Phase i study of PD 0332991, a cyclin-dependent kinase inhibitor, administered in 3-week cycles (Schedule 2/1) Journal Article
| Authors: | Schwartz, G. K.; LoRusso, P. M.; Dickson, M. A.; Randolph, S. S.; Shaik, M. N.; Wilner, K. D.; Courtney, R.; O'Dwyer, P. J. |
| Article Title: | Phase i study of PD 0332991, a cyclin-dependent kinase inhibitor, administered in 3-week cycles (Schedule 2/1) |
| Abstract: | Background:This phase I, open-label, first-in-human study determined dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of PD 0332991, an oral cyclin-dependent kinase 4/6 inhibitor with potent anti-proliferative activity in vitro/vivo.Methods:A total of 33 patients with retinoblastoma protein-positive advanced solid tumours or non-Hodgkin's lymphoma refractory to standard therapy or for which no therapy was available received PD 0332991 once daily (QD) for 14 days followed by 7 days off treatment (21-day cycles; Schedule 2/1).Results:Six patients had DLTs (18%; four receiving 200 mg QD; two receiving 225 mg QD); the MTD was 200 mg QD. Treatment-related, non-haematological adverse events occurred in 29 patients (88%) during cycle 1 and 27 patients (82%) thereafter. Adverse events were generally mild-moderate. Of 31 evaluable patients, one with testicular cancer achieved a partial response; nine had stable disease (10 cycles in three cases). PD 0332991 was slowly absorbed (mean T max 4.2 h) and eliminated (mean half-life 26.7 h). Volume of distribution was large (mean 3241 l) with dose-proportional exposure. Using a maximum effective concentration model, neutropenia was proportional to exposure.Conclusion:PD 0332991 was generally well tolerated, with DLTs related mainly to myelosuppression. The MTD, 200 mg QD, is recommended for phase II study. © 2011 Cancer Research UK All rights reserved. |
| Keywords: | non-hodgkin's lymphoma; cdk inhibitor; g1/s checkpoint; pd 0332991; retinoblastoma-positive solid tumours |
| Journal Title: | British Journal of Cancer |
| Volume: | 104 |
| Issue: | 12 |
| ISSN: | 0007-0920 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2011-06-07 |
| Start Page: | 1862 |
| End Page: | 1868 |
| Language: | English |
| DOI: | 10.1038/bjc.2011.177 |
| PROVIDER: | scopus |
| PUBMED: | 21610706 |
| PMCID: | PMC3111206 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 23 June 2011" - "CODEN: BJCAA" - "Source: Scopus" |
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