Zoladex (goserelin acetate implant) - 5 indications

Scroll down for more information on each indication:

• the palliative treatment of advanced carcinoma of the prostate, approved 1991
• the management of endometriosis, approved 1993
• use in the palliative treatment of advanced breast cancer in pre- and perimenopausal women, approved 1995
• use as an endometrial-thinning agent prior to endometrial ablation for dysfunctional uterine bleeding, approved 1997
• use in combination with flutamide for the management of locally confined carcinoma of the prostate, approved 1998

General Information

Zoladex (goserelin acetate implant) is a Gonadotropin Releasing Hormone (GnRH) agonist.

Zoladex is specifically indicated for:  

• the palliative treatment of advanced carcinoma of the prostate
• the management of endometriosis
• use in the palliative treatment of advanced breast cancer in pre- and perimenopausal women
• use as an endometrial-thinning agent prior to endometrial ablation for dysfunctional uterine bleeding
• use in combination with flutamide for the management of locally confined carcinoma of the prostate

Zoladex is supplied as a 3.6 mg implant and a 10.8 mg implant (for prostate cancer indications only).

Dosing and Treatment Duration:

The 10.8 mg should be implanted subcutaneously every 12 weeks into the anterior abdominal wall below the navel line using an aseptic technique under the supervision of a physician.

The 3.6 mg implant should be administered subcutaneously every 28 days into the anterior abdominal wall below the navel line using an aseptic technique under the supervision of a physician.

Scroll down for the duration of treatment for each indication.

Mechanism of Action

Zoladex (goserelin acetate implant) is a Gonadotropin Releasing Hormone (GnRH) agonist. Zoladex acts as an inhibitor of pituitary gonadotropin secretion when administered in the biodegradable formulation. In animal and in vitro studies, administration of goserelin resulted in the regression or inhibition of growth of the hormonally sensitive dimethylbenzanthracene (DMBA)-induced rat mammary tumor and Dunning R3327 prostate tumor.

Side Effects

Adverse effects associated with the use of Zoladex in men may include, but are not limited to, the following:

• hot flashes
• sexual dysfunction
• decreased erections
• lower urinary tract symptoms

Adverse effects associated with the use of Zoladex in women may include, but are not limited to, the following:

• hot flushes
• headache
• sweating
• acne
• emotional lability
• depression
• decreased libido
• vaginitis
• breast atrophy
• seborrhea
• peripheral edema

Indication 1 - the palliative treatment of advanced carcinoma of the prostate

approved 1991

Treatment Duration

For the management of advanced prostate cancer, Zoladex is intended for long-term administration unless clinically inappropriate.

Clinical Trial Results

In controlled studies of patients with advanced prostatic cancer comparing Zoladex to orchiectomy, the long-term endocrine responses and objective responses were similar between the two treatment arms. Additionally, duration of survival was similar between the two treatment arms in a comparative trial.

Indication 2 - the management of endometriosis

approved 1993

Treatment Duration

For the management of endometriosis, the recommended duration of administration is 6 months

Clinical Trial Results

In controlled clinical studies using the 3.6 mg formulation every 28 days for 6 months, Zoladex was shown to be as effective as danazol therapy in relieving clinical symptoms (dysmenorrhea, dyspareunia and pelvic pain) and signs (pelvic tenderness, pelvic induration) of endometriosis and decreasing the size of endometrial lesions as determined by laparoscopy. In one study comparing Zoladex with danazol (800 mg/day), 63% of Zoladex-treated patients and 42% of danazol-treated patients had a greater than or equal to 50% reduction in the extent of endometrial lesions. In the second study comparing Zoladex with danazol (600 mg/day), 62% of Zoladex-treated and 51% of danazol-treated patients had a greater than or equal to 50% reduction in the extent of endometrial lesions. In these two studies, Zoladex led to amenorrhea in 92% and 80%, respectively, of all treated women within 8 weeks after initial administration. Menses usually resumed within 8 weeks following completion of therapy. Within 4 weeks following initial administration, clinical symptoms were significantly reduced, and at the end of treatment were, on average, reduced by approximately 84%.

Indication 3 - use in the palliative treatment of advanced breast cancer in pre- and perimenopausal women

approved 1995

Treatment Duration

For the management of advanced breast cancer, Zoladex is intended for long-term administration unless clinically inappropriate.

