Delving into the Latest Updates on KW-2170 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

KW 2170

Target

Top II

Mechanism

Top II inhibitors(Topoisomerase II inhibitors)

Therapeutic Areas

Neoplasms

Active Indication-

Inactive Indication

NeoplasmsSolid tumor

Originator Organization

Kyowa Kirin Co., Ltd.

Active Organization-

Inactive Organization

Kyowa Kirin Co., Ltd.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC20H24ClN5O4

InChIKeyAEDHWZKHJZUUHV-UHFFFAOYSA-N

CAS Registry207862-44-0

A prospective phase II trial was performed in patients with persistent or recurrent epithelial ovarian or primary peritoneal carcinoma and measurable disease. Patients could have platinum-sensitive or refractory disease and could have received any number of prior treatments. One treatment cycle consisted of KW-2170 administered at a dose of 18 mg/m(2) weekly for 3 weeks followed by a 21-day rest period. Toxicity was assessed using the NCI Common Toxicity Criteria (Version 2.0), and dose reduction was allowed for significant toxicity. Response to therapy was assessed in patients who completed at least 2 cycles using RECIST criteria.

RESULTS:

A total of 28 patients were enrolled in this phase II trial at 5 separate centers. Of the 28 patients evaluated, all had stage III/IV disease at initial diagnosis. The median number of prior therapeutic regimens in these patients was 4 (range 1-8). The median number of KW-2170 cycles administered was 2 (range 1-5). Treatment-related toxicity in this heavily pretreated population was acceptable as only 6 patients (21%) had grade 3-4 neutropenia. Dose reductions occurred in 6 patients (21%) for grades 1-4 neutropenia, and no patient had febrile neutropenia. Four patients completed less than 1 cycle; 3 secondary to progressive disease, and one due to Gram-positive sepsis. Of patients receiving at least 2 full cycles, 10 patients (55%) had stable disease with a median of 4.5 months (range 3-10) to disease progression. All other patients were removed from the study after 1-2 cycles of therapy with no significant clinical effect noted.

CONCLUSIONS:

Although associated with relatively little toxicity, KW-2170 at the dose and schedule evaluated demonstrated little clinical activity in this heavily pretreated population of recurrent ovarian cancer patients. Whether KW-2170 would have greater clinical activity in a more treatment naive group of patients at an increased dose awaits clinical trial evaluation.

01 Nov 2004·Cancer chemotherapy and pharmacologyQ4 · MEDICINE

Phase I and pharmacokinetic study of KW-2170, a novel pyrazoloacridone compound, in patients with malignant tumors

Q4 · MEDICINE

Article

Author: Takashi Kuwabara ; Shigemitu Takashima ; Toshiaki Saeki ; Keisuke Aiba ; Toyoaki Hida ; Makoto Ogawa ; Noboru Horikoshi ; Kenji Eguchi ; Takahiko Sugiura

PURPOSE:

The primary purposes of this study were to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD), to recommend a dose for phase II studies, and to analyze the pharmacokinetics of KW-2170. A secondary purpose was to assess tumor response to KW-2170.

EXPERIMENTAL DESIGN:

KW-2170 was given as a 30-min i.v. infusion every 4 weeks. Doses were escalated from 1.0 mg/m2 according to a modified Fibonacci method.

RESULTS:

A total of 45 cycles of KW-2170 were delivered to 41 patients at doses ranging from 1.0 to 53.0 mg/m2. The primary DLT was neutropenia which was observed in two of six patients treated at 32.0 mg/m2 and in two of two patients treated at 53.0 mg/m2; therefore, the MTD was 53.0 mg/m2. Although no patients showed a complete response (CR)or partial response (PR), 15 patients were evaluated a shaving freedom from progression at the 1-month time-point, with two demonstrating slight tumor shrinkage in their metastatic lesions. None of the patients experienced significant cardiotoxicity. The plasma concentration of KW-2170 declined in a triphasic manner. The half-life, total clearance (CLtot) and volume of distribution (Vdss) were nearly constant and independent of dose, and showed a relatively small interpatient variability. A linear relationship was observed between dose and maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC 0-infinity). In addition, there was a good correlation between neutropenia and AUC 0- infinity. This suggests that toxicity may be dependent on systemic exposure to the drug. Two oxi-dative metabolites were observed in the patients' plasma and urine.

CONCLUSIONS:

The primary DLT of KW-2170 in this study was neutropenia, with a MTD of 53 mg/m2.A significant linear relationship was observed between neutropenia and AUC 0- infinity. We estimate the recommended dose for phase II studies to be 41.0 mg/m2.

01 Oct 2002·IDrugs : the investigational drugs journal

Article

Author: Verschraegen, Claire F

The pyrazoloacridone, KW-2170, an alkylating agent and topoisomerase II inhibitor, is being developed by Kyowa Hakko Kogyo as a potential treatment for cancer [273964], [409111], [422561]. By December 2001, KW-2170 had entered phase II trials in the US, following approval for the trial from the FDA, which was received in November 2001. At this time, the company planned to extend the phase II trials to Australia, Singapore, Taiwan and Costa Rica using data from US phase I trials. Accelerated Japanese trials were also planned, and an NDA was anticipated for 2006, with non-small-cell lung cancer, prostate cancer, colorectal cancer, ovarian cancer and breast cancer as the targets [434794], [444539]. By August 2002, Japanese phase I trials had been completed [460177].

100 Deals associated with KW-2170

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