Adjuvant Therapy of Resected Non-small Cell Lung Cancer: can We Move Forward?

Abstract

Twenty years ago, an individual patient data meta-analysis of eight cisplatin-based adjuvant chemotherapy (AC) studies in completely resected early stage non-small cell lung cancer (NSCLC) demonstrated a 13 % reduction of the risk of death favoring chemotherapy that was of borderline statistical significance (p = 0.08). This marginal benefit boosted a new generation of randomized trials to evaluate the role of modern platinum-based regimens in resectable stages of NSCLC and, although individual studies generated conflicting results, overall they contributed to confirm the role of AC which is now recommended for completely resected stage II and III NSCLC, mostly 4 cycles, while subset analyses suggested a benefit in patients with large IB tumors. Cisplatin-based therapy was the core regimen of those adjuvant clinical trials and even if a substitution with other platinum-derived was also suggested, mainly based on extrapolated data from studies in advanced disease, cisplatin was confirmed to be slightly superior to carboplatin and is still the drug of choice in the adjuvant setting. Currently, any attempt to improve efficacy of cisplatin-based chemotherapy through antiangiogenic drugs association or pharmacogenomics approaches have failed, while results of additional studies are eagerly awaited. In the context of promising targeted therapies, even if several randomized trials in the advanced setting evaluated tyrosine kinase inhibitors (TKis) versus platinum-based chemotherapy and showed impressive results, clinical experience with TKIs in the adjuvant setting is still limited and most of the trials have not required patients to be molecularly tested for the drug-specific molecular predictive factor. At the present time, the role of targeted agents as adjuvant approaches remains largely not investigated. Finally, with the negative experience of the use of vaccines in this setting, the integration of immunotherapy (mainly immunocheckpoint inhibitors) in platinum-based schedules has just started to be evaluated, representing a potential future clinical option, but still far from clinical practice.

Usefulness of Plasma Exosomal MicroRNA-451a as a Noninvasive Biomarker for Early Prediction of Recurrence and Prognosis of Non-Small Cell Lung Cancer

“…Furthermore, our data show that exosomal miR451a is an independent predictive factor for recurrence and prognosis in stages I, II, and III. It has been reported that about 21-55% of stage I, II, and III patients experience recurrence after curative surgery, and adjuvant chemotherapy was conducted on these patients [2][3][4]. For accurate individualized treatment, an effective biomarker for the selection of high-risk patients is needed.…”

“…In addition, it was reported that the 5-year recurrence rates after curative surgery among NSCLC patients with pathological stage (stage) I, II, or III cancer are 21, DOI: 10.1159/000487006 36, and 55%, respectively [2]. To prevent recurrence, adjuvant chemotherapy was administered to patients with stage IB, II, and III cancer who underwent curative surgery [3,4]. Chemotherapy without certain selection criteria tends to lead to overtreatment of patients, which in turn leads to severe side effects.…”

Alantolactone induces apoptosis, promotes STAT3 glutathionylation and enhances chemosensitivity of A549 lung adenocarcinoma cells to doxorubicin via oxidative stress

“…Unfortunately, more than 70% cases of NSCLC are diagnosed at an advanced stage 3 . Thus, only about 25–30% cases of NSCLC are suitable for an effective surgical resection 4 . Radiotherapy, chemotherapy and targeted therapy are recommended treatment options for advanced stage NSCLC 3 .…”

Antilung cancer effect of ergosterol and cisplatin-loaded liposomes modified with cyclic arginine-glycine-aspartic acid and octa-arginine peptides

“…[ 30 ] Statistics indicate that 70%–80% of the drugs used for single combination chemotherapy of malignant tumors are platinum based. [ 31 ] Although platinum-based anticancer drugs have achieved great success, there are many obstacles to their clinical applications, such as low targeting ability, low side effect threshold, and drug resistance. [ 32 ] Furthermore, we found that the alcohol extracts of Antrodia camphorata showed good inhibitory effects on the proliferation of A549 cells [Supplementary Material: Figure S1].…”