[Clinical efficacy of induction chemoimmunotherapy for locally advanced hypopharyngeal carcinoma: a prospective phase â ¡ study].

Objective: To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR. Methods: A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m2 day 1, cisplatin 25 mg/m2 days 1-3, and capecitabine 800 mg/m2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results: A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm3. The T stage (OR=12.71, 95%CI: 1.4-112.5, P=0.022) and the volume (OR=7.1, 95%CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion: The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

Effects of taxane-induced peripheral neuropathy on hand dexterity impairment: evaluation of quantitative and subjective assessments.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) commonly involves hand dexterity impairment. However, the factors affecting hand dexterity impairment are unknown and there is currently no established treatment. The purpose of the current study was to clarify factors influencing hand dexterity impairment in taxane-induced peripheral neuropathy using subjective and objective assessments. METHODS: We assessed patient characteristics, treatment-related factors, subjective symptoms of CIPN (Patient Neurotoxicity Questionnaire [PNQ]), psychological symptoms, and upper limb dysfunction (Quick Disabilities of the Arm, Shoulder and Hand [Quick DASH]). Quantitative assessments were pinch strength, sensory threshold, hand dexterity impairment, and grip force control. Multiple regression analysis was performed using hand dexterity impairment as the dependent variable and age and PNQ, Quick DASH, and control of grip force as independent variables. RESULTS: Forty-three breast cancer patients were included in the analysis. Hand dexterity impairment in taxane-induced peripheral neuropathy patients was significantly correlated with age, grip force control, and PNQ sensory scores (p < 0.008). Multiple regression analysis demonstrated that PNQ sensory scores and grip force control were significantly associated with hand dexterity impairment (p < 0.01). CONCLUSION: Subjective symptoms (numbness and pain) and grip force control contributed to impaired hand dexterity in taxane-induced peripheral neuropathy.

Comparison of efficacy and safety of 5-FU or capecitabine combined with cisplatin and docetaxel (mDCF and mDCX) as a first-line chemotherapy regimen in her 2-negative metastatic gastric cancer patients: A retrospective study.

The prognosis of metastatic gastric cancer (GC) is poor, with a median survival time of less than a year. Capecitabine is a prodrug, metabolized by thymidine phosphorylase to its cytotoxic metabolite (5-FU). Few studies have compared capecitabine and 5-FU in mGC. In this retrospective study, we compared the efficacy and safety of modified DCF (mDCF) (docetaxel, cisplatin, and 5-FU) and modified DCX (mDCX) (docetaxel, cisplatin, and capecitabine) regimens for first-line treatment in patients with mGC. The study included 112 mGC patients treated with either mDCF (n = 69) or mDCX (n = 43) between 2010 and 2021. Demographic data, response rate, progression-free survival (PFS), overall survival (OS), and adverse events were evaluated. The complete response rate in the mDCF group was 10.1%, whereas the complete response rate in the mDCX group was 2.3%. The partial response rate for mDCF and mDCX were 29% and 37%, respectively. The 2 treatment arms of the study had the same objective rate of response and disease control rate (DCR). PFS and OS rates were comparable between the 2 groups. The median PFS in the mDCF and mDCX arms were 6.0 months (95% CI, 4.87-7.14) and 5.0 months (95% CI, 4.10-5.90) respectively (P = .08). The median OS in the mDCF and mDCX arms were 9.0 months (95% CI, 7.53-10.47) and 9.0 months (95% CI, 6.87-11.11) respectively (P = .07). Neutropenia, asthenia, stomatitis, and nausea/vomiting were the most frequently reported grade 3 to 4 adverse events (AEs). The rates of grade 3/4 AEs and dose reduction were comparable between the 2 groups. There was no treatment discontinuation due to grade 3 to 4 AE. As a first-line treatment for patients with mGC, mDCX and mDCF regimens have comparable efficacy and tolerability profiles.

Efficacy of the traditional Chinese medicine, Buyang Huanwu Decoction, at preventing taxane-induced peripheral neuropathy in breast cancer patients: A prospective, randomized, controlled study.

