A search of the literature did not find strong evidence to support the use of weekly doxorubicin in the treatment of advanced or metastatic breast cancer. The expert reference panel supported publication of the protocol on the basis of the information summarised below. The committee was most strongly influenced by the small prospective randomised study by Gundersen et al. The trial, involving 128 patients, compared weekly doxorubicin and VAC (vincristine, doxorubicin and cyclophosphamide) in patients with advanced breast cancer.r
Between June 1982 and December 1983, 62 patients were randomised to receive doxorubicin 20 mg/week and 66 patients were randomised to receive VAC (vincristine 2 mg, doxorubicin 50 mg/m2 and cyclophosphamide 600 mg/m2 q21 days).r It should be noted that all patients had previously received hormonal treatment, 27% of patients in the doxorubicin group compared with 12% in the VAC group received adjuvant CMF and 1 patient in the doxorubicin group received chemotherapy for advanced disease.
A small study by Richards et al. (n=59) comparing weekly doxorubicin 25 mg/m2 with three weekly doxorubicin 75 mg/m2 showed that although responses and toxicity were similar between treatment arms, there was a siginificant reduction in psychological distress in patients receiving three weekly doxorubicin.r
Source |
Study & Year Published |
Supports Use |
Is the dose and regimen consistent with the protocol? |
Comments |
Phase II trials |
Gundersen et al 1986r |
Yes |
No |
Doxorubicin 20 mg/week |
|
Richards et al 1992r |
Yes |
No |
Doxorubicin 25 mg/m2/week |
Case series |
- |
N/A |
- |
|
Observational studies |
- |
N/A |
- |
|
Guidelines |
Date published/revised |
Supports Use |
Is the dose and regimen consistent with the protocol? |
Comments |
NCCN |
v.1 2012 |
Yes |
Yes |
|
BCCA |
May 2009 |
Yes |
Yes |
|
CCO |
December 2011 |
Yes |
Yes |
Study used doxorubicin 10 to 20 mg/m2 |
Efficacy
There was found to be no significant difference between patients receiving weekly doxorubicin or VAC in relation to response rate, duration of remission or overall survival.r
Outcome r |
Doxorubicin
(n=62) |
VAC
(n=66) |
p-value |
Objective response (%) |
31 |
36 |
0.62 |
Median duration of complete remissions (months) |
11.3 |
8 |
- |
Median duration of partial remissions (months) |
5 |
7 |
- |
Toxicity
Nil or negligible side effects were observed in approximately 40% of patients receiving weekly doxorubicin, while almost all patients in the VAC group experienced some degree of toxicity. Myelosuppression, nausea, vomiting and alopecia were more common in patients receiving VAC compared to those receiving weekly doxorubicin.r
Toxicityr |
Doxorubicin %
(n=62) |
VAC %
(n=66) |
p-value |
None |
40 |
2 |
< 0.001 |
Nausea |
34 |
85 |
< 0.005 |
Vomiting |
6 |
65 |
< 0.001 |
Alopecia |
8 |
79 |
< 0.001 |
Depression |
10 |
20 |
0.26 |
Neuropathy |
0 |
16 |
0.005 |