Randomized phase II – study evaluating EGFR targeting therapy with Cetuximab in combination with radiotherapy and chemotherapy for patients with locally advanced pancreatic cancer – PARC: study protocol [ISRCTN56652283]

Abstract

Background: Pancreatic cancer is the fourth commonest cause of death from cancer in men and women. Advantages in surgical techniques, radiation therapy techniques, chemotherapeutic regimes, and different combined-modality approaches have yielded only a modest impact on the prognosis of patients with pancreatic cancer. Thus there is clearly a need for additional strategies. One approach involves using the identification of a number of molecular targets that may be responsible for the resistance of cancer cells to radiation or to other cytotoxic agents. As such, these molecular determinants may serve as targets for augmentation of the radiotherapy or chemotherapy response. Of these, the epidermal growth factor receptor (EGFR) has been a molecular target of considerable interest and investigation, and there has been a tremendous surge of interest in pursuing targeted therapy of cancers via inhibition of the EGFR.

Combination of EGFR/HER2 Tyrosine Kinase Inhibition by BIBW 2992 and BIBW 2669 with Irradiation in FaDu Human Squamous Cell Carcinoma

“…a : Normierung auf das Volumen zu Beginn der Substanzbehandlung; b : Normierung auf das Volumen zum Zeitpunkt der Bestrahlung. ments on the anti-EGFR monoclonal antibody C225, which does not radiosensitize FaDu tumor cells in vitro either, local tumor control after combination with fractionated irradiation in vivo was improved by inhibition of clonogenic cell repopulation and improvement of reoxygenation [21,23]. Both mechanisms can be investigated only in vivo using long-term fractionated irradiation schedules and local control as experimental endpoint [5,22].…”

Expression and differential signaling of heregulins in pancreatic cancer cells

“…61 Further clinical investigations are ongoing. 62 In the group of tyrosine kinase inhibitors, gefitinib (Iressa ' ) inhibits pancreatic cancer cell growth and invasiveness by blocking ErbB1-dependent pathways, suggesting that gefitinib may offer a new approach for the treatment of pancreatic cancer. 63 A phase-I trial reported, however, that the combination of gefitinib, capecitabine and radiation in pancreatic cancer patients resulted in significant patient toxicity.…”

Pancreatic cancer — Outlook: targeted therapy

“…The most frequent grade 3 or 4 toxicities were neutropenia, asthenia, abdominal pain and thrombocytopenia [12,16] . A phase II trial evaluating cetuximab therapy in combination with modulated radiation therapy (IMRT) and gemcitabine is currently recruiting patients [17] .…”