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Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study. Patients and methods:After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out.Results: Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures. Conclusion:Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures.

PURPOSE Patients with pretreated estrogen receptor (ER)–positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer have poor prognosis. Elacestrant is a novel, oral selective ER degrader that demonstrated activity in early studies. METHODS This randomized, open-label, phase III trial enrolled patients with ER-positive/HER2-negative advanced breast cancer who had one-two lines of endocrine therapy, required pretreatment with a cyclin-dependent kinase 4/6 inhibitor, and ≤ 1 chemotherapy. Patients were randomly assigned to elacestrant 400 mg orally once daily or standard-of-care (SOC) endocrine monotherapy. Primary end points were progression-free survival (PFS) by blinded independent central review in all patients and patients with detectable ESR1 mutations. RESULTS Patients were randomly assigned to elacestrant (n = 239) or SOC (n = 238). ESR1 mutation was detected in 47.8% of patients, and 43.4% received two prior endocrine therapies. PFS was prolonged in all patients (hazard ratio = 0.70; 95% CI, 0.55 to 0.88; P = .002) and patients with ESR1 mutation (hazard ratio = 0.55; 95% CI, 0.39 to 0.77; P = .0005). Treatment-related grade 3/4 adverse events occurred in 7.2% receiving elacestrant and 3.1% receiving SOC. Treatment-related adverse events leading to treatment discontinuations were 3.4% in the elacestrant arm versus 0.9% in SOC. Nausea of any grade occurred in 35.0% receiving elacestrant and 18.8% receiving SOC (grade 3/4, 2.5% and 0.9%, respectively). CONCLUSION Elacestrant is the first oral selective ER degrader demonstrating a significant PFS improvement versus SOC both in the overall population and in patients with ESR1 mutations with manageable safety in a phase III trial for patients with ER-positive/HER2-negative advanced breast cancer.

High-grade OXA neurotoxicity can be predicted by clinical and neurophysiological information obtained at mid-treatment. Neurological assessment of acute neuropathy symptoms and radial and dorsal sural nerves NCS should be carefully monitored to predict and hopefully prevent the induction of severe OXAIPN.

BACKGROUND:The objective of the current prospective, multicenter, international study was to trace the incidence and severity of acute oxaliplatin-induced peripheral neuropathy (OXLIPN) and to determine its clinical pattern. The authors also specifically tested whether patients who had more symptoms of acute OXLIPN eventually would develop a more severe chronic, cumulative form of OXLIPN. METHODS: One hundred seventy patients (mean AE standard deviation age, 63.7 AE 8.7 years) who were scheduled to receive either combined leucovorin, 5-fluoruracil, and oxaliplatin (FOLFOX) or combined capecitabine and oxaliplatin (XELOX) for metastatic colorectal cancer were monitored prospectively at baseline and were followed in 4 European sites. The incidence of hyperexcitability symptoms secondary to acute OXLIPN was assessed by using a descriptive questionnaire (yes/no question) at each clinical evaluation. Motor and neurosensory criteria according to version 3 of the National Cancer Institute's Common Toxicity Criteria were applied to clinically grade the severity of OXLIPN. RESULTS: Acute OXLIPN was present in 146 of 170 patients (85.9%). The vast majority of these patients manifested cold-induced perioral (95.2%) or pharyngolaryngeal (91.8%) dysesthesias. Severe acute OXLIPN that required prolongation of oxaliplatin infusion from 2 hours to 4 to 6 hours occurred in 32 of 146 patients (21.9%). The increased number of acute OXLIPN symptoms was correlated significantly (Spearman rho correlation coefficient [r]) with both the development (r ¼ 0.602; P < .001) and the degree of the chronic, cumulative form (r ¼ 0.702; P < .001). CONCLUSIONS: The current results indicated that the vast majority of patients with colorectal cancer who receive oxaliplatin-based chemotherapy will manifest symptoms of a transient acute syndrome soon after oxaliplatin administration. Patients who have a more complex combination of acute phenomena related to axonal hyperexcitability are those who eventually develop more severe OXLIPN. Therefore, it may be advisable to test agents against acute OXLIPN to verify their effects on the chronic form. Cancer 2013;119:438-44. V C 2012 American Cancer Society.KEYWORDS: oxaliplatin, neurotoxicity, acute neuropathy, hyperexcitability, peripheral nerve damage. INTRODUCTIONColorectal cancer (CRC) represents the third most common type of cancer and the second leading cause of cancer-related deaths in the Western world. 1 Therapeutic management of CRC is challenging and depends on the disease stage at diagnosis. Current knowledge indicates that oxaliplatin (OXL)-based combination regimens, in the form of either combined leucovorin, 5-fluoruracil, and OXL (FOLFOX) or combined capecitabine and OXL (XELOX), have demonstrated substantial cytotoxic synergy in the adjuvant setting and in the advanced or metastatic setting and, thus, are associated with prolonged disease progression-free and overall survival. 2 However, peripheral neuropathy is currently recognized as 1 of the major nonhematologic toxicities of OXL with a...

