Cetuximab plus chronomodulated irinotecan, 5-fluorouracil, leucovorin and oxaliplatin as neoadjuvant chemotherapy in colorectal liver metastases: POCHER trial

Abstract

Background:We assessed the effectiveness of cetuximab plus chronomodulated irinotecan, 5-fluorouracil (5-FU), leucovorin (FA) and oxaliplatin (L-OHP) (chrono-IFLO) administered as neoadjuvant chemotherapy to increase the resectability of colorectal liver metastases.Methods:This was a phase II prospective trial with rate of liver metastases resection as primary end point. Forty-three patients with unresectable metastases were enroled: 9 with metastases >5 cm; 29 with multinodular (>4) disease; 1 with hilar location; 4 with extrahepatic lung disease. Treatment consisted of cetuximab at day 1 plus chronomodulated irinotecan 5-FU, FA and L-OHP for 2–6 days every 2 weeks. After the first 17 patients, doses were reduced for irinotecan to 110 mg m−2, 5-FU to 550 mg m−2 per day and L-OHP to 15 mg m−2 per day.Results:Macroscopically complete resections were performed in 26 out of 43 patients (60%) after a median of 6 (range 3–15) cycles. Partial response was noticed in 34 patients (79%). Median overall survival was 37 months (95% CI: 21–53 months), with a 2-year survival of 68% in the entire population, 80.6% in resected patients and 47.1% in unresected patients (P=0.01). Grade 3/4 diarrhoea occurred in 93% and 36% of patients before and after dose reduction.Conclusion:Cetuximab plus chrono-IFLO achieved 60% complete resectability of colorectal liver metastases.

Potentially resectable metastatic colorectal cancer: An individualized approach to conversion therapy

“…The metastasis resection and conversion rates were then evaluated retrospectively and no clear definition of resectability was provided. The efficacy of chemotherapeutic associations in doublets or triplets has been established [ [15], [16], [17], [18], [19], [20], [21]] and afterwards, also the association between chemotherapy and monoclonal antibodies has proven to be effective [ [13], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36]]. The results in terms of OS and overall response rate (ORR) of the main phase II and III studies are summarized in Table 1.…”

Cetuximab in first line treatment of metastatic colorectal cancer

“…Al contrario l'associazione bevacizumab + FOLFOX non ha dimostrato questo effetto, rispetto al regime chemioterapico standard. L'efficacia degli anticorpi anti-EGFR in questo contesto è confermata anche da panitumumab che sembra produrre risultati sostanzialmente in linea, anche se la capacità di convertire le metastasi epatiche alla resecabilità da parte di cetuximab è comprovata da diversi studi di fase II [77,78]. [79].…”

“…I tassi di resezione trovati negli studi clinici CRYSTAL e OPUS sembrano sottostimare il numero di casi eleggibili alla chirurgia, e la probabilità di successo terapeutico dell'intervento, che può considerarsi pari al 95%. Un elevato tasso di resezione, pari al 60% dei casi, è stato evidenziato anche nello studio POCHER [78] uno studio italiano di fase II, che ha arruolato 43 soggetti con CRC metastatico non operabile. In questa coorte la sopravvivenza mediana è stata pari a 37 mesi e il tasso di sopravvivenza a 2 anni pari al 68%.…”

Systemic treatment of liver metastases from colorectal cancer

“…Recent data from single arm phase II trials with different 5FU/FA, irinotecan and oxaliplatin schedules in combination with either bevacizumab or EGFR antibodies consistently reported a high ORR of about 80% [Assenat et al 2011;Bruera et al 2010;Garufi et al 2010;Lonardi and Fornaro, 2012;Masi et al 2010]. In particular, the four-drug regimens with EGFR antibodies were compromised by grade 3/4 diarrhoea, leading to dose reduction of chemotherapy with maintained efficacy.…”