BACKGROUND: Buyang Huanwu Decoction (BYHWD) is a traditional Chinese prescription, originally derived from Yi Lin Gai Cuo during the Qing Dynasty. This study aimed to evaluate the efficacy and safety of BYHWD in the prevention of taxane-induced peripheral neuropathy (TIPN) in patients with breast cancer. METHODS: This single-center, statistician-blinded, parallel-group, simple randomized, no-treatment controlled study was conducted at the China-Japan Friendship Hospital in Beijing. Sixty breast cancer patients scheduled to receive nab-paclitaxel-based chemotherapy were randomly assigned to either the BYHWD group (N = 30) or the control group (N = 30) using simple randomization procedures. The data analysts were unaware of the treatment allocation. The primary efficacy endpoints were the incidence and severity of TIPN in the 2 groups, assessed using the Common Terminology Criteria for Adverse Events (CTCAE) and Patients' Neurotoxicity Questionnaire (PNQ). The secondary efficacy endpoint was the score of Functional Assessment of Cancer Therapy-Breast for both groups. The primary safety endpoints were routine blood test results and liver and renal functions. Both groups were subjected to 4 chemotherapy cycles. Efficacy and safety analyses were conducted on an intention-to-treat basis. RESULTS: The incidence of TIPN in the BYHWD group was 50.0%, which was lower than the 80.0% incidence in the control group (ß = -1.881 [95%CI -3.274, -.488]; P = .008, adjusted). The probability of TIPN in the BYHWD group was 15.2% of that in the control group, representing a significant reduction in incidence (odds ratio = .152, [95%CI .038, 0.614]; P = .008, adjusted). The CTCAE and PNQ grades of the BYHWD group were 1.527 and 1.495 points lower than those of the control group at the same cycle, respectively (CTCAE: ß = -1.527 [95%CI -2.522, -.533]; P = .003, adjusted; PNQ: ß = -1.495 [95%CI -2.501, -.489]; P = .004, adjusted, respectively). After treatment, the Functional Assessment of Cancer Therapy-Breast scores in the BYHWD group were significantly better than those in the control group (P = .003), especially in the physiological, functional, and additional concerns domains. CONCLUSION: Buyang Huanwu decoction (BYHWD) can effectively prevent TIPN and improve the quality of life in patients with breast cancer.

Quantitative analysis of the effect of docetaxel-induced edema on quality of life in patients with breast cancer and related factors: a prospective cohort study.

BACKGROUND: Systemic edema is an adverse effect of docetaxel chemotherapy and causes distress to patients, including those receiving this agent for breast cancer. However, its characteristics and factors related to its effect on quality of life (QoL) have not been adequately investigated. In this study, we assessed systemic edema quantitatively, explored related factors, and evaluated QoL in patients receiving docetaxel for breast cancer. METHODS: The study had a prospective cohort design and included 37 patients with no known history of swelling who were treated with docetaxel between September 2019 and April 2022. Patients were examined at the start, middle, and end of their course of treatment and 1 and 2 months later. Body water content, body mass, fat mass, and muscle mass were quantified using bioelectrical impedance analysis. Systemic edema was evaluated with reference to the Common Terminology Criteria for Adverse Events. The timing of development of systemic edema at any anatomical site that was grade 2 or worse was recorded. QoL was assessed using the Quality of Life-Anti Cancer Drug scale. Nutrition was evaluated using the Brief-type self-administered diet history questionnaire. Multivariable logistic regression analysis was performed to identify related factors. QoL was also compared between patients with edema and those without edema. RESULTS: Systemic edema developed in 67% of the study participants and was most prevalent at the end of treatment. Body fat mass (adjusted odds ratio [aOR] 0.802, 95% confidence interval [CI] 0.651-0.988, p = 0.038), disease stage (aOR 3.279, 95% CI 0.493-21.793, p = 0.219), and history of alcohol consumption (aOR 0.141, 95% CI 0.013-1.521, p = 0.106) were identified as risk factors for docetaxel-induced edema. Participants who developed systemic edema experienced more physical, vital, and emotional distress 1 month after treatment than those who did not. There was no association between systemic edema and nutrition. CONCLUSIONS: Systemic edema may develop after treatment with docetaxel and increase distress in patients with a high body fat mass. Patients at risk of systemic edema should be informed in advance about the potential frequency, location, and timing of its onset and encouraged to self-manage this condition.

Effectiveness and safety of primary prophylaxis of G-CSF during chemotherapy for prostate cancer, Japanese clinical guideline for appropriate use of G-CSF: clinical practice guidelines for the use of G-CSF 2022.

BACKGROUND: Docetaxel (DTX) is commonly used as a primary chemotherapy, and cabazitaxel (CBZ) has shown efficacy in patients who are DTX resistant. Primary prophylactic granulocyte colony stimulating factor (G-CSF) therapy is currently used with CBZ treatment in routine clinical care in Japan. METHODS: In this study, we performed a systematic review following the Minds guidelines to investigate the effectiveness and safety of primary prophylaxis with G-CSF during chemotherapy for prostate cancer and to construct G-CSF guidelines for primary prophylaxis use during chemotherapy. A comprehensive literature search of various electronic databases (PubMed, Cochrane Library, and Ichushi) was performed on January 10, 2020, to identify studies published between January 1990 and December 31, 2019 that investigate the impact of primary prophylaxis with G-CSF during CBZ administration on clinical outcomes. RESULTS: Ultimately, nine articles were included in the qualitative systematic review. Primary G-CSF prophylaxis during CBZ administration for metastatic castration-resistant prostate cancer was difficult to assess in terms of correlation with overall survival, mortality from infection, and patients' quality of life. These difficulties were owing to the lack of randomized controlled trials comparing patients with and without primary prophylaxis of G-CSF during CBZ administration. However, some retrospective studies have suggested that it may reduce the incidence of febrile neutropenia. CONCLUSION: G-CSF may be beneficial as primary prophylaxis during CBZ administration for metastatic castration resistant prostate cancer, and we made a "weak recommendation to perform" with an annotation of the relevant regimen.

Genetic determinants of taxane-induced peripheral neuropathy.

The efficacy of taxane­containing regimens has been demonstrated for various cancers, particularly ovarian, endometrial, breast, lung, and prostate cancers. However, extensive taxane-induced toxicities limit their use. Prediction and management of many toxic complications in cancer patients have evolved significantly over the last decade. Peripheral neuropathy is the most typical non-hematological taxane-related complication, and it has a multifactorial pathogenesis. It is often dose-dependent and progressive during therapy and sometimes even after treatment. Unfortunately, the prediction of these common adverse events remains unclear. In the past few years, several polymorphisms of candidate genes with a possible role in the development of this consequence were studied. This minireview aims to highlight the critical yet underappreciated roles of genetic predictors that may increase susceptibility to taxane-induced peripheral neuropathy in cancer patients (Ref. 40). Keywords: taxanes, paclitaxel, docetaxel, peripheral neuropathy, risk factors, genetic polymorphisms.

ONYCHOLYSIS AS A COMPLICATION OF TAXANE-BASED CHEMOTHERAPY WITH CONCOMITANT CRYOTHERAPY IN BREAST CANCER PATIENTS: TWO CASE REPORTS.

Nail changes are a common side effect of taxane chemotherapy, although onycholysis is quite a rare complication the correct management of which is poorly standardized. These case reports provide a description and analysis of onycholysis, a rare but noteworthy complication observed during taxane-based chemotherapy with concomitant cryotherapy in two patients with breast cancer. Despite prophylactic measures, both cases experienced nail complications during Paclitaxel treatment, underlining the complex nature of onycholysis during taxane therapy and highlighting the critical role of nail assessment and infection screening.

Prognostic Value of the Modeled Prostate-Specific Antigen KELIM Confirmation in Metastatic Castration-Resistant Prostate Cancer Treated With Taxanes in FIRSTANA.

PURPOSE: In a previous exploratory study, modeled early longitudinal prostate-specific antigen (PSA) kinetics observed within the 100-first treatment days with androgen deprivation therapy with or without docetaxel was associated with progression-free survival (PFS) and overall survival (OS) in patients with prostate cancer with rising PSA levels after primary local therapy. This prognostic value had to be confirmed in different settings. The objectives were to assess PSA kinetics modeling in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with chemotherapy in FIRSTANA trial and to investigate modeled PSA kinetic parameters prognostic/predictive value. MATERIALS AND METHODS: FIRSTANA phase III trial (ClinicalTrials.gov identifier: NCT01308567) assessed whether cabazitaxel is superior to docetaxel in terms of PFS/OS in patients with chemotherapy-naïve mCRPC. PSA longitudinal kinetics was assessed using the previous kinetic-pharmacodynamics model. Patient modeled ELIMination rate constant K (PSA.KELIM) was used to categorize favorable/unfavorable PSA declines (standardized PSA.KELIM < or ≥ 1.0 days-1) and further correlated with PFS/OS. RESULTS: In total, 1,050 of 1,168 enrolled patients were assessable for PSA.KELIM estimation. The median PSA.KELIM was 0.02 days-1. In univariate analyses, PSA.KELIM exhibited a significant prognostic value regarding survival: unfavorable versus favorable PSA.KELIM; median PFS, 3.6 months (95% CI, 3.0 to 4.2) versus 4.7 months (95% CI, 3.9 to 5.2), P = .002; median OS, 17.4 months (95% CI, 14.8 to 19.3) versus 28.4 months (95% CI, 26.7 to 31.6), P < .001. In multivariate analyses, PSA.KELIM was significant for PFS (hazard ratio [HR], 0.79 [95% CI, 0.67 to 0.93], P = .005) and OS (HR, 0.51 [95% CI, 0.44 to 0.60], P < .001), together with baseline radiological tumor progression and PSA doubling time. PSA.KELIM predictive value was not significant across treatment arms. CONCLUSION: This external validation study confirmed previous results about modeled PSA longitudinal kinetics prognostic value regarding PFS/OS in patients with mCRPC treated with taxanes. PSA.KELIM could be used to identify a subpopulation with poor prognosis, who may benefit from treatment intensification.

Nivolumab combined docetaxel versus nivolumab in patients with previously treated nonsmall cell lung cancer: a phase 2 study.

The current standard second-line treatment is immune checkpoint inhibitors monotherapy for nonsmall cell lung cancer (NSCLC) patients. The objective of this phase 2 study was to evaluate the efficacy and safety of nivolumab plus docetaxel compared with nivolumab monotherapy for second-line therapy in immunotherapy-naive patients with advanced NSCLC. Progression-free survival (PFS) was the primary endpoint of this phase 2 study. Patients were randomized to receive nivolumab plus docetaxel or nivolumab monotherapy. From July 2019 to June 2022, a total of 22 patients were recruited, with significantly longer median PFS observed in the nivolumab plus docetaxel group (4.0 months) compared to the nivolumab group (2.0 months), P  = 0.0019. The study was closed in June 2022 due to slow recruitment. The objective response rate was 10.0% [95% confidence interval (CI), 0-28.6] in the nivolumab group and 25% (95% CI, 0.5-49.5) in the nivolumab + docetaxel group ( P  = 0.346). Disease control was significantly higher in the nivolumab plus docetaxel arm (40.0% versus 83.3%, P  = 0.035). There was also an improvement in overall survival (OS) in the nivolumab + docetaxel arm, but this was not statistically significant (10.0 months versus 7.2 months, P  = 0.129). The addition of docetaxel to nivolumab was well-tolerated, with adverse events more common in the combination group. Despite the small sample size, the results suggest that the addition of docetaxel to nivolumab may be a promising treatment option for NSCLC patients progressing on platinum-based chemotherapy, with trends towards improved OS observed.

Efficacy and safety of nanoparticle albumin-bound paclitaxel in taxane-pretreated metastatic breast cancer patients.

