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Purpose: Paclitaxel, a widely used chemotherapeutic drug, can cause peripheral neuropathies leading to dose reductions and treatment suspensions and decreasing the quality of life of patients. It has been suggested that genetic variants altering paclitaxel pharmacokinetics increase neuropathy risk, but the major causes of interindividual differences in susceptibility to paclitaxel toxicity remain unexplained. We carried out a wholeexome sequencing (WES) study to identify genetic susceptibility variants associated with paclitaxel neuropathy.Experimental Design: Blood samples from 8 patients with severe paclitaxel-induced peripheral neuropathy were selected for WES. An independent cohort of 228 cancer patients with complete paclitaxel neuropathy data was used for variant screening by DHPLC and association analysis. HEK293 cells were used for heterologous expression and characterization of two novel CYP3A4 enzymes.Results: WES revealed 2 patients with rare CYP3A4 variants, a premature stop codon (CYP3A4 Ã 20 allele) and a novel missense variant (CYP3A4 Ã 25, p.P389S) causing reduced enzyme expression. Screening for CYP3A4 variants in the independent cohort revealed three additional CYP3A4 Ã 20 carriers, and two patients with missense variants exhibiting diminished enzyme activity (CYP3A4 Ã 8 and the novel CYP3A4 Ã 27 allele, p.L475V). Relative to CYP3A4 wild-type patients, those carrying CYP3A4 defective variants had more severe neuropathy (2-and 1.3-fold higher risk of neuropathy for loss-of-function and missense variants, respectively, P ¼ 0.045) and higher probability of neuropathy-induced paclitaxel treatment modifications (7-and 3-fold higher risk for loss-of-function and missense variants, respectively, P ¼ 5.9 Â 10 À5 ).Conclusion: This is the first description of a genetic marker associated with paclitaxel treatment modifications caused by neuropathy. CYP3A4 defective variants may provide a basis for paclitaxel treatment individualization.

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Background/Objective: This study sought to assess the psychometric properties of the 9-item Shared Decision-Making Questionnaire (SDM-Q-9) in patients with resected, non-metastatic cancer and eligible for adjuvant chemotherapy. Method: A total of 568 patients were recruited from a multi-institutional, prospective, transversal study. Patients answered the SDM-Q-9 after visiting their medical oncologist who, in turn, completed the SDM-Q–Physician version. Reliability, factorial structures [exploratory factor analysis (EFA), confirmatory factor analysis (CFA)], and convergent validity of the SDM-Q-9 scores were explored. Results: SDM-Q-9 showed a clear factorial structure, compatible with a strong and replicable general factor and a secondary group factor, in patients with resected, non-metastatic cancer. Total sum scores derived from the general factor showed good reliability in terms of omega coefficient: .90. The association between patient and physician perception of SDM was weak and failed to reach statistical significance. Males and patients over 60 years of age displayed the greatest satisfaction with SDM. Conclusions: SDM-Q-9 can aid in evaluating SDM from the cancer patients’ perspective. SDM-Q-9 is helpful in studies examining patient perspectives of SDM and as an indicator of the degree of quality and satisfaction with health care and patient-physician relationship.