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-dependent are necessary. Docetaxel and topotecan are non-cross-resistance cytotoxic agents with activity in a variety of malignancies. The goal of this study was to determine the maximum tolerated dose of docetaxel and continuous infusion topotecan using two sequences of administration. EXPERIMENTAL DESIGN:Patients were randomized to schedule A or B and enrolled in four escalating-dose cohorts. On schedule A, docetaxel was administered over 1 h and followed by topotecan administered over 72 h. On schedule B, topotecan was given as a 72 h continuous infusion followed by a 1 h infusion of docetaxel. While the doses for the docetaxel and topotecan were the same for schedule A and schedule B, the toxicities, and thus the determination of maximum tolerated dose (MTD), were assessed independently. The plasma pharmacokinetic disposition of topotecan and docetaxel were evaluated during the first cycle of each sequence to assess drug interactions. RESULTS:Thirty patients, 20 males and 10 females were evaluable for toxicity and response. Four patients were chemonaive. Mean number cycles given were 3. Grade 3/4 thrombocytopenia and neutropenia were comparable on both schedules, as was the dose-limiting toxicity (DLT) for both schedules. There were no apparent differences in absolute neutrophil count or platelet nadirs between schedules A and B for three of the four cohorts. The principal non-hematologic toxicity was nausea and vomiting. The time of overlap of topotecan lactone or total concentrations and docetaxel concentrations were greater on schedule A as compared with schedule B and was associated with reduced clearance of docetaxel on schedule A as compared to schedule B. However, the mean clearance for docetaxel (18 for all 16 L h(-1) m(-2) and 29 for all 28 L h(-1) m(-2) on schedules A and B, respectively, and topotecan 16 for all 10 L h(-1) m(-2) and 7 for all 6 L h(-1) m(-2) on schedules A and B, respectively) were not statistically different (P > 0.05). CONCLUSIONS:The observed toxicity was not sequence-dependent, despite the observed change in kinetics. Docetaxel and topotecan can be administered with acceptable toxicity at the recommended phase-II dose of docetaxel 60 mg m(-2) and topotecan 0.85 mg m(-2) day(-1)x3 days.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Posey JA,Wang H,Hamilton J,Delgrosso A,Zhang R,Freda T,Zamboni WCdoi
10.1007/s00280-004-0925-8keywords:
subject
Has Abstractpub_date
2005-08-01 00:00:00pages
182-8issue
2eissn
0344-5704issn
1432-0843journal_volume
56pub_type
临床试验,杂志文章,随机对照试验abstract::A model incorporating recent information regarding the specificity of a high-performance liquid chromatographic assay for "active" platinum in plasma ultrafiltrate, and the concept of mobile and fixed metabolites, was developed for cancer patients treated with cisplatin. Model parameters were determined using plasma a...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00252955
更新日期:1987-01-01 00:00:00
abstract:INTRODUCTION:A combined therapy MEK inhibitor, Cobimetinib (CB) and BRAF inhibitor, Vemurafenib (VMF), results in an improvement in progression-free survival among patients with BRAF V600-mutated metastatic melanoma. VMF skin adverse effects attributed to ERK paradoxical activation are decreased by the adjunction of CB...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-017-3300-2
更新日期:2017-05-01 00:00:00
abstract::The consequences at the cardiac level of adriamycin treatment alone or in association with the cardiac glycoside beta-methyldigoxin, were evaluated with reference to the PEP/LVET ratio, heart rate, and minimum blood pressure. The variation usually seen in the PEP/LVET ratio when adriamycin is administered alone was no...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00258290
更新日期:1979-01-01 00:00:00
abstract::BS compounds, a series of new dihydropyridines, successfully overcame multidrug resistance in P388/ADR cells in vitro. These agents synergistically potentiated the cytotoxicity of Adriamycin to P388/ADR cells at a concentration of 1-2 microM, whereas they showed hardly any synergistic effect in the parental cell line ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257444
更新日期:1989-01-01 00:00:00
abstract:BACKGROUND:This phase 1 study evaluated the safety, tolerability, pharmacokinetics and efficacy of patritumab (U3-1287) Process 2, a new formulation of fully human anti-HER3 monoclonal antibody in combination with erlotinib, an epidermal growth factor receptortyrosine kinase inhibitor (EGFR-TKI) in prior chemotherapy t...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3231-3
更新日期:2017-03-01 00:00:00
abstract:PURPOSE:Cisplatin and radiation therapy remain the current standard for treating locally advanced SCCHN. Novel treatment approaches are needed, especially in patients with human papilloma virus (HPV)-negative disease who have worse outcomes despite multimodality therapy. METHODS:Using our institutional review board ap...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2584-8