BACKGROUND: Taxanes are the basic components of breast cancer chemotherapy. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) shows improved antitumor effects because of more targeted delivery. However, the effects of nab-paclitaxel have not been systematically studied in patients with metastatic breast cancer (MBC) pretreated with taxanes. Considering the limited treatment options for MBC, this study retrospectively evaluated the clinical efficacy and adverse effects of nab-paclitaxel in patients with taxane-pretreated MBC. METHODS: Patients who had previously received taxanes and subsequently received nab-paclitaxel chemotherapy for MBC at Jiangsu Cancer Hospital between October 2014 and April 2022 were included for analysis. The primary end point was progression-free survival (PFS), and the secondary end points were the objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), and side effects. RESULTS: A total of 236 female patients with MBC were included. The median PFS was 7.20 months (95% confidence interval [CI], 6.63-7.80 months), and the ORR, DCR, and CBR were 29.55% (95% CI, 23.50%-35.60%), 83.64% (95% CI, 78.70%-88.60%), and 56.36% (95% CI, 49.80%-63.00%), respectively. Following nab-paclitaxel treatment, the median PFS of patients who were sensitive to taxanes during previous treatments was significantly longer than that of patients who were resistant to taxanes (7.57 months vs. 4.43 months, p < .001). The most common adverse events were sensory neuropathy (89.83%), neutropenia (48.73%), leukopenia (46.61%), and anemia (35.59%). CONCLUSION: Nab-paclitaxel demonstrated clinical activity in taxane-pretreated patients with MBC. This beneficial effect was observed both in patients who were sensitive and resistant to taxanes during previous treatments. These results suggest nab-paclitaxel as the preferred chemotherapy regimen in patients with MBC, regardless of their sensitivity to taxanes during previous treatments.

Chemotherapy-related adverse effects with anthracycline and taxane-containing regimens in patients with localized Breast cancer: a descriptive study : Mohammed VI University Hospital, Medical Oncology Department, Marrakech, Morocco.

BACKGROUND: Although the side effects of chemotherapy are frequently described in research studies, there is little evidence on how common they are in everyday clinical care. This study's goal was to assess the most prevalent short-term side effects experienced by patients with localized breast cancer, undergoing chemotherapy based on anthracyclines and taxane-containing treatments, at the medical oncology department of the Mohammed VI University Hospital of Marrakech, Morocco. METHODS: This was a descriptive study. We conducted a listening session at the outpatient department of the hospital with the help of a structured questionnaire. The session engaged 122 women who had undergone cycles of chemotherapy. A chi-square test was used to compare the incidence and relative risk of short side effects with both anthracycline and taxane-containing regimens. RESULTS: The average age of participants was 49.1 years. In both regimens, the findings highlighted the frequency and relative risk of the following adverse effects: systemic symptoms (fever, asthenia and sleep disorder), gastrointestinal toxicity (Vomiting, nausea, diarrhoea, constipation, mucositis and loss of appetite), dermatological toxicity (Skin reactions on hands/feet, nail toxicity, allergies, alopecia and peripheral edema), neurological toxicity (neuropathy), arthromyalgia and ocular toxicity. CONCLUSIONS: In conclusion, it is crucial for healthcare professionals to be conscious of the significance of these adverse effects. They must also know how to manage them. Likewise, the listening approach highlights its importance in the daily follow-up and monitoring of patients.

Obstetric and neonatal outcomes following taxane use during pregnancy: a systematic review.

