Does prophylactic treatment with proteolytic enzymes reduce acute toxicity of adjuvant pelvic irradiation? Results of a double-blind randomized trial.
OBJECTIVE
Does prophylactic treatment with proteolytic enzymes reduce acute toxicity of adjuvant pelvic radiotherapy?


METHODS
Fifty-six patients with an indication for adjuvant pelvic irradiation after curative surgery were double-blind randomized. All patients took 3 x 4 capsules study medication daily during radiotherapy. Twenty-eight patients in the enzyme group (EG) received capsules containing papain, trypsin and chymotrypsin, 28 in the placebo group (PG) received placebo capsules. All patients were irradiated with 5 x 1.8 Gy weekly to 50.4 Gy using four-field-box technique after CT-based planning. Primary objective was the grade of diarrhea, nausea, vomiting, fatigue and epitheliolysis during radiotherapy. Secondary objectives were the number of supportive medications and treatment interruptions due to acute toxicity.


RESULTS
None/mild diarrhea: 43% EG, 64% PG. Moderate/severe diarrhea: 57% EG, 36% PG (P = 0.11). Mean duration: 11 days in EG, 10 days in PG. None/mild nausea: 93% EG, 93% PG. Moderate/severe nausea: 7% EG, 7% PG. None/mild vomiting: 100% EG, 97% PG. None/mild fatigue: 82% EG, 93% PG. Moderate/severe fatigue: 18% EG, 7% PG (P = 0.23). None/mild epitheliolysis: 75% EG, 93% PG. Moderate/severe epitheliolysis: 25% EG, 7% PG (P = 0.16). Treatment interruption (mean days): 2.44 in EG, 1.46 in PG. Number of supportive medication: 29 in EG, 19 in PG.


CONCLUSIONS
The prophylactic use of proteolytic enzymes does not reduce acute toxicities, treatment interruptions and number of supportive medication and therefore does not improve tolerance of adjuvant pelvic radiotherapy.
Martin
Thomas
T
Strahlenklinik, Klinikum Offenbach, Starkenburgring 66, 63069 Offenbach am Main, Germany.
Uhder
Kerstin
K
Kurek
Ralf
R
Roeddiger
Sandra
S
Schneider
Lida
L
Vogt
Hans-Georg
HG
Heyd
Reinhard
R
Zamboglou
Nikolaos
N
D002918:Chymotrypsin; D003131:Combined Modality Therapy; D003967:Diarrhea / Q000517:prevention & control; D004311:Double-Blind Method; D004338:Drug Combinations; D005221:Fatigue / Q000517:prevention & control; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000517:prevention & control; D010184:Pancreatic Extracts / Q000627:therapeutic use*; D010206:Papain / Q000627:therapeutic use*; D010386:Pelvic Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D010447:Peptide Hydrolases / Q000627:therapeutic use*; D011832:Radiation Injuries / Q000517:prevention & control*; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012871:Skin Diseases / Q000517:prevention & control; D013949:Thymus Extracts / Q000627:therapeutic use*; D016896:Treatment Outcome; D014357:Trypsin; D014839:Vomiting / Q000517:prevention & control
D004338:Drug Combinations; D010184:Pancreatic Extracts; D013949:Thymus Extracts; C009685:chymotrypsin, papain, trypsin drug combination; D010447:Peptide Hydrolases; D002918:Chymotrypsin; D014357:Trypsin; D010206:Papain