Chemotherapy used during chemoradiation for advanced rectal cancer is adequate for radiosensitisation but suboptimal for systemic control. The aim of this study was to assess tolerability and local/systemic control of a new regimen interdigitating intensive chemotherapy, bevacizumab (Bev) and radical radiotherapy.
This was a single arm prospective trial for patients presenting with untreated synchronous symptomatic primary and metastatic rectal cancer. The treatment regimen was 12 weeks long. FOLFOX chemotherapy comprised oxaliplatin (Ox) 100 mg/m2 day 1, leucovorin 200 mg/m2 day 1, 5-FU 400 mg/m2 bolus day 1, then continuous infusion 2.4 g/m2 over 46 hours was given in week 1, 6, and 11. Pelvic radiotherapy (25.2 Gy in 3 weeks in 1.8 Gy/fr with concurrent Ox 85 mg/m2 day 1 and 5-FU continuous infusion 200 mg/m2/day) was given in week 3-5, and week 8-10. Bev 5 mg/kg was given in week 1, 3, 5, 7, 9, 11. In total patients received in 12 weeks, 3 courses of FOLFOX, 50.4 Gy with Ox/5-FU, and 2-weekly Bev. All patients were staged with CT, MRI and FDG-PET before and 4 weeks after treatment.
Thirty patients were treated in this trial. The median age was 58 (range 36-75) years. 56.7% were male. Rectal primary MRI-stage was T2 3%, T3 73% and T4 24%. Liver metastasis was present in 80%. 33% had more than one site of metastasis. 24 patients (80% [80% CI:68%-89%]) reached week 12 of the treatment. Chemotherapy dose modification was required in 63%, mainly for haematologic toxicity (neutropaenia G4 23% G3 23%, febrile neutropaenia G3 3%, thrombocytopaenia G4 3%). PET (SUV) response 4 weeks post-therapy for pelvic disease was CR + PR 100% [95% CI:88%-100%] (CR 14%), and for distant disease was CR + PR 93% [95% CI:76%-99%] (CR 41%). At 24 months, freedom from failure for pelvic and distant disease were 86% [95% CI:75%-100%] and 28% [95% CI:15%-50%] respectively. Overall survival at 24 months was 67% [95% CI:52%-86%].
It is feasible to deliver interdigitating intensive chemotherapy with bevacizumab and radiotherapy to treat primary and metastatic rectal cancer simultaneously. Favourable tumour control rates are encouraging. This treatment design warrants further investigation.
Clinical trial identification
Legal entity responsible for the study
Peter MacCallum Cancer Centre
Peter MacCallum Cancer Centre and Roche
All authors have declared no conflicts of interest.