Is There a Benefit From Lycopene Supplementation in Men With Prostate Cancer? A Systematic Review

F Haseen; MM Cantwell; JM O'Sullivan; LJ Murray

Disclosures

Prostate Cancer Prostatic Dis. 2009;12(4):316–324 

In This Article

Results

Application of the search strategy yielded 133 reports in MEDLINE, 85 in EMBASE, 135 in Web of Science, 22 in CINAHL Plus, 2 in AMED and 15 in CENTRAL. Removal of duplicates resulted in 269 potentially eligible studies. A flowchart shows the exclusion factors and numbers of articles for each factor (Figure 1). Of the 269 references screened, 11 met the inclusion criteria, but two RCTs[27,28] and one before-after study[29] were excluded as they were repeat publications.

Figure 1.

Flowchart of study selection process.

In all, eight intervention studies were identified and evaluated. Five had no control (before-after design)[30–34] and one had an unmatched control group;[35] it was unclear how the control group was selected. The remaining two studies were RCTs, but one[36] was very small and included 35 patients with data available for analysis from only 26 patients. The other study,[37] an RCT of lycopene supplementation for 2 years in addition to orchidectomy, was also small (54 patients), and neither RCT achieved a Jadad score of 3 or higher. Table 1 summarizes the type and duration of intervention and the outcome measures in these studies. Studies tested lycopene with variations in dose (4–120 mg per day), duration (3 weeks to 2 years) and composition (tablet, capsule, tomato sauce, tomato paste/juice), as well as with diverse patient populations (for example, with localized or metastatic disease, hormone refractory, recurrence). Meta-analysis was not possible as the studies were highly heterogeneous.

Change in PSA Levels

All studies reported on the change in serum PSA level as a measure of disease progression, although PSA changes were reported in different ways, for example, normalization of PSA (to <4 ng ml−1), proportion of patients with a 50% reduction in PSA, differences in mean PSA levels between intervention and control arms, percentage change in PSA after treatment, and so on (Table 2). Three before-after studies reported a significant reduction in PSA after intervention,[30–32] whereas two did not see any change in PSA.[33,34] In the study by Kim et al.,[35] 32 prostate cancer patients awaiting prostatectomy and treated with lycopene supplementation (tomato sauce 30 mg per day) for 3 weeks were compared with 34 controls also undergoing prostatectomy for prostate cancer. Mean PSA decreased after treatment from 10.9 to 8.7 ng ml−1 (P<0.001) and was lower in the treatment group than in the control group (13.8 ng ml−1). There was no significant difference in the percentage change in mean PSA between the intervention and nonintervention arms in the RCT undertaken by Kucuk et al.[36] in which men received lycopene supplementation (30 mg per day) by capsule for a short period (3 weeks) before radical prostatectomy. In the larger RCT involving men with metastatic prostate cancer treated by orchidectomy,[37] lycopene supplementation (4 mg per day for 2 years) was associated with a lower mean PSA after treatment (3.0 ng ml−1 in the intervention and 9.0 ng ml−1 in the nonintervention arms, P<0.001). Furthermore, 11 (40%) patients in the orchidectomy arm and 21 (78%) in the orchidectomy and lycopene group had a complete PSA response (reduced to <4 ng ml−1), P<0.05.

Cancer-related Symptoms

Lycopene was shown to be potentially effective in ameliorating cancer-related symptoms (pain, urinary tract symptoms) in one RCT[37] and in one before-after study.[30] In the before-after design trial by Ansari and Gupta,[30] bone pain significantly improved after administration of 10 mg per day lycopene for 3 months. Moreover, 62% of patients managed to cut down their dose of analgesics. Analgesic use for body pain was also less evident in the supplemented group as opposed to the control group in RCT as well (15 vs 25%).[37]

A significant improvement in urinary peak flow rate was observed in the lycopene-supplemented group compared with the control arm in the RCT. After intervention, the urinary peak flow rate was 12.2 ml s−1 in the lycopene group compared with 11.0 ml s−1 in the control group (P<0.04), although they were comparable at baseline. Moreover, a subjective improvement in voiding symptoms (frequency, urgency and dysuria) was reported more in the supplemented group (80 vs 50%).[37] Before supplementation, 90% patients had associated lower urinary tract symptoms (LUTSs) and after supplementation, LUTS improved along with urinary flow rate in 61% of patients in the before-after study.[30]

Evidence of Progression from Bone Scans

In their RCT, Ansari and Gupta[37] examined disease progression using bone scans. A significantly higher proportion of patients had a complete response (normal bone scan) in the intervention group compared with control group at the end of the trial (25 vs 15%, P<0.02). Moreover, progressive disease (development of any new 'hot spot' on bone scans) was significantly less common in the intervention group (P<0.02). Bone pain and use of analgesics showed a direct relationship with bone scan response, and patients with a complete response required no analgesic. A 25% reduction in overall metastatic lesions was also reported in the before-after study.[30]

Effect on Survival

Survival is, of course, one of the most important measures of prostate cancer progression. Three studies reported survival rates,[30,33,37] although none provided power calculations to show that they had sufficient power to detect a difference in these rates. Longer overall survival was observed in the supplemented group than in the control group in the trial by Ansari and Gupta;[37] after a mean follow-up period of 25.5 months, 19 patients (35%) died, 12 (22%) in the control group and 7 (13%) in the supplemented group (P<0.001). Follow-up in this study was brief, hence no information was provided on long-term survival.

Toxicity/Side Effects

Side effects were examined in the four before-after studies[30,31,33,34] and in the two RCTs.[36,37] None of the studies reported severe toxicity or intolerance related to lycopene supplementation according to National Cancer Institute Common Toxicity Criteria.[38] One patient from the study undertaken by Clark et al.[34] discontinued lycopene because of grade 2 diarrhea (4–6 stools per day or nocturnal stools), and side effects, plausibly due to lycopene supplementation, were observed in the study by Jatoi et al.[33] and included diarrhea, nausea, abdominal distension, flatulence, vomiting, anorexia and dyspepsia, although all were mild/moderate (grade 1 or 2, National Cancer Institute Common Toxicity Criteria).[38] As these studies did not include a control group, these effects cannot be definitely ascribed to lycopene use. In the RCTs, no adverse effects or reactions were reported during and after supplementation in the intervention arm.

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