Multicenter Phase II Study Evaluating Two Cycles of Docetaxel, Cisplatin and Cetuximab as Induction Regimen Prior to Surgery in Chemotherapy-Naive Patients with NSCLC Stage IB-IIIA (INN06-Study)

Abstract

BackgroundDifferent strategies for neoadjuvant chemotherapy in patients with early stage NSCLC have already been evaluated. The aim of this study was to evaluate the tolerability and efficacy of a chemoimmunotherapy when limited to two cycles.MethodsBetween 01/2007 and 03/2010 41 patients with primarily resectable NSCLC stage IB to IIIA were included. Treatment consisted of two cycles cisplatin (40 mg/m2 d1+2) and docetaxel (75 mg/m2 d1) q3 weeks, accompanied by the administration of cetuximab (400 mg/m2 d1, then 250 mg weekly). The primary endpoint was radiological response according to RECIST.Results40 patients were evaluable for toxicity, 39 for response. The main grade 3/4 toxicities were: neutropenia 25%, leucopenia 11%, febrile neutropenia 6%, nausea 8% and rash 8%. 20 patients achieved a partial response, 17 a stable disease, 2 were not evaluable. 37 patients (95%) underwent surgery and in three of them a complete pathological response was achieved. At a median follow-up of 44.2 months, 41% of the patients had died, median progression-free survival was 22.5 months.ConclusionsTwo cycles of cisplatin/ docetaxel/ cetuximab showed promising efficacy in the neoadjuvant treatment of early-stage NSCLC and rapid operation was possible in 95% of patients. Toxicities were manageable and as expected.Trial RegistrationEU Clinical Trials Register; Eudract-Nr: 2006-004639-31

Targeted therapies for the treatment of non-small-cell lung cancer: Monoclonal antibodies and biological inhibitors

“…Previous studies showed an increase in survival rates in clinical trials using this treatment combined with chemotherapy 51-54 . Presently, there are promising studies using cetuximab in combination with other drugs, such as cisplatin and docetaxel, as neoadjuvant treatment of early-stage NSCLC 55 . Although it is a rare, severe allergic reactions during the first infusion can lead to respiratory reactions and elevated blood pressure.…”

“… Related Molecule Target Mechanism of action Potentials adverse effects Reference Cetuximab EGF receptor Inhibition of cell proliferation, enhanced apoptosis, and reduced angiogenesis, invasiveness and metastasis. Rash on face and chest, diarrhea, loss of appetite and fatigue 54-59 Bevacizumab VEGF Selectively binds to VEGF and prevents interaction with its receptor. Anti-angiogenic agent, which prevents the abnormal growth of blood vessels around tumor.…”

“… 51-54 Presently, there are promising studies using cetuximab in combination with other drugs, such as cisplatin and docetaxel, as neoadjuvant treatment of early-stage NSCLC. 55 Although it is a rare, severe allergic reactions during the first infusion can lead to respiratory reactions and elevated blood pressure. In addition, some patients develop skin alterations, such as rashes, acne and infections.…”