National Cancer Institute-Common Toxicity Criteria Research Articles

Auctox A New Method to Evaluate the Safety of Anticancer Drugs

The evaluation of anticancer drugs safety is currently based on considering the worst Adverse Event (AE) in a particular patient. The aim of the study was to define a new method which would better describe the impact of treatment on Quality of Life (QoL), combining Patient Reported Outcomes (PROs) and the monitoring of all AEs. A comparative approach to the classic National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) classification was performed to assess the interest of monitoring Area Under the Curve (AUC) of toxicities on quality of life. A negative impact on global health status, assessed by the VAS of EQ-5D-3L, was significantly identified for three AEs based on CTCAE grade alone versus seven when considering AUCtox assessment.

Efficacy and safety of eribulin plus gemcitabine in second-line or beyond for patients with HER2-negative metastatic breast cancer: A multi-center, open-label, single-arm, phase II study.

e13102 Background: Eribulin is a non-taxane microtubule inhibitor approved in China for the treatment of patients with advanced breast cancer who progress after ≥2 lines of chemotherapy. Eribulin was shown to improve overall survival (OS) in various subgroups of patients with metastatic breast cancer (MBC) who were pretreated with an anthracycline and taxane. Furthermore, combination chemotherapy with eribulin plus gemcitabine led to a similar progression free-survival (PFS) benefit, with less neurotoxicity, as paclitaxel plus gemcitabine in patients with MBC who had not received prior cytotoxic chemotherapy for metastatic disease. However, the effect of eribulin plus gemcitabine on PFS in second-line or beyond remain unclear. Methods: This phase II, open-label, single-arm study was conducted at 13 institutions in China (NCT05263882). Patients with histologically confirmed HER2-negative MBC who had received at ≥1 prior taxane-containing chemotherapeutic regimen for advanced disease and had received anthracycline-containing regimens in the adjuvant setting, were enrolled between Nov 2021 and Oct 2022. Eligible patients received eribulin 1.4 mg/m2 and gemcitabine 1.0 g/m2 intravenously on days 1 and 8 of a 21-day cycle. Efficacy outcomes included PFS, objective response rate (ORR), and disease control rate (DCR), evaluated using RECIST v1.1. Adverse events (AEs) were graded according to The National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.0. Results: In total, 54 patients were included; 39 (72.2 %) were HR+/HER2- and 15 (27.8 %) were triple negative, the median age was 49.5 years (range: 31-70) and sites of metastasis were the liver (57.4%), lung (37.0%), bone (59.3%), brain (11.1%) and lymph nodes (53.7%). The median number of previous chemotherapy lines was 3 (range: 2-7): eribulin plus gemcitabine was used in second-line for 15 (27.8%) patients, third-line for 20 (37.0%) patients, fourth-line for 7 (13.0%) patients and ≥fifth-line in 12 (22.2%) patients. The median PFS was 7.7 months. The ORR was 40.7% and the DCR was 66.7%. Best overall responses and PFS rates at 3 and 6 months are shown. The most common grade 3-4 AEs were hematological: Leukopenia (35.2%), anemia (18.6%) and thrombocytopenia (9.4%). No treatment-related death was reported. Conclusions: Eribulin plus gemcitabine is effective in heavily pretreated patients with HER2-negative MBC with a predictable, manageable safety profile. Clinical trial information: NCT05263882 . [Table: see text]

Failure pattern and suggestions for target volume delineation of carcinoma showing thymus-like differentiation treated with intensity-modulated radiotherapy

BackgroundTo review our long-term clinical experience, analyze the failure patterns, and give suggestions for target volume delineation of carcinoma showing thymus-like differentiation (CASTLE) treated with intensity-modulated radiotherapy (IMRT).MethodsFrom April 2008 to May 2019, 30 patients with CASTLE treated by postoperative or radical IMRT in our center were retrospectively reviewed. A total dose of 56-60 Gy in 28–30 fractions was prescribed to patients without residual disease and 66 Gy in 33 fractions for patients with residual or unresectable disease. Survival rates were calculated using the Kaplan-Meier method. Treatment-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0.ResultsAmong the 30 patients, 12 (40%) received partial resection or biopsy. Lateral lymph node metastasis was observed in 7 (23.3%) patients. During follow-up, regional lymph node recurrence occurred in 2 patients and distant metastasis in 5 patients. With a median follow-up time of 63.5 months, the 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), overall survival (OS) and progression-free survival (PFS) rates were 100, 88.9, 78.9, 93.1 and 78.9%, respectively. For patients with no lateral neck node metastasis, prophylactic radiotherapy for lateral neck nodal regions failed to improve RRFS (p = 0.381) and OS (p = 0.153).ConclusionDistant metastasis was the major failure pattern for CASTLE after surgery and IMRT. For patients with no lateral neck node metastasis, the omission of irradiation for lateral neck nodal regions seems to be safe and feasible.

Blood neurofilament light chain as a biomarker for monitoring and predicting paclitaxel-induced peripheral neuropathy in patients with gynecological cancers.

