Intermittent versus continuous androgen suppression for prostatic cancer

Paulo De Conti; Álvaro N Atallah; Homero O Arruda; Bernardo GO Soares; Regina P El Dib; Timothy J Wilt

doi:10.1002/14651858.CD005009.pub2

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Analysis 1.1

Comparison 1 Intermittent versus continuous androgen suppression (both groups received 200 mg/day of cyproterone acetate), Outcome 1 Secondary Side Effects.

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Analysis 1.2

Comparison 1 Intermittent versus continuous androgen suppression (both groups received 200 mg/day of cyproterone acetate), Outcome 2 Primary Side Effects.

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Analysis 1.3

Comparison 1 Intermittent versus continuous androgen suppression (both groups received 200 mg/day of cyproterone acetate), Outcome 3 Sexual Impotence.

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Analysis 1.4

Comparison 1 Intermittent versus continuous androgen suppression (both groups received 200 mg/day of cyproterone acetate), Outcome 4 Permanately impotent.

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Analysis 2.1

Comparison 2 Intermittent vs continuous (buserelin 2 monthly depot (6.6 mg); nilutamide first 4 weeks 300 mg od, 150 mg od), Outcome 1 Side Effects.

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Analysis 3.1

Comparison 3 Intermittent versus continuous (flutamide (3 times 250 mg, daily) and goserelin acetate (3.6 mg, monthly)), Outcome 1 Biochemical androgen‐independence of the prostate tumors.

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Analysis 3.2

Comparison 3 Intermittent versus continuous (flutamide (3 times 250 mg, daily) and goserelin acetate (3.6 mg, monthly)), Outcome 2 Side Effects (severe gastrointestinal tract).

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Analysis 3.3

Comparison 3 Intermittent versus continuous (flutamide (3 times 250 mg, daily) and goserelin acetate (3.6 mg, monthly)), Outcome 3 Biochemical Progression Rates/mean time to progression of 3 years (progr. defined as 3 rises after a nadir).

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Comparison 1. Intermittent versus continuous androgen suppression (both groups received 200 mg/day of cyproterone acetate)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Secondary Side Effects Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Gastrointestinal, Gynecomastia and Asthenia	1	43	Risk Ratio (M‐H, Fixed, 95% CI)	0.29 [0.06, 1.32]
2 Primary Side Effects Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 Gastritis with intensive vomiting and inferior members edema	1	43	Risk Ratio (M‐H, Fixed, 95% CI)	0.36 [0.04, 3.67]
3 Sexual Impotence Show forest plot	1	43	Risk Ratio (M‐H, Fixed, 95% CI)	0.73 [0.57, 0.94]

4 Permanately impotent Show forest plot	1	43	Risk Ratio (M‐H, Fixed, 95% CI)	2.19 [0.09, 50.93]

Comparison 1. Intermittent versus continuous androgen suppression (both groups received 200 mg/day of cyproterone acetate)

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Comparison 2. Intermittent vs continuous (buserelin 2 monthly depot (6.6 mg); nilutamide first 4 weeks 300 mg od, 150 mg od)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Side Effects Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Hot Flushes	1	193	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.66, 1.10]
1.2 Visual Disturbances	1	193	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.66, 1.48]
1.3 Nausea	1	193	Risk Ratio (M‐H, Fixed, 95% CI)	0.57 [0.29, 1.14]
1.4 Constipation	1	193	Risk Ratio (M‐H, Fixed, 95% CI)	0.43 [0.19, 1.01]
1.5 Dyspnea	1	193	Risk Ratio (M‐H, Fixed, 95% CI)	0.49 [0.19, 1.26]
1.6 Erectile dysfunction	1	193	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.38, 2.09]
1.7 Depression	1	193	Risk Ratio (M‐H, Fixed, 95% CI)	0.54 [0.21, 1.40]
1.8 Liver enzyme increase	1	193	Risk Ratio (M‐H, Fixed, 95% CI)	1.58 [0.54, 4.67]
1.9 Gynaecomastia	1	193	Risk Ratio (M‐H, Fixed, 95% CI)	0.57 [0.17, 1.87]
1.10 Anemia	1	193	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.22, 2.86]
1.11 Alcohol intolerence	1	193	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.17, 3.23]

Comparison 2. Intermittent vs continuous (buserelin 2 monthly depot (6.6 mg); nilutamide first 4 weeks 300 mg od, 150 mg od)

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Comparison 3. Intermittent versus continuous (flutamide (3 times 250 mg, daily) and goserelin acetate (3.6 mg, monthly))

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Biochemical androgen‐independence of the prostate tumors Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Biochemical androgen‐independence of the prostate tumors ‐ Biopsy Gleason Score 4‐6	1	68	Risk Ratio (M‐H, Fixed, 95% CI)	0.9 [0.63, 1.29]
1.2 Biochemical androgen‐independence of the prostate tumors ‐ Biopsy Gleason Score 7	1	68	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [0.30, 5.20]
1.3 Biochemical androgen‐independence of the prostate tumors ‐ Biopsy Gleason Score 8‐10	1	68	Risk Ratio (M‐H, Fixed, 95% CI)	1.18 [0.53, 2.62]
2 Side Effects (severe gastrointestinal tract) Show forest plot	1	68	Risk Ratio (M‐H, Fixed, 95% CI)	0.47 [0.04, 4.96]

3 Biochemical Progression Rates/mean time to progression of 3 years (progr. defined as 3 rises after a nadir) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 Biopsy Gleason Score < = 6	1	43	Risk Ratio (M‐H, Fixed, 95% CI)	0.21 [0.03, 1.65]
3.2 Biopsy Gleason Score > 6	1	25	Risk Ratio (M‐H, Fixed, 95% CI)	0.10 [0.01, 0.67]
3.3 Stage M0	1	33	Risk Ratio (M‐H, Fixed, 95% CI)	0.08 [0.00, 1.28]
3.4 Stage M+	1	20	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.12, 2.14]

Comparison 3. Intermittent versus continuous (flutamide (3 times 250 mg, daily) and goserelin acetate (3.6 mg, monthly))

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