MEMPHISA dose-intense sequential schedule of
doxorubicin/docetaxel (Taxotere) plus growth factor was no more
effective than standard simultaneous administration in treating
metastatic breast cancer.
Lee Schwartzberg, MD, of Response Oncology, Inc., Memphis, and his
colleagues compared the dose-intense sequential schedulegiving
maximum tolerated doses of each drug in sequence and shortening the
interval between doseswith standard administration of the drugs
among 98 randomized patients. Dr. Schwartzberg presented the results
at the ASCO annual meeting.
Sequential schedules are attractive because they enable clinicians to
deliver full doses of each drug. Dr. Schwartzbergs group
assigned patients with metastatic breast cancer who had received no
prior chemotherapy for metastatic disease to receive an equal total
dose of doxorubicin and docetaxel as induction treatment.
Patients were randomized to either simultaneous administration
(doxorubicin 45 mg/m² + docetaxel 75 mg/m² every 21 days
for four cycles) or sequential administration (doxorubicin 90
mg/m² every 14 days for two cycles followed by docetaxel 100
mg/m² every 14 days for three cycles).
G-CSF (Neupogen) was scheduled on days 3 to 10 in the sequential arm
but given only after a neutropenic episode in the simultaneous arm.
Response was assessed after induction. Responding patients were
eligible for high-dose consolidation.
Dose Densities Differ
Dr. Schwartzberg reported that 37% of the patients had metastatic
disease at diagnosis, 54% had prior adjuvant therapy, and 31% had
liver involvement. Median delivered dose intensity and cumulative
dose for both drugs were similar in both arms.
The median dose density was markedly higher for the sequential arm,
but this did not translate into greater efficacy. Although
researchers were able to deliver more than 90% of the planned doses,
the overall response rate, time to progression, event-free survival,
and overall survival were about the same on both regimens, according
to Dr. Schwartzberg (see Table).
There was significantly more neutropenia in the simultaneous arm of
the study, but more skin toxicity (a painful erythroderma beginning
in the hands and feet and extending to the total body) in the
Delivered dose density is higher with the sequential schedule,
but without an improvement in response rate, event-free survival, or
overall survival, Dr. Schwartzberg concluded. A
dose-dense, growth-factorsupported sequential treatment offers
no advantage over a standard combination schedule.
In discussing this study, Clifford Hudis, MD, of Memorial
Sloan-Kettering Cancer Center, said, Sequential vs concurrent
doxorubicin/docetaxel had no difference in efficacy and little
difference in toxicity. This was a disappointing result...but not a
completely fair test of dose-dense chemotherapy.