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BACKGROUND:The current prospective, multicenter study sought to identify single nucleotide polymorphisms of voltage-gated sodium channels (SCNAs) genes that might confer susceptibility to an increased incidence and severity of oxaliplatin-induced peripheral neuropathy (OXAIPN) in patients treated with either leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX) or oxaliplatin plus capecitabine (XELOX) for colorectal cancer (CRC). METHODS: A total of 200 patients with CRC were genotyped with real-time polymerase chain reaction using locked nucleic acid hydrolysis probes or allele-specific primers. All patients had received oxaliplatin-based chemotherapy, either in the adjuvant or metastatic setting. The incidence and severity of cumulative OXAIPN was graded using the clinical version of the Total Neuropathy Score and the neurosensory National Cancer Institute Common Toxicity Criteria (version 3.0). The incidence of acute OXAIPN was assessed using a descriptive questionnaire (yes=no response format) at each clinical evaluation. Acute OXAIPN was present in 169 of 200 patients (84.5%), whereas after treatment discontinuation, the cumulative=chronic form of neurotoxicity occurred in 145 of 200 patients (72.5%). RESULTS: In the logistic regression analysis adjusted for confounding factors, the overdominant model (CT vs CC 1 TT) of 2 single nucleotide polymorphisms (ie, SCN4A-rs2302237 and SCN10A-rs1263292) emerged as being significantly associated with an increased incidence of acute OXAIPN (rs2302237: odds ratio of 2.62 [95% confidence interval (95% CI), 1.15-6.00]; P 5.019; and rs12632942: OR of 0.39 [95% CI, 0.17-0.88]; P 5.023). However, only SCN4A-rs2302237 emerged as also being predictive of the clinical severity of acute OXAIPN (OR, 2.50 [95% CI, 1.35-4.63]; P 5.0029) and the occurrence of cumulative=chronic OXAIPN (OR, 2.47 [95% CI, 1.04-5.85]; P 5.037). CONCLUSIONS: The results of the current study provide evidence to support a causal relationship between SCNA polymorphisms and OXAIPN. However, further studies from independent groups are warranted to confirm these results. Cancer 2013;119:3570-7.

Gene expression profiling tests are used in an attempt to determine the right treatment for the right person with early-stage breast cancer that may have spread to nearby lymph nodes but not to distant parts of the body. These new diagnostic approaches are designed to spare people who do not need additional treatment (adjuvant therapy) the side effects of unnecessary treatment, and allow people who may benefit from adjuvant therapy to receive it. In the present review we discuss in detail the major diagnostic tests available such as MammaPrint dx, Oncotype dx, PAM50, Mammostrat, IHC4, MapQuant DX, Theros-Breast Cancer Gene Expression Ratio Assay, and their potential clinical applications.