NEW YORKA new regimen of weekly paclitaxel (Taxol) plus the
monoclonal antibody trastuzumab (Herceptin) produced an overall
response rate of 60% among metastatic breast cancer patients,
regardless of HER2 status, according to a study presented at the ASCO
In conventional dosing, trastuzumab has been given weekly and
paclitaxel every 3 weeks. Giving a lower dose of paclitaxel
more often is based on the concept of dose density, lead
investigator Andrew Seidman, MD, of Memorial Sloan-Kettering, said in
an interview. Allowing less time between may offer less
opportunity for drug-resistant cells to grow.
He noted further that the weekly regimen has already demonstrated
significant antitumor activity and remarkable
tolerability and safety.
study involved 95 patients with a mean age of 51 years. They were
given weekly paclitaxel at 90 mg/m² (1-hour infusion) and weekly
trastuzumab (4-mg/kg loading dose in a 90-minute IV infusion and then
2 mg/kg in a 30-minute IV infusion) (see Figure).
The median number of prior regimens was 1, with 59% having had prior
adjuvant therapy, 66% prior anthracycline treatment, and 13% prior
paclitaxel therapy at least 1 year previously.
Predictor of Response
Investigators measured HER2 overexpression through a variety of
assays (DAKO, p-Abl, CB-11, TAB-250, FISH).
The overall response rate among 88 evaluable patients, Dr. Seidman
reported, was 60.2% (three complete responses), regardless of HER2
status, with a median response duration of 6 months. The range of
responses among HER2-positive patients across the various assays was
67% to 83% (see Table 1).
FISH was a very good predictor of response, Dr. Seidman
said. Those who showed gene amplification had a 75% chance of
response and those without, a 48% chancea significant
difference (see Table 2).
Dr. Seidman added that immunohistochemistry testing of specimens
stored for prolonged periods can lead to false negatives, while
polyclonal antibody tests, such as DAKO, can produce false positives.
The simple message is that monoclonal antibodies and FISH seem
to be more optimal predictors of therapeutic response, Dr.
The major dose-limiting toxicity was neuropathy (10% grade 3, 1%
grade 4). Neutropenia occurred in 14%, with three episodes of febrile
Because of prior concerns about potential cardiac toxicity,
investigators carefully monitored patients for left ventricular
hypertrophy and found evidence of congestive heart failure in two
patients and myocardial infarction in two more, for a major cardiac
event rate of 6%.
Our data afford some measure of comfort that this combined use
of paclitaxel and trastuzumab is safe for the myocardium of the vast
majority of patients, Dr. Seidman stated.
He concluded that the regimen of weekly paclitaxel and trastuzumab
had significant activity in patients who overexpressed HER2 and in
those who did not. This trial cannot definitively answer
whether trastuzumab is likely to contribute anything to the
nonoverexpressersbut we have integrated trastuzumab dosing to a
portion of that group in CALGB [Cancer and Leukemia Group B] 9840, a
trial of weekly paclitaxel vs paclitaxel every 3 weeks, Dr.