An exploratory study of sunitinib plus paclitaxel as first-line treatment for patients with advanced breast cancer.
BACKGROUND
Sunitinib has shown single-agent activity in patients with previously treated metastatic breast cancer (MBC). We investigated the safety of the combination of sunitinib and paclitaxel in an exploratory study of patients with locally advanced or MBC.


METHODS
Patients received oral sunitinib 25 mg/day (with escalation to 37.5 mg/day as tolerated) on a continuous daily dosing schedule and paclitaxel 90 mg/m(2) on days 1, 8, and 15 of each 28-day cycle. Study endpoints included safety (primary endpoint), pharmacokinetics, and antitumor activity.


RESULTS
Twenty-two patients were enrolled. The most frequent adverse events (AEs) were fatigue/asthenia (77%), dysgeusia (68%), and diarrhea (64%). Grade 3 AEs included neutropenia (43%), fatigue/asthenia (27%), neuropathy (18%), and diarrhea (14%). No drug-drug interaction was observed on the basis of pharmacokinetic analysis. Of 18 patients with measurable disease at baseline, 7 (38.9%) achieved objective responses (including 2 complete and 5 partial responses). Clinical responses were observed in three of nine patients with triple-negative receptor status (estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor-2 negative).


CONCLUSIONS
These data indicate that sunitinib and paclitaxel in combination are well tolerated in patients with locally advanced or MBC. No drug-drug interaction was detected and there was preliminary evidence of antitumor activity.
Kozloff
M
M
Department of Oncology, Cancer Research Center, Ingalls Memorial Hospital, Harvey, IL. Electronic address: mfkozloff@aol.com.
Chuang
E
E
Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY.
Starr
A
A
Department of Oncology, Cancer Research Center, Ingalls Memorial Hospital, Harvey, IL.
Gowland
P A
PA
Department of Oncology, Cancer Research Center, Ingalls Memorial Hospital, Harvey, IL.
Cataruozolo
P E
PE
Research and Development, Pfizer Oncology, La Jolla, CA.
Collier
M
M
Research and Development, Pfizer Oncology, La Jolla, CA.
Verkh
L
L
Research and Development, Pfizer Oncology, La Jolla, CA.
Huang
X
X
Research and Development, Pfizer Oncology, La Jolla, CA.
Kern
K A
KA
Research and Development, Pfizer Oncology, La Jolla, CA.
Miller
K
K
Division of Hematology-Oncology, Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008207:Lymphatic Metastasis; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D010865:Pilot Projects; D011758:Pyrroles / Q000008:administration & dosage; D000077210:Sunitinib; D015996:Survival Rate; D014018:Tissue Distribution; D016896:Treatment Outcome
D007211:Indoles; D011758:Pyrroles; D017239:Paclitaxel; D000077210:Sunitinib