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).

BACKGROUND: Different 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. METHODS: Between 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. RESULTS: 40 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. CONCLUSIONS: Two 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 REGISTRATION: EU Clinical Trials Register; Eudract-Nr: 2006-004639-31.

No predictive value of cytotoxic or helper T-cell precursor frequencies for outcome when analyzed from the graft after stem cell transplantation.

The predictive value of limiting dilution analyses (LDA) measuring cytotoxic and helper T-lymphocyte precursor (CTLp and HTLp) frequencies for outcome after stem cell transplantation (SCT) is still a matter of debate. One reason may be that CTLp and HTLp frequencies are determined in peripheral blood mononuclear cells (PBMC) and this responder cell population does not reflect the cell type composition of the graft. We assessed whether CTLp and HTLp LDA can predict complications after human leukocyte antigen (HLA)-identical SCT when CTLp and HTLp frequencies are analyzed in PBMC of the respective stem cell graft [bone marrow (BMMC) or granulocyte colony-stimulating factor (G-CSF)-mobilized PBMC] and compared to PBMC of PB. Host-specific CTLp frequencies measured in 25 patients and HTLp frequencies analyzed in 6 patients were low in all responder cell sources. CTLp and HTLp frequencies seen against HLA-mismatched unrelated third-party cells were high, but third-party-specific CTLp and HTLp frequencies were lower in G-CSF-PBMC than in PBMC ( p=0.047 for CTLp frequencies). Host-specific CTLp frequencies analyzed in all responder cell sources did not predict acute or chronic graft-versus-host disease (GVHD). Lower CTLp frequencies were detected in all responder cell sources from patients who relapsed after SCT than in patients without relapse, but the differences between both groups were statistically significant only in PBMC. In conclusion, a significant correlation was detected only between relapse and CTLp frequencies measured in PBMC. The lower frequency of third-party-specific cells in G-CSF-PBMC indicates that the mobilization procedure with G-CSF itself may influence results.

Comparison of automated cellular imaging system and manual microscopy for immunohistochemically stained cryostat sections of lung cancer specimens applying p53, ki-67 and p120.

Seventy-one frozen lung tissue specimens from 52 patients suffering from non-small cell lung cancer (NSCLC) were analysed in this study. Cryostat sections were stained with monoclonal antibodies against p53, ki-67 and p120, all of which are of prognostic value in NSCLC. Slides were evaluated by standard manual microscopy (MM) and using a new Automated Cellular Imaging System (ACIS). The results obtained with ACIS correlated significantly with MM examination (p<0.001). However, ACIS showed a higher sensitivity, especially for specimens with a low infiltration volume. In 15 (6.8%) MM negative cases singular positive cells were identified with ACIS. In cases with a high infiltration volume subjective (MM) quantitation tended to overestimate the number of infiltrating cells. ACIS guaranteed a high reproducibility of data. We conclude that ACIS-assisted analysis is a valid means of investigating the p53, ki-67 and p120 antibody expression in cryostat sections of lung cancer specimens. ACIS can complement conventional manual microscopy due to its higher accuracy, sensitivity and better reproducibility of data.