Paclitaxel and carboplatin as first-line chemotherapy combined with
gefitinib (IRESSA) in patients with advanced breast cancer: a phase I/II
study conducted by the Hellenic Cooperative Oncology Group
Paclitaxel (lTaxol(R)) and carboplatin are an effective combination
regimen for treating advanced breast cancer. Gefitinib (IRESSA) is the
first epidermal growth factor receptor tyrosine kinase inhibitor to be
approved for cancer treatment. This multicenter phase II trial treated
68 patients with advanced breast cancer with paclitaxel ( 175 mg/ m 2
over 3 h) and 3-weekly carboplatin ( area under the curve of 6) for six
cycles, and 250 mg/ day gefitinib orally. Median age was 57 ( range 35 -
77) years, patients had performance status 0 (69.1%), 1 (27.9%) 2
(2.9%), 82.4% of patients had visceral metastases and 63.2% had
received adjuvant chemotherapy. Forty-eight (70.6%) patients completed
six cycles of chemotherapy and 20 (29.4%) patients discontinued
treatment ( seven [10.3%] due to disease progression, seven [
10.3%] due to toxicity,five [7.4%] withdrew consent and one
[1.5%] died after the first cycle). Sixty-three (92.7%) patients
were evaluable for response; nine (13.2%) had complete responses, 30
(44.1%) had partial responses, 21 (30.9%) had stable disease and three
(4.4%) had disease progression. Grade 3/4 adverse events in >= 5% of
patients except of alopecia, included neutropenia (17.7%), anemia (
10.3%), diarrhea ( 7.4%), thrombocytopenia (5.9%) and peripheral
neuropathy ( 5.9%). Of those tumor biopsies available for
immunohistochemical analysis ( n= 60), 5.0% were positive and 35.0%
negative for expression of all HER-family receptors. Comparable numbers
of tumor biopsies were nuclear p27(kipl) positive and negative (39.7 and
42.7%, respectively), with the majority (72.1%) negative for
cytoplasmic p27(kipl). The observed efficacy data in this study were
similar to those reported for the combination of paclitaxel and
carboplatin alone