BACKGROUND: The use of taxanes following the first trimester of pregnancy is endorsed by current clinical guidelines. However, evidence regarding their safety in terms of obstetric and neonatal outcomes is limited. METHODS: A comprehensive literature search was performed using the MEDLINE, CENTRAL and Web of Sciences databases from their inception up to 12/16/2022. Eligibility criteria included gestational taxane use, presentation of original findings, and individual case data presented. A descriptive statistical analysis was undertaken. RESULTS: A total of 159 patients treated with taxane-containing regimens during pregnancy were identified, resulting in 162 fetuses exposed in utero. The majority of patients had breast cancer (n = 88; 55.3%) or cervical cancer (n = 45; 28.3%). The most commonly employed taxane was paclitaxel (n = 131; 82.4%). A total of 111 (69.8%) patients were also treated with other cytotoxic drugs during pregnancy, including platinum salts (n = 70; 63.0%) and doxorubicin/cyclophosphamide (n = 20; 18.0%). While most patients received taxanes during the second trimester of pregnancy (n = 79; 70.0%), two were exposed to taxanes in the first trimester. Obstetric outcomes were reported in 105 (66.0%) cases, with the most frequent adverse events being preterm contractions or premature rupture of membranes (n = 12; 11.4%), pre-eclampsia/HELLP syndrome (n = 6; 5.7%), and oligohydramnios/anhydramnios (n = 6; 5.7%). All cases with pregnancy outcome available resulted in live births (n = 132). Overall, 72 (54.5%) neonates were delivered preterm, 40 (30.3%) were classified as small for gestational age (SGA), and 2 (1.5%) had an Apgar score of < 7 at 5 min. Perinatal complications included acute respiratory distress syndrome (n = 14; 10.6%), hyperbilirubinemia (n = 5; 3.8%), and hypoglycemia (n = 2; 1.5%). In addition, 7 (5.3%) cases of congenital malformations were reported. At a median follow-up of 16 months, offspring health status was available for 86 (65.2%), of which 13 (15.1%) had a documented complication, including delayed speech development, recurrent otitis media, and acute myeloid leukemia. CONCLUSIONS: Taxanes appear to be safe following the first trimester of pregnancy, with obstetric and fetal outcomes being similar to those observed in the general obstetric population. Future studies should aim to determine the most effective taxane regimen and dosage for use during gestation, with a specific focus on treatment safety.

Electroacupuncture use for treatment of taxane-induced peripheral neuropathy in patients with breast cancer: protocol for a pilot, randomised, blinded, sham-controlled trial (EA for CIPN).

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of neurotoxic chemotherapy. Acute symptoms of CIPN during treatment can lead to dose reduction and cessation. Trials using electroacupuncture (EA) to treat established CIPN postchemotherapy have shown some efficacy. The current trial aims to assess the feasibility and preliminary efficacy of using EA to treat CIPN during chemotherapy. METHODS AND ANALYSIS: The current study is a single-centre, 1:1 randomised, sham-controlled pilot study set in a tertiary cancer hospital in Sydney, Australia, and will recruit 40 adult patients with early breast cancer undergoing adjuvant or neoadjuvant paclitaxel chemotherapy. Patients who develop CIPN within the first 6 weeks of chemotherapy will receive either true EA or sham-EA once a week for 10 weeks. The coprimary endpoints are recruitment and adherence rate, successful blinding of patients and compliance with the follow-up period. Secondary endpoints are mean change of CIPN symptoms from randomisation to end of treatment, sustained change in CIPN symptoms at 8-week and 24-week follow-up postchemotherapy, proportion of subjects attaining completion of 12 weeks of chemotherapy without dose reduction or cessation, change in acupuncture expectancy response pretreatment, during treatment and posttreatment. The primary assessment tool for the secondary endpoints will be a validated patient-reported outcome measure (European Organisation for Research and Treatment of Cancer Quality of Life Chemotherapy-Induced Peripheral Neuropathy) captured weekly from randomisation to week 12 of chemotherapy. ETHICS AND DISSEMINATION: The study protocol (2021/ETH12123) has been approved by the institutional Human Research Ethics Committee at St Vincent's Hospital Sydney and Chris O'Brien Lifehouse. Informed consent will be obtained prior to starting study-related procedures. The results will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: ACTRN12622000081718.

Taxanes for the treatment of breast cancer during pregnancy: an international cohort study.