更新日期:2014-11-01 00:00:00
abstract:OBJECTIVES:To assess the cardiovascular safety, tolerability and efficacy of high doses of granisetron for the treatment of nausea and vomiting in patients undergoing highly emetogenic chemotherapy. METHODS:Patients with histologically confirmed malignant disease were given an intravenous infusion of granisetron, 160 ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-003-0689-6
更新日期:2004-02-01 00:00:00
abstract::Etoposide has demonstrated highly significant clinical activity against a wide variety of neoplasms, including germ-cell malignancies, small-cell lung cancer, non-Hodgkin's lymphomas, leukemias, Kaposi's sarcoma, neuroblastoma, and soft-tissue sarcomas. It is also one of the important agents in the preparatory regimen...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/BF00684875
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:We have previously reported that intra-arterial chemotherapy prolongs the survival of patients with advanced HCC (aHCC); however, whether the response to intra-arterial chemotherapy depends on the etiology of underlying liver cirrhosis (LC) is still unknown. AIM:The aim of this study was to assess any influenc...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0851-2
更新日期:2009-06-01 00:00:00
abstract:PURPOSE:Pemetrexed, a multi-targeted antifolate that disrupts synthesis of both purines and pyrimidines, is approved for use in malignant pleural mesothelioma and non-small cell lung cancer. Pemetrexed is currently being evaluated for anti-tumor activity in a variety of solid and central nervous system tumors. We studi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0285-7
更新日期:2007-03-01 00:00:00
abstract::Trastuzumab has deeply and radically changed the course of HER2-positive breast cancer disease. The recent development of a subcutaneous (SC) formulation of trastuzumab is an important step towards improved patients' care. SC trastuzumab at a fixed dose of 600 mg administered every 3 weeks for about 5 min provides a v...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2289-4
更新日期:2013-12-01 00:00:00
abstract:PURPOSE:This study aimed to compare the survival of patients enrolled in phase 1 trials in recent decades. METHODS:The medical records of consecutive patients with advanced cancer who participated in single-agent oncology phase 1 trials from 1995 to 2015 at a single institution were retrospectively investigated. RESU...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03992-2
更新日期:2020-02-01 00:00:00
abstract:PURPOSE:6-Gingerol, a major biochemical and pharmacological active ingredient of ginger, has shown anti-inflammatory and antitumor activities against various cancers. Searching for natural products with fewer side effects for developing adjunctive therapeutic options is necessary. METHODS:The effects of 6-gingerol on ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03999-9
更新日期:2020-02-01 00:00:00
abstract:PURPOSE:This phase I study was undertaken to evaluate the safety and tolerability of prolonged infusional etoposide, and to evaluate its pharmacokinetic/pharmacodynamic profile in patients with advanced cancer. METHODS:A group of 17 patients received a 7-day infusion of etoposide (schedule A) every 21 days at doses fr...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800050511
更新日期:1996-01-01 00:00:00
abstract:PURPOSE:Thymidylate synthase (TS) is one of the target molecules for the antitumor effects of fluoropyrimidine drugs. The cellular thymidylate synthase level is one of the determining factors for the antitumor activity of fluoropyrimidines. TYMS, which encodes TS, has been reported to possess 28-bp tandem repeat sequen...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-1018-z
更新日期:2005-11-01 00:00:00
abstract:OBJECTIVES:The aim of this phase II study was to evaluate the response rate to gemcitabine combined with cisplatin in patients with locally advanced, metastatic or recurrent biliary tract cancer who had received no prior chemotherapy. METHODS:The treatment consisted of cisplatin 70 mg/m(2) in intravenous infusion foll...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-007-0444-5
更新日期:2008-01-01 00:00:00
abstract:PURPOSE:Little information is available about changes in renal function after cisplatin-based chemotherapy (CBCT) in patients with a solitary kidney. The authors evaluated the renal safety and efficacy of CBCT after nephroureterectomy for upper urinary tract-urothelial carcinoma (UUT-UC). METHODS:The data of patients ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1349-2
更新日期:2011-04-01 00:00:00
abstract::D-3-Azido-3-deoxy-myo-inositol (3AMI) is an inhibitor of the growth of v-sis-transformed NIH 3T3 cells but not of wild-type NIH 3T3 cells, whose effects may be mediated through the phosphatidylinositol-3'-kinase pathway. We studied some properties of the cellular pharmacology of 3AMI using high-specific-activity [3H]-...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686287
