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-erythema (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.