OBJECTIVE: To present the characteristics of drug hypersensitivity reactions (DHRs) among taxane recipients with non-small cell lung carcinoma (NSCLC), and to describe the results of rapid drug desensitization (RDD).
METHODS: A retrospective cross-sectional study included 45 patients who were treated with taxane for NSCLC and were found to be hypersensitive to taxane. All patients were administered the standard 3-bag, 12-step RDD protocol following the development of DHR. RDD success was evaluated separately for each cycle, and successful RDD was defined as the completion of the cycle with application of 12 steps of the desensitization protocol and the absence of early and/or late reactions afterwards.
RESULTS: Among 45 patients hypersensitive to taxane 43 (95.6%) successfully received taxane cycles with desensitization. Failed RDD occurred in only 2 (4.4%) patients. The total number of desensitization cycles was 183, of which 181 (98.9%) were successful. The mean age of patients with successful desensitization was 59.42 ± 10.48 years and 37 (86.0%) of them were male.
CONCLUSIONS: RDD is a reliable procedure that enables effective administration and completion of first-line taxane treatments in taxane-sensitive patients.

BACKGROUND: Anticancer agents are responsible for a majority of adverse drug reactions (ADRs) in cancer patients. ADR reporting with anticancer drugs is very rare in India due to the lack of awareness and knowledge about the Pharmacovigilance Programme of India. Hence, this study was done to assess the pattern of ADRs with anticancer agents in cancer patients and to increase awareness about ADR monitoring among healthcare professionals.
METHODS: This is an observational, retrospective and non-interventional study conducted in an ADR monitoring centre (AMC) in Govt. Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab, North India. Voluntarily reported ADR forms with anticancer drugs as suspected drugs over a period of seven years from January 2016 to December 2022 were analyzed. Various parameters were analyzed, which include demographic details of the patients, type of ADR, department reporting ADR and suspected drug. Causality assessment, severity assessment and preventability assessment were done according to the World Health Organization Uppsala Monitoring Centre (WHO-UMC) scale, modified Hartwig and Siegel scale and modified Schumock and Thornton scale, respectively.
RESULTS: The maximum numbers of ADRs were reported in the age group of 41-60 years (68.29%) and in females (59.75%). The maximum number of ADRs was reported with the use of taxanes (docetaxel and paclitaxel) (24.39%), targeted drugs (geftinib, imatinib, bortezomib, bevacizumab, rituximab and pazopanib) (24.39%) and platinum co-ordination complexes (cisplatin, oxaliplatin and carboplatin) (17.07%). Majority of the ADRs reported were shivering and ADRs on the skin. Majority of the ADRs were probable (64.70%), mild in nature (85.29%), definitely preventable (45.58%) and probably preventable (45.58%).
CONCLUSIONS: ADR monitoring is needed to increase the outcome of anticancer drug treatment in cancer patients. The quality of treatment in cancer patients can be improved through the timely management of these ADRs. It is a need of the present era to inform healthcare professionals about the Pharmacovigilance Programme to increase the reporting of ADRs due to anticancer drugs.

A common severe neurotoxic side effect of breast cancer (BC) therapy is chemotherapy-induced peripheral neuropathy (CIPN) and intervention is highly needed for the detection, prevention, and treatment of CIPN at an early stage. As the eye is susceptible to neurotoxic stimuli, the present study aims to determine whether CIPN signs in paclitaxel-treated BC patients correlate with ocular changes by applying advanced non-invasive biophotonic in vivo imaging. Patients (n = 14, 10 controls) underwent monitoring sessions after diagnosis, during, and after therapy (T0-T3). Monitoring sessions included general anamnesis, assessment of their quality of life, neurological scores, ophthalmological status, macular optical coherence tomography (OCT), and imaging of their subbasal nerve plexus (SNP) by large-area confocal laser-scanning microscopy (CLSM). At T0, no significant differences were detected between patients and controls. During treatment, patients\' scores significantly changed while the greatest differences were found between T0 and T3. None of the patients developed severe CIPN but retinal thickenings could be detected. CLSM revealed large SNP mosaics with identical areas while corneal nerves remained stable. The study represents the first longitudinal study combining oncological examinations with advanced biophotonic imaging techniques, demonstrating a powerful tool for the objective assessment of the severity of neurotoxic events with ocular structures acting as potential biomarkers.

