Toxicity and complications of preoperative chemoradiotherapy for locally advanced rectal cancer.
BACKGROUND
Capecitabine is an attractive radiosensitizer. In this study acute toxicity and surgical complications were evaluated in patients with locally advanced rectal cancer following total mesorectal excision (TME) after preoperative chemoradiotherapy (CRT) with capecitabine.


METHODS
Between 2004 and 2008, consecutive patients with clinical tumour category (cT) 3-4 (with a threatened circumferential resection margin or cT3 within 5 cm of the anal verge) or clinical node category 2 rectal cancer were treated with preoperative CRT (25 × 2 Gy, capecitabine 825 mg/m(2) twice daily, days 1-33). TME followed 6 weeks later. Toxicity was scored according to the Common Terminology Criteria (version 3.0) and Radiation Therapy Oncology Group scoring systems. Treatment-related surgical complications were evaluated for up to 30 days after discharge from hospital using the modified Clavien-Dindo classification.


RESULTS
Some 147 patients were analysed. The mean cumulative dose of capecitabine was 95 per cent and 98·0 per cent of patients received at least 45 Gy. One patient died from sepsis following haematological toxicity. Grade 3-5 toxicity developed in 32 patients (21·8 per cent), especially diarrhoea (10·2 per cent) and radiation dermatitis (11·6 per cent). There were no deaths within 30 days after surgery. Anastomotic leakage and perineal wound complications developed after 13 of 47 low anterior resections and 23 of 62 abdominoperineal resections. Surgical reintervention was required in 30 patients. Twenty-seven patients (19·6 per cent) of 138 patients who had a laparotomy were readmitted within 30 days after initial hospital discharge.


CONCLUSIONS
Preoperative CRT with capecitabine is associated with acceptable acute toxicity, significant surgical morbidity but minimal postoperative mortality.
Department of Gastroenterology and Hepatology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
H A M
HA
Swellengrebel
C A M
CA
Marijnen
V J
VJ
Verwaal
A
A
Vincent
G
G
Heuff
M F
MF
Gerhards
A A W
AA
van Geloven
W F
WF
van Tets
M
M
Verheij
A
A
Cats
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000209:etiology*; D011300:Preoperative Care / Q000379:methods; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects*; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery*
D000964:Antimetabolites, Antineoplastic; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil