Study enrollment was initially Obtain: This Covers Up Each
And Everything On Palbociclib limited to chemotherapy na ve patients. A protocol amendment during the active enrollment period allowed enrollment of patients with 0 or 1 previous chemotherapy regimens and required that all patients had developed Grade 2 thrombocytopenia in a pre vious chemotherapy treatment setting. Alternatively, patients with no previous chemotherapy treatment should have developed Grade 2 thrombocytopenia during a pre vious AI chemotherapy cycle, with AI at the same dose and schedule planned in the 2 cycles following enrollment into the study. An additional change in this amendment allowed enrollment for patients with thromboembolic events 6 months previously. prior to this amend ment patients with a history of TEEs were excluded from the study.
A subsequent protocol amendment required that patients have adequate cardiac function at baseline, as measured by echocardiogram or multiple gated acquisition scan, as newly avail able in vitro data demonstrated that eltrombopag was an inhibitor of breast cancer resistance protein efflux transporter, for which doxorubicin and potentially its metabolite, doxorubicinol, are substrates. As these find ings suggested that eltrombopag had the potential to increase doxorubicin plasma concentrations, the pro tocol was amended to implement additional cardiac moni toring and PK sampling for doxorubicin. Patients were excluded if they had 1 previous chemo therapy regimens in any disease setting. preexisting cardiovascular disease. any known clotting disorder as sociated with hypercoagulability.
prior treatment that affected platelet function or anticoagulants for 3 con secutive days within 2 weeks of the study start and until the end of the study. recent history of drug induced thrombocytopenia. history of prior radiotherapy to more than 20% bone marrow bearing sites. planned cata ract surgery. or any clinical abnormality or laboratory parameters that interfered with study treatment or con ferred a risk for participation in the study. Study assessments, procedures, and analyses Assessments performed at screening included evaluation of eligibility criteria. medical history. routine physical examination. ECOG performance status. risk factors for kidney impairment and cataracts. 12 lead electrocardio gram, laboratory assessments, and ophthalmologic examination.
The July 2009 amendment required cardiac monitoring using ECHO or MUGA scans at baseline and every 3 cycles. Physical examinations were performed on study Day 1 of each cycle and on the last day of Cycle 6 or upon withdrawal from study. Ophthalmic assessment was performed at study completion withdrawal and also at the 6 month follow up visit. Bleeding events, AE toxicity assessment, and concomitant medications were assessed at each study visit and on the last day of Cycle 6 or upon withdrawal from the study. Additional safety assess ments were com pleted throughout the study at protocol specified time points.