UNASSIGNED: Chemotherapeutic agents can have both serious side effects and ototoxicity, which can be caused by direct toxic effects or by metabolic derangement by the agents. Cabazitaxel (CBZ) is a next-generation semi-synthetic taxane derivative that is effective in both preclinical models of human tumors that are sensitive or resistant to chemotherapy and in patients suffering from progressive prostate cancer despite docetaxel treatment. The primary aim of this study is to investigate the ototoxicity of CBZ in a rat model.
UNASSIGNED: : A total of 24 adult male Wistar-Albino rats were equally and randomly divided into four groups. CBZ (Jevtana, Sanofi-Aventis USA) was intraperitoneally administered to Groups 2, 3, and 4 at doses of 0.5, 1.0, and 1.5 mg/kg/week, respectively, for 4 consecutive weeks; Group 1 received only i.p. saline at the same time. At the end of the study, the animals were sacrificed and their cochlea removed for histopathological examination.
UNASSIGNED: : Intraperitoneal administration of CBZ exerted an ototoxic effect on rats, and the histopathological results became worse in a dose-dependent manner (P < 0.05).
UNASSIGNED: : Our findings suggest that CBZ may be an ototoxic agent and can damage the cochlea. More clinical studies should be conducted to understand its ototoxicity.

UNASSIGNED: This phase 2 study evaluated the safety of adjuvant chemoradiation (CTRT) for breast cancer.
UNASSIGNED: From April 2019 to 2020, 60 patients with stage II-III invasive breast cancer planned for adjuvant taxane-based chemotherapy and radiotherapy (RT) were accrued. Local ± regional (excluding the internal mammary nodal region) RT (40 Gy in 15 fractions ± boost) was started with the third cycle of an adjuvant taxane in a 3-weekly schedule or with the eighth cycle in a weekly schedule.
UNASSIGNED: Thirty-six patients received 3-weekly paclitaxel regimen and 24 received weekly paclitaxel regimen. The commonly used technique was three-dimensional conformal RT which was employed in 58% of patients. Regional RT, including the medial supraclavicular region, was done in 42 patients (70%). No dose-limiting (grade 3 or 4) toxicity was documented and all patients completed CTRT without any treatment interruption. The median ejection fraction pre and post CTRT 6 months was 60% (p = 0.177). The median value of cardiac enzyme (Troponin T ng/L) decreased from 37 to 20 (p = 0.009) post CTRT 6 months. Of the 54 patients who underwent the pulmonary function tests, there was no significant difference in various parameters like functional vital capacity (FVC) (2.29 versus 2.2 L, p = 0.375), forced expiratory volume at 1 second (FEV1) (1.86; 1.82; p = 0.365), FEV1/FVC (81.5; 81.43; p = 0.9) and diffusion lung capacity for carbon monoxide (88.3; 87.6; p = 0.62). At a median follow-up of 34 months, the 3-year actuarial rate of disease-free survival and overall survival was 75% and 98.3%, respectively. Quality of life scores (QOL) improved after treatment for most of the domains comparable to the pre-RT scores.
UNASSIGNED: Taxane-based adjuvant CTRT is a safe option and results in minimal toxicity and excellent compliance. It has favourable impact on cardio-pulmonary profile and QOL scores.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common toxicity of taxanes for which there is no effective intervention. Genomic CIPN risk determination has yielded promising, but inconsistent results. The present study assessed the utility of a collective SNP cluster identified using novel analytics to describe taxane-associated CIPN risk.
METHODS: We analyzed GWAS data derived from ECOG-5103, first identifying SNPs that were most strongly associated with CIPN using Fisher\'s ratio (FR). We then ranked ordered those SNPs which discriminated CIPN-positive (CIPN +) from CIPN-negative phenotypes based on their discriminatory power and developed the cluster of SNPs which provided the highest predictive accuracy using leave-one-out cross-validation (LOOCV).
RESULTS: Using aggregated genotype data obtained from the previously reported ECOG-5103 clinical trial (in which two different arrays were used, HumanOmniExpress (727,227 SNPs) and HumanOmni1-Quad1 (1,131,857 SNPs)), we identified a 267 SNP cluster which was associated with a CIPN + phenotype with an accuracy of 96.1%.
CONCLUSIONS: A cluster of SNPs was identified which prospectively discriminated patients most likely to develop symptomatic CIPN following taxane exposure as part of a breast cancer chemotherapy regimen. Validation using an independent patient cohort should be performed.

