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Famotidine as a radioprotector for rectal mucosa in prostate cancer patients treated with radiotherapy

Phase I/II randomized placebo-controlled trial

Famotidin als Schutz der Enddarmschleimhaut vor Strahlenbelastung während der Strahlentherapie von Prostatakarzinompatienten

Randomisierte plazebokontrollierte Phase-I/II-Studie

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Abstract

Background and purpose

Acute bowel toxicity significantly affects the quality of life of patients treated with pelvic radiotherapy. This study was performed to assess whether pretreatment with famotidine can reduce acute radiation toxicities in patients undergoing radiotherapy for prostate cancer.

Patients and methods

Between April 2012 and February 2013, 36 patients undergoing radiotherapy for prostate cancer were enrolled to receive either placebo or famotidine. The patients received external-beam radiotherapy up to 70 Gy at daily fractions of 1.8–2 Gy (5 days/week). Oral famotidine 40 mg (80 mg/day) or placebo was administered twice daily (4 and 3 h prior to each radiotherapy fraction). Bowel and bladder acute toxicities were evaluated weekly during radiotherapy and once thereafter according to RTOG grading criteria.

Results

Famotidine was well tolerated. No grade III or higher acute toxicities were noted in the two groups. Grade II rectal toxicity developed significantly more often in patients receiving placebo than in patients receiving famotidine (10/18 vs. 2/16, p = 0.009). Moreover, no rectal bleeding occurred in the famotidine group, while 5 patients in the placebo group experienced rectal bleeding during treatment (p = 0.046). The duration of rectal toxicity in the radiotherapy course was also reduced in the famotidine group (15.7 vs. 25.2 days, p = 0.027). No significant difference between the two groups was observed in terms of urinary toxicity.

Conclusion

We demonstrated for the first time that famotidine significantly reduces radiation-induced injury on rectal mucosa representing a suitable radioprotector for patients treated with radiotherapy for prostate cancer.

Zusammenfassung

Hintergrund und Ziel

Die akute Darmtoxizität in der Strahlentherapie beeinflusst maßgeblich die Lebensqualität der Patienten. Die Studie dient zur Klärung des Famotidineinsatzes in der Vorbehandlung von Prostatakarzinompatienten zur Reduktion der Strahlenbelastung während der Strahlentherapie.

Patienten und Methoden

Von April 2012 bis Februar 2013 wurden 36 Prostatakarzinompatienten in eine Studiengruppe mit Famotidingabe bzw. in eine Vergleichsgruppe rekrutiert. Die perkutanen Strahlendosis von bis zu 70 Gy wurde auf täglich 1,8–2 Gy (5 Tage/Woche) fraktioniert. Famotidin (40 mg/Dosis) oder ein Placebomedikament wurde täglich im Abstand von 4 bzw. 3 h zu jeder Strahlungseinheit verabreicht. Das entspricht 2 täglichen Dosen von je 40 mg (Gesamtdosis: 80 mg/Tag) bzw. 2 Placebogaben. Die Darm- und Blasentoxizitätswerte wurden wöchentlich während und im Anschluss an die Bestrahlung anhand der Radiation-therapy-oncology-group(RTOG)-Kriterien ausgewertet.

Ergebnisse

Famotidin war gut verträglich. In beiden Gruppen wurde kein Toxizitätswert unter 3 registriert. In der Stufe II der Enddarmtoxizität wurden eindeutig höhere Werte in der Plazebogruppe im Vergleich zur Famotidingruppe (10/18 vs. 2/16, p = 0,009) verzeichnet. Zudem traten in der Famotidin­gruppe keine Blutung im Enddarm auf, während solche Blutungen bei 5 Patienten aus der Plazebogruppe während der Behandlung beobachtet wurden (p = 0,046). Die Dauer der Enddarmtoxizität war im Strahlentherapiekurs in der Famotidingruppe ebenfalls reduziert (15,7 vs. 25,2 Tage, p = 0,027). Bezüglich der Harnblasentoxizitätswerte wurde kein signifikanter Unterschied zwischen den beiden Gruppen beobachtet.

Schlussfolgerung

Zum ersten Mal wurde eine signifikante Reduktion der strahleninduzierten Enddarmschleimhautbelastung durch Famotidin als geeigneter Schutz vor Bestrahlung bei Prostatakarzinompatienten gezeigt.

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Acknowledgments

This study was supported by Shahid Beheshti University of Medical Sciences, Tehran, Iran. We would like to thank Dr SMR Aghamiri and AH Heidari for their collaboration. We also thank the staff of the radiotherapy departments of Pars and Shohada-e-Tajrish Hospitals.

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Conflict of interest

A. Razzaghdoust, H. Mozdarani, and B. Mofid state that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Radiology, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    A. Razzaghdoust

  2. Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    H. Mozdarani

  3. Department of Radiotherapy, Shohada-e- Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    B. Mofid

Authors
  1. A. Razzaghdoust
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  2. H. Mozdarani
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  3. B. Mofid
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Correspondence to H. Mozdarani.

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Razzaghdoust, A., Mozdarani, H. & Mofid, B. Famotidine as a radioprotector for rectal mucosa in prostate cancer patients treated with radiotherapy. Strahlenther Onkol 190, 739–744 (2014). https://doi.org/10.1007/s00066-014-0602-8

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  • DOI: https://doi.org/10.1007/s00066-014-0602-8

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