Avasopasem manganese (GC4419) protects against cisplatin-induced chronic kidney disease: An exploratory analysis of renal metrics from a randomized phase 2b clinical trial in head and neck cancer patients.

Head and neck squamous cell carcinoma (HNSCC) patients treated with high-dose cisplatin concurrently with radiotherapy (hdCis-RT) commonly suffer kidney injury leading to acute and chronic kidney disease (AKD and CKD, respectively). We conducted a retrospective analysis of renal function and kidney injury-related plasma biomarkers in a subset of HNSCC subjects receiving hdCis-RT in a double-blinded, placebo-controlled clinical trial (NCT02508389) evaluating the superoxide dismutase mimetic, avasopasem manganese (AVA), an investigational new drug. We found that 90 mg AVA treatment prevented a significant reduction in estimated glomerular filtration rate (eGFR) three months as well as six and twelve months after treatment compared to 30 mg AVA and placebo. Moreover, AVA treatment may have allowed renal repair in the first 22 days following cisplatin treatment as evidenced by an increase in epithelial growth factor (EGF), known to aid in renal recovery. An upward trend was also observed in plasma iron homeostasis proteins including total iron (Fe-blood) and iron saturation (Fe-saturation) in the 90 mg AVA group versus placebo. These data support the hypothesis that treatment with 90 mg AVA mitigates cisplatin-induced CKD by inhibiting hdCis-induced renal changes and promoting renal recovery.

Reporting of tobacco use and tobacco-related analyses in cancer cooperative group clinical trials: a systematic scoping review.

BACKGROUND: Continued smoking after a diagnosis of cancer negatively impacts cancer outcomes, but the impact of tobacco on newer treatments options is not well established. Collecting and evaluating tobacco use in clinical trials may advance understanding of the consequences of tobacco use on treatment modalities, but little is known about the frequency of reporting and analysis of tobacco use in cancer cooperative clinical trial groups. PATIENTS AND METHODS: A comprehensive literature search was conducted to identify cancer cooperative group clinical trials published from January 2017-October 2019. Eligible studies evaluated either systemic and/or radiation therapies, included ≥100 adult patients, and reported on at least one of: overall survival, disease/progression-free survival, response rates, toxicities/adverse events, or quality-of-life. RESULTS: A total of 91 studies representing 90 trials met inclusion criteria with trial start dates ranging from 1995 to 2015 with 14% involving lung and 5% head and neck cancer patients. A total of 19 studies reported baseline tobacco use; 2 reported collecting follow-up tobacco use. Seven studies reported analysis of the impact of baseline tobacco use on clinical outcomes. There was significant heterogeneity in the reporting of baseline tobacco use: 7 reported never/ever status, 10 reported never/ex-smoker/current smoker status, and 4 reported measuring smoking intensity. None reported verifying smoking status or second-hand smoke exposure. Trials of lung and head and neck cancers were more likely to report baseline tobacco use than other disease sites (83% versus 6%, P < 0.001). CONCLUSIONS: Few cancer cooperative group clinical trials report and analyze trial participants' tobacco use. Significant heterogeneity exists in reporting tobacco use. Routine standardized collection and reporting of tobacco use at baseline and follow-up in clinical trials should be implemented to enable investigators to evaluate the impact of tobacco use on new cancer therapies.