Phase i study of PD 0332991, a cyclin-dependent kinase inhibitor, administered in 3-week cycles (Schedule 2/1)

G. K. Schwartz, P. M. Lorusso, M. A. Dickson, S. S. Randolph, M. N. Shaik, K. D. Wilner, R. Courtney, P. J. O'Dwyer

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225 Scopus citations


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.

Original languageEnglish
Pages (from-to)1862-1868
Number of pages7
JournalBritish Journal of Cancer
Issue number12
StatePublished - 7 Jun 2011
Externally publishedYes


  • CDK inhibitor
  • G1/S checkpoint
  • PD 0332991
  • non-Hodgkin's lymphoma
  • retinoblastoma-positive solid tumours


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