BACKGROUND: (Neo-)adjuvant chemotherapy for breast cancer is effective but has deleterious side effects on muscle tissue, resulting in reduced skeletal muscle mass, muscle function, and cardiorespiratory fitness. Various exercise regimens during cancer treatment have been shown to counteract some of these side effects. However, no study has compared the effect of high-intensity training versus low-to-moderate intensity training on muscle tissue cellular outcomes and physical function in patients with breast cancer during chemotherapy.
OBJECTIVE: The aim of this substudy within the Physical Training in Cancer (Phys-Can) consortium is to evaluate and compare the effects of high and low-to-moderate intensity exercise on muscle cellular outcomes, muscle function, and cardiorespiratory fitness in women with breast cancer undergoing (neo-)adjuvant chemotherapy. We further aim to investigate if the effects of chemotherapy including taxanes on muscles will be different from those of taxane-free chemotherapy.
METHODS: Eighty women recently diagnosed with breast cancer scheduled to start (neo-)adjuvant chemotherapy will be randomized to a combination of strength and endurance training, either at high intensity or at low-to-moderate intensity. Testing of muscle function and cardiorespiratory fitness and collection of muscle biopsies from the vastus lateralis muscle will be performed before the first cycle of chemotherapy (or after 1 week, when not possible) (T0), halfway through chemotherapy (T1), and after completion of chemotherapy (T2). It is estimated that approximately 50% of the participants will be willing to undergo muscle biopsies. To separate the effect of the treatment itself, a usual care group with no supervised training will also be included, and in this group, testing and collection of muscle biopsies will be performed at T0 and T2 only.
RESULTS: This study is funded by Active Against Cancer (Aktiv mot kreft) (May 2013) and the Norwegian Cancer Society (December 2018). Inclusion started in December 2016 and the last participant is expected to be recruited in December 2022. As of June 2022, we enrolled 38 (19 with biopsies) participants to the high-intensity training group, 36 (19 with biopsies) participants to the low-to-moderate intensity training group, and 17 (16 with biopsies) participants to the usual care group. Data analyses will start in fall 2022. The first results are expected to be published in spring 2024.
CONCLUSIONS: This study will generate new knowledge about the effects of different training intensities for women with breast cancer during chemotherapy treatment. It will give further insight into how chemotherapy affects the muscle tissue and how physical training at different intensities may counteract the treatment side effects in muscles. The results of this study will inform the development and refinement of exercise programs that are effective and compatible with the multidisciplinary management of breast cancer.
BACKGROUND: ClinicalTrials.gov NCT05218876; https://tinyurl.com/ysaj9dhm.
UNASSIGNED: DERR1-10.2196/40811.

Taxanes have a favorable pharmacokinetic profile for intraperitoneal application. We report our initial experience with taxane-PIPAC (pressurized intraperitoneal chemotherapy) for unresectable peritoneal metastases from different primary sites in terms of safety, feasibility, response rate, and conversion to resectability. In this retrospective study, PIPAC was performed alone or in combination with systemic chemotherapy. Paclitaxel was used as a single agent, whereas docetaxel was used in combination with cisplatin-adriamycin or oxaliplatin-adriamycin. From December 2019 to December 2021, 47 patients underwent 82 PIPAC procedures (1 PIPAC in 55.3%, 2 in 29.7%, 3 in 14.8%). The most common primary sites were ovarian cancer (31.9%), gastric cancer (23.4%), and colorectal cancer (21.2%). Docetaxel-cisplatin-adriamycin was used in 33 (70.2%) patients, docetaxel-oxaliplatin-adriamycin in 12 (25.5%), and paclitaxel alone in 2 (4.2%) patients. Grade 1-2 complications were observed in 24 (51%) and grade 3-4 complications in 6 (12.7%) patients (8.5% of 82 PIPACs). 16/47 (34.0%) patients had a clinical response to PIPAC. The mean PCI was 25.9 ± 9.2 for the first PIPACs and 22.4 ± 9 for the subsequent PIPACs with an average reduction of 3.6 points [change in PCI ranged from - 14 to + 8]. The PRGS was 1/2 in 4/47 (8.5%) patients (19.0% patients with > 1 PIPAC). A reduction in ascites was observed in 35.4% presenting with ascites. Nine (19.1%) patients had conversion to operability leading to a subsequent cytoreductive surgery in 8 (17%) patients. PIPAC with docetaxel is feasible and safe. The role of PIPAC with both docetaxel and paclitaxel either alone or in combination with other drugs should be investigated in prospective studies.