ObjectiveWe aimed to evaluate the potential of serum neurofilament light chain (sNfL) and serum brain-derived neurotrophic factor (sBDNF) as reliable biomarkers for paclitaxel-induced peripheral neuropathy (PIPN).MethodsForty-eight patients with gynecologic cancer scheduled to undergo six cycles of paclitaxel-based chemotherapy at the National Cancer Center of Korea between September 2020 and January 2022 were prospectively assessed during and after chemotherapy.ResultsAt the end of the chemotherapy, 12 (25%) patients were classified as having grade 3 PIPN according to the National Cancer Institute-Common Toxicity Criteria. The sNfL levels increased during paclitaxel treatment in all patients. After two, four, and six cycles, patients with grade 3 PIPN exhibited higher mean sNfL levels than those in the 0–2 grade range (p = 0.004, p = 001, and p < 0.001, respectively). For sNfL levels ≥ 124 pg/mL, after two cycles of chemotherapy, the sensitivity and specificity for predicting grade 3 PIPN at the end of treatment were 80% and 79%, respectively. Over the course of paclitaxel-based treatment, sBDNF levels continued to decrease regardless of the severity of PIPN. At the end of treatment and six months after chemotherapy, patients with grade 3 PIPN had lower sBDNF levels than those within the 0–2 grade range (p =0.037 and 0.02, respectively), and the patients in the latter group had better clinical symptoms six months after the end of treatment.ConclusionsThe sNfL levels during paclitaxel-based chemotherapy reflect ongoing neuroaxonal injury and serve as reliable biomarkers of PIPN severity. The sNfL levels during early treatment with paclitaxel might be prognostic indicators for PIPN progression. Low sBDNF levels 6 months after chemotherapy might adversely affect PIPN recovery.

The characterization of oxaliplatin-induced peripheral neuropathy using electromyography in gastrointestinal cancer patients

Oxaliplatin-induced peripheral neuropathy (OIPN) is a common dose-dependent chemotherapy complication in gastrointestinal cancer (GIC). This side effect may restrict therapeutic dose elevation of oxaliplatin. Here, OIPN frequency and determinants of neuropathy appearance in oxaliplatin-treated GIC patients. A total of 102 GIC patients who underwent chemotherapy with fluorouracil, folinic acid and oxaliplatin (FOLFOX4) regimen participated in this longitudinal study. Electromyography (EMG) was accomplished for ulnar, radial, sural, peroneal nerves and superficial peroneal nerve (SPN) before, 3, and 6 months after treatment. National Cancer Institute-Common Toxicity Criteria V.3 and clinical version of the Total Neuropathy Score were used for the neuropathy diagnosis at six months after treatment onset. Of all entered patients, twelve people discontinued this study, and five patients passed away. About 85 patients remained three and six months after chemotherapy onset. Approximately 95% of patients three months after chemotherapy demonstrated OIPN manifestations. Finally, data for 81 patients having neuropathy were analyzed. Mean age of patient 64.0±10.9 years. There were about 3.7%, 30.9%, 63% grade III, II, I of neuropathy, respectively. Interestingly, a significant decrease in action potential (AP) amplitude of SPN, sural and radial nerves but not ulnar and peroneal was observed after treatment onset. However, only the ulnar nerve indicated a substantial deceleration of nerve conduction. Age, sex, weight, past medical diseases, smoking and acute neuropathy were not significantly associated with OIPN. The occurrence of OIPN is detectable by electrophysiological changes of SPN, radial, and sural nerves at three and six months after starting chemotherapy with the FOLFOX4 regimen.

Effect of Levofloxacin on the Efficacy and Adverse Events in Intravesical Bacillus Calmette-Guerin Treatment for Bladder Cancer: Results of a Randomized, Prospective, Multicenter Study

BackgroundAlthough bacillus Calmette-Guerin (BCG) is a standard treatment for high-risk non–muscle-invasive bladder cancer (NMIBC), a high rate of adverse events with a variety of grades remains a difficulty. ObjectiveIn this randomized, prospective, multicenter study, we examined whether levofloxacin, given after each intravesical instillation of BCG, could improve its tolerance in patients with intermediate- to high-risk urothelial carcinoma of the bladder without compromising its efficacy. Design, setting, and participantsOverall, 106 Japanese patients (85 men and 21 women; age: median, 69.5 yr) with primary or recurrent NMIBC were randomized after transurethral resection to induce treatment with intravesical BCG plus levofloxacin (group 1) or BCG alone (group 2). InterventionPatients who underwent intravesical instillation of BCG were randomized with or without levofloxacin administration. Outcome measurements and statistical analysisAdverse events were assessed using the National Cancer Institute-Common Toxicity Criteria version 3.0. Cumulative incidence functions and Kaplan-Meier methods were applied to estimate survival outcomes. Results and limitationsThere was no significant difference in baseline characteristics between the groups. The completion rate of group 1 (85.5%) was not significantly lower than that of group 2 (76.5%; p = 0.321). There was no significant difference in the completion rate of patients with pollakisuria, painful micturition, gross hematuria, fever elevation, and others between the groups. The incidence of adverse events in patients with high-grade pollakisuria (7.3% vs 25.4%, p = 0.041) and fever (0% vs 9.1%, p = 0.034) was significantly lower in group 1. The 5-yr progression-free and cancer-specific survival rates were significantly better in group 1. ConclusionsProphylactic levofloxacin administration may reduce the severity of adverse events and contribute to better outcomes from BCG intravesical therapy in patients with NMIBC. Patient summaryLevofloxacin administration seems to be a safe and effective therapy for non–muscle-invasive bladder cancer patients treated with bacillus Calmette-Guerin intravesical therapy.

