The evidence supporting this protocol is provided by a multicentre, randomised trial involving 136 patients comparing goserelin with surgical ovariectomy in premenopausal patients with receptor-positive metastatic breast cancer.r
Between August 1987 and July 1995, 69 patients were randomised to receive goserelin 3.6 mg SC depot every 4 weeks and 67 patients were randomised to undergo ovariectomy. For patients receiving goserelin, the dose could be increased to goserelin 7.2 mg every 4 weeks if after 8 weeks the patient had not become amenorrhoeic. Patients in the ovariectomy arm were offered crossover if there was clear progression at least 6 weeks following surgery.r
The primary objectives were failure-free survival (FFS) and overall survival (OS) and the secondary objectives were objective response rates and toxicity. The study was designed as an equivalence trial and because of slow accrual, it was terminated early, resulting in a final power of 60%.r
Efficacy
FFS and OS were similar for goserelin and ovariectomy. The goserelin to ovariectomy death hazards ratio was 0.80 and the associated 95% confidence interval (CI) was 0.53 to 1.20. The test of 50% improvement in survival due to ovariectomy was rejected at P =0.006. Goserelin lowered serum oestradiol to postmenopausal levelsr.
Kaplan-Meier analysis of (A) Failure-free survival (FFS) and (B) Overall survival (OS)r
(A)
© Journal of Clinical Oncology 1998
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(B)
© Journal of Clinical Oncology 1998
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Toxicity
Hot flashes (75% vs 46%) and tumour flare (16% vs 3%) were more common with goserelin.r
Toxicityr
Grade 1 and 2 (> 5% patients) |
Goserelin
(n=68) % |
Ovariectomy
(n=65) % |
Hot flashes |
66 |
43 |
Tumour flare |
16 |
3 |
Bone pain |
6 |
3 |
Leukopenia |
9 |
2 |
Nausea |
10 |
6 |
Oedema |
7 |
0 |
Malaise |
6 |
2 |
Sweats |
6 |
3 |
Vomiting |
3 |
6 |