Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II)

Background A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC. Methods This multicentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy (three 3-week cycles of CAPOX (capecitabine, oxaliplatin), four 2-week cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) or FOLFORI (5-fluorouracil, leucovorin, irinotecan)) followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged using MRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 × 2.0 Gy or 28 × 1.8 Gy in radiotherapy-naive patients, and 15 × 2.0 Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825 mg/m2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-term oncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life. Discussion This trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections

A small mammal model of tumour implantation, dissemination and growth factor expression after partial hepatectomy

Background: Surgical resection remains the most effective therapy for metastatic colorectal cancer confined to the liver, although the extrahepatic recurrence rate is high. Aim of the study: To develop a mammal model in order to investigate by which mechanisms liver surgery affects distant tumour recurrence. Methods: In this animal study the effect of partial hepatectomy (phX) on the development of tumour noduli in the lungs was evaluated. CC531 rat colon carcinoma cells were inoculated i.v. 24 h before, during or 24 h after surgery. Rat serum was obtained at different time-points after phX and added to in vitro CC531 cell cultures. Finally, phX was compared with an ileum resection (ilX). Results: phX leads to increased tumour noduli in the lungs, compared to Sham operation (p = 0.002), but only when performed directly before the injection of tumour cells and not when performed 24 h before or after the inoculation. Comparable results were obtained for ilX. No growth stimulation of tumour cells after incubation with rat serum, obtained at different time-points after phX, could be detected in vitro. Conclusion: Not only phX, but also surgery, in general promotes distant tumour recurrence exerting the effect during the early phase of tumour cell adhesion and not during tumour outgrowth. (C) 2007 Elsevier Ltd. All rights reserved