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. METHODS:Six subjects were administrated an oral suspension containing 5 mg of 14C-labeled HMPL-013 (100 μCi) in a fasted state. Blood and excreta samples were collected at the designated time points or intervals for pharmacokinetics and radiometric analyses. Safety assessments were conducted throughout the study. RESULTS:Over a 336-h post-dose collection period, mean recovery was 90.11% of the radiolabeled dose, with 60.31% in urine and 29.80% in feces. Mean C max, AUC0-∞, and T max for HMPL-013 in plasma were 113 ng/mL, 4797 h ng/mL, and 2 h, respectively. Radioactivity and HMPL-013 were cleared from circulation with terminal half-lives of 41.1 and 33.4 h. HMPL-013 was the predominant circulating radioactive component, representing 72.48% of the total radioactivity. M11 was the major circulating metabolite, accounting for 17.31% of the total radioactivity. An additional seven circulating metabolites were identified, each accounting for less than 5% of the total radioactivity. In urine, HMPL-013 accounted for only 0.50% of the administered dose. Three major metabolites M285, M381, and M409-4 were identified in urine accounting for 10.48, 21.16, and 8.92% of the dose, respectively. In feces, HMPL-013 accounted for 5.34% of the dose. M205, M365-2, and M380 were the major metabolites, accounting for 2.29, 3.30, and 2.59% of the dose, respectively. CONCLUSION:HMPL-013 was well tolerated and absorbed rapidly, with parent compound being the predominant circulating component. HMPL-013 was extensively metabolized prior to excretion, and urine was the major route of excretion.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Zhou S,Shao F,Xu Z,Wang L,Jin K,Xie L,Chen J,Liu Y,Zhang H,Ou Ndoi
10.1007/s00280-017-3394-6subject
Has Abstractpub_date
2017-09-01 00:00:00pages
563-573issue
3eissn
0344-5704issn
1432-0843pii
10.1007/s00280-017-3394-6journal_volume
80pub_type
杂志文章abstract:BACKGROUND:Camptothecin (CPT) is an anticancer agent that kills cells by converting DNA topoisomerase I into a DNA-damaging agent. Although CPT and its derivatives are now being used to treat tumors in a variety of clinical protocols, the low water solubility of the drug and its unique pharmacodynamics and reactivity i...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-002-0463-1
更新日期:2002-08-01 00:00:00
abstract:BACKGROUND:No specific treatment guidelines are available for triple-negative breast cancers, defined by a lack of expression of estrogen (ER), progesterone (PgR), and HER2 receptors. PATIENTS AND METHODS:We investigated in patients with T2-T3 N0-3 ER, PgR <10% and HER2 negative breast cancers the activity both in ter...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-007-0652-z
更新日期:2008-09-01 00:00:00
abstract::In order to determine if any inherent sensitivity differences may exist between VP16-213 and VM26 individual human tumors were grown in vitro and drug sensitivities were determined using the soft agar clonogenic assay method. Only nine of the 34 tumors tested so far showed a differing sensitivity to VP16-213 and VM26 ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254531
更新日期:1982-01-01 00:00:00
abstract:BACKGROUND:Recently, melatonin has been associated with cancer both in vitro and in vivo. However, the value of melatonin in the treatment of cancer remains disputable. Hence, we performed a systematic review of randomized controlled trials (RCTs) of melatonin in solid tumor cancer patients and observed its effect on t...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s00280-012-1828-8
更新日期:2012-05-01 00:00:00
abstract::To evaluate the value of beta-2-microglobulin as an indicator of acute and long-term cis-platinum-induced nephrotoxicity, 51Cr-EDTA clearance and serum concentration and urinary excretion of beta-2-microglobulin were measured in 18 patients treated with a regimen including cis-platinum. Before treatment all values wer...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00258126
更新日期:1985-01-01 00:00:00
abstract::A variety of purine analogs inhibit the growth and induce the differentiation of human promyelocytic leukemia (HL-60) cells that lack the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Mechanisms by which purine analogs induce differentiation offer unique potential for cancer chemotherap...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00689581
更新日期:1989-01-01 00:00:00