Efficacy of Wen-Luo-Tong on Peripheral Neuropathy Induced by Chemotherapy or Target Therapy: A Randomized, Double-Blinded, Placebo-Controlled Trial.

To evaluate the efficacy of Wen-Luo-Tong Granules (WLT) local administration in the treatment of patients with peripheral neuropathy (PN) induced by chemotherapy or target therapy. This study is a randomized, double-blinded, and placebo-controlled trial. Seventy-eight patients with PN induced by chemotherapy or target therapy were enrolled from China-Japan Friendship Hospital between July 2019 and January 2020. They were randomly assigned to WLT (39 cases) and control groups (39 cases) using a block randomization method. The WLT group received WLT (hand and foot bath) plus oral Mecobalamin for 1 week, while the control group received placebo plus oral Mecobalamin. The primary endpoint was PN grade evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE). The secondary endpoints included quantitative touch-detection threshold, neuropathy symptoms, Quality of Life Questionnaire-Chemotherapy Induced Peripheral Neuropathy (QLQ-CIPN20), and Quality of Life Questionnaire-Core30 (QLQ-C30). After treatment, the PN grade in the WLT group was significantly lower than that in the control group (1.00 ± 0.29 vs. 1.75 ± 0.68, P<0.01). The total effective rate in the WLT group was significantly higher than that in the control group (82.05% vs. 51.28%, P<0.01). Compared with the control group, the touch-detection thresholds at fingertips, neuropathy symptom score, QLQ-CIPN 20 (sensory scale, motor scale, autonomic scale, and sum score), and QLQ-C30 (physical functioning, role functioning, emotional functioning, and global health) in the WLT group significantly improved after treatment (P<0.01 or P<0.05). WLT local administration was significantly effective in the treatment of patients with PN induced by chemotherapy or target therapy. (Trial registration No. ChiCTR1900023862).

Efficacy and safety of inetetamab in combination with chemotherapy as first-line treatment of HER2-positive metastatic breast cancer: a subgroup analysis in the HOPES study.

Our aim was to evaluate the efficacy and safety of inetetamab plus chemotherapy in the first-line treatment of HER2-positive metastatic breast cancer. A HOPES study was conducted on patients with HER2-positive metastatic breast cancer. Eligible patients were randomly divided into test group and control group at a 2:1 ratio. Among them, patients in test group received inetetamab plus vinorelbine. Concurrently, patients in the control group received vinorelbine. During the trial, safety evaluation was conducted every 4 weeks and efficacy evaluation was conducted every 8 weeks. As assessed by the Response Criteria Evaluation in Solid Tumors (RECIST) 1.0 criteria, the primary endpoint was progression-free survival (PFS) and the secondary endpoints included objective response rate (ORR) and disease control rate (DCR). Safety was estimated according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0. Efficacy and safety of the postoperative recurrent-metastases first-line subgroup in the HOPES registry study of inetetamab was analyzed and compared with previous clinical studies of trastuzumab in the first-line treatment of HER2-positive metastatic breast cancer. In total, we included 315 patients. Among them, 114 patients in the postoperative recurrent-metastases first-line subgroup were assigned to the full analysis set (FAS) (test group, 72; and control group, 42). The test group significantly prolonged median PFS (mPFS) (11.1 vs. 3.3 months of the control group; P<0.0001). ORR and DCR were remarkably higher than the control group (ORR, 61.5% vs. 29.7% with an increase of 31.8%, P=0.0224; DCR, 93.8% vs. 59.4% with an increase of 34.4%, P=0.0003). Efficacy and safety of postoperative recurrent-metastases first-line subgroup in the HOPES study was comparable to previous clinical studies of trastuzumab as first-line treatment of HER2-positive metastatic breast cancer. Inetetamab has shown efficacy and safety equivalent to trastuzumab for patients in the first-line treatment of postoperative recurrence-metastases HER2-positive breast cancer, which confirms its important status and potential as first-line treatment. Inetetamab provides more first-line targeted therapy options for patients with HER2-positive metastatic breast cancer.

