Camrelizumab as a novel third or post-third-line treatment strategy in small cell lung cancer: a retrospective study of 12 patients.

Background: Small cell lung cancer (SCLC) constitutes 15% of all lung cancer cases, with a comparatively low survival rate. The advent of immune checkpoint inhibitors (ICIs) has provided new alternatives for treating SCLC. However, the effectiveness of camrelizumab in the treatment of SCLC remains unclear. This retrospective case series was designed to investigate the efficacy and safety of camrelizumab in SCLC patients. Methods: The study enrolled SCLC patients recorded as having received more than one cycle of camrelizumab in the electronic medical record system. Data related to clinical and survival times were collected and statistically analyzed. Results: From August 2019 to December 2021, the study enrolled 12 SCLC patients. The objective response rate was 41.7% (95% confidence interval [CI]: 15.2%-72.3%). The disease control rate was 83.3% (95% CI: 51.6%-97.9%). The median progression-free survival (PFS) for all patients was 4.0 months. Notably, the median PFS of patients in third- or post-third-line subgroups was 7 months (95% CI: 1.12-12.88 months). The median overall survival (OS) for all eligible patients was 10.0 months (95% CI: 7.35-12.65 months), with a 1-year survival rate of 25%. Notably, the OS of patients treated with third- or post-third-line therapy was 5-34 months, with a 1-year survival rate of 75%. The two most prevalent non-hematological adverse events associated with the immune response were pneumonitis (44.4%) and reactive cutaneous capillary endothelial proliferation (44.4%). One patient experienced an exacerbation of preexisting diabetes and reached grade 3 hyperglycemia. There were no grade 4/5 immune-related adverse events. Conclusion: This case series highlights the potential benefits and safety concerns of camrelizumab in SCLC patients. These findings suggest a possible strategy for third- and post-third-line treatments of SCLC. However, the conclusion is limited due to the study's retrospective nature and small sample size. Therefore, large-scale randomized controlled studies are needed to determine its efficacy.

Raltitrexed enhanced antitumor effect of anlotinib in human esophageal squamous carcinoma cells on proliferation, invasiveness, and apoptosis.

BACKGROUND: Anlotinib is a multi-targeted receptor tyrosine kinase inhibitor (TKI) which has exhibited encouraging clinical activity in advanced non-small cell lung cancer (NSCLC) and soft tissue sarcoma. Raltitrexed is well known to be effective in the treatment of colorectal cancer in China. The present study aims to investigate the combinatory antitumor effect of anlotinib and raltitrexed on human esophageal squamous carcinoma cells and further explore the molecular mechanisms in vitro. METHODS: Human esophageal squamous cell lines KYSE-30 and TE-1 were treated with anlotinib or raltitrexed, or both, then cell proliferation was measured by MTS and colony formation assay; cell migration and invasion were detected by wound-healing and transwell assays; cell apoptosis rate was studied by flow cytometry and the transcription of apoptosis-associated proteins were monitored by quantitative polymerase chain reaction (qPCR) analysis. Finally, western blot was performed to check phosphorylation of apoptotic proteins after treatment. RESULTS: Treatment with raltitrexed and anlotinib showed enhanced inhibitory effects on cell proliferation, migration and invasiveness compared with raltitrexed or anlotinib monotherapy. Meanwhile, raltitrexed combined with anlotinib strongly increased cell apoptosis percentage. Moreover, the combined treatment down-regulated mRNA level of the anti-apoptotic protein Bcl-2 and invasiveness-associated protein matrix metalloproteinases-9 (MMP-9), while up-regulated pro-apoptotic Bax and caspase-3 transcription. Western blotting showed that the combination of raltitrexed and anlotinib could inhibit the expression of phosphorylated Akt (p-Akt), Erk (p-Erk) and MMP-9. CONCLUSIONS: This study indicated that raltitrexed enhanced the antitumor effects of anlotinib on human ESCC cells by down-regulating phosphorylation of Akt and Erk, providing a novel treatment option for patients with esophageal squamous cell carcinoma (ESCC).

Concomitant Statins and the Survival of Patients with Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors: A Meta-Analysis.

Statins are suggested to improve cancer survival by possible anti-inflammatory effect. However, it remains unclear if concomitant use of statins could improve the efficacy of immune checkpoint inhibitors (ICIs) in patients with non-small-cell lung cancer (NSCLC). Accordingly, a meta-analysis was performed to systematically evaluate the effect of concomitant statins in NSCLC patients receiving ICIs. Relevant studies were obtained by literature search in PubMed, Embase, and Web of Science databases. A conservative random-effect model was used to combine the results. Eight cohorts including 2382 patients were included. The programmed death-1/ligand-1 inhibitors were used in seven studies; while the cytotoxic T-lymphocyte-associated protein 4 inhibitors were used in the other study. It was shown that concomitant use of statin did not significantly affect the progression-free survival (PFS, hazard ratio (HR): 0.86, 95% confidence interval (CI): 0.70 to 1.07, P=0.17; I 2 = 62%) or overall survival (OS, HR: 0.86, 95% CI: 0.74 to 1.01, P=0.07; I 2 = 29%) of NSCLC patients receiving ICIs. Subgroup analyses showed consistent results in studies with univariate or multivariate analytic models (P for subgroup analysis = 0.97 and 0.38 for the outcome of PFS and OS, respectively). In conclusion, concomitant use of statin seemed to have no significant influence on the survival of patients with NSCLC who were treated with ICIs.

Drug therapy for bone metastasis of malignant tumor: theory, progress, and potential.

Bone is a common metastatic site of malignancies, caused by the complex interaction between tumor cells and the bone microenvironment. The complicated procedure covers multiple targets for therapeutic strategies against bone metastasis. At the present, only bisphosphonates and denosumab are currently approved for the prevention of skeletal-related events. But it is still ineffective for some patients, and none of them are proven to prolong the overall survival of patients with bone metastasis. Thus, new bone-modifying agents and therapeutic strategies are required. The review aimed to generalize the basic theory of bone metastasis and major put emphasis on the development of fundamental and potential target drugs in the behavior of bone metastasis. The summary of the drug development process helps to provide ideas for finding new and effective treatments for bone metastasis.

Bone metabolism markers: Indicators of loading dose intravenous ibandronate treatment for bone metastases from breast cancer.

To investigate the changes in bone metabolism markers after second-line treatment with loading dose intravenous (i.v.) ibandronate in patients with bone metastases (BM) from breast cancer, 80 patients were enrolled in this study during January 2010 to April 2014. All the patients were treated with a second-line loading dose ibandronate for advanced breast cancer with BM and moderate-to-severe bone pain. Ibandronate (6 mg) was intravenously administered on three consecutive days followed by maintenance treatment every 3-4 weeks. Clinical data, including pain score, Karnofsky performance status (KPS) score, and changes in bone metabolism markers, were analyzed. Sixty-two patients were included in the final analysis. Compared with their pre-treatment scores, patients exhibited significantly increased KPS scores (P < .01) and a reduced dose of analgesic medication (oxycodone) (P < .01) after 3 and 6 weeks' post-treatment. The levels of serum bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRACP-5b), and cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) were significantly reduced after 3 and 6 weeks' post-treatment (P < .001). Aside from a few adverse events, no liver or renal toxicity was observed. Bone metabolism markers decreased by varying degrees after treatment with a loading dose of ibandronate in patients with BM from breast cancer. It might be convenient using bone metabolism markers to potentially evaluate the efficacy of bisphosphonates treatment for bone metastasis.