[The acute toxicity of the simultaneous radiochemotherapy of rectal carcinoma].
OBJECTIVE
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.


METHODS
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-erythema (16% vs. 41%, p = 0.04) was noted.


CONCLUSIONS
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.
Rödel
C
C
Strahlentherapeutische Klinik, Universität Erlangen-Nürnberg.
Fietkau
R
R
Keilholz
L
L
Grabenbauer
G G
GG
Kessler
H
H
Martus
P
P
Sauer
R
R
D000208:Acute Disease; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D002277:Carcinoma / Q000150:complications* / Q000188:drug therapy / Q000532:radiotherapy; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000150:complications / Q000188:drug therapy / Q000532:radiotherapy; D011182:Postoperative Care / Q000009:adverse effects; D011300:Preoperative Care / Q000009:adverse effects; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000532:radiotherapy; D012189:Retrospective Studies
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil