Zusammenfassung
Ziel
Retrospektive Untersuchung von Art und Ausprägung der therapieassoziierten Toxizität der simultanen Radiochemotherapie des Rektumkarzinoms zur Bestimmung wesentlicher Einflußfaktoren ihres Auftretens.
Patienten und Methode
Von 1987 bis 1995 wurde bei 120 Patienten mit Rektumkarzinom (73 Primärtumoren. 47 Rezidivtumoren) eine simultane Radiochemotherapie durchgeführt. 56 Patienten wurden präoperativ, 64 Patienten postoperativ behandelt. Die Bestrahlung erfolgte über eine Vier-Felder-Technik mit 6- bis 10-MV-Photonen. Die Einzeldosis betrug 1,8 Gy im Referenzpunkt (Isozentrum, ICRU 50), die Gesamtdosis lag bei 50,4 Gy (Range: 41,4 bis 56 Gy) ±5,4 Gy (Range: 3,6 bis 19,8 Gy) Boost. In der ersten und fünften Bestrahlungswoche erhielten die Patienten an fünf aufeinanderfolgenden Tagen eine Dosis von täglich 1000 mg/m2 5-Fluorouracil (Maximaldosis 1800 mg) als intravenöse Dauerinfusion über 120 Stunden. Die Toxizitätsanalyse erfolgte gemäß (modifizierter) WHO- Kriterien.
Ergebnisse
Grad-4-Akuttoxizität wurde bei nur drei Patienten beobachtet (Leukopenie, Sepsis, Herzrhythmusstörungen). Grad-3-Akuttoxizität trat insbesondere als Diarrhö (33%), perineale Epitheliolysen (37%) und Leukopenie (10%) auf. Bei zusätzlicher Bestrahlung des paraaortalen Lymphabflußgebietes (bis L3) zeigte sich ein signifikanter Anstieg an Grad-3-Diarrhö (68% vs. 25%, p=0,0003) und Grad-3-Leukopenie (18% vs. 8%, p=0,03). Nach abdominoperinealer Exstirpation litten signifikant weniger Patienten unter Grad-3-Diarrhö (8% vs. 47% nach kontinenzerhaltender Operation, p=0,0006), höhergradige Hauttoxizität war bei diesen Patienten dagegen signifikant häufiger (56% vs. 29%, p=0,02). Bei Frauen war im Vergleich zu Männern die Toxizität signifikant höher (Grad-3-Diarrhö: 39% vs. 16%, p=0,04; Grad-2/3-Übelkeit/Erbrechen: 21% vs. 8%, p=0,018; Grad-2/3-Leukopenie: 53% vs. 31%, p=0,02). Bei der präoperativen Radiochemotherapie war die Grad-3-Diarrhö (11% vs. 29%, p=0,03) und Grad-3-Hauttoxizität (16% vs. 41%, p=0,04) signifikant reduziert.
Schlußfolgerung
Wesentliche Einflußfaktoren der Akuttoxizität bei simultaner Radiochemotherapie des Rektumkarzinoms sind Bestrahlungsvolumen, Operationsart. Geschlecht und Therapiesequenz. Ein Monitoring der 5-FU-Clearance (bei Frauen geringer als bei Männern) und eine entsprechende individuelle Anpassung der 5-FU-Dosis könnten zu einer Optimierung der Therapie beitragen. Die Reduzierung der akuten Nebenwirkungen durch die präoperative Radiochemotherapie liefert ein gewichtiges Argument für die neoadjuvante Radiochemotherapie des Rektumkarzinoms.
Abstract
Aim
We retrospectively examined the acute toxicity of (neo-)adjuvant combined treatment for rectal cancer in an attempt to evaluate potential factors that influence the severity of toxic side effects.
Patients and Method
Between 1987 and 1995, 120 patients with rectal cancer (73 patients with primary tumor, 47 with recurrent disease) received chemoradiation for rectal cancer. Fifty-six patients received preoperative chemoradiation, 64 patients were treated postoperatively. Radiation was given by 4-field box technique with 6 to 10 MV-photons. Daily fraction size was 1.8 Gy, total dose 50.4 Gy (range: 41,4 to 56 Gy) ±5.4 Gy (range: 3,6 to 19,8 Gy) local boost in selected cases, specified to the ICRU reference point. During the first and fifth week of radiation 5-FU at a dose of 1000 m2/d for 120 hours was administered by continuous infusion. Toxicity was recorded following (modified) WHO-criteria.
Results
Acute grade 3 toxicity occurred mainly as diarrhea (33%), perineal skin reaction (37%), and leukopenia (10%). Extension of the treatment volume including paraaortic lymph nodes (L3) led to a significant increase of grade 3-diarrhea (68% vs. 25%, p=0.0003) and grade 3-leukopenia (18% vs. 8%, p=0.03). After abdominoperineal resection less patients suffered from grade 3-diarrhea (8% vs. 47% after sphincter preserving procedures, p=0.0006), whereas severe perineal erythema occurred more frequently (56% vs. 29%, p=0.02). Women had significantly more toxic side effects (grade 3-diarrhea: 39% vs. 16% in men, p=0,04; grade 2 to 3-nausea/emesis: 21% vs. 8% in men, p=0.018; grade 2 to 3-leukopenia 53% vs. 31% in men, p=0.02). After preoperative chemoradiation a significant reduction of grade 3-diarrhea (11% vs 29%, p=0.03) and grade 3-crythema (16% vs. 41%, p=0.04) was noted.
Conclusion
Treatment volume, type of surgery, sex and sequence of treatment modalities are the most important factors that influence the severity of toxic side effects. Individual adjustment of 5-FU dosage by monitoring its systemic clearance (which is lower in women) could help to avoid toxic side effects. The reduced acute toxicity of the preoperative approach provides a further argument in favor of the neoadjuvant chemoradiation for rectal cancer.
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Rödel, C., Fietkau, R., Keilholz, L. et al. Akuttoxizität der simultanen Radiochemotherapie des Rektumkarzinoms. Strahlenther. Onkol. 173, 415–421 (1997). https://doi.org/10.1007/BF03038317
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DOI: https://doi.org/10.1007/BF03038317