Rechallenges without desensitization following platinum-based chemotherapy reactions.

BACKGROUND: There is increasing interest in non-desensitization protocols as a potential way to reintroduce chemotherapy following hypersensitivity reactions (HSR). OBJECTIVE: To provide insight into the potential utility of non-desensitization reintroduction, particularly at institutions where allergy consultation may not be available. METHODS: For 70 patients with platinum HSR who underwent rechallenge with standard (≤2 hours), extended (1-bag, 1-step, 4-6 hours), or titrated (4-to-5-bag and -step, 6-7.5 hours) infusions between 1/2014 and 7/2019, demographics and clinical characteristics were reviewed and initial and breakthrough reactions (BTR) were graded using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Tolerance (no BTR) and completion (dose completed despite BTR) were compared using Fisher's exact test. RESULTS: Patients (mean [standard deviation] age 57 [13] years, initial HSR grade 2 [1]), were rechallenged with standard (n = 8), extended (n = 23), or titrated (n = 22) infusions after oxaliplatin HSR; and standard (n = 5) or titrated (n = 12) after carboplatin HSR. Tolerance and completion were higher for extended versus (vs) standard (tolerance-87%-vs-8%, p < 0.005; completion-96%-vs-38%, p < 0.005) and titrated versus standard (tolerance-76%-vs-8%, p < 0.005; completion-79%-vs-38%, p < 0.05) infusions. CONCLUSIONS: Extended and titrated infusions may increase reintroduction safety compared to standard infusions. Further investigation into extended infusions may provide a safe alternative to standard infusions in patients who may not have access to desensitization at their institution.

Cancer survivors and neurotoxic chemotherapy: hearing loss and tinnitus.

OBJECTIVES: Little is known about hearing loss and tinnitus associated with neurotoxic chemotherapy. Study evaluated for differences in occurrence rates and effects of hearing loss and tinnitus in survivors who received a platinum alone, a taxane alone or a platinum and taxane containing regimen. METHODS: Total of 273 survivors with breast, gastrointestinal, gynaecological or lung cancer completed self-report measures of hearing loss and tinnitus and had an audiometric assessment that obtained pure tone air conduction thresholds bilaterally at frequencies of between 0.25 kHz to 16.0 kHz. To adjust for age-related and gender-related changes in hearing, each survivor's audiogram was evaluated using the National Health and Nutrition Examination Survey-modified Occupational Safety and Health Administration standards. Survivor was classified as having hearing loss if at any frequency they scored poorer than the 50th percentile for their age and gender. Survivors were categorised as having tinnitus if they reported that for >10% of their time awake, they were consciously aware of their tinnitus. Differences among the chemotherapy groups were evaluated using parametric and non-parametric tests. RESULTS: For most of the demographic and clinical characteristics, no differences were found among the three chemotherapy groups. Occurrence rates for audiogram-confirmed hearing loss ranged from 52.3% to 71.4%. Occurrence rates for tinnitus ranged from 37.1% to 40.0%. No differences were found among the three chemotherapy groups in the occurrence rates or effects of hearing loss and tinnitus. CONCLUSION: These findings suggest that regardless of the chemotherapy regimen common mechanistic pathway(s) may underlie these two neurotoxicities.

Similarities in the Neuropathy Phenotype of Cancer Survivors Who Received Different Classes of Chemotherapy Drugs.

With the advent of platinum and taxane compounds used as single agents or in combination regimens, survival rates for some of the most common cancers have improved substantially. However, information on differences in the chemotherapy-induced peripheral neuropathy (CIPN) phenotype among single and combination regimens is limited. Study's purposes were to evaluate for differences in demographic and clinical characteristics; subjective and objective measures of CIPN; as well as the severity of common symptoms and quality of life among survivors who received platinum- (n = 95), taxane- (n = 200), or platinum and taxane-containing (n = 131) regimens. Patients completed self-report questionnaires (ie, duration of CIPN, pain intensity, pain qualities, pain interference) and underwent a physical examination that evaluated light touch, pain, and cold sensations and balance. For most of the subjective and objective measures of CIPN, as well as symptom severity and quality of life scores, no differences were found among the 3 chemotherapy groups. In all 3 chemotherapy treatment groups, CIPN was a painful, small fiber, and length dependent neuropathy. These findings support the hypothesis that CIPN induced by different classes of chemotherapy, as single agents or in combination, produce a similar CIPN phenotype which raises the possibility that CIPN induced by diverse chemotherapy protocols has the same underlying mechanism. PERSPECTIVE: In this study, that compared patients who received only platinum, only taxane, or both platinum and taxane containing regimens, no differences were found among the 3 groups in the CIPN phenotype. Findings raise the possibility that CIPN induced by diverse chemotherapy protocols has the same underlying mechanism.

Associations between cytokine gene variations and self-reported sleep disturbance in women following breast cancer surgery.

PURPOSE OF THE RESEARCH: To attempt to replicate the associations found in our previous study of patients and family caregivers between interleukin 6 (IL6) and nuclear factor kappa beta 2 (NFKB2) and sleep disturbance and to identify additional genetic associations in a larger sample of patients with breast cancer. METHODS AND SAMPLE: Patients with breast cancer (n = 398) were recruited prior to surgery and followed for six months. Patients completed a self-report measure of sleep disturbance and provided a blood sample for genomic analyses. Growth mixture modeling was used to identify distinct latent classes of patients with higher and lower levels of sleep disturbance. KEY RESULTS: Patients who were younger and who had higher comorbidity and lower functional status were more likely to be in the high sustained sleep disturbance class. Variations in three cytokine genes (i.e., IL1 receptor 2 (IL1R2), IL13, NFKB2) predicted latent class membership. CONCLUSIONS: Polymorphisms in cytokine genes may partially explain inter-individual variability in sleep disturbance. Determination of high risk phenotypes and associated molecular markers may allow for earlier identification of patients at higher risk for developing sleep disturbance and lead to the development of more targeted clinical interventions.