Cancer Chemother Pharmacol (2006) 58: 809–815
DOI 10.1007/s00280-006-0222-9
ORIGINAL ARTICLE
Hugo E. R. Ford · Yoon-Sim Yap · David W. Miles
Andreas Makris · Marcia Hall · Liz Miller
Mark Harries · Ian E. Smith · Stephen R. D. Johnston
A phase II study of weekly docetaxel in patients with anthracycline
pretreated metastatic breast cancer
Received: 7 January 2006 / Accepted: 20 February 2006 / Published online: 10 March 2006
© Springer-Verlag 2006
Abstract Background: Docetaxel has signiWcant activity
in metastatic breast cancer and weekly schedules are
associated with less myelosuppression than 3-weekly
schedules. We evaluated the toxicity and the activity of
weekly docetaxel in anthracycline-pretreated patients.
Patients and methods: A total of 42 patients were studied.
Treatment consisted of docetaxel 35 mg/m
2
weekly as a
30-min infusion for 6 weeks followed by a 2-week rest,
with dexamethasone 8 mg i.v. pre-medication and 4 mg
orally 12-hourly for 48 h following treatment. Results:
The median age of the patients was 53 years (range 34–
74). Twenty-six (62%) patients had received prior chemo-
therapy for advanced disease. Patients received a median
10 weeks of treatment (range 1–24). 11 had a partial
response (ORR 26%; 95% CI 13–39%), Wve of whom had
relapsed <12 months since the end of previous anthra-
cycline-based chemotherapy. In addition six patients
(14%) had stable disease for >16 weeks. Myelosuppres-
sion was rare with only 2 patients (5%) experiencing
grade 3 neutropenia (no grade 4 neutropenia). Non-hae-
matological grade III toxicities were as follows: fatigue
17%, neuropathy 0%, hyperlacrimation 5%, stomatitis
7%, diarrhoea 14%, and cutaneous toxicity 19%. Skin
toxicity consisted of limb/palmar–plantar erythematous
reactions, or Wxed-plaque erythrodysaesthesia. Conclu-
sions: Weekly docetaxel has moderate activity in women
with anthracycline pre-treated breast cancer. Although
the level of myelosuppression is lower than 3-weekly reg-
imens, this weekly regimen cannot be recommended due
to the signiWcant non-haematological toxicities associ-
ated with the treatment.
Keywords Metastatic breast cancer · Docetaxel ·
Weekly chemotherapy
Introduction
Docetaxel (Taxotere®) is an active drug for the treat-
ment of patients with metastatic breast cancer. A phase
III study conWrmed that docetaxel had signiWcantly
higher eYcacy than mitomycin and vinblastine (overall
response rate 30 vs. 12%) in patients who had previously
received anthracyclines [31]. A recent phase III trial com-
paring 3-weekly docetaxel with 3-weekly paclitaxel in
women failing anthracyclines reported that docetaxel
was superior in terms of response rate (32 vs. 25%),
median time to progression (5.7 vs. 3.6 months) and
overall survival (15.4 vs. 12.7 months) [21]. Docetaxel is
conventionally administered as a 3-weekly infusion, and
at the standard dose of 100 mg/m
2
every 3 weeks the inci-
dence of grade 3/4 neutropenia approaches 90% and is
the dose-limiting toxicity. Other common toxicities
include hypersensitivity reactions, asthenia, cutaneous/
nail toxicity and Xuid retention.
There are a number of potential advantages to weekly
administration of chemotherapy. Weekly scheduling may
potentially increase dose density to prevent emergence and
re-growth of drug-resistant cell clones by more frequent
exposure to cytotoxic agents. The therapeutic index may
also be improved with the reduction of grade 3–4 myelo-
suppression by giving lower doses more frequently. In
addition some data have suggested that the taxanes (par-
ticularly paclitaxel) may have anti-angiogenic properties
[4, 23], and two studies have suggested that this eVect
could be greater with docetaxel than with paclitaxel
H. E. R. Ford · Y.-S. Yap · L. Miller · I. E. Smith
S. R. D. Johnston (&)
Department of Medicine – Breast Unit, Royal Marsden NHS Trust,
233 Fulham Road, SW3 6JJ London, United Kingdom
E-mail: stephen.johnston@rmh.nhs.uk
Tel.: +44-207-8082748
Fax: +44-207-8082563
D. W. Miles · A. Makris · M. Hall
Mount Vernon Cancer Centre, Northwood,
Middlesex, UK
D. W. Miles · M. Harries
Department of Medical Oncology,
Guy’s & St Thomas’s NHS Trust, London, UK