Phase II Trial of Thalidomide, Irinotecan and Gemcitabine in Chemonaive Patients with Advanced Non-Small Cell Lung Cancer

Jazieh, Abdul Rahman; Komrokji, Rami; Gupta, Abha; Patil, Shekar; Flora, Douglas; Knapp, Mark; Issa, Majd; Karim, Nagla Abdel

doi:10.3109/07357900801944856

Cited by 10 publications

(7 citation statements)

References 17 publications

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“…Thalidomide became one of the “hotspots” in treatment of multiple myeloma and showed an amazing effect: 80% of patients derived clinical benefits from thalidomide mono-treatment [ 16 ]. Based on the data in multiple myeloma studies, thalidomide has been recommended for use in numerous clinical trials for treating solid tumors, including lung cancer, esophageal cancer, hepatocellular carcinoma, and renal cell carcinoma [ 17 – 20 ], of the utilization has suggested certain therapeutic efficacy.…”

Section: Introductionmentioning

confidence: 99%

Synergistic Inhibition of Thalidomide and Icotinib on Human Non-Small Cell Lung Carcinomas Through ERK and AKT Signaling

et al. 2018

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BackgroundEpidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been widely used in the treatment of non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations. However, the survival of patients with EGFR-TKI administration is limited by the inevitable development of acquired drug resistance. Recently, multi-targeted drugs combination has been shown to be a promising strategy to improve the efficacy of EGFR-TKI treatment and enable the reduction of drug resistance in NSCLC.Material/MethodsHumanized NSCLC cell lines PC9 and A549 were co-cultured with thalidomide and/or icotinib to test for anti-tumor efficiency. Cell proliferation was measured by MTT assay, cell apoptosis by flow cytometry and cell migration by wound healing assay. Western blot was performed to determine the expression of caspase-3, -8, -9, Bax, EGFR, VEGF-R, AKT, ERK, MMP2, MMP9, and NF-κB. The xenograft mouse model was used to explore the effects of thalidomide and icotinib in vivo. Immunohistochemical testing was used to determine the expression of Ki-67 and TUNEL staining in tumor tissues.ResultsTreatments of thalidomide and/or icotinib reduced cell viability, induced apoptosis, and suppressed migration. Attenuation of pEGFR and pVEGF-R resulted in deactivation of ERK and AKT pathways, which eventually increased the anti-proliferative response. In PC9 xenograft model, combined administration of thalidomide and icotinib restrained tumor growth with remarkable reduced Ki-67 index and increased TUNEL positive cells.ConclusionsThalidomide sensitizes icotinib to increase apoptosis and prevent migration, and it may be a potentially promising anti-tumor drug in lung cancer multi-modality therapy.

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Section: Introductionmentioning

confidence: 99%

Synergistic Inhibition of Thalidomide and Icotinib on Human Non-Small Cell Lung Carcinomas Through ERK and AKT Signaling

et al. 2018

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“…At present, this drug is approved for multiple myeloma and currently used experimentally to treat various cancers, dermatological, neurological and inflammatory diseases [6,7,8]. The clinical use of thalidomide in CACS is still controversial despite some researches indicating that orally administered thalidomide could improve CACS symptoms and patient quality of life (QoL) [9,10].…”

Section: Introductionmentioning

confidence: 99%

Clinical Studies on the Treatment of Cancer Cachexia with Megestrol Acetate plus Thalidomide

