/m2/h, total-body clearance of 5-FU decreases from 600 ml/min/m2 to less than 90 ml/min/m2. Previously published values for catabolism of 5-FU by rat hepatocytes can be used to simulate the plasma concentrations of ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00434346
更新日期:1985-01-01 00:00:00
abstract:OBJECTIVE:To study the pharmacokinetics of neamine in rats and to evaluate its anti-cervical cancer activity. METHODS:The plasma level of neamine was determined by HPLC-ELSD. Pharmacokinetic parameters were calculated using DAS 2.0 software. Tissue microarray analysis was conducted to examine angiogenin (ANG) expressi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2658-7
更新日期:2015-03-01 00:00:00
abstract:PURPOSE:To develop more potent procaspase-3 activator, 7 novel derivatives of PAC-1 were synthesized and evaluated. Among them, SM-1 stood out for its promising activity and good pharmacokinetics properties. The purpose of this study is to elucidate the pharmacological mechanism of SM-1 and evaluate its efficacy and to...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3115-6
更新日期:2016-09-01 00:00:00
abstract::N2,N4,N6-Trihydroxymethyl-N2,N4,N6-trimethylmelamine (Trimelamol) is a water-soluble synthetic s-triazine which, unlike hexamethylmelamine (HMM) and pentamethylmelamine (PMM), does not require metabolic activation. The physico-chemical characteristics of Trimelamol were studied with the aim of overcoming the problems ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00256694
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:Angiotensin (1-7) [A(1-7)] is a bioactive peptide of the renin angiotensin system that stimulates the number of bone marrow progenitors and hematopoietic recovery after myelosuppression. We evaluated the combination of A(1-7) with colony-stimulating factors, Neupogen and Epogen, on bone marrow progenitors and t...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2312-9
更新日期:2013-12-01 00:00:00
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
更新日期:2007-08-01 00:00:00
abstract:BACKGROUND:Chemotherapy for breast cancer is associated with a high risk of neutropenia. Pegfilgrastim reduces the risk of neutropenic fever but commonly causes bone pain. OBJECTIVE:Evaluate whether a reduced dose of pegfilgrastim (3 mg) reduced the frequency of bone pain without compromising efficacy. METHODS:Record...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-018-3607-7
更新日期:2018-07-01 00:00:00
abstract::Dihydroartemisinin, a more water-soluble metabolite of artemisinin derivatives, is a safe and most effective antimalarial analog of artemisinin. In the present study, we investigated the antiangiogenic activity of dihydroartemisinin in vitro and in vivo, and investigated dihydroartemisinin-induced apoptosis in human u...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-003-0751-4
更新日期:2004-05-01 00:00:00
abstract::A phase II trial of idarubicin was performed in 24 patients with advanced lymphoma. The drug was administered in a dose of 10-15 mg/m2 i.v. or 15-70 mg/m2 p.o. (single dose) every 3 weeks. There were four partial responses and four minor responses. All but one of the responders had received prior doxorubicin therapy. ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00262782
更新日期:1988-01-01 00:00:00
abstract:PURPOSE:Although irinotecan monotherapy is often used in third-line treatment after the failure of taxanes in Japanese clinical practice, its survival benefit is still unclear. The aim of this study is to investigate the efficacy and safety of irinotecan monotherapy as third-line treatment. METHODS:Clinical data from ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3138-z
更新日期:2016-10-01 00:00:00
abstract::Brain microdialysis was applied to sample free methotrexate (MTX) concentrations in brain extracellular fluid of normal and RG-2 glioma-bearing rats. All animals received 50 mg/kg of MTX intra-arterially following which serial blood and interstitial fluid samples were collected for 3 h and measured for MTX by an HPLC ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050518
更新日期:1996-01-01 00:00:00
abstract::AspCNU and SarCNU are two amino acid amide congeners (L-asparaginamide and sarcosinamide congeners) of chloroethylnitrosoureas. The in vitro myelotoxicity of these agents compared with BCNU at 1-8 micrograms/ml was determined in bone marrow cells from normal volunteers in the CFU-C assay. AspCNU and SarCNU were signif...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00434356
更新日期:1985-01-01 00:00:00
abstract::The risk of potential drug-drug interactions (PDI) is poorly studied in oncology. We included 105 patients with advanced non-small-cell lung cancer (NSCLC), 100 patients with advanced breast cancer (BC) and 100 patients of the palliative care unit (PCU) receiving systemic palliative treatment between 2010 and 2015. Al...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03783-9
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND:The cyclin-dependent kinase inhibitor flavopiridol increases irinotecan- and fluorouracil-induced apoptosis. We conducted a phase I trial of FOLFIRI + flavopiridol in patients with advanced solid tumors. DESIGN:FOLFIRI + flavopiridol were administered every 2 weeks. Based on sequence-dependent inhibition, f...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1269-1
更新日期:2010-11-01 00:00:00
abstract::Sodium cyanate (NaOCN) at a dose of 250 mg/kg was shown to decrease protein synthesis in P388 leukemia tumor cells to approximately 52% of control values at 2 h and 32% at 5 h after NaOCN administration, without a corresponding decrease in various normal tissues of the tumor-bearing CD2Fl mice. CD2Fl mice that had rec...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254597
更新日期:1984-01-01 00:00:00