abstract::The development of more effective treatment strategies currently provides the only realistic hope of reducing breast cancer mortality. Among such treatments, high-dose chemotherapy (HDC) has been proposed to be a potentially curative strategy. Consideration of the factors involved in the successful treatment of human ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s002800051067
更新日期:1997-01-01 00:00:00
abstract:PURPOSE:Tyrosine kinase inhibitors (TKI) that target MET signaling have shown promise in various types of cancer, including lung cancer. Combination strategies have been proposed and developed to increase their therapeutic index. Based on preclinical synergy between inhibition of MET and topoisomerase I, a phase I stud...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-018-3672-y
更新日期:2018-10-01 00:00:00
abstract:PURPOSE:The safety of S-1 in recurrent colorectal cancer patients with chronic myeloid leukemia (CML) treated with dasatinib has not been established. We evaluated the safety and pharmacokinetics of S-1 in a recurrent colon cancer patient with CML treated with dasatinib. PATIENT:A 70-year-old man had undergone surgery...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2620-8
更新日期:2014-12-01 00:00:00
abstract::CD-1 mice are commonly used in oncology metabolism and toxicity to support drug discovery and development and to examine drug metabolism and toxicity properties of new chemical entities. On the other hand, athymic nude mice are the preferred animals to investigate tumor growth inhibition. Therefore, a frequently asked...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-004-0898-7
更新日期:2005-02-01 00:00:00
abstract:PURPOSE:Many patients with non-small cell lung cancer (NSCLC) are eligible only for palliative radiation (RT) at presentation. This study was designed to assess the feasibility of adding the anti-EGFR monoclonal antibody nimotuzumab to palliative thoracic RT. METHODS:Patients with stage IIB, III or IV NSCLC considered...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1379-9
更新日期:2011-04-01 00:00:00
abstract:PURPOSE:To determine toxicities, maximally tolerated dose (MTD), pharmacokinetic profile, and potential antitumor activity of MTA, a novel antifolate compound which inhibits the enzymes thymidylate synthase (TS), glycinamide ribonucleotide formyltransferase (GARFT), and dihydrofolate reductase (DHFR). METHODS:Patients...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s002800050992
更新日期:1999-01-01 00:00:00
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
doi:10.1007/s00280-007-0505-9
更新日期:2008-02-01 00:00:00
abstract:PURPOSE:To assess the safety of the association of radiotherapy (RT) and systemic treatments for patients with metastatic malignant melanoma (mMM). METHODS:A retrospective analysis included consecutive patients treated with palliative RT, and at least one line of systemic therapy for mMM between 2001 and 2016. Treatme...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03806-5
更新日期:2019-05-01 00:00:00
abstract::Ankinomycin is a new antitumor antibiotic found in the culture broth of Streptomyces sp. SF2587. Ankinomycin showed marked cytotoxicity and antitumor activity against some murine leukemias, but the activity against murine solid tumors was rather weak because of its strong acute toxicity. We synthesized ankinomycin acy...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685831
更新日期:1993-01-01 00:00:00
abstract::Thirty-two evaluable patients with advanced measurable gastric adenocarcinoma were treated with a combination of 5-fluorouracil, adriamycin, and BCNU (FAB). Two complete and fourteen partial responses were observed, with an overall response rate of 50%. The median duration of response was 10 months, and the median sur...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00256545
更新日期:1984-01-01 00:00:00
abstract:PURPOSE:Bevacizumab (BV) prolongs the survival of colorectal cancer patients when combined with irinotecan (CPT-11)-based regimens. In the AVF2107g study, the area under the curve (AUC) ratio for bolus CPT-11/5-fluorouracil (5-FU)/leucovorin (LV) (IFL) with the BV arm to bolus IFL with placebo indicated that SN-38 conc...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-009-1051-4
更新日期:2010-02-01 00:00:00
abstract:PURPOSE:Troxacitabine (BCH-4556, l-(-)-OddC, Troxatyl) is a novel beta- l-nucleoside analogue with potent antineoplastic activity both in vitro and in several tumor models in vivo, and is presently in phase II clinical trials. The combination of the cytosine analogues troxacitabine and araC (1-beta- d-arabinofuranosylc...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-003-0699-4
