LAPATINIB AND RADIOTHERAPY-A TOXIC COMBINATION

Breast Cancer Res Treat. 2013 Nov 7. [Epub ahead of print]

A phase I study of lapatinib with whole brain radiotherapy in patients with Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer brain metastases.

Lin NU, Freedman RA, Ramakrishna N, Younger J, Storniolo AM, Bellon JR, Come SE, Gelman RS, Harris GJ, Henderson MA, Macdonald SM, Mahadevan A,Eisenberg E, Ligibel JA, Mayer EL, Moy B, Eichler AF, Winer EP.

Source

Harvard Medical School, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA, nlin@partners.org.

Abstract

Brain metastases are common in patients with advanced, Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer. We evaluated the maximum tolerated dose (MTD) and feasibility of lapatinib given concurrently with whole brain radiotherapy (WBRT). Eligible patients had (HER2)-positive breast cancer and ≥1 brain metastasis. Patients received lapatinib 750 mg twice on day one followed by 1000, 1250, or 1500 mg once daily. WBRT (37.5 Gy, 15 fractions) began 1-8 days after starting lapatinib. Lapatinib was continued through WBRT. Following WBRT, patients received trastuzumab 2 mg/kg weekly and lapatinib 1000 mg once daily. The regimen would be considered feasible if <3 17="" 1="" 28="" 3="" 46="" 4="" 59-92="" 6="" 79="" 7="" a="" although="" among="" and="" at="" be="" because="" between="" by="" careful="" central="" cns="" concurrent="" confidence="" considered="" could="" criteria="" diarrhea="" did="" disease="" dlts:="" dlts="" dose-limiting="" dose="" during="" embolus="" enrolled="" escalation="" evaluable="" experienced="" feasibility="" five="" for="" future="" given="" grade="" had="" high="" hypoxia="" interval="" lapatinib-wbrt="" meet="" mg="" monitoring.="" months.="" mtd="" mucositis="" n="" nbsp="" nervous="" no="" non-cns="" not="" objective="" of="" only.="" or="" orr="" overall="" p="" patients="" pre-defined="" pre-specified="" progression-free="" pts="" pulmonary="" rash="" rate="" receiving="" relationship="" remained="" response="" safety="" some="" still="" study="" the="" thirty-five="" toxicity="" treated="" treatment="" two="" uncertain.="" volumetric="" was="" were="" with="">