Background This study aimed to characterize the neurotoxicity of three different regimens of nab‐paclitaxel compared with a standard regimen of solvent‐based (sb) paclitaxel for the first‐line treatment of HER2‐negative metastatic breast cancer based on the Total Neurotoxicity Score (TNS), a tool specifically developed to assess chemotherapy‐induced neurotoxicity. Materials and Methods This was a randomized, open‐label study testing 4‐week cycles of 80 mg/m2 sb‐paclitaxel (PACL80/w) on days 1, 8, and 15; 100 mg/m2 nab‐paclitaxel on days 1, 8, and 15 (NAB100/w); 150 mg/m2 nab‐paclitaxel on days 1, 8, and 15 (NAB150/w); and 150 mg/m2 nab‐paclitaxel on days 1 and 15 (NAB150/2w). In addition to the TNS, neuropathy was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI‐CTCAE). Tumor response and quality of life were also evaluated. Results Neurotoxicity, as evaluated by the TNS, did not significantly differ between the sb‐paclitaxel group and any of the nab‐paclitaxel groups. The frequency of (any grade) polyneuropathy, as measured by the NCI‐CTCAE, was lower in the PACL80/w (n = 7, 50%) and NAB150/2w (n = 10, 62.5%) groups than in the NAB100/w (n = 13, 81.3%) or NAB150/w (n = 11, 78.6%) group. Although the differences were not statistically significant, compared with the other groups, in the NAB150/w group, the time to occurrence of grade ≥2 polyneuropathy was shorter, and the median time to recovery from grade ≥2 polyneuropathy was longer. Dose delays and reductions due to neurotoxicity and impact of neurotoxicity on the patients’ experience of symptoms and functional limitations was greater with NAB150/w. Among the seven polymorphisms selected for genotyping, the variant alleles of EPHA5‐rs7349683, EPHA6‐rs301927, and EPHA8‐rs209709 were associated with an increased risk of paclitaxel‐induced neuropathy. Conclusion The results of this exploratory study showed that, regardless of the dose, nab‐paclitaxel did not differ from sb‐paclitaxel in terms of neurotoxicity as evaluated with the TNS. However, results from NCI‐CTCAE, dose delays and reductions, and functional tools consistently indicate that NAB150/w regimen is associated with a greater risk of chemotherapy‐induced neuropathy. Thus, our results question the superiority of the TNS over NCI‐CTCAE for evaluating chemotherapy‐induced neuropathy and guiding treatment decisions in this context. The selection of the nab‐paclitaxel regimen should be individualized based on the clinical context and potentially supported by pharmacogenetic analysis. Registry: EudraCT, 2012‐002361‐36; NCT01763710 Implications for Practice The results of this study call into question the superiority of the Total Neurotoxicity Score over the National Cancer Institute Common Terminology Criteria for Adverse Events for evaluating chemotherapy‐induced neuropathy and guiding treatment decisions in this context and suggest that a regimen of 150 mg/m2 nab‐paclitaxel administered on days 1, 8, and 15 is associated with a greater risk of chemot...

ObjectiveDuring clinical practice, it can be challenging, given the lack of response biomarkers, to identify the patients with metastatic breast cancer (mbca) who would benefit most from the addition of bevacizumab to first-line standard chemotherapy. The aim of the present review was to summarize the relevant scientific evidence and to discuss the experience of a group of experts in using bevacizumab to treat mbca.MethodsA panel of 17 Spanish oncology experts met to discuss the literature and their experience in the use of bevacizumab as first-line treatment for mbca. During the meeting, discussions focused on three main issues: the profile of the patients who could benefit most from bevacizumab, the optimal bevacizumab treatment duration, and the safety profile of bevacizumab.ResultsThe subset of mbca patients who would benefit the most from the addition of bevacizumab to first-line standard chemotherapy are those with clinically defined aggressive disease. Treatment with bevacizumab should be maintained until disease progression or the appearance of unacceptable toxicity. In the mbca setting, the toxicity profile of bevacizumab is well known and can be managed in clinical practice after adequate training.ConclusionsThis expert group recommends administering bevacizumab as first-line treatment in patients with clinically aggressive disease.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis belong to a severe dermatopathic spectrum that includes frequently fatal mucocutaneous manifestations consisting of whole epidermal necrosis and sloughing with bullous transformation, blistering, and further skin detachment. Notably, cancer patients are at higher risk of developing SJS than the general population as a consequence of both the nature of neoplastic disease and frequent exposure to anticancer drugs. Ribociclib is a newly approved cycline-dependent kinase inhibitor that has been recently associated with a single case of SJS. We hereby present a case of ribociclib-related SJS. Early detection of threatening skin lesions is crucial to permit the immediate discontinuation of ribociclib given the predictable and unacceptable risk level. In cases of established SJS, early aggressive support should be initiated, ribociclib should be abruptly discontinued, and specific treatment based on actual evidence should be started.

SummaryWe report the case of a 32-year-old patient with a left atrium myxosarcoma, presenting with congestive heart failure. It is a rare cardiac malignant primary tumor that seems to derive from the same cellular line as myxomas, but the prognosis is very different. These tumors present local recidives and distance metastasis, so the mean survival is about 1 year, independent of any therapeutical option.

Objective: interlukin 12 (IL-12) is a cytokine that may enhance the proliferation and cytotoxic activity of T lymphocytes and natural killer (NK) cells. A relationship between extensive intratumoral infiltration of NK cells and longer survival rates in colorectal cancer (CRC) patients was previously noted. Preliminary evidence suggests that the combined administration of IL-12 and IL-2 may produce additive immunomodulatory activity. The purpose of this study was to determine whether the systemic administration of IL-12 (+/-IL-2) may induce an immune response against CRC as induced by 1,2-dimethylhydrazine (DMH).Methods: sixty-five 6-week-old Wistar rats were treated with weekly subcutaneous injections of DMH for 26 weeks at a dose of 20 mg/kg of body weight. Once tumoral induction was over, the animals were randomly allocated to one of three groups: I, control; II, intraperitoneal injections of IL-12; III, intraperitoneal injections of IL-12 combined with IL-2. At 30 weeks, all surviving animals were sacrificed. We studied the following parameters in each rat -number of tumors, size of tumors, and total tumoral volume.Tumor samples were studied using the monoclonal antibody CD 57 for the detection of NK cells. The extent of NK infiltration was classified as small, less than 50 NK cells/50 high-power field (HPF); moderate, 50 to 150 NK cells/50 HPF, and extensive, more than 150 NK cells/50 HPF.Results: thirty-five rats died before completion of the carcinogen exposure, and 30 rats were randomized (10 each group). In group II, 2 animals died during treatment. All rats in groups I and III developed tumors, while in group II two rats (25%) were tumorfree. Moreover, only one rat in group II developed multiple neoplasms, in contrast with group I and group III, where six rats (60%) and seven rats (70%), respectively, had more than one tumor. We found statistically significant differences in the mean number of tumors found in group II when compared to group I (p=0.028) and group III (p = 0.019). Other parameters measured, such as biggest tumor size and total tumoral volume were found to be lower in group II, although no statistical differences were found between groups. Only 10% of rats in group I showed moderated/extensive NK cell infiltration, vs. 60% of rats in group II (p = 0.077) and 70% in group III (p = 0.02).Conclusion: The administration of DMH to rodents provides a reliable and consistent means of inducing CRC that may be suitable for the evaluation of anti-cancer therapies. Our findings suggest that IL-12 is effective against the development of experimental CRC. Its antineoplastic effect could be attributed to the stimulus of this cytokine on the intratumoral infiltration of NK cells.