Use of Cranberry Extract as Prophylaxis for Prostate Carcinoma Radiotherapy

Kyle Savio, Mercer University College of Pharmacy

In the treatment of prostate cancer, pelvic targeted radiotherapy has been used to kill cancer cells in the prostate and surrounding lymph nodes. Tissue damage to the genitourinary tract, possibly leading to lower urinary tract infections (LUTI), is associated with this type of radiotherapy. [1] It has been reported that 70-95% of all LUTI are caused by Escherichia coli (E. coli). [2] Uropathogenic E. coli can adhere to the cell walls and tissues of the bladder and urinary tract using adhesins on their fimbriae (hair-like extensions on surface). It has been shown that cranberry contains inhibitors of these bacterial adhesins, which aim to inhibit E. coli from latching onto cell walls and colonizing into infections. [3]

Enteric-coated and highly standardized cranberry extract reduces antibiotic and nonsteroidal anti-inflammatory drug use for urinary tract infections during radiotherapy for prostate carcinoma [4]
Design Randomized, open-label, controlled; N= 924
Objective To evaluate prophylactic role of cranberry extract in reducing lower urinary tract infection (LUTI) episodes and urinary discomfort
Study Groups Cranberry extract (n= 489); untreated (n= 435)
Methods Included were patients with prostatic adenocarcinoma being treated with radical, post-surgery, or personalized radiation therapy. Exclusion criteria included: patients with history of pelvic external beam radiation therapy (EBRT), previous pelvic malignancies, and renal failure. The Karnofsky score was used to assess patient quality of life on a scale of 0-100 (0-miserable, 100-optimal).

The treatment group was administered 200 mg of enteric-coated, highly standardized cranberry extract. All patients underwent weekly examination to assess urinary symptoms, nonsteroidal anti-inflammatory drug (NSAID), and antibiotic use. Urine cultures were performed at week 3 and at week 6, with extra cultures performed on request in cases of severe dysuria.

Duration 6-7 weeks
Primary Outcome Measure Incidence of LUTI
Secondary Outcome Measure Incidence of LUTI recurrence, days of treatment with antibiotics, number of subjects treated with NSAIDs, episodes of dysuria
Baseline Characteristics
  Treated Untreated
Mean age, years (SD) 69.63 (7.16) 70.15 (6.45)
Karnofsky score (SD) 91.43 (4.99) 92.59 (5.71)
Irradiation
  Radical, % 54.60 59.08
  Postsurgical, % 43.35 39.77
  Personalized, % 2.05 1.15
  *Prostate, % 50.10 67.82
  *Prostate + Lymph nodes, % 49.90 32.18
Surgery, % 54.60 48.74

*p< 0.01 between groups

 

Results for Primary Outcomes
  Treated, n (%) Untreated, n (%) p-value
Escherichia coli 21 (39.6) 54 (50.5) 0.002
Enterococcus faecalis 16 (30.2) 21 (19.6) 0.04
Total 53 (100) 107 (100) 0.0001

 

Results for Secondary Outcomes
  Treated Untreated p-value
Cumulative antibiotic treatment, days 285 585 0.001
NSAID use, n 113 201 0.001
No dysuria, n 307 159 0.001
LUTI recurrences, n (%) 4 (0.82) 10 (2.3) 0.04

 

Adverse Events Common Adverse Events: N/A
Serious Adverse Events: N/A
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions The prophylactic use of cranberry showed reductions of antibiotic treatment by ~50%, prevented LUTI episodes, and reduced urinary discomfort and frequency.

 

The treatment group included more patients receiving radiation therapy for prostate and lymph nodes, a noted risk factor for LUTI. This may have caused the treatment group to experience more incidences of LUTI and negatively skew the efficacy of cranberry. In addition to Escherichia coli, cranberry was effective in reducing LUTI caused by Enterococcus faecalis. This indicates a potential for studies to differentiate mechanisms of cranberry extract against gram negative and positive bacteria. Cranberry extract provided benefit with no associated adverse events as well as reducing use of NSAID and antibiotics. Low risk prophylactic therapy can be encouraging for patients with cancer, as numerous therapies are known to cause further complications and adverse events.

 

References

[1] National Comprehensive Cancer Network (NCCN) Guidelines for Patients, Prostate Cancer. National Comprehensive Cancer Network. Version 1. 2016.

[2] Behzadi P, Behzadi E, et al. A survey on urinary tract infections associated with the three most common uropathogenic bacteria. Maedica (Buchar). 2010;5(2):111-5.

[3] Ofek I, Goldhar J, et al. Anti-Escherichia coli adhesin activity of cranberry and blueberry juices. N Engl J Med. 1991;324(22):1599.

[4] Bonetta A, Roviello G, Generali D, et al. Enteric-coated and highly standardized cranberry extract reduces antibiotic and nonsteroidal anti-inflammatory drug use for urinary tract infections during radiotherapy for prostate carcinoma. Res Rep Urol. 2017;9:65-69.

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