Prevention, Evaluation, and Treatment of Chemotherapy and Radiotherapy Induced Oral Mucositis

Oral mucositis is a frequent adverse effect of cancer treatment that includes radiotherapy (RT) and chemotherapy (CT). It is related to worse outcomes because of pain, nutritional problems, effects on quality of life, changes in cancer treatment, the risk of infection, and financial costs. It affects 20% to 80% of people receiving chemotherapy, and almost all patients receive head and neck radiation therapy. This review presents the current understanding and discusses evidence-based clinical management strategies for oral mucositis. The current model of mucositis pathogenesis is comprised of five broad stages. The two widely used grading systems for routine clinical care and research on mucositis are the WHO (World Health Organization) and Oral Mucositis Scale and the National Cancer Institute's Common Toxicity Criteria (NCI-CTC). The effective use of assessment scales, nonpharmacologic treatment modalities such as good professional oral hygiene, cryotherapy, and photobiomodulation, and pharmacologic therapies such as KGF-1 (palifermin) and benzydamine-containing mouthwash are important for mucositis prevention, and topical morphine is effective for the treatment of mucositis induced by radiotherapy or chemotherapy. Mucoadhesive hydrogel and anti-inflammatory medications such as celecoxib, misoprostol, and rebamipide are reported to be effective for radiation-induced mucositis. However, additional experimental studies are required to confirm the evidence.

Diagnostic tools should be used for the diagnosis of chemotherapy induced peripheral neuropathy in breast cancer patients receiving taxanes.

BackgroundThough the incidence, characteristics, and pathogenesis of chemotherapy induced peripheral neuropathy (CIPN) by taxane based chemotherapy were extensively studied, diagnostic guidelines extent only recently.AimTo observationally investigate whether specific tests can be used to predict and monitor CIPN severity.MethodsFourteen female breast cancer patients receiving paclitaxel or docetaxel were evaluated using the McGill Pain Questionnaire (MPQ), National Cancer Institute Common Toxicity Criteria (NCI‐CTC) grading, clinical total neuropathy score (TNSc), quantitative sensory testing (QST) of pressure pain threshold (PPT), and numeric rating scale (NRS) scores and stocking and glove distribution testing (SGDT), at the start (T0), midst (T1), and end (T2) of their treatment and after 3 months (T3).ResultsAt T3, patients scored NCI‐CTC neuropathy grade 1 (14.3%), 2 (64.3%), and 3 (14.3%) respectively. Fifty percentage scored at least grade 1 at T0, with complaints not caused by CIPN. Pain, if present, was denominated “tingling” and “cold” in the MPQ. Median TNSc score increased from T0 (2.43) to T1 (4.71) to T2 (5.50) to T3 (5.57), as did pinprick and cold sensation disturbances in SGDT. PPT and associated NRS remained unchanged. TNSc and SGDT at T1 could not predict the NCI‐CTC grade at T3.ConclusionNCI‐CTC, TNSc, and stocking and glove distribution testing can be used in the early diagnosis and monitoring of CIPN, with false‐positive findings at baseline. Final NCI‐CTC grades could not be predicted.

First-in-human phase I/Ib open-label dose-escalation study of GWN323 (anti-GITR) as a single agent and in combination with spartalizumab (anti-PD-1) in patients with advanced solid tumors and lymphomas

BackgroundGWN323 is an IgG1 monoclonal antibody (mAb) against the glucocorticoid-induced tumor necrosis factor receptor-related protein. This first-in-human, open-label phase I/Ib study aimed to investigate the safety and tolerability and to...

Azithromycin oral suspension in prevention and management of oral mucositis in patients undergoing hematopoietic stem cell transplantation: a randomized controlled trial.

This study aimed to investigate the effects of azithromycin suspension on oral mucositis in patients undergoing hematopoietic stem cell transplantation (HSCT). The study was designed as a single-blind randomized controlled trial in Taleghani medical center affiliated to Shahid Beheshti University of Medical Sciences Tehran Iran. Patients undergoing HSCT were randomly assigned to intervention or control groups. Azithromycin suspension was administered twice daily by gargling for 30s and swallowing, on the first day of chemotherapy for patients in the intervention group. Graded oral mucositis (OM) occurrence based on National Cancer Institute Common Toxicity Criteria (NCI-CTC) scale (grade 0 to 5) was considered the main outcome, and the Numerical Rating Scale (NRS:0-10) measured the severity of OM symptoms. In a duration of 15months, 88 patients were randomly assigned and finally 70 patients were evaluable for study outcomes (randomized 1:1 to azithromycin versus no-azithromycin). The incidence and duration of the mucositis significantly improved in the intervention group compared to the control. Azithromycin use was consistent with a lower rate of dryness (P < 0.001), dysphagia (P < 0.001), and loss of sense of taste (P < 0.001). Also, in the intervention group, lower intensity of pain due to mucositis (P = 0.01) and lower duration of mucositis were observed (p = 0.045). No significant adverse drug reaction was observed in patients receiving azithromycin. Based on the result from this study, azithromycin suspension is an effective option in the prevention and treatment of chemotherapy-induced OM. Further study is needed to assess the effect of azithromycin and comparison with other therapeutic options. Iranian Registry of Clinical Trials: IRCT201603093210N13.