INTRODUCTION: The addition of taxanes to anthracycline-based chemotherapy is considered standard of care in the treatment of breast cancer. However, there are insufficient data regarding the safety of taxanes during pregnancy. The aim of this study was to describe the incidence of obstetric and neonatal adverse events associated with the use of taxane-containing chemotherapy regimens for the treatment of breast cancer during pregnancy. METHODS: This is a multicenter, international cohort study of breast cancer patients treated with taxanes during pregnancy. A descriptive analysis was undertaken to synthetize available data. RESULTS: A total of 103 patients were included, most of whom were treated with paclitaxel and anthracyclines given in sequence during gestation (90.1%). The median gestational age at taxane initiation was 28 weeks (range = 12-37 weeks). Grade 3-4 adverse events were reported in 7 of 103 (6.8%) patients. The most common reported obstetric complications were intrauterine growth restriction (n = 8 of 94, 8.5%) and preterm premature rupture of membranes (n = 5 of 94, 5.3%). The live birth rate was 92 of 94 (97.9%), and the median gestational age at delivery was 37 weeks (range = 32-40 weeks). Admission to an intensive care unit was reported in 14 of 88 (15.9%) neonates, and 17 of 70 (24.3%) live births resulted in small for gestational age neonates. Congenital malformations were reported in 2 of 93 (2.2%). CONCLUSION: Obstetric and neonatal outcomes after taxane exposure during pregnancy were generally favorable and did not seem to differ from those reported in the literature with standard anthracycline-based regimens. This study supports the use of taxanes during gestation when clinically indicated.

Randomized adaptive selection trial of cryotherapy, compression therapy, and placebo to prevent taxane-induced peripheral neuropathy in patients with breast cancer.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating adverse effect of taxane therapy. Small non-randomized studies in patients with early-stage breast cancer (ESBC) suggest both cryotherapy and compression therapy may prevent CIPN. It is unknown which is more effective. METHODS: We conducted a randomized phase IIB adaptive sequential selection trial of cryotherapy vs. compression therapy vs. placebo ("loose" gloves/socks) during taxane chemotherapy. Participants were randomized in triplets. Garments were worn for 90-120 min, beginning 15 min prior and continuing for 15 min following the infusion. The primary goal was to select the best intervention based on a Levin-Robbins-Leu sequential selection procedure. The primary endpoint was a < 5-point decrease in the Functional Assessment of Cancer Therapy Neurotoxicity (FACT-NTX) at 12 weeks. An arm was eliminated if it had four or more fewer successes than the currently leading arm. Secondary endpoints included intervention adherence and patient-reported comfort/satisfaction. RESULTS: Between April 2019 and April 2021, 63 patients were randomized (cryotherapy (20); compression (22); placebo (21)). Most patients (60.3%) were treated with docetaxel. The stopping criterion was met after the 17th triplet (n = 51) was evaluated; success at 12 weeks occurred in 11 (64.7%) on compression therapy, 7 (41.1%) on cryotherapy, and 7 (41.1%) on placebo. Adherence to the intervention was lowest with cryotherapy (35.0%) compared to compression (72.7%) and placebo (76.2%). CONCLUSION: Compression therapy was the most effective intervention in this phase IIB selection trial to prevent CIPN and was well tolerated. Compression therapy for the prevention of CIPN should be evaluated in a phase III study. CLINICAL TRIAL REGISTRATION: ClinicaTrials.gov Identifier: NCT03873272.

High-resolution nerve ultrasound and corneal confocal microscopy in taxane-induced polyneuropathy.

BACKGROUND AND PURPOSE: The role of high-resolution nerve ultrasound (HRUS) and corneal confocal microscopy (CCM) in the early detection of taxane-induced polyneuropathy (TIPN) is unclear. The present prospective longitudinal controlled observational pilot study estimates the role of HRUS and CCM in the early diagnosis of TIPN in breast cancer patients. METHODS: Fifteen breast cancer patients receiving paclitaxel and 15 healthy age matched controls were included. Visits before and 3 weeks, 8 weeks and 6 months after treatment included clinical examination, the total neuropathy score, nerve conduction studies (NCS), monocular CCM including corneal nerve fibre length, density and branching and HRUS of bilateral median, ulnar, radial, tibial, peroneal and sural nerves. Patients were compared between different visits and to healthy controls. RESULTS: Total neuropathy score increased from 2.2 at baseline to 5.8 (p < 0.001) at week 8. NCS showed a decreased sensory amplitude in the sural, radial, ulnar and median nerve after 6 months (p < 0.001). HRUS revealed a significant increase of cross-sectional area in the sural nerve (p = 0.004), the median nerve (p = 0.003) at the carpal tunnel and the ulnar nerve in the forearm (p = 0.006) after 6 months. CCM showed no changes at different visits. CONCLUSIONS: Corneal confocal microscopy and HRUS do not detect early signs of TIPN during the paclitaxel treatment period. HRUS and NCS might detect congruent signs of an axonal, predominantly sensory polyneuropathy after 6 months. The clinical examination remains the most sensitive tool in the early detection of TIPN in breast cancer patients.

