Search

Background: Monosialotetrahexosylganglioside (GM1) is a neuroprotective glycosphingolipid that repairs nerves. Oxaliplatin-based chemotherapy is neurotoxic. This study assessed the efficacy of GM1 for preventing oxaliplatin-induced peripheral neurotoxicity (OIPN) in colorectal cancer (CRC) patients receiving oxaliplatin-based chemotherapy., Methods: In total, 196 patients with stage II/III CRC undergoing adjuvant chemotherapy with mFOLFOX6 were randomly assigned to intravenous GM1 or a placebo. The primary endpoint was the rate of grade 2 or worse cumulative neurotoxicity (NCI-CTCAE). The secondary endpoints were chronic cumulative neurotoxicity (EORTC QLQ-CIPN20), time to grade 2 neurotoxicity (NCI-CTCAE or the oxaliplatin-specific neuropathy scale), acute neurotoxicity (analog scale), rates of dose reduction or withdrawal due to OIPN, 3-year disease-free survival (DFS) and adverse events., Results: There were no significant differences between the arms in the rate of NCI-CTCAE grade 2 or worse neurotoxicity (GM1: 33.7% vs placebo: 31.6%; P = .76) or neuropathy measured by the EORTC QLQ-CIPN20 or time to grade 2 neurotoxicity using NCI-CTCAE and the oxaliplatin-specific neuropathy scale. GM1 substantially decreased participant-reported acute neurotoxicity (sensitivity to cold items [P < .01], discomfort swallowing cold liquids [P < .01], throat discomfort [P < .01], muscle cramps [P < .01]). The rates of dose reduction or withdrawal were not significantly different between the arms (P = .08). The 3-year DFS rates were 85% and 83% in the GM1 and placebo arms, respectively (P = .19). There were no differences in toxicity between the arms., Conclusion: Patients receiving GM1 were less troubled by the symptoms of acute neuropathy. However, we do not support the use of GM1 to prevent cumulative neurotoxicity. (ClinicalTrials.gov number, NCT02251977)., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated., Methods: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation., Results: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively., Conclusions: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment., Trial Registration: ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443., Competing Interests: There are no conflicts of interest

Background: As a surrogate marker of systemic inflammation, the lymphocyte-to-monocyte ratio (LMR) is an independent prognostic factor for various malignancies. This study investigated the prognostic significance of the pre-chemotherapy LMR in patients with previously untreated metastatic colorectal cancer (mCRC) receiving chemotherapy., Methods: The present study included newly diagnosed mCRC patients treated between January 2005 and December 2013 with FOLFOX chemotherapy, specifically oxaliplatin 180 mg/m(2) on day 1, with leucovorin 400 mg/m(2) administered as a 2-hour infusion before the administration of 5-fluorouracil 400 mg/m(2) as an intravenous bolus injection, and 5-fluorouracil 2400 mg/m(2) as a 46-h infusion immediately after 5-fluorouracil bolus injection. The LMR was calculated as the absolute count of lymphocytes divided by the absolute count of monocytes. COX proportional hazards analysis was performed to evaluate the association of LMR with survival outcomes., Results: A total of 488 patients were included. Patients with high pre-chemotherapy LMR experienced significant improvements in progression-free survival (PFS, 9.2 vs. 7.6 months, P < 0.001) and overall survival (OS, 19.4 vs. 16.6 months, P < 0.001) compared with patients with low pre-chemotherapy LMR. Subsequent COX multivariate analysis showed that high pre-chemotherapy LMR (≥3.11) was an independent favorable prognostic factor for PFS and OS. Additionally, patients whose LMR remained high (high-high subgroup), increased (low-high subgroup), or decreased (high-low subgroup) following chemotherapy showed better results in terms of PFS and OS than patients whose LMR remained low (low-low subgroup) after chemotherapy., Conclusions: For patients with previously untreated mCRC receiving FOLFOX chemotherapy, an elevated pre-chemotherapy LMR is an independent favorable prognostic factor for PFS and OS, and changes in the LMR before and after chemotherapy seem to predict the benefit of chemotherapy.