Use of Bendamustine Combined with Rituximab in Chronic Lymphocytic Leukemia Patients: A Single Center Experience

Background:There is no single standard treatment (tx) modality for symptomatic chronic lymphocytic leukemia (CLL) patients (pts). Fludarabine, cyclophosphamide, and rituximab (FCR) is the prefered regimen for healthy, young pts (<65 years). However, through the disease course almost all pts in this group will relapse and may become refractory to fludarabine-containing regimens. Additionally, for older adults (>65 years) and pts with comorbidities fludarabine is not a suitable agent. Bendamustine combined with rituximab (BR) is an acceptable alternative in these patient groups.Aim: To evaluate the efficacy and safety of BR in previously untreated or relapsed/refractory (R/R) CLL pts.Patients and Methods: Ptswho received BR as first- or further lines of tx were enrolled in the study. Data were analysed as of August 2017. The standard dose of bendamustine was 70 mg/m2 in D1 and D2 for R/R pts and 90 mg/m2 in D1 and D2 for tx naive pts. Rituximab dose was 375 mg/m2 in the first cycle and 500 mg/m2 in consecutive cycles. Pts' demographics, disease stages, biological and cytogenetic prognostic markers, comorbidities, previous treatments, bendamustine dose, cycle durations, use of G-CSF, adverse events (AEs), tx responses and follow-up periods were noted retrospectively. Evaluation of response was established according to NCI-WG guidelines [Hallek et al, 2008]. All toxicities were assessed according to the National Cancer Institute's Common Toxicity Criteria (NCI-CTC), version 4.Results: Nineteen ptswere enrolled in the study (Table 1). Thirteen pts were male and the median age at the time of BR treatment was 61 years (range, 41-80 years), with 9 pts (47%) older than 65 years. At the time of diagnosis, 7 pts (37%) were Rai stage IV. Del(13q), del(11q), and del(17p) were positive in 5, 1, and 2 pts, respectively. All pts had active disease as defined by the NCI-WG. Five pts received BR as first-line. Of the previously treated 14 pts, 71% had received fludarabine with either alkylating agents and/or rituximab. Median number of previous lines of tx was 2.Among comorbidities, hypertension (32%), asthma/COPD (32%) and type 2 diabetes mellitus (3%) were the three most common.Bendamustine dose ranged from 70 mg to 100 mg/m2. According to the physicians' decision, bendamustine was started as 70 mg in first cycle of tx and was escalated to the planned dose in all pts but three. All 6 intended courses were administered to 15 pts (79%), and in the remaining 4 pts, 3 died due to infections and one patient required early discontinuation due to prolonged neutropenia. In 8 pts (42%) tx cycle prolonged to 35 days and in 11 cases (58%) G-CSF were used during tx.After a median follow-up of 17 months (mos), five of 19 pts (26%) had progressed at the time of analysis, and median time to next treatment (TTNT) was 12 mos (range, 5-34 mos). Treatment responses are shown in Table 2. During the follow-up 5 pts (26%) died. Two had multiple comorbidities, three received bendamustine doses ≥90 mg/m2. Deaths were due to R/R disease and/or infections. Median OS after treatment was 13 mos (range, 5-34 mos).Overall, grade III-IV AEs occurred in 14 cases (74%): the most common toxicity was hematologic AEs (anemia in 2, neutropenia in 12, and thrombocytopenia in 2 cases), and serious infection occurred in six pts (2 bacterial pneumonia, 4 neutropenic fever). Non-hematologic toxicities were grade II rash in one, and grade II nausea in one patient.Conclusion: BR is effective and safe in treatment naive CLL patients and shows notable activity in R/R pts. Major toxic effect are myelosuppresion and infections. Higher doses of bendamustine should be avoided in patients with comorbidities and older age. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Real-world effectiveness of eribulin in heavily pretreated patients with metastatic breast cancer in China: A multicenter retrospective study.

e13057 Background: Eribulin is a nontaxane microtubule inhibitor approved in China for patients with locally advanced or metastatic breast cancer previously treated with anthracyclines and taxane. The aim of this study was to evaluate the efficacy and safety profile of eribulin and explore potential predictive factors for the efficacy of eribulin among Chinese women with metastatic breast cancer (MBC) in real-world practice. Methods: A total of 272 consecutive MBC patients who were treated with eribulin from November 2019 to October 2020 in 9 institutions nationwide were included in this study. Eribulin was administered intravenously at a dose of 1.4 mg/m2 on days 1 and 8 of a 21-day cycle. Efficacy outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Adverse events (AEs) were graded according to The National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.0. Results: Eribulin showed a median PFS of 3.9 months (95% confidence interval [CI] 3.3–4.3); however, the OS data were immature. The ORR was 16.2%, and the CBR was 21.7%. A total of 51.8% of patients received eribulin monotherapy, and 48.2% of patients were treated with eribulin combine with targeted therapy or other chemotherapy. The number of metastatic sites, duration of previous taxane treatment for MBC, and combination regimen with bevacizumab were significant in Cox multivariate analysis (p=0.048, p=0.039, and p=0.045, respectively) and were significantly associated with PFS of eribulin. The most common AEs with eribulin treatment were hematological toxicities, including neutropenia, leukopenia, and anemia. Conclusions: This is the first cohort of eribulin real-world data base on retrieval currently after eribulin launched in China. Eribulin was effective with a manageable toxicity profile in clinical practice. Furthermore, when prescribed in combination with other agents, eribulin did not increase the toxic effects of each agents. Eribulin monotherapy or combine with other agents is alternative for the heavily pretreated patients with MBC. [Table: see text]

