scispace - formally typeset
Open AccessJournal ArticleDOI

Phase II Trial of the CDK4 Inhibitor PD0332991 in Patients With Advanced CDK4-Amplified Well-Differentiated or Dedifferentiated Liposarcoma

Mark A. Dickson, +13 more
- 01 Jun 2013 - 
- Vol. 31, Iss: 16, pp 2024-2028
TLDR
Treatment with theCDK4 inhibitor PD0332991 was associated with a favorable progression-free rate in patients with CDK4-amplified and RB-expressing WDLS/DDLS who had progressive disease despite systemic therapy.
Abstract: 
Purpose CDK4 is amplified in 90% of well-differentiated (WDLS) and dedifferentiated liposarcomas (DDLS). The selective cyclin-dependent kinase 4 (CDK4)/CDK6 inhibitor PD0332991 inhibits growth and induces senescence in cell lines and xenografts. In a phase I trial of PD0332991, several patients with WDLS or DDLS experienced prolonged stable disease. We performed an open-label phase II study to determine the safety and efficacy of PD0332991 in patients with advanced WDLS/DDLS.

read more

Content maybe subject to copyright    Report

Citations
More filters
Journal ArticleDOI

Targeting nuclear kinases in cancer: development of cell cycle kinase inhibitors

Todd M. Pitts, +3 more
- 01 May 2014 - 
TL;DR: An overview of the current compounds being developed clinically to target these nuclear kinases involved in regulating the cell cycle and mitosis is provided.
Journal ArticleDOI

Antimitotic drugs in cancer chemotherapy: promises and pitfalls.

Isabel Marzo, +1 more
- 15 Sep 2013 - 
TL;DR: The most recent preclinical information on those new antimitotic drugs, as well as the possible molecular bases underlying their lack of clinical efficiency, are discussed.
Journal ArticleDOI

Preclinical Characterization of Novel Chordoma Cell Systems and Their Targeting by Pharmocological Inhibitors of the CDK4/6 Cell-Cycle Pathway

Adrian von Witzleben, +14 more
- 15 Sep 2015 - 
TL;DR: In the newly validated system, palbociclib treatment efficiently inhibited tumor cell growth in vitro and a drug responder versus nonresponder molecular signature was defined on the basis of immunohistochemical expression of CDK4/6/pRb (S780).
Journal ArticleDOI

Inhibiting CDK in Cancer Therapy: Current Evidence and Future Directions

Smruthi Vijayaraghavan, +3 more
- 01 Feb 2018 - 
TL;DR: Ongoing research is evaluating CDK4/6i for additional breast cancer subtypes and non-breast malignancies with promising early phase clinical trial results and exploring potential resistance mechanisms to this treatment.
Journal ArticleDOI

Inhibition of CDK4/6 by Palbociclib Significantly Extends Survival in Medulloblastoma Patient-Derived Xenograft Mouse Models

Michelle L. Cook Sangar, +8 more
- 01 Oct 2017 - 
TL;DR: Bioinformatics analysis followed by in vivo studies in patient-derived xenograft (PDX) models were used to identify and validate CDK 4/6 inhibition as an effective therapeutic strategy for medulloblastoma, particularly group 3 MYC-amplified tumors that have the worst clinical prognosis.
References
More filters
Journal ArticleDOI

New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)

Elizabeth Eisenhauer, +15 more
- 01 Jan 2009 - 
TL;DR: The revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions, and a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included.
Book

Statistical methods for rates and proportions

Joseph L. Fleiss
TL;DR: In this paper, the basic theory of Maximum Likelihood Estimation (MLE) is used to detect a difference between two different proportions of a given proportion in a single proportion.
Journal ArticleDOI

Statistical Methods for Rates and Proportions.

B. S. Everitt, +1 more
- 01 Sep 1973 - 
Journal Article

[New response evaluation criteria in solid tumours-revised RECIST guideline (version 1.1)].

Hirokazu Watanabe, +9 more
- 01 Dec 2009 - 
TL;DR: This paper is an overview of the new response evaluation criteria in solid tumours: revised RECIST guideline (version 1. 1), with a focus on updated contents.
Journal Article

Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts

David W. Fry, +10 more
- 01 Nov 2004 - 
TL;DR: Results indicate that inhibition of Cdk4/6 alone is sufficient to cause tumor regression and a net reduction in tumor burden in some tumors.
Related Papers (5)

Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts

David W. Fry, +10 more
- 01 Nov 2004 - 

PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro

Richard S. Finn, +11 more
- 29 Oct 2009 - 

Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial

Winette T. A. van der Graaf, +22 more
- 19 May 2012 - 

The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study

Richard S. Finn, +17 more
- 01 Jan 2015 - 

Pazopanib, a Multikinase Angiogenesis Inhibitor, in Patients With Relapsed or Refractory Advanced Soft Tissue Sarcoma: A Phase II Study From the European Organisation for Research and Treatment of Cancer―Soft Tissue and Bone Sarcoma Group (EORTC Study 62043)

Stefan Sleijfer, +12 more
- 01 Jul 2009 -