Boogerd et al. (1992)

Boogerd et al. (1992)
Design: Prospective case series (prognosis), evidence level: 3
Country: Netherlands, the
Inclusion criteria:
Patients with breast cancer and unresectable or recurrent brain metastases
Exclusion criteria:
Clouded consciousness persisting after corticosteroid therapy
Hemiplegia persisting after corticosteroid therapy
Meningeal carcinomatosis
Serious myelosuppression
Short life expectancy (not defined)
Second primary tumour
Population:
Number of patients = 22, age range 33 to 72 years, mean age = 49 years
Interventions:
CMF (n = 20):
Cyclophosphamide at 100 mg per m2 orally on days 1 to 14 + methotrexate at 40 mg per m2 i.v. on days 1 and 8 + 5′-fluorouracil at 600 mg per ml i.v. on days 1 and 8 in 4 week cycles for 6 cycles (or 9 cycles depending on response).

CAF (n = 2):
Cyclophosphamide at 500 mg per m2 i.v. + doxorubicin at 50 mg per m2 i.v. + 5′-fluorouracil at 500 mg per ml i.v. once every 3 weeks.

Dose modifications were put in place if patients experienced grade 2 haematological toxicity.

20/22 patients received dexamethasone, the dosage of which was tapered depending on the neurological response to therapy.

For stable disease or progression of brain disease WBRT replaced chemotherapy unless previously irradiated in which case chemotherapy was repeated.
Outcomes:
Tumour response: Complete response (CR), Partial response (PR), Minimal response (MR), Stable disease (SD), Disease progression (PD), No evidence of disease (ND), Not evaluable (NE). Overall survival (OS) measured from the day of the diagnostic scan. Response duration (RD).
Follow up:
Brain metastases were originally diagnosed by CT scan.

Patients underwent neurological examination and assessment of systemic disease every three weeks or earlier in the case of disease progression. Tumour response was evaluated at week 2, 6 and 9 or at clinical progression.

4/22 patients were not examined at 3 weeks due to death from pulmonary embolism, intracranial haemorrhage or gastric perforation.

11 patients died from neurological disease, 3 from systemic disease, 3 from intercurrent disease and 5 patients were still alive at the end of the study.
Results:
Neurological response (n = 18):
Systemic disease:
CR = 1
PR = 2
SD = 10
ND = 3
NE = 5
PD = 1

CNS response:
CR = 2
PR = 10
MR = 1
SD = 1
NE = 6
PD = 2

Median RD: chemotherapy (n = 22) = 30 weeks (range: 15–66)
Median RD: RT (n = 29) = 10 weeks (range: 8–91)

Median OS: chemotherapy = 25 weeks (range: 2–83)
Median OS: RT = 10 weeks (range: 1–107)

Median OS of patients responding to chemotherapy = 66 weeks (range: 22–83)
Median OS of patients responding to RT = 26 weeks (range: 18–107)

Median OS: solitary metastases (n = 6) = 26 weeks
Median OS: single metastasis (n = 5) = 9 weeks

Grade 3 or 4 adverse events:
Haematological toxicity = 4

6/7 patients responded to chemotherapy despite relapsing previously on the same regime.
General comments:
This paper describes a comparison between a prospective series of patients with brain metastases from breast cancer who received chemotherapy and a historical control group which had received WBRT. The groups did not appear to be well matched in some respects and there was no statistical analyses offered. Hence, although data are included for both groups, comparisons between them should be viewed with caution.

Patients were recruited from September 1987 and the study was closed in September 1990. 17/22 patients had multiple metastases and 5/22 patients had a single lesion. 4/5 single lesions were inoperable recurrences of previously resected or irradiated metastases. 6/22 patients had only CNS metastases and the remaining 16 patients had more disseminated disease, although only 10 of these had progressive disease at the time of the study.

From: Chapter 6, Management of specific problems

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Advanced Breast Cancer: Diagnosis and Treatment.
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