Low Geriatric Nutritional Risk Index Is Associated with Poorer Prognosis in Elderly Diffuse Large B-Cell Lymphoma Patients Unfit for Intensive Anthracycline-Containing Therapy: A Real-World Study.

Nutritional assessments, including the Geriatric Nutritional Risk Index (GNRI), have emerged as prediction tools for long-term survival in various cancers. This study aimed to investigate the therapeutic strategy and explore the prognostic factors in the elderly patients (≥65 years) with diffuse large B cell lymphoma (DLBCL). The cutoff value of the GNRI score (92.5) was obtained using the receiver operating characteristic curve. Among these patients (n = 205), 129 (62.9%) did not receive standard R-CHOP chemotherapy. Old age (≥80 years), poor performance status, low serum albumin level, and comorbidities were the major factors associated with less intensive anti-lymphoma treatment. Further analysis demonstrated that a lower GNRI score (<92.5) was linked to more unfavorable clinical features. In the patients who received non-anthracycline-containing regimens (non-R-CHOP), multivariate analysis showed that a low GNRI can serve as an independent predictive factor for worse progression-free (HR, 2.85; 95% CI, 1.05-7.72; p = 0.039) and overall survival (HR, 2.98; 95% CI, 1.02-8.90; p = 0.045). In summary, nutritional evaluation plays a role in DLBCL treatment and the GNRI score can serve as a feasible predictive tool for clinical outcomes in frail elderly DLBCL patients treated with non-anthracycline-containing regimens.

Oxidative stress, redox signaling, and metal chelation in anthracycline cardiotoxicity and pharmacological cardioprotection.

SIGNIFICANCE: Anthracyclines (doxorubicin, daunorubicin, or epirubicin) rank among the most effective anticancer drugs, but their clinical usefulness is hampered by the risk of cardiotoxicity. The most feared are the chronic forms of cardiotoxicity, characterized by irreversible cardiac damage and congestive heart failure. Although the pathogenesis of anthracycline cardiotoxicity seems to be complex, the pivotal role has been traditionally attributed to the iron-mediated formation of reactive oxygen species (ROS). In clinics, the bisdioxopiperazine agent dexrazoxane (ICRF-187) reduces the risk of anthracycline cardiotoxicity without a significant effect on response to chemotherapy. The prevailing concept describes dexrazoxane as a prodrug undergoing bioactivation to an iron-chelating agent ADR-925, which may inhibit anthracycline-induced ROS formation and oxidative damage to cardiomyocytes. RECENT ADVANCES: A considerable body of evidence points to mitochondria as the key targets for anthracycline cardiotoxicity, and therefore it could be also crucial for effective cardioprotection. Numerous antioxidants and several iron chelators have been tested in vitro and in vivo with variable outcomes. None of these compounds have matched or even surpassed the effectiveness of dexrazoxane in chronic anthracycline cardiotoxicity settings, despite being stronger chelators and/or antioxidants. CRITICAL ISSUES: The interpretation of many findings is complicated by the heterogeneity of experimental models and frequent employment of acute high-dose treatments with limited translatability to clinical practice. FUTURE DIRECTIONS: Dexrazoxane may be the key to the enigma of anthracycline cardiotoxicity, and therefore it warrants further investigation, including the search for alternative/complementary modes of cardioprotective action beyond simple iron chelation.

In vitro modeling of the structure-activity determinants of anthracycline cardiotoxicity.

Doxorubicin and other anthracyclines rank among the most effective anticancer drugs ever developed. Unfortunately, the clinical use of anthracyclines is limited by a dose-related life-threatening cardiotoxicity. Understanding how anthracyclines induce cardiotoxicity is essential to improve their therapeutic index or to identify analogues that retain activity while also inducing less severe cardiac damage. Here, we briefly review the prevailing hypotheses on anthracycline-induced cardiotoxicity. We also attempt to establish cause-and-effect relations between the structure of a given anthracycline and its cardiotoxicity when administered as a single agent or during the course of multiagent chemotherapies. Finally, we discuss how the hypotheses generated by preclinical models eventually translate into phase I-II clinical trials.

Evaluation of mutagenic and genotoxic activities of new derivatives of anthracyclines.

The phenomenon of multidrug resistance is connected with an increased efflux of cytotoxic agents from the cells and is a serious problem in the treatment with anthracycline antibiotics. Search for new antitumor drugs from the anthracycline group are focused on the syntheris of derivatives with changes in saccharide and anthracycline parts. The genotoxic activity of selected nine new derivatives of anthracycline was evaluate basing on reference tests: micronucleus test in vitro and the Ames test. A correlation was observed between the results obtained in the Ames test and those received in the micronucleus test. In both tests, derivative WP903 demonstrated a strong genotoxic action.