Inflammation has been demonstrated to be widely involved in the carcinogenesis of nasopharyngeal carcinoma (NPC). However, the prognostic significance of lymphocyte to monocyte ratio (LMR) in metastatic NPC is not fully addressed. The purpose of the study is to investigate the prognostic impact of pre-treatment absolute lymphocyte count (ALC), absolute monocyte count (AMC), and LMR on patients with newly diagnosed metastatic NPC undergoing chemotherapy. Between January 2006 and December 2010, patients with newly diagnosed metastatic NPC undergoing chemotherapy were retrospectively collected. The prognostic significance of baseline clinical features and inflammatory markers was investigated. A total of 256 patients were eligible for the study. The best cut-off value of ALC, AMC, and LMR was 2.25 × 10(9)/L, 0.35 × 10(9)/L, and 5.07, respectively. Patients in the high LMR group had a significantly longer overall survival (OS) (25.0 months [24.50-25.49]) than patients in the low LMR group (16.0 months [15.51-16.49]; p < 0.001). In addition, ALC ≥ 2.25 × 10(9)/L (HR, 0.59; 95% CI, 0.43-0.81; p = 0.001) and LMR ≥ 5.07 (HR, 0.42; 95% CI, 0.30-0.59; p <  .001) remained as independent prognostic factors for superior OS, while AMC did not retained its prognostic significance in COX multivariate analysis. Pre-treatment ALC and LMR were demonstrated to be independent prognostic factors in patient with newly diagnosed metastatic NPC receiving chemotherapy. Future prospective studies are needed to validate the findings.

The link between circulating lymphocyte-to-monocyte ratio (LMR) and newly diagnosed metastatic non-small cell lung cancer (NSCLC) is not fully defined. The study was conducted to evaluate the prognostic impact of LMR on survival outcomes in previously untreated metastatic NSCLC patients receiving platinum-based doublet. Chemotherapy-naive metastatic NSCLC patients undergoing platinum-based doublet were retrospectively enrolled. Clinical features regarding gender, age, Eastern Cooperative Oncology Group (ECOG) performance status, histology, absolute lymphocyte count (ALC), absolute monocyte count (AMC) and LMR were collected to determinate their prognostic impact on progression-free survival (PFS) and overall survival (OS). Up to 370 patients were eligible for the study. By univariate analysis, ECOG performance status, histology, ALC, AMC and LMR were showed to be significantly associated with PFS and OS. In subsequent Cox multivariate analysis, non-squamous cell carcinoma, ALC ≥ 2.45 × 10(9)/L, AMC <0.45 × 10(9)/L and LMR ≥ 4.56 were demonstrated to be independently correlated with better PFS. In addition, independent favorable prognostic factors for OS were only limited to LMR ≥ 4.56 and non-squamous cell carcinoma, whereas ECOG performance status of 2 and AMC ≥ 0.45 × 10(9)/L remained as independently inferior prognostic indicators for OS. Our findings implicate that circulating AMC and LMR are regarded as independent prognostic factors for PFS and OS in previously untreated metastatic NSCLC patients receiving platinum-based doublet.

Background: The prognostic significance of the circulating absolute monocyte count (AMC) in patients with locally advanced hepatocellular carcinoma (HCC) is uncertain. This study was designed to assess the association of circulating AMC with survival outcomes in patients diagnosed with locally advanced or metastatic HCC receiving systemic chemotherapy., Materials and Methods: Between January 1, 2005 and December 30, 2012, locally advanced or metastatic HCC patients who had Child-Pugh stage A or B disease and received systemic chemotherapy were retrospectively enrolled. Patient features including gender, age, extrahepatic metastasis, Child-Pugh stage, serum alpha-fetoprotein(AFP) level and AMC were collected to investigate their prognostic impact on overall survival(OS)., Results: A total of 216 patients were eligible for the study. The optimal cut-off value of AMC for OS analysis was 0.38×10⁹/L. Median OS was 5.84 months in low-AMC group (95% confidence interval [CI], 5.23 to 6.45), and 5.21 months in high-AMC group (95% CI, 4.37 to 6.04; p=0.003). In COX multivariate analysis, elevated AMC remained as an independent prognostic factor for worse OS (HR, 1.578; 95% CI, 1.120 to 2.223, p=0.009)., Conclusions: Our results indiicate that circulating AMC is confirmed to be an independent prognostic factor for OS in patients with locally advanced or metastatic HCC receiving systemic chemotherapy.