Phase II Trial of Neoadjuvant Therapy with Carboplatin, Gemcitabine plus Thalidomide for Stages IIB and III Non-small Cell Lung Cancer

Dudek, Arkadiusz Z.; Leśniewski-Kmak, Krzysztof; Larson, Timothy; Dragnev, Konstantin H.; Isaksson, Rachel; Gupta, Vinita; Maddaus, Michael A.; Kratzke, Robert A.

doi:10.1097/jto.0b013e3181add877

Cited by 8 publications

(2 citation statements)

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“…Two parallel non-randomised phase II studies in patients with malignant mesothelioma treated with single agent thalidomide or thalidomide combined with carboplatin and gemcitabine reported pre-treatment VEGF serum levels were prognostic, and increases in VEGF levels on treatment were associated with a worse prognosis (Kao et al , 2012). A small phase II trial of neo-adjuvant carboplatin–gemcitabine chemotherapy with thalidomide in 15 patients with stage IIB–IIIA NSCLC showed that a higher baseline IL-8 was associated with a significantly greater risk of disease recurrence post-operatively, although an increase in IL-8 after treatment was associated with a reduced risk of recurrence (Dudek et al , 2009). Biomarker levels in this study of patients with relatively low volume disease were lower than in our NSCLC patients with stage IIIB and IV disease.…”

Section: Discussionmentioning

confidence: 99%

Analysis of circulating angiogenic biomarkers from patients in two phase III trials in lung cancer of chemotherapy alone or chemotherapy and thalidomide

et al. 2012

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Background:Thalidomide has potent anti-inflammatory and anti-angiogenic properties. It was evaluated in combination with chemotherapy in two randomised placebo-controlled trials in patients with small cell lung cancer (SCLC, n=724) and advanced non-small cell lung cancer (NSCLC, n=722). Neither study demonstrated an improvement in overall survival with the addition of thalidomide to chemotherapy. This study investigated circulating angiogenic biomarkers in a subset of these patients.Methods:Serial plasma samples were collected in a cohort of patients enrolled in these two trials (n=95). Vascular endothelial growth factor (VEGF), soluble truncated form of VEGF receptor-2 (sVEGFR-2), interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α), basic fibroblast growth factor (bFGF) and soluble intercellular adhesion molecule-1 (sICAM-1) levels were measured by enzyme-linked immunosorbent assays. Results were correlated with patient clinical data including stage, response rate and progression-free survival (PFS).Results:Baseline biomarker levels were not significantly different between SCLC and NSCLC. For pooled treatment groups, limited stage SCLC was associated with lower baseline VEGF (P=0.046), sICAM-1 (P=0.008) and IL-8 (P=0.070) than extensive stage disease. Low baseline IL-8 was associated with a significantly improved PFS in both SCLC and NSCLC (P=0.028), and a greater reduction in IL-8 was associated with a significantly improved tumour response (P=0.035). Baseline angiogenic factor levels, however, did not predict response to thalidomide.Conclusion:Circulating angiogenic biomarkers did not identify patients who benefited from thalidomide treatment.

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Section: Discussionmentioning

confidence: 99%

Analysis of circulating angiogenic biomarkers from patients in two phase III trials in lung cancer of chemotherapy alone or chemotherapy and thalidomide

et al. 2012

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“…Neoadjuvant therapy aims to reduce tumor size and burden, while acting on occult micro-metastatic disease, thereby increasing the likelihood of downstaging and complete surgical resection, as well as reducing the risk of recurrence ( 5 ). Previous studies have demonstrated that neoadjuvant therapy could be a cornerstone towards improved efficacy and survival for patients ( 6 – 8 ).…”

Section: Introductionmentioning

confidence: 99%

An open, observational clinical study of neoadjuvant therapy in resectable stage III non-small cell lung cancer

Qi,

Gu,

Shen

et al. 2023

Front. Oncol.

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BackgroundThis open, observational clinical study aimed to investigate the efficacy, safety and survival outcomes of neoadjuvant chemotherapy, neoadjuvant immunotherapy with(out) chemotherapy and neoadjuvant targeted therapy among resectable stage III non-small cell lung cancer (NSCLC) patients (NCT04197076) in real world. 48 of the 57 evaluable patients were included in this interim analysis.MethodsThis study was conducted at Shanghai Chest Hospital and included eligible NSCLC patients who were 18 years or older and had resectable clinical stage III disease. Surgical resection was conducted after neoadjuvant chemotherapy (13 patients), immunotherapy with(out) chemotherapy (26 patients), and targeted therapy (9 patients). Disease-free survival (DFS) was evaluated as the primary endpoint. The secondary endpoint was pathological complete response (pCR) rate. Clinical response rate (cRR), related adverse events (AEs), surgical feasibility and pathological features were also discussed in this study.ResultsSignificant differences in DFS were noted between chemotherapy and immunotherapy [7.7 months (range, 3.1 to 23.2 months) vs. 9.6 months (range, 4.0 to 47.9 months); P=0.032], and between chemotherapy and targeted therapy [7.7 months (range, 3.1 to 23.2 months) vs. 13.2 months (range, 7.5 to 32.2 months); P=0.015], but not between immunotherapy and targeted therapy (P=0.500). Subgroup analysis also favored neoadjuvant immunotherapy and targeted therapy. 5 patients achieved pathological complete response (pCR), all of whom were in the neoadjuvant immunotherapy arm, leading to a pCR rate of 19.2% in this arm. Treatment-emergent adverse events (TEAEs) of over grade 3 occurred in 11 patients (19.3%), with 5 (29.4%) in the chemotherapy arm, 5 (16.7%) in the immunotherapy arm and 1 (10.0%) in the targeted therapy arm. One grade 4 and one grade 2 surgery-related serious adverse event occurred in the neoadjuvant chemotherapy and immunotherapy arm, respectively.ConclusionIn patients diagnosed with resectable stage III NSCLC, neoadjuvant immunotherapy and neoadjuvant targeted therapy were associated with significantly longer disease-free survival compared with neoadjuvant chemotherapy. Clinical and pathological response rates were also higher in the immunotherapy and targeted therapy arm. Adverse events were found to be manageable and similar across all three groups, and surgical feasibility favored immunotherapy or targeted therapy rather than chemotherapy.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT04197076.

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Angiogenesis and Lung Cancer

Shi

Siemann

2011

Medical Radiology

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Phase II Trial of Neoadjuvant Therapy with Carboplatin, Gemcitabine plus Thalidomide for Stages IIB and III Non-small Cell Lung Cancer

Abstract: This neoadjuvant regimen was well tolerated and effective in inoperable NSCLC and warrants additional investigation.

Cited by 8 publications

References 26 publications

Analysis of circulating angiogenic biomarkers from patients in two phase III trials in lung cancer of chemotherapy alone or chemotherapy and thalidomide

Analysis of circulating angiogenic biomarkers from patients in two phase III trials in lung cancer of chemotherapy alone or chemotherapy and thalidomide

An open, observational clinical study of neoadjuvant therapy in resectable stage III non-small cell lung cancer

Angiogenesis and Lung Cancer

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