Incidence, description, predictors, and consequences of persistent taxane-induced peripheral neuropathy.

PURPOSE OF REVIEW: This review aims to provide insights into persistent taxane-induced peripheral neuropathy (TIPN). The primary objective is to describe the incidence, predictors, and consequences of TIPN lasting at least 1 year after the end of taxane treatment. RECENT FINDINGS: Studies show varying rates of TIPN persistence, with an estimated 30-40% and 40-60% resolving by 1- and 3-year post-treatment. TIPN in the feet and motor symptoms show less resolution post-treatment. Patients who are older or have higher body weight may experience less TIPN resolution, but results may be confounded by TIPN development during treatment. Persistent TIPN negatively impacts long-term functional ability, including gait, balance, and the ability to work. It also reduces overall quality of life (QOL), particularly affecting physical and social aspects. SUMMARY: Clinicians should be aware of the potential for persistent TIPN and its impact on patients' function and QOL. Future research should focus on large prospective studies with systematic TIPN assessments during and after treatment to better understand which symptoms and patient characteristics predict resolution. This information can guide treatment decisions, balancing the need for effective chemotherapy with minimizing long-term impairments in function and QOL.

Febrile neutropenia incidence and the variable toxicity profile between brand and generic docetaxel in the adjuvant treatment of breast cancer with docetaxel and cyclophosphamide regimen.

OBJECTIVE: To assess the incidence of febrile neutropenia without primary granulocyte colony-stimulating factor prophylaxis in patients undergoing chemotherapy with adjuvant docetaxel and cyclophosphamide, and to evaluate the toxicity profile of brand-name docetaxel (Taxotere ® ) and the generic formulation. METHODS: This retrospective study was conducted using data obtained from electronic medical records of patients treated at a Brazilian cancer center. Patients with breast cancer who underwent adjuvant treatment between January 2016 and June 2019 were selected. Data were analyzed using chi-square and Fisher correlation of variables, and multivariate analyses were adjusted for propensity score. RESULTS: A total of 231 patients with a mean age of 55.9 years at the time of treatment were included in the study. The majority (93.9%) had luminal histology, 84.8% were at clinical stage I, and 98.2% had a good performance status. The overall incidence of febrile neutropenia in the study population was 13.4% (31 cases). The use of brand-name docetaxel (Taxotere ® ) was the only factor associated with febrile neutropenia occurrence (OR= 3.55, 95%CI= 1.58-7.94, p=0.002). CONCLUSION: In patients with breast cancer who require treatment with adjuvant docetaxel and cyclophosphamide regimen, the toxicity profile differs between brand-name and generic docetaxel. Regardless of the formulation used, the incidence of febrile neutropenia was less than 20%, which may allow for the omission of primary prophylactic granulocyte colony-stimulating factor use in this setting.

Dose-Dense Docetaxel-Cyclophosphamide and Epirubicin-Cisplatin(ddDCEP): Analysis of an Alternative Platinum-Containing Regimen in 116 Patients with Early Triple Negative Breast Cancer.

We assessed the efficacy, tolerability, and cost-effectiveness of a novel neoadjuvant regimen comprising docetaxel-cyclophosphamide alternating with epirubicin-cisplatin (ddDCEP) administered biweekly for 16 weeks in 116 patients with early triple-negative breast cancer. This regimen achieved a high pathological complete response (ypT0/TisN0) rate of 55.2% and favorable survival outcomes (30-month event-free survival, 91.2%; overall survival, 97%). Febrile neutropenia was observed in 4.3% of patients, and 98% completed at least six of eight cycles. ddDCEP was more cost-effective than contemporary carboplatin-based regimens. This novel approach offers an economically viable and effective alternative to current chemoimmunotherapy regimens, and merits further investigation.