Dataset Information

Advanced small cell lung cancer (SCLC): new challenges and new expectations.

ABSTRACT: Small cell lung cancer (SCLC) remains one of the most lethal malignancies and a major health riddle. The therapeutic options are limited. The combination of etoposide or irinotecan with platinum chemotherapy is the standard of care at any stage. The last decade systemic efforts have been done to reveal specific therapeutic targets for small cell lung carcinomas. In this review, we focus on the new therapeutic strategies of SCLC, including immune-related treatment that may change the prognosis of the disease. The main genetic mutations observed in SCLC are TP53 and RB1 mutations; however, it is well known that these molecules are not yet targetable. In recent years, research has revealed other frequent genetic alterations and activated signaling pathways that might be an effective treatment target. Loss of PTEN, activating PI3K mutations, inhibition of NOTCH pathway and aurora kinase activation are among them. Moreover, FDGFR1 amplification, activation of the Hedgehog pathway and repair-protein PARP1 seem to participate in SCLC tumorigenesis. These new findings have identified some interesting targets. Moreover, immunotherapy tries to find its place in the treatment of SCLC. Immune checkpoint inhibitors are under investigation in phase I to III clinical trials. We hope that in next years the treatment of SCLC patients will be improved with the administration of targeting therapy and the introduction of immunotherapy.

SUBMITTER: Tsoukalas N

PROVIDER: S-EPMC5952028 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Advanced small cell lung cancer (SCLC): new challenges and new expectations.

Tsoukalas Nikolaos N Aravantinou-Fatorou Eleni E Baxevanos Panagiotis P Tolia Maria M Tsapakidis Konstantinos K Galanopoulos Michail M Liontos Michail M Kyrgias George G

Annals of translational medicine 20180401 8

Small cell lung cancer (SCLC) remains one of the most lethal malignancies and a major health riddle. The therapeutic options are limited. The combination of etoposide or irinotecan with platinum chemotherapy is the standard of care at any stage. The last decade systemic efforts have been done to reveal specific therapeutic targets for small cell lung carcinomas. In this review, we focus on the new therapeutic strategies of SCLC, including immune-related treatment that may change the prognosis of ...[more]

PMID: 29862234

Similar Datasets

Project description:Background:Etoposide-/platinum-based chemotherapy is the standard first-line treatment for extensive-disease small cell lung cancer (SCLC), but responses are short-lived and subsequent options limited. Here, we present our experience with paclitaxel in advanced treatment lines. Methods:We retrospectively studied the clinical course of all paclitaxel-treated SCLC patients between 2005 and 2015 in our institution. Prognostic and predictive factors were analyzed by Kaplan-Meier and Cox regression analyses. Results:A total of 185 patients [119 men, median age 65 years, median ECOG performance status (PS) 1] were identified. One hundred and sixty-eight patients had extensive disease (ED) at the time of paclitaxel therapy. Paclitaxel was mainly given as third- or fourth-line therapy (93%). The response rate (RR) was 17% and disease control rate (DCR) 28%. Patients reached a median progression-free survival (PFS) of 1.6 (95% CI: 1.4-1.8) months and median overall survival (OS) of 3.3 (95% CI: 2.8-3.9) months. Main toxicities were fatigue (25%) and polyneuropathy (17%). Dose reduction of ?25% was associated with shorter PFS [1.9 (95% CI: 1.5-2.3) vs. 1.4 (95% CI: 1.3-1.5) months; P=0.004]. Further independent predictive factors for PFS were gender, age, and hepatic/brain metastases (P<0.05). Tumor response to paclitaxel, PS, number and location of metastases, dose reduction, and smoking history were significant factors for OS in univariable analyses (P<0.05), while PS, dose reduction, status of cerebral/hepatic metastases, tumor response, and smoking history were retained as independent prognostic factors in multivariable testing. Notably, ECOG PS 2 patients had toxicity rates similar to ECOG PS 0-1 patients (63% vs. 62%), as well as a comparable DCR (29% vs. 28%), which was associated with prolonged survival (4.5 vs. 3.2 months for refractory cases, P=0.034). Conclusions:Paclitaxel has clinically relevant activity in heavily pretreated SCLC. While patients with good PS and no cerebral/hepatic metastases derive the greatest benefit, ECOG PS 2 per se should not be used as a criterion to exclude patients.

Project description:Small-cell lung cancer (SCLC) accounts for 13-15% of all new lung cancer cases in the US. The tumor has a tendency to disseminate early resulting in 80-85% of patients being diagnosed with extensive disease (ES-SCLC). Chemotherapy has provided SCLC patients considerable survival benefits over the past three decades. Nonetheless, most patients relapse and rarely survive beyond 2 years. Despite consistent overall response rates of ?50%, until recently, median survival times and 2-year survivals only ranged between 7-10 months and 10-20%, respectively. Several chemotherapy agents possess activity against SCLC, both, as single agents and in combinations but etoposide-platinum emerged as the preferred first line regimen. Upon relapse, many patients remain candidates for additional therapy. However, the sensitivity of relapsed SCLC to further therapies is markedly reduced and dependent upon the level and duration of response to the initial treatment (platinum-sensitive vs. resistant relapse). Multiple factors suggest a therapeutic role for immunotherapy in SCLC: SCLC has been associated with immune-mediated paraneoplastic processes (cerebellar degeneration, limbic encephalitis, and Lambert-Eaton syndrome) and patients presenting with these paraneoplastic syndromes have shown more favorable outcomes, suggesting an underlying immune response mechanism.Comprehensive genomic profiling of SCLC indicates that the majority lack functional p53 (90%) and Rb1 (65%). These universal genetic aberrations facilitate poor genomic stability, thus perpetuating the generation of tumor associated antigens, amenable to targeting with immunotherapy.SCLC has one of the highest mutational loads, likely a reflection of the myriad of insults inflicted by smoking-related carcinogens. The relationship between tumor mutational load and response to immune checkpoint inhibitors has been established in multiple solid tumors, including preliminary results in relapsed SCLC. In this manuscript, we review the early (some failed and discontinued, some partly successful, and still ongoing) attempts to incorporate immunotherapy (particularly vaccine based approaches) to the treatment of SCLC, and the latest attempts (mostly incorporating the use of checkpoint inhibitors), including those with favorable but preliminary results (CheckMate 032, Keynote 028 and 158), and those with more definitive positive (iMpower 133 and CASPIAN) and negative (CheckMate 331 and 451) results.

Dataset Information

Advanced small cell lung cancer (SCLC): new challenges and new expectations.

Publications

Advanced small cell lung cancer (SCLC): new challenges and new expectations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets