Gleevec, breast cancer - Phase II Trial - Didn't Work

[Guest guest]

A phase II trial of imatinib mesylate monotherapy in patients with

metastatic breast cancer.

Modi S, Seidman AD, Dickler M, Moasser M, D' G, Moynahan ME,

Menell J, Panageas KS, Tan LK, Norton L, Hudis CA.

Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

Background. Imatinib mesylate is a potent inhibitor of Abl, KIT, and

PDGFR tyrosine kinases. Breast cancer has variable expression of KIT and

PDGFR therefore we conducted a phase II trial to evaluate the safety and

efficacy of imatinib in patients with metastatic breast cancer

(MBC).Patients and methods. Eligible patients had measurable and

progressive MBC, with no limits on prior chemo- or hormonal therapy.

Imatinib was initially administered at a dose of 400 mg orally twice a

day with provisions for dose reductions based on toxicities. The primary

endpoint was clinical benefit based on RECIST criteria. Tumor specimens

were tested for expression of KIT and PDGFR tyrosine kinases.Results.

Sixteen patients were enrolled and treated. Median age was 55 years

(range: 35-73); median number of prior chemotherapy regimens for MBC was

4 (range 1-8). The main non-hematologic toxicities were (Grades 1/2;

Grade 3): fatigue (56%; 6%), edema (38%; 19%), nausea (31%; 19%),

vomiting (38%; 0%), anorexia (38%; 0%), diarrhea (19%; 6%), and rash

(25%; 6%). Grade 3/4 hematologic and biochemical abnormalities were

minimal. There was no evidence of clinical benefit. The median duration

of therapy on trial was 28 days (range 2-71). Of the 13 testable cases:

1 was KIT positive and 4 were PDGFR positive.Conclusion. Imatinib

therapy at doses of 800 mg/day was associated with significant toxicity

in patients with heavily pre-treated MBC. Our results do not indicate

activity for imatinib monotherapy in these unselected patients.

__