更新日期:2003-12-01 00:00:00
abstract:PURPOSE:ASNA1 is homologous to E. coli ArsA, a well characterized ATPase involved in efflux of arsenite and antimonite. Cells resistant to arsenite and antimonite are cross-resistant to the chemotherapeutic drug cisplatin. ASNA1 is also an essential ATPase for the insertion of tail-anchored proteins into ER membranes a...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0762-2
更新日期:2009-02-01 00:00:00
abstract:BACKGROUND:Fenretinide is a synthetic retinoid that can induce cytotoxicity by several mechanisms. Achieving effective systemic exposure with oral formulations has been challenging. An intravenous lipid emulsion fenretinide formulation was developed to overcome this barrier. We conducted a study to establish the maximu...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04224-8
更新日期:2021-01-10 00:00:00
abstract:PURPOSE:Oxaliplatin (OHP) in combination with 5-fluorouracil/leucovorin (FOLFOX) is clinically used as frontline therapy in patients with advanced colorectal carcinoma (CRC), with response rates ranging from 46 to 71%. This combination is now considered a standard treatment for metastatic CRC and also in the post-opera...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1476-9
更新日期:2011-04-01 00:00:00
abstract:PURPOSE:High-dose methotrexate (HD-MTX) is widely used in the treatment of non-Hodgkin lymphoma (NHL), but the pharmacokinetic properties of HD-MTX in Chinese adult patients with NHL have not yet been established through an approach that integrates genetic covariates. The purposes of this study were to identify both ph...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04058-4
更新日期:2020-05-01 00:00:00
abstract:BACKGROUND:Peritoneal surface malignancy resulting from local dissemination is a common manifestation of treatment failure of gastrointestinal cancers. Although the management of carcinomatosis has been improved with an aggressive surgical approach of extensive cytoreduction followed by heated intraoperative intraperit...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0238-1
更新日期:2007-02-01 00:00:00
abstract:PURPOSE:To evaluate the feasibility, toxicity and efficacy of the combination of docetaxel and mitomycin C as second-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS:Thirty-eight patients with histologically confirmed, locally advanced or metastatic NSCLC were includ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0198-5
更新日期:2006-10-01 00:00:00
abstract:PURPOSE:A metronomic schedule of chemotherapy (resulting in a greater frequency of drug delivery) has shown efficacy in head and neck cancer. Our aim was to investigate the overall survival in tongue cancer patients with metronomic neoadjuvant chemotherapy with bleomycin compared to those with surgery alone. METHODS:I...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3141-4
更新日期:2016-10-01 00:00:00
abstract::The discovery of targetable mutations, which cause gene rearrangement, led to a major advancement in the treatment of patients with non-small cell lung cancer (NSCLC), and cancers with such mutations can be paired with drugs which specifically target them. c-ros oncogene (ROS1) positive NSCLC is one molecular subtype ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-019-03902-6
更新日期:2019-10-01 00:00:00
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
doi:10.1007/BF00256699
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:Trifluorothymidine (TFT) is a fluoropyrimidine that is part of the novel combination metabolite TAS-102, in which TFT is combined with a potent thymidine phosphorylase inhibitor (TPI). TAS-102 is currently tested as an orally chemotherapeutic agent in different schedules in a phase I study. In its monophosphate...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0033-4
更新日期:2006-01-01 00:00:00
abstract::Elevations of serum lipid peroxide levels were demonstrated in mice after an equitoxic dose of doxorubicin. When BDF1 mice were injected with doxorubicin (20 mg/kg body weight, IP), lipid peroxide levels in sera were elevated 1 day after the injection and the levels declined on subsequent days. 5-Fluorouracil (400 mg/...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254735
更新日期:1979-01-01 00:00:00
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
更新日期:2009-12-01 00:00:00