In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 610-610
Abstract:
610 Background: Liposomal formulations including pegylated liposomal doxorubicin (PLD) were developed to improve the therapeutic index of anthracyclines (A). Lapatinib (L) is a selective, highly competitive inhibitor of ErbB1 and ErbB2 tyrosine kinases. Conventional doxorubicin plus trastuzumab was effective but with unacceptable cardiac toxicity. PLD plus L may be effective with less cardiac risk. Methods: This is a phase I, dose-escalation trial of PLD 20, 30, 45 and 60 mg/m 2 IV every 4 weeks (maximum of 8 doses) and L, 1500 mg po daily until progression in patients (pts) with MBC. ErbB2 positivity was not required. Prior chemotherapy, endocrine therapy and trastuzumab were allowed. A subsequent amendment allowed prior L. Prior A use was limited to 240 mg/m 2 of doxorubicin or 600 mg/m 2 of epirubicin. Concomitant CYP3A4 inducers/ inhibitors were not allowed. A left ventricular ejection fraction (LVEF) of 〉 50% was required. The primary objective was to evaluate the safety (particularly cardiac), tolerability and feasibility of PLD and L. Results: 23 pts (PLD: 20 mg/m 2 - 4 pts; 30 mg/m 2 - 3 pts; 45 mg/m 2 – 13 pts; 60 mg/m 2 - 3 pts) have been treated; total of 73 treatment cycles. Dose-limiting toxicity (DLT) was not reached. One pt had an LVEF drop to 〈 50% after 4 cycles accompanied by a pericardial effusion due to progressive disease. Treatment-related grade III/IV adverse events included: 4 pts with hand-foot-syndrome (HFS), 2 pts each with leukopenia, infection, and skin changes, 1 pt each with pain, fatigue, diarrhea, mucositis, hypoalbuminemia, anemia, cough, pleural effusion, and edema. Grade 3 HFS occurred in 2 of 3 pts in the 60 mg/m 2 cohort. Response data in 21 evaluable pts: 4 PR, 5 SD, and 12 PD. Preliminary pharmacokinetic (PK) analyses (7 pts) indicate L has no effect on PLD (45 mg/m 2 ) concentrations, but L concentrations were approximately 2-fold higher the day of PLD dosing. Conclusions: In 23 pts treated, PLD plus L was well tolerated with manageable toxicities and no treatment-related cardiac toxicity. DLT was not reached however grade 3 HFS occurred in 2 of 3 pts in the 60 mg/m 2 cohort. Preliminary PK analyses demonstrate no effect of L on PLD, but an effect of PLD on L the day of PLD dosing.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.610
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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