Clinical Trial Results

The Southwest Oncology Group conducted a prospective, randomized clinical trial (SWOG-8692 [INT-0075]) in premenopausal women with advanced estrogen receptor positive or progesterone receptor positive breast cancer which compared Zoladex with oophorectomy. On the basis of interim data from 124 women, the best objective response (CR+PR) for the Zoladex group is 22% versus 12% for the oophorectomy group. The median time to treatment failure is 6.7 months for patients treated with Zoladex and 5.5 months for patients treated with oophorectomy. The median survival time for the Zoladex arm is 33.2 months and for the oophorectomy arm is 33.6 months. Subjective responses based on measures of pain control and performance status were observed with both treatments; 48% of the women in the Zoladex treatment group and 50% in the oophorectomy group had subjective responses. In the clinical trial (SWOG-8692 [INT–0075]), the mean post treatment estradiol level was reported as 17.8 pg/mL. During the conduct of the clinical trial, women whose estradiol levels were not reduced to the postmenopausal range, received two Zoladex depots, thus, increasing the dose of Zoladex from 3.6 mg to 7.2 mg.

Indication 4 - use as an endometrial-thinning agent prior to endometrial ablation for dysfunctional uterine bleeding

approved 1997

Treatment Duration

For use as an endometrial-thinning agent prior to endometrial ablation, the dosing recommendation is one or two depots (with each depot given four weeks apart). When one depot is administered, surgery should be performed at four weeks. When two depots are administered, surgery should be performed within two to four weeks following administration of the second depot.

Clinical Trial Results

Two trials were conducted with Zoladex prior to endometrial ablation for dysfunctional uterine bleeding.

Trial 0022, was a double-blind, prospective, randomized, parallel-group multicenter trial conducted in 358 premenopausal women with dysfunctional uterine bleeding. Eligible patients were randomized to receive either two depots of Zoladex 3.6 mg (n=180) or two placebo injections (n=178) administered four weeks apart. One hundred seventy five patients in each group underwent endometrial ablation using either diathermy loop alone or in combination with rollerball approximately 2 weeks after the second injection. Endometrial thickness was assessed immediately before surgery using a transvaginal ultrasonic probe. The incidence of amenorrhea was compared between the Zoladex and placebo groups at 24 weeks after endometrial ablation. The median endometrial thickness before surgery was significantly less in the Zoladex treatment group (1.50 mm) compared to the placebo group (3.55 mm). Six months after surgery, 40% of patients (70/175) treated with Zoladex in Trial 0022 reported amenorrhea as compared with 26% who had received placebo injections (44/171), a difference that was statistically significant.

Trial 0003, was a single center, open-label, randomized trial in premenopausal women with dysfunctional uterine bleeding. The trial allowed for a comparison of 1 depot of Zoladex and 2 depots of Zoladex administered 4 weeks apart with ablation using Nd: YAG laser occurring 4 weeks after Zoladex administration. Forty patients were randomized into each of the Zoladex treatment groups. The median endometrial thickness before surgery was significantly less in the group treated with two depots (0.5 mm) compared to the group treated with one depot (1 mm). No difference in the incidence of amenorrhea was found at 24 weeks (24% in both groups). Of the 74 patients that completed the trial, 53% reported hypomenorrhea and 20% reported normal menses six months after surgery.

Indication 5 - use in combination with flutamide for the management of locally confined carcinoma of the prostate

approved 1998

Treatment Duration

Stage B2-C Prostatic Carcinoma: When Zoladex is given in combination with radiotherapy and flutamide for patients with Stage T2b-T4 (Stage B2-C) prostatic carcinoma, treatment should be started 8 weeks prior to initiating radiotherapy and should continue during radiation therapy. A treatment regimen using a Zoladex 3.6 mg depot 8 weeks before radiotherapy, followed in 28 days by the Zoladex 10.8 mg depot, can be administered. Alternatively, four injections of 3.6 mg depot can be administered at 28-day intervals, two depots preceding and two during radiotherapy.

Clinical Trial Results

The effects of hormonal treatment combined with radiation were studied in 466 patients (231 Zoladex + flutamide + radiation, 235 radiation alone) with bulky primary tumors confined to the prostate (stage B2) or extending beyond the capsule (stage C), with or without pelvic node involvement. In this multicentered, controlled trial, administration of Zoladex (3.6 mg depot) and flutamide capsules (250 mg t.i.d.) prior to and during radiation was associated with a significantly lower rate of local failure compared to radiation alone (16% vs 33% at 4 years). The combination therapy also resulted in a trend toward reduction in the incidence of distant metastases (27% vs 36% at 4 years). Median disease-free survival was significantly increased in patients who received complete hormonal therapy combined with radiation as compared to those patients who received radiation alone (4.4 vs 2.6 years). Inclusion of normal PSA level as a criterion for disease-free survival also resulted in significantly increased median disease-free survival in patients receiving the combination therapy (2.7 vs 1.5 years).