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:To differentiate the antagonistic and agonistic effect of toremifene at the level of the hypothalamus-hypophysis axis a leutinizing hormone-releasing hormone (LHRH) test was performed during a phase II clinical trial. METHODS:In 15 postmenopausal patients with advanced breast cancer, follicle-stimulating hormo...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050811
更新日期:1998-01-01 00:00:00
abstract:OBJECTIVES:ATP-binding cassette subfamily C member 4 (ABCC4) encoding MRP4 protein is involved in pediatric acute lymphoblastic leukemia (ALL) drug resistance. The nonsynonymous single nucleotide polymorphism (SNP) rs2274407 (G912T; K304N) is located in the 3' splice acceptor site of exon 8 of ABCC4 pre-mRNA. The aim o...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-017-3340-7
更新日期:2017-07-01 00:00:00
abstract:PURPOSE:Extrapulmonary neuroendocrine carcinomas (EPNEC) are rarely observed and are associated with poor outcomes. Based on the clinicopathological similarity, treatment used for small cell lung carcinoma has also been employed for EPNEC, but the response to such therapy has not been well examined. The goal of this st...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-015-2706-y
更新日期:2015-04-01 00:00:00
abstract::The pharmacokinetics of doxorubicin (DOX) and doxorubicinol (DOXol) was studied in six patients with various advanced neoplastic diseases who received 28-72 mg/m2 DOX (nine courses). Plasma and parotid saliva were collected over a 48-h period, and DOX and DOXol were quantified by high-performance liquid chromatography...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686315
更新日期:1992-01-01 00:00:00
abstract::Cyclophosphamide (Cy) is widely used as an effective cytotoxic drug, but its use is limited because of its toxicity. In this report, we describe for the first time the ability of purified protein A (P) of Staphylococcus aureus to reduce Cy-induced toxicity in rats. Protein A-treated animals recover quickly from the to...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00552727
更新日期:1985-01-01 00:00:00
abstract: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). Seconda...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-015-2872-y
更新日期:2015-12-01 00:00:00
abstract:PURPOSE:The platinum agent oxaliplatin could be useful in treatment of cancer in pregnant women, but it is fetotoxic in rats and its effect on the human fetus is unknown. METHODS:Oxaliplatin was administered to a 25-year-old pregnant woman with metastatic rectal cancer from 20 to 30 weeks gestational age as part of th...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0731-9
更新日期:2009-01-01 00:00:00
abstract::Chemotherapy-induced intestinal damage is a very important dose-limiting side effect for which there is no definitive prophylaxis or treatment. This is in part due to the lack of understanding of its pathophysiology and impact on intestinal differentiation. The objective of this study was to investigate the gene expre...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0119-z
更新日期:2006-06-01 00:00:00
abstract:PURPOSE:The effect of an anticancer treatment on tumor cell proliferation in vitro can be described as a three-dimensional surface where the inhibitory effect is related to drug concentration and treatment time. The analysis of this kind of response surface could provide critical information: for example, it could indi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-003-0688-7
更新日期:2003-12-01 00:00:00
abstract::Antibodies can be used to target cancer therapies to malignant tissue; the approach is attractive because conventional treatments such as chemo- and radiotherapy are dose limited due to toxicity in normal tissues. Effective targeting relies on appropriate pharmacokinetics of antibody-based therapeutics, ideally showin...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/pl00014055
更新日期:2000-01-01 00:00:00
abstract::Intravenous (i.v.) administration of sodium thiosulfate reduces the toxicity of cis-diamminedichloroplatinum (II) (CDDP). This effect, which allows the use of increased CDDP doses, has been exploited clinically in the intraperitoneal (i.p.) treatment of intraabdominal tumors. Recently, attempts have been made to treat...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257358
更新日期:1988-01-01 00:00:00
abstract:PURPOSE:To evaluate the efficacy and safety of FOLFIRI regimen in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin. METHODS:The FOLFIRI regimen consisted of intravenous infusion of irinotecan 180 mg/m(2) on day 1 plus leucovorin (LV) 400 mg/m(2) on day 1 plus 5-fluorouracil (5-FU...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1301-5
更新日期:2011-01-01 00:00:00