Oberhoff et al. (2001)

Oberhoff et al. (2001)
Design: Phase II study (prognosis), evidence level: 3
Country: Germany
Inclusion criteria:
Age ≥ 18 years
Histologically or cytologically confirmed diagnosis of breast cancer
At least one Bidimensionally measurable brain metastasis
Prior adjuvant and/or palliative endocrine or cytotoxic therapies allowed
Sufficient liver, kidney and bone marrow function
WHO performance status 0–2
Life expectancy > 3 months
Written informed consent.
Exclusion criteria:
Concomitant endocrine treatment or chemotherapy
Simultaneous RT (except for bone metastases)
Prior WBRT.
Number of patients = 24, age range 36 to 74 years, mean age = 58 years
Topotecan was given at 1.5 mg per m2 per day as a 30 minute infusion for 5 days every 21 days. 10/24 patients also received corticosteroids.

Treatment was continued until disease progression at which point RT was administered as second line.
Tumour response: Complete response (CR), Partial response (PR), Stable disease (SD), Disease progression (PD), Not evaluable (NE). Adverse events. Duration of response (RD). Overall survival (OS).
Follow up:
Response evaluation was performed prior to treatment initiation and then prior to every third cycle using a CT or MRI scan.

Adverse events were assessed before each treatment cycle using routine clinical and laboratory tests.

3/24 patients were excluded from the study for personal reasons (n = 2) and glioblastoma (n = 1). 5 patients who had completed only one cycle of treatment were excluded from the response evaluation. The reasons for non-completion were because of side effects (n = 1) or rapid tumour progression (n = 4).
Median number of treatment cycles per patient = 3 (range: 1–11)

Median time to best response = 76 days (range: 35–161)

Tumour response (n = 16):
CR = 1
PR = 5
SD = 5
PD = 5
NE = 0

Median RD = 124 days (range: 35–151 days)
Median duration of SD = 45 days (range: 41–161 days)
Median OS = 6.25 months (95% CI: 4.7–9.6 months, range: 1.25–13.2 months)

Grade 3/4 adverse events (for 93 treatment cycles):
Haemoglobin = 11/2
White blood cells = 35/17
Neutrophils = 11/12
Platelets = 26/10
Stomatitis = 3/0
Constipation = 7/1
Sensorium = 1/0
Pain = 2/1
Fever = 2/0
Infection = 5/0.
General comments:
This paper describes a prospective phase II study of 24 patients treated with topotecan chemotherapy for brain metastases from breast cancer at a single institute between June 1998 and October 1999.

Survival analyses were by the method of Kaplan-Meier.

18/24 patients had extracranial metastases and in 10 of these patients disease was present in more than one other organ.

This is a well reported but rather small and statistically underpowered pilot study.

From: Chapter 6, Management of specific problems

Cover of Advanced Breast Cancer
Advanced Breast Cancer: Diagnosis and Treatment.
NICE Clinical Guidelines, No. 81.
National Collaborating Centre for Cancer (UK).
Copyright © 2009, National Collaborating Centre for Cancer.

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