Wen

Cao

et al. 2012

Chemotherapy

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Background: The management of cancer-related anorexia/cachexia syndrome (CACS) is a great challenge in clinical practice. To date, practice guidelines for the prevention and treatment of CACS are lacking. The authors conducted a randomized study to confirm the effectiveness and safety of treatment of CACS utilizing megestrol acetate (MA) plus thalidomide. Methods: One hundred and two candidates with CACS were randomly assigned to two treatment groups (trial group and control group): the trial group received MA (160 mg po, bid) plus thalidomide (50 mg po, bid), while the control group received MA (160 mg po, bid) alone. Treatment duration was 8 weeks. Results: Analysis of the trial group demonstrated a significant increase from baseline in body weight (<0.01), quality of life (p = 0.02), appetite (p = 0.01), and grip strength (p = 0.01), and a significant decrease in fatigue, Glasgow Prognostic Score (p = 0.05), Eastern Cooperative Oncology Group performance status (p = 0.03), IL-6 (p < 0.01), and tumor necrosis factor-α (p = 0.02). In contrast, in the control group, endpoints with a significant improvement from baseline included body weight (p < 0.02) and appetite (p = 0.02). The mean changes in the endpoints from baseline in the trial group were significantly greater compared with the control group: in the primary endpoints, body weight (p = 0.05), fatigue (p < 0.01) and quality of life (p = 0.01), and in the secondary endpoints, grip strength (p = 0.05), Glasgow Prognostic Score (p = 0.02), Eastern Cooperative Oncology Group performance status (p = 0.02), IL-6 (p < 0.01) and tumor necrosis factor-α (p = 0.01). Toxicity was found to be relatively negligible in both groups. Conclusion: A combination regimen of MA and thalidomide is more effective than MA alone in the treatment of CACS.

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“…A phase II study [18] explored the safety of combining thalidomide with carboplatin and paclitaxel for stage IIIA, IIIB, or IV NSCLC and indicated that this therapy was well tolerated and supported further investigation. Another trial [16] combining thalidomide with irinotecan and gemcitabine showed that this combination is active in advanced NSCLC with a manageable toxicity profile. In 2008, He et al .…”

Section: Discussionmentioning

confidence: 99%

“…The advantages of thalidomide include convenient administration, lower costs and immunomodulatory properties [13, 14]. A study in mice showed that thalidomide can suppress tumor growth [15], and many phase II trials have indicated that thalidomide was well tolerated and has potential to improve survival in patients with advanced NSCLC [16–18]. Therefore, several randomized controlled clinical trials comparing therapy with or without thalidomide in the treatment of advanced NSCLC have been launched.…”

Section: Introductionmentioning

confidence: 99%

The efficacy and safety of thalidomide-based therapy in patients with advanced non-small cell lung cancer: a meta-analysis

Liu¹,

He²,

Ding³

et al. 2014

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Several randomized controlled clinical trials have compared therapy with or without thalidomide in the treatment of advanced non-small cell lung cancer (NSCLC). However, these studies did not produce consistent results. We carried out a meta-analysis to determine the efficacy and safety of thalidomide-based therapy in patients with advanced NSCLC. For this meta-analysis, we selected randomized clinical trials that compared thalidomide in combination with other therapy or other therapy alone in patients with advanced NSCLC. The outcomes included median overall survival (OS), one- and two-year survival, tumor response, and toxicities. Hazard ratios (HRs) or risk ratios (RRs) were reported with 95% confidence intervals (CIs). A total of 5 eligible trials were included for the meta-analysis, with 729 patients in the thalidomide group and 711 patients in the control group. Compared with non-thalidomide-based therapy, patients receiving thalidomide plus other therapy did not differ significantly in terms of one- and two-year survival or tumor response (RR = 1.32, 95% CI: 0.66–2.63, p = 0.43; RR = 1.22, 95% CI: 0.48–3.11, p = 0.68; RR = 1.05, 95% CI: 0.92–1.19, p = 0.51, respectively). However, thalidomide-based therapy induced more grade 3–4 dizziness and constipation (RR = 2.05, 95% CI: 1.10–3.81, p = 0.02; RR = 4.78, 95% CI: 1.84–12.38, p = 0.001, respectively). The addition of thalidomide to other therapy did not improve survival and tumor response in patients with advanced NSCLC, and thalidomide-based therapy was associated with more grade 3/4 dizziness and constipation.

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Phase II Trial of Thalidomide, Irinotecan and Gemcitabine in Chemonaive Patients with Advanced Non-Small Cell Lung Cancer

Cited by 10 publications

References 17 publications

Synergistic Inhibition of Thalidomide and Icotinib on Human Non-Small Cell Lung Carcinomas Through ERK and AKT Signaling

Synergistic Inhibition of Thalidomide and Icotinib on Human Non-Small Cell Lung Carcinomas Through ERK and AKT Signaling

Clinical Studies on the Treatment of Cancer Cachexia with Megestrol Acetate plus Thalidomide

The efficacy and safety of thalidomide-based therapy in patients with advanced non-small cell lung cancer: a meta-analysis

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