Cetuximab plus gemcitabine/oxaliplatin (GEMOXCET) in first-line metastatic pancreatic cancer: a multicentre phase II study

Abstract

Targeting the epidermal growth factor receptor pathway in pancreatic cancer seems to be an attractive therapeutic approach. This study assessed the efficacy of cetuximab plus the combination of gemcitabine/oxaliplatin in metastatic pancreatic cancer. Eligible subjects had histological or cytological diagnosis of metastatic pancreatic adenocarcinoma. The primary end point was response according to RECIST. Patients received cetuximab 400 mg m À2 at first infusion followed by weekly 250 mg m À2 combined with gemcitabine 1000 mg m À2 as a 100 min infusion on day 1 and oxaliplatin 100 mg m À2 as a 2-h infusion on day 2 every 2 weeks. Between January 2005 and August 2006, a total of 64 patients (22 women (34%), 42 men (66%); median age 64 years (range 31 -78)) were enrolled at seven study centres. On October 2007, a total of 17 patients were alive. Sixty-two patients were evaluable for baseline and 61 for assessment of response to treatment in an intention-to-treat analysis. Six patients had an incomplete drug combination within the first cycle of the treatment plan (n ¼ 4 hypersensitivity reactions to the first cetuximab infusion, n ¼ 2 refused to continue therapy). Reported grade 3/4 toxicities (% of patients) were leukopaenia 15%, anaemia 8%, thrombocytopaenia 10%, diarrhoea 7%, nausea 18%, infection 18% and allergy 7%. Cetuximab-attributable skin reactions occurred as follows: grade 0: 20%, grade 1: 41%, grade 2: 30% and grade 3: 10%. The intention-to-treat analysis of 61 evaluable patients showed an overall response rate of 33%, including 1 (2%) complete and 19 (31%) partial remissions. There were 31% patients with stable and 36% with progressive disease or discontinuation of the therapy before re-staging. The presence of a grade 2 or higher skin rash was associated with a higher likelihood of achieving objective response. Median time to progression was 118 days, with a median overall survival of 213 days. A clinical benefit response was noted in 24 of the evaluable 61 patients (39%). The addition of cetuximab to the combination of gemcitabine and oxaliplatin is well tolerated but does not increase response or survival in patients with metastatic pancreatic cancer.

Gold nanoparticles as novel agents for cancer therapy

“…An important demonstration of the potential of multifunctional GNPs for drug delivery was the use of 5-nm GNPs as a delivery vehicle, covalently bound to cetuximab, as an active targeting agent and gemcitabine as a therapeutic payload in pancreatic cancer [28]. The epidermal growth factor receptor (EGFR) is overexpressed in up to 60% of pancreatic cancers and the combination of cetuximab and gemcitabine has been investigated in Phase II trials of this disease [29]. Patra et al [30] demonstrated that high intratumoural gold concentrations (4500 mg g 21 ) could be achieved using this approach compared with 600 mg g 21 with untargeted GNPs with minimal accumulation in the liver or kidney.…”

Effects of the HIF-1α and NF-κB loop on epithelial-mesenchymal transition and chemoresistance induced by hypoxia in pancreatic cancer cells

“…Even systemic therapy with gemcitabine, a current first-line treatment for advanced pancreatic cancer, offers only modest benefit due to pre-existing or acquired chemoresistance (2,3). Furthermore, clinical studies indicate that only 12% of patients with advanced pancreatic cancer exhibit a response to gemcitabine (4).…”

Antitumor and apoptosis-promoting properties of emodin, an anthraquinone derivative from Rheum officinale Baill, against pancreatic cancer in mice via inhibition of Akt activation

“…Moreover, combination treatment consisting of gemcitabine and 5-fluorouracil (5-FU) (8), oxaliplatin (9), cisplatin (10) or irinotecan (11) has also resulted in improved responses in patients with advanced pancreatic cancer. Although numerous doublet or triplet gemcitabine combination therapies have been shown to provide modest survival benefits compared to monotherapy, the response and median survival in patients with advanced pancreatic cancer do not increase (12). Therefore, development of novel drugs or therapies with high antitumor activity, commercial availability, low cost and low toxicity is imperative.…”