Prognostic Nutritional Index (PNI) in Patients With Breast Cancer Treated With Neoadjuvant Chemotherapy as a Useful Prognostic Indicator.

ObjectivePrognostic nutritional index (PNI), calculated as serum albumin (ALB) (g/L) + 5 × total lymphocyte count (109/L), is initially used to evaluate nutritional status in patients undergoing surgery and may evaluate the therapeutic effects and predict the survival of various solid tumors. The present study aimed to evaluate the potential prognostic significance of PNI in breast cancer patients receiving neoadjuvant chemotherapy (NACT).MethodsA total of 785 breast cancer patients treated with neoadjuvant chemotherapy were enrolled in this retrospective study. The optimal cutoff value of PNI by receiver operating characteristic curve stratified patients into a low-PNI group (<51) and a high PNI group (≥51). The associations between breast cancer and clinicopathological variables by PNI were determined by chi-square test or Fisher’s exact test. Kaplan–Meier plots and log-rank test were used to evaluate the clinical outcomes of disease-free survival (DFS) and overall survival (OS). The prognostic value of PNI was analyzed by univariate and multivariate Cox proportional hazards regression models. The toxicity of NACT was accessed by the National Cancer Institute Common Toxicity Criteria (NCI-CTC).ResultsThe results indicated that PNI had prognostic significance by an optimal cutoff value of 51 on DFS and OS in univariate and multivariate Cox regression survival analyses. Breast cancer patients with a high PNI value had longer DFS and OS than those with a low PNI value [47.64 vs. 36.60 months, P < 0.0001, hazard ratio (HR) = 0.264, 95%CI = 0.160–0.435; 73.61 vs. 64.97 months, P < 0.0001, HR = 0.319, 95%CI = 0.207–0.491, respectively]. Furthermore, the results indicated that patients with high PNI had longer DFS and OS than those with low PNI in early stage and advanced breast cancer, especially in advanced breast cancer. The mean DFS and OS times for breast cancer patients with high PNI by the log-rank test were longer than in those with low PNI in different molecular subtypes. Moreover, the mean DFS and OS times in patients with high PNI by the log-rank test were longer than in those patients with low PNI without or with lymph vessel invasion. The common toxicities after neoadjuvant chemotherapy were hematologic and gastrointestinal reaction, and the PNI had no significance on the toxicities of all enrolled patients, except in anemia, leukopenia, and myelosuppression.ConclusionPretreatment PNI with the advantages of being convenient, noninvasive, and reproducible was a useful prognostic indicator for breast cancer patients receiving neoadjuvant chemotherapy and is a promising biomarker for breast cancer on treatment strategy decisions.

Real-world effectiveness of eribulin in heavily pretreated patients with metastatic breast cancer in China: a multicenter retrospective study.

Background:Eribulin is a nontaxane microtubule inhibitor approved in China for patients with advanced breast cancer who show progression after ⩾2 lines of chemotherapy. The aim of this study was to determine the efficacy and safety profile of eribulin and explore potential predictive factors for the efficacy of eribulin among Chinese women with metastatic breast cancer (MBC) in real-world practice.Patients and Methods:A total of 272 consecutive MBC patients who were treated with eribulin between November 2019 and October 2020 in 9 institutions nationwide were included in this study. Eribulin was administered intravenously at a dose of 1.4 mg/m2 on days 1 and 8 of a 21-day cycle. Efficacy outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Adverse events (AEs) were graded according to The National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.0.Results:Eribulin showed a median PFS of 4.1 months (95% confidence interval [CI] 3.6–4.6); however, the OS data were immature. The ORR was 17.6% and the CBR was 24.6%. A total of 51.8% of patients received eribulin monotherapy, while 48.2% of patients were treated with eribulin plus targeted therapy or other chemotherapy. The number of metastatic sites, duration of previous taxane treatment for MBC, and combination with bevacizumab were significant in Cox multivariate analysis (p = 0.023, p = 0.048, and p = 0.046, respectively) and were significantly associated with PFS of eribulin. The most common AEs with eribulin treatment were hematological toxicities, including neutropenia, leukopenia, and anemia.Conclusion:Eribulin was effective with a manageable toxicity profile in clinical practice. Furthermore, when prescribed in combination with other agents, eribulin did not increase the toxic effects of each agent. Eribulin monotherapy or plus other agents is an alternative for the heavily pretreated patients with MBC.

