A J Breugom1, W van Gijn1, E W Muller2, Å Berglund3, C B M van den Broek1, T Fokstuen4, H Gelderblom5, E Kapiteijn5, J W H Leer6, C A M Marijnen2, H Martijn7, E Meershoek-Klein Kranenbarg1, I D Nagtegaal8, L Påhlman9, C J A Punt10, H Putter11, A G H Roodvoets1, H J T Rutten12, W H Steup13, B Glimelius14, C J H van de Velde15. 1. Department of Surgery, Leiden University Medical Centre, Leiden. 2. Department of Internal Medicine, Slingeland Hospital, Doetinchem, The Netherlands. 3. Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala. 4. Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden. 5. Department of Clinical Oncology, Leiden University Medical Centre, Leiden. 6. Department of Radiotherapy, Radboud University Medical Centre, Nijmegen. 7. Department of Radiotherapy, Catharina Hospital, Eindhoven. 8. Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands. 9. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. 10. Department of Medical Oncology, Academic Medical Centre, Amsterdam. 11. Department of Medical Statistics and Bio-informatics, Leiden University Medical Centre, Leiden. 12. Department of Surgery, Catharina Hospital, Eindhoven. 13. Department of Surgery, HAGA Hospital, The Hague, The Netherlands. 14. Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden. 15. Department of Surgery, Leiden University Medical Centre, Leiden c.j.h.van_de_velde@lumc.nl.
Abstract
BACKGROUND: The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated withpreoperative (chemo)radiotherapy and total mesorectal excision (TME). PATIENTS AND METHODS: The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1:1) to observation or adjuvant chemotherapy after preoperative (chemo)radiotherapy and TME. Radiotherapy consisted of 5 × 5 Gy. Chemoradiotherapy consisted of 25 × 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival. RESULTS: Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.39; P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60-1.07; P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39). CONCLUSION: The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual. REGISTRATION NUMBER: Dutch Colorectal Cancer group, CKTO 2003-16, ISRCTN36266738.
RCT Entities:
BACKGROUND: The discussion on the role of adjuvant chemotherapy for rectal cancerpatients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancerpatients treated with preoperative (chemo)radiotherapy and total mesorectal excision (TME). PATIENTS AND METHODS: The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1:1) to observation or adjuvant chemotherapy after preoperative (chemo)radiotherapy and TME. Radiotherapy consisted of 5 × 5 Gy. Chemoradiotherapy consisted of 25 × 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival. RESULTS: Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.39; P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60-1.07; P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39). CONCLUSION: The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual. REGISTRATION NUMBER: Dutch Colorectal Cancer group, CKTO 2003-16, ISRCTN36266738.