BACKGROUND: Taxanes are one of the most effective chemotherapies (CT) in breast cancer (BC), but the efficacy of taxanes rechallenge in early metastatic relapse has been poorly studied in patients previously treated by taxanes in the (neo)adjuvant setting. Our study aimed to analyse the efficacy of taxane rechallenge in case of early metastatic relapse in a multicentre retrospective observational study compared with other chemotherapies.
METHODS: We analysed the French national ESME metastatic BC (MBC) database and selected HER2- MBC patients who received CT in first-line treatment for a metastatic relapse occurring 3-24 months after previous (neo)adjuvant taxanes treatment.
RESULTS: Of 23,501 female patients with MBC in ESME, 1057 met the selection criteria. 58.4% received a taxane-based regimen (75.4% concomitant bevacizumab) and 41.6% received other CT. In hormone-receptor positive (HR+)/HER2- MBC, multivariate analysis showed no difference in OS between taxanes without bevacizumab compared to other CT (HZR = 1.3 [0.97; 1.74], but taxanes was significantly associated with worse PFS (HZR = 1.48 [1.14; 1.93]). In TNBC, taxanes without bevacizumab and carboplatin/gemcitabine were not superior to other CT for OS (HZR = 1.07 [0.79; 1.44] and HZR = 0.81 [0.58; 1.13], respectively), while for PFS, taxanes was inferior (HZR = 1.33 [1.06-1.67]) and carboplatin plus gemcitabine was superior to other CT (HZR = 0.63 [0.46; 0.87]). For both subtypes, the worse outcome observed with paclitaxel was no longer observed with the addition of bevacizumab.
CONCLUSIONS: With the limitation of retrospective design, taxanes rechallenge in early metastatic relapse of BC may result in a worse PFS in TNBC and HR+/HER2- MBC, which was not observed with the addition of bevacizumab.

OBJECTIVE: Taxane-based chemotherapy is the primary treatment for premenopausal breast cancer. Although being inconsistent, research suggests that variant alleles alter pharmacokinetics through reduced function of OATP transporters (limiting hepatic uptake), CYP-450 enzymes (hampering drug metabolism), and ABC transporters (decreasing clearance). Reduced function of DNA repair enzymes may hamper effectiveness through dose-limiting toxicities. We investigated whether single-nucleotide polymorphisms (SNPs) were associated with breast cancer recurrence or mortality in premenopausal women diagnosed with breast cancer.
METHODS: We conducted a population-based cohort study of premenopausal women diagnosed with non-distant metastatic breast cancer in Denmark during 2007‒2011, when guidelines recommended adjuvant combination chemotherapy (taxanes, anthracyclines, and cyclophosphamide). Using archived formalin-fixed paraffin-embedded primary tumor tissue, we genotyped 26 SNPs using TaqMan assays. Danish health registries provided data on breast cancer recurrence (through September 25, 2017) and death (through December 31, 2019). We fit Cox regression models to calculate crude hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and mortality across genotypes.
RESULTS: Among 2,262 women, 249 experienced recurrence (cumulative incidence: 13%) and 259 died (cumulative incidence: 16%) during follow-up (median 7.0 and 10.1 years, respectively). Mortality was increased in variant carriers of GSTP1 rs1138272 (HR: 1.30, 95% CI 0.95-1.78) and CYP3A rs10273424 (HR: 1.33, 95% CI 0.98-1.81). SLCO1B1 rs2306283 (encoding OATP1B1) variant carriers had decreased recurrence (HR: 0.82, 95% CI 0.64-1.07) and mortality (HR: 0.77, 95% CI 0.60-0.98).
CONCLUSIONS: Docetaxel effectiveness was influenced by SNPs in GSTP1, CYP3A, and SLCO1B1 in premenopausal women with non-distant metastatic breast cancer, likely related to altered docetaxel pharmacokinetics. These SNPs may help determine individual benefit from taxane-based chemotherapy.