Efficacy and safety of propolis mouthwash in management of radiotherapy induced oral mucositis; A randomized, double blind clinical trial.

Propolis has been used for the management of oral mucositis in a number of studies. Due to lack of sufficient evidence especially in radiotherapy induced oral mucositis, the present study was designed to evaluate the efficacy and safety of propolis mouthwash in oral mucositis and dysphagia in patients undergoing head and neck radiotherapy. This study was a prospective, randomised, double-blind, placebo-controlled trial. The patients randomly divided into two groups receiving either the propolis or the placebo mouthwash. Patients were advised to rinse their mouth with 15 mL three times daily for four weeks. Severity of mucositis and dysphagia were evaluated by the National Cancer Institute Common Toxicity Criteria (NCI-CTC) and Common Terminology Criteria for Adverse Events (CTCAE), respectively. Thirty patients completed the study. Each group consisted of 15 patients. Although, there is not any significant difference between two groups in the first week of radiotherapy, a significant difference was seen in the second, the third and the fourth week (p = 0.03, 0.02, 0.02, respectively). Dysphagia reported as a mild score in the propolis group only in the fourth week which is significant compared with the placebo group (p = 0.01). There is not any serious adverse effect related to propolis or placebo during the study. It seems that propolis mouthwash is an effective and safe medication for alleviation of oral mucositis and dysphagia in patients under head and neck radiotherapy.

Effectiveness of Acupuncture Treatment on Chemotherapy-Induced Peripheral Neuropathy: A Pilot, Randomized, Assessor-Blinded, Controlled Trial.

Objective This pilot study aims to evaluate the effectiveness and safety of acupuncture in the treatment of chemotherapy-induced peripheral neuropathy (CIPN). Methods This study was a pilot randomized controlled trial, which was conducted with cooperation between Beijing University of Chinese Medicine (BUCM), China, and Tehran University of Medical Science (TUMS), Iran. Forty participants with CIPN were randomly assigned (1 : 1) to receive twelve sessions of acupuncture (20 minutes each session over 4 weeks) or take one 300 mg tablet of vitamin B1 and three 300 mg capsules of gabapentin per day for 4 weeks, after which both groups were followed up for 4 weeks. The primary endpoint was CIPN symptom severity measured by the Numerical Rating Scale (NRS). The secondary endpoints included sensory neuropathy grade evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE), neurophysiological assessment of CIPN by the nerve conduction study (NCS), and the patient overall satisfaction with treatment. Safety was assessed at each visit. Results The NRS and NCI-CTCAE sensory neuropathy grading scales decreased significantly over time in both groups (both P < 0.001), with a significantly higher reduction in the acupuncture group (P < 0.001 and P = 0.03, respectively). In addition, the acupuncture group showed a higher overall satisfaction with the treatment at the end of treatment and after 4 weeks follow-up, in comparison with the vit B1 and gabapentin group (P = 0.01 and P = 0.001, respectively). The NCS (except for the latency of the sural nerve) in the acupuncture group improved significantly (P < 0.05), while improvement in the vit B1 and gabapentin group was not observed (P > 0.05). Conclusion Our study revealed that acupuncture, as a kind of traditional Chinese therapeutic method, is significantly effective and safe in the treatment of CIPN. Moreover, acupuncture is more effective than using vitamin B1 and gabapentin as the conventional treatment. Trial registration. This trial is registered with the Iranian Registry of Clinical Trials (IRCT20190615043900N1).

Serum neurofilament light chain levels as a biomarker of neuroaxonal injury and severity of oxaliplatin-induced peripheral neuropathy

We set out to determine the usability of serum neurofilament light chain (sNfL), serum glial fibrillary acidic protein (sGFAP), and retinal parameters by using optical coherence tomography (OCT) as reliable biomarkers of the progression of oxaliplatin-induced peripheral neuropathy (OIPN). Forty-three patients scheduled to undergo oxaliplatin-based chemotherapy at the National Cancer Center of Korea between June 2018 and October 2019 were prospectively assessed at baseline, 3 months, and 6 months of chemotherapy. Patients were assessed on clinical scales and underwent OCT, sNfL, and sGFAP level measurement at each follow-up visit. By applying the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), OIPN was classified as grade 1 in 12 (28%) patients, grade 2 in 25 (58%), and grade 3 in 5 (12%) at 6 months of chemotherapy. sNfL levels increased during oxaliplatin administration, while serial sGFAP levels or retinal parameters did not change. Patients with grade-3 OIPN showed significantly higher mean sNfL levels than patients with grade 0–2 OIPN at 6 months of treatment. At 4–6 months after completion of chemotherapy, sNfL levels were significantly reduced compared to the levels at 6 months of chemotherapy. Monitoring of sNfL during chemotherapy can indicate ongoing neuroaxonal injury and the severity of OIPN.

