A phase II trial of imatinib mesylate monotherapy in patients with metastatic breast cancer.
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).


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.


CONCLUSIONS
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.
Modi
Shanu
S
Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Seidman
Andrew D
AD
Dickler
Maura
M
Moasser
Mark
M
D'Andrea
Gabriella
G
Moynahan
Mary Ellen
ME
Menell
Jennifer
J
Panageas
Katherine S
KS
Tan
Lee K
LK
Norton
Larry
L
Hudis
Clifford A
CA
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D015996:Survival Rate
D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D017479:Receptors, Platelet-Derived Growth Factor