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

Abstract

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.

Role of nicotinamide N-methyltransferase in non-small cell lung cancer: in vitro effect of shRNA-mediated gene silencing on tumourigenicity

“…Approximately 50% of patients with pathological stage I NSCLC die within 5 years of pulmonary resection, mainly because of distant metastasis and local recurrence. For patients with unresectable locally advanced NSCLC, treated with combined chemo-radiotherapy, the overall 5-year survival rate is 8 -17%, while the median survival of patients with metastatic disease, treated with platinum-based chemotherapy, ranges from 8 to 10 months ( Liu et al, 2014 ;Pei et al, 2014 ).…”

Survival analysis of dogs with advanced primary lung carcinoma treated by metronomic cyclophosphamide, piroxicam and thalidomide

“…In human oncology, the addition of thalidomide to MTD chemotherapy protocols has resulted in a higher incidence of severe non‐hematologic toxicities (ie, dizziness, constipation, rash and venous thromboembolic events), raising significant concerns on the safety profile of such strategies. Differently, the results of this study and of previous veterinary studies would suggest that thalidomide has a safe toxicity profile even if combined with MC strategies . Except for mild transient sedation, which is usually dammed administering the drug in the evening, side effects are usually not reported regardless of the dose or regimen .…”

“…Concerning metronomic cyclophosphamide, this has not been widely used in advanced NSCLC; however, a recent study comparing patients with advanced NSCLC receiving radiation and MC cyclophosphamide vs radiation only has shown a small but significant survival advantage if MC cyclophosphamide was added . Conversely, it should be mentioned that several randomized controlled clinical trials comparing MTD chemotherapy/chemoradiotherapy with or without thalidomide did not produce consistent results, questioning the role of thalidomide in the management of NSCLC . However, we are not aware of a study combining MC cyclophosphamide and thalidomide in humans.…”

Thalidomide combined with transcatheter artierial chemoembolzation for primary hepatocellular carcinoma: a systematic review and meta-analysis

“…The use of thalidomide has been proved to be beneficial in treating and delaying progression of several diseases, including HCC, multiple myeloma, and lung cancer. Several meta-analyses have evaluated the effectiveness of thalidomide in managements of multiple myeloma [ 17 , 18 , 55 – 61 ] and lung cancer [ 20 ]. These studies demonstrated that thalidomide maintenance therapy improved survival and disease control rates, which is in accordance with our main findings.…”

“…Thalidomide is not only capable of inhibiting angiogenesis, but also modulating immunity [ 15 , 16 ]. Thalidomide alone or in combination with other regimen has been widely used in treating cancers such as multiple myeloma [ 17 , 18 ], HCC [ 4 , 19 ], lung cancer [ 20 ], and bladder cancer [ 21 ]. With regards to HCC, many clinical retrospective studies or RCTs [ 3 , 19 , 22 – 29 ] evaluated the effect of adding thalidomide to TACE on patients with primary HCC, and the results of most of these studies are positive.…”