PD03-06 EFFECTS OF LEVOFLOXACIN ON BACILLUS CALMETTE-GUERIN-INDUCED TOXICITY IN PATIENTS WITH NONMUSCLE INVASIVE BLADDER CANCER: RESULTS OF A RANDOMIZED, PROSPECTIVE, MULTICENTER STUDY

You have accessJournal of UrologyBladder Cancer: Non-invasive I (PD03)1 Apr 2020PD03-06 EFFECTS OF LEVOFLOXACIN ON BACILLUS CALMETTE-GUERIN-INDUCED TOXICITY IN PATIENTS WITH NONMUSCLE INVASIVE BLADDER CANCER: RESULTS OF A RANDOMIZED, PROSPECTIVE, MULTICENTER STUDY Kazuyuki Numakura*, Mizuki Kobayashi, Toshiya Ishida, Katsumi Okane, Kazumasa Suzuki, Naotake Shimoda, Takehiro Suzuki, Teruaki Kumazawa, Ryusei Sasaki, Hisami Fukuda, Taketoshi Nara, Sohei Kanda, Huang Mingguo, Mitsuru Saito, Shintaro Narita, Takamitsu Inoue, Norihiko Tsuchiya, and Tomonori Habuchi Kazuyuki Numakura*Kazuyuki Numakura* More articles by this author , Mizuki KobayashiMizuki Kobayashi More articles by this author , Toshiya IshidaToshiya Ishida More articles by this author , Katsumi OkaneKatsumi Okane More articles by this author , Kazumasa SuzukiKazumasa Suzuki More articles by this author , Naotake ShimodaNaotake Shimoda More articles by this author , Takehiro SuzukiTakehiro Suzuki More articles by this author , Teruaki KumazawaTeruaki Kumazawa More articles by this author , Ryusei SasakiRyusei Sasaki More articles by this author , Hisami Fukuda Hisami Fukuda More articles by this author , Taketoshi Nara Taketoshi Nara More articles by this author , Sohei KandaSohei Kanda More articles by this author , Huang MingguoHuang Mingguo More articles by this author , Mitsuru SaitoMitsuru Saito More articles by this author , Shintaro NaritaShintaro Narita More articles by this author , Takamitsu InoueTakamitsu Inoue More articles by this author , Norihiko Tsuchiya Norihiko Tsuchiya More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000823.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Although bacillus Calmette-Guerin (BCG) is a standard of care for especially high-risk nonmuscle-invasive bladder cancer (NMIBC), a high rate of adverse events (AEs) remains a major problem. In this randomized, prospective, multicenter study, we examined whether levofloxacin (LVFX) given after each intravesical instillation of BCG could improve its tolerance in patients with intermediate- to high-risk urothelial carcinoma of the bladder. We also investigated the impact of LVFX on the antitumor efficacy of BCG. METHODS: In this study, 100 patients with primary or recurrent NMIBC (Ta/T1, CIS, G1-G3) were randomized to induction treatment with intravesical BCG plus LVFX in group 1 (n=52) or BCG alone in group 2 (n=48). AEs were assessed using a National Cancer Institute-Common Toxicity Criteria Version 3.0. The median patient ages were 69.5 years (46 – 80) and the median follow up period was 36 months (12 – 128). All patients were Japanese, consisting of 80 men and 20 women. RESULTS: There was no significant difference in baseline characteristics and symptoms between the groups. Overall, there were no significant differences decreases in the rate of patients having with pollakisuria, miction pain, gross hematuria, fever elevation, and others between the group 1 and group 2. The rate of BCG discontinuation was not different between the groups (24.5% vs 13.7%, p = 0.207). However, the incidence of AEs with grade II or more pollakisuria and fever elevation was significantly lower (5.9% vs 28.2%, p = 0.016; 0% vs 8.2%, p=0.034) in the group 1 (Table 1). The 5-year progression-free and cancer-specific survival rates were better in the group I (HR 0.26, 95%CI 0.57-0.81, p = 0.011; 1 HR 0.13, 95%CI 0.01-0.74, p = 0.006) (Figure 1). CONCLUSIONS: Prophylactic LVFX may reduce the severity of AEs and can contribute to better outcomes from BCG intravesical therapy in patients with NMIBC, improving compliance with the BCG course. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e74-e74 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kazuyuki Numakura* More articles by this author Mizuki Kobayashi More articles by this author Toshiya Ishida More articles by this author Katsumi Okane More articles by this author Kazumasa Suzuki More articles by this author Naotake Shimoda More articles by this author Takehiro Suzuki More articles by this author Teruaki Kumazawa More articles by this author Ryusei Sasaki More articles by this author Hisami Fukuda More articles by this author Taketoshi Nara More articles by this author Sohei Kanda More articles by this author Huang Mingguo More articles by this author Mitsuru Saito More articles by this author Shintaro Narita More articles by this author Takamitsu Inoue More articles by this author Norihiko Tsuchiya More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement PDF downloadLoading ...