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Effect of a Prostaglandin – Given Rectally for Prevention of Radiation-Induced Acute Proctitis – on Late Rectal Toxicity

Results of a Phase III Randomized, Placebo-Controlled, Double-Blind Study

Effekt eines Prostaglandins – rektal gegeben zur Prävention von radiotherapieinduzierter akuter Proktitis – auf die späte rektale Toxizität. Ergebnisse einer randomisierten, plazebokontrollierten, doppelblinden Phase-III-Studie

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Background and Purpose:

To assess the late effect of a prostaglandin, given rectally during irradiation, on late rectal toxicity. In the acute treatment setting no significant differences in reducing the incidence of acute proctitis symptoms in patients receiving misoprostol, however, significantly more rectal bleeding had been reported.

Patients and Methods:

A total of 100 patients who had undergone radiotherapy for prostate cancer had been entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. The toxicity was evaluated yearly after cessation of irradiation by the RTOG/LENT-SOMA scale.

Results:

The median follow-up was 50 months. 20 patients suffered from grade 1, four patients from grade 2 as well, and three patients only from grade 2 toxicity. Frequency, bleeding and urgency were the most commonly reported symptoms. In keeping with other studies and clinical experience, the symptoms peaked within the first 2 years with a median for grade 1 of 13 months and for grade 2 of 15 months. The presence of acute toxicity grade 2 showed a correlation with the development of any late toxicity (p = 0.03). Any acute rectal bleeding was significant correlated with any late rectal bleeding (p = 0.017).

Conclusion:

Misoprostol given as once-daily suppository for prevention of acute radiation-induced proctitis does neither influence the incidence and severity of radiation-induced acute nor late rectal toxicity. Misoprostol has no negative impact on the incidence and severity of late rectal bleeding, in contrast to acute rectal bleeding. The routine clinical use of misoprostol suppositories cannot be recommended.

Hintergrund und Ziel:

Diese Untersuchung wurde durchgeführt, um einen potentiellen Einfluss von zur Prophylaxe der akuten Proktitis rektal gegebenem Misoprostol auf radiogene rektale Spätreaktionen zu evaluieren.

Patienten und Methodik:

100 Patienten, die mit Radiotherapie bei Prostatakarzinom behandelt wurden, wurden in diese randomisierte, plazebokontrollierte, doppelblinde Phase-III-Studie mit Misoprostol- bzw. Plazebozäpfchen eingeschlossen. Die Toxizität wurde jährlich anhand der RTOG- und LENT-SOMA-Skalen erhoben.

Ergebnisse:

Der mediane Nachbeobachtungszeitraum betrug 50 Monate. Bei 20 Patienten trat eine Grad-1-, bei vier ebenfalls eine Grad-2- und bei drei Patienten nur eine Grad-2-Toxizität auf. Frequenz, Blutung und Stuhldrang waren die häufigsten Symptome. Vergleichbar mit anderen Studien und klinischer Erfahrung, traten die Symptome am häufigsten innerhalb der ersten 2 Jahre mit einer medianen Zeit von 13 Monaten für Grad-1- und 15 Monaten für Grad-2-Proktitis auf. Das Vorhandensein akuter Grad-2-Toxizität zeigte eine Korrelation mit der Entwicklung von später Toxizität (p = 0,03). Akute Blutung war signifikant korreliert mit später Blutung (p = 0,017).

Schlussfolgerung:

Misoprostol, einmal täglich als Zäpfchen zur Prävention der akuten radiotherapieinduzierten Proktitis gegeben, beeinflusst weder die Inzidenz und Schwere der radiotherapieinduzierten akuten noch der späten rektalen Toxizität. Misoprostol hat keinen negativen Einfluss auf die Häufigkeit und Schwere von später rektaler Blutung im Gegensatz zu akuter Blutung. Der Routineeinsatz von Misoprostolzäpfchen kann nicht empfohlen werden.

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Authors and Affiliations

  1. Department of Radiotherapy and Radiooncology, University of Göttingen, Göttingen, Germany

    Tereza Kertesz, Markus K. A. Herrmann, Hans Christiansen, Robert M. Hermann, Clemens F. Hess &  Andrea Hille

  2. Department of Medical Statistics, University of Göttingen, Göttingen, Germany

    Antonia Zapf

  3. Department of Radiotherapy and Radiooncology, University of Brest, Brest, France

    Olivier Pradier

  4. Department of Radiotherapy and Radiooncology, University of Mainz, Mainz, Germany

    Heinz Schmidberger

  5. Klinik für Strahlentherapie, Universität Göttingen, Robert-Koch-Straße 40, 37075, Göttingen, Germany

    Andrea Hille

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  1. Tereza Kertesz
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Kertesz, T., Herrmann, M.K.A., Zapf, A. et al. Effect of a Prostaglandin – Given Rectally for Prevention of Radiation-Induced Acute Proctitis – on Late Rectal Toxicity. Strahlenther Onkol 185, 596–602 (2009). https://doi.org/10.1007/s00066-009-1978-8

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  • DOI: https://doi.org/10.1007/s00066-009-1978-8

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