National Cancer Institute Common Terminology Criteria For Adverse Events Research Articles

Abstract PO4-18-07: A dose escalation and cohort expansion study of the CDK9 inhibitor KB-0742 in triple negative breast cancer and transcriptionally addicted relapsed or refractory solid tumors

Abstract Background: MYC deregulation is a hallmark of triple negative breast cancer (TNBC) and is associated with aggressive tumors and poor clinical outcomes. Although MYC remains undrugged, targeting of its cofactors has emerged as an attractive strategy to inhibit MYC oncogenic activity. Cyclin-dependent kinase 9 (CDK9) is a critical regulator of oncogenic MYC expression and an important MYC cofactor. KB-0742 is an oral CDK9 inhibitor that demonstrates promising preclinical activity against TNBC. In a real-world cohort, TNBCs have higher MYC expression and higher rates of MYC genomic amplification than other breast cancer subtypes. In primary patient-derived cell lines, KB-0742 treatment results in stronger cytotoxic effects in TNBC as compared to other subtypes. In patient-derived organoids and patient-derived xenografts, CDK9 inhibition by KB-0742 drives antiproliferative and anti-tumor growth effects, including in models that are resistant to standard of care. KB-0742 strongly downregulates MYC protein levels at doses that only partially inhibit CDK9 activity, suggesting a therapeutic window for tumor-specific activity (Saffran, D.C. et al, 2021). KB-0742 is currently being evaluated in a phase 1/2 dose escalation and cohort expansion study in patients with TNBC and other transcriptionally addicted tumors (NCT04718675). Trial design: This phase 1/2 study includes two parts: dose escalation (part 1) and cohort expansion (part 2). Part 2 includes cohort A (solid tumors with high prevalence of MYC overexpression including TNBC, non-small cell lung cancer and ovarian) and cohort B (other transcriptionally addicted tumor types including sarcomas, adenoid cystic carcinoma, nut midline carcinoma and small cell lung cancer). KB-0742 is dosed orally once daily for 3 consecutive days, followed by 4 days, off on a weekly basis in 28-day cycles until unacceptable toxicity or disease progression. Eligibility criteria: Part 1 dose escalation is open to patients with relapsed or refractory solid tumors. Part 2 is defined by tumor indications in cohorts A and B. Eligibly criteria include age > 18 years (≥ 12 years old and with a body weight ≥ 40 kg part 2 for cohort B), acceptable organ function, and ECOG PS < 2. Specific aims: Primary objectives include evaluation of pharmacokinetics (PK), pharmacodynamics (PD), safety, tolerability, preliminary anti-tumor activity, and identifying a maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). PK measurements include Cmax, tmax, AUC0-last, accumulation ratio (Racc) and t1/2. Safety data will be evaluated per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. The Modified Continuous Reassessment Method (mCRM) (Goodman et al., Stat Med 1995) will guide dose escalation and MTD. RP2D nomination is informed by PD in peripheral blood mononuclear cells using assays to evaluate phosphorylation of the CDK9 substrate serine 2 on the RNA Polymerase II C-terminal domain (pSER2) and CDK9-responsive gene expression. Radiographic tumor response to KB-0742 in patients is assessed every other cycle starting from cycle two after treatment using RECIST 1.1 criteria. Target accrual: Targeted total enrollment is 170 patients. For additional information, contact clinicaltrials@kronosbio.com Citation Format: Monica Mita, Alain Mita, Miguel Villalona-Calero, Noah Federman, Drew Rasco, David Spigel, Jia Luo, Gregory Cote, Richard Cutler, Pavan Kumar, Crystal MacKenzie, Charles Lin, Jorge DiMartino, Elizabeth Olek, Brian Van Tine. A dose escalation and cohort expansion study of the CDK9 inhibitor KB-0742 in triple negative breast cancer and transcriptionally addicted relapsed or refractory solid tumors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-18-07.

Abstract PO1-04-10: Body Mass Index and Treatment Efficacy in advanced Luminal Breast Cancer: Insights from the GEICAM/2013-02 (PEARL) trial

Abstract Background: Endocrine therapy (ET) and treatment directed against molecular targets (CDK 4/6, PI3K, mTOR) constitute the basis of initial treatments for patients with advanced luminal breast cancer. Most of these treatments are oral and have been developed at a fixed dose, without weight adjusted dosing. There is little evidence on the influence that patients’ weight might have on clinical outcomes of these oral drugs in the context of a randomized clinical trial. The present study analyzes the potential impact of the weight of patients treated in the two cohorts of the PEARL trial (NCT02028507) on Progression-Free Survival (PFS), Overall Survival (OS) and the incidence of side effects in each treatment arm. Methods: GEICAM/2013-02 (PEARL) is a multicenter, phase III randomized clinical trial that enrolled patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC) who progressed to a prior aromatase inhibitor. Patients were randomized 1:1 to receive ET + palbociclib or capecitabine. Patient weight was assessed based on baseline body mass index (BMI) categories: normal (BMI ≤25 Kg/m2), overweight (BMI 25-29.9 Kg/m2) and obesity (BMI ≥30 Kg/m2). Cox's stratified proportional hazard model was used for survival analysis. Adverse events were assessed and graded according to National Cancer Institute common terminology criteria for adverse events (NCI-CTCAE) version 4.0. Results: A total of 600 patients were included in the study and all were evaluable for the weight-based analysis, including 301 in the ET +palbociclib arm and 299 in the capecitabine arm. The distribution of patient’s weights is shown in Table 1. For the Intention-to-treat (ITT) population, no significant difference in the median OS was found between the different weight categories (Normal: 32.8 months vs overweight: 31.9 months, [p=0.467]; obese: 32 months [p=0.407]). Specifically, for patients with normal weight, the median PFS was 9.3 months in the ET + palbociclib group compared to 9.0 months in the capecitabine group (hazard ratio (HR) 0.83, 95% confidence interval [CI]: 0.61-1.13; p=0.23). In the overweight group, the PFS was 7.5 months in the ET+palbociclib group and 11.1 months in the capecitabine group (HR 1.17, 95% CI: 0.87-1.58; p=0.30) while for the obese group, the PFS was 5.7 months vs 11.7 months (HR 1.14, 95% CI: 0.82-1.59; p=0.43), respectively. No substantial differences in the incidence of grade ≥ 3 events were observed when considering weight categories in the different treatment groups (capecitabine arm (Normal: 60%, Overweight: 70.4%, Obese: 61.6%) and ET+palbociclib arm (Normal: 74.5%, Overweight: 76.1%, Obese: 51.6%). Conclusions: Our findings, despite not finding statistically significant differences, suggest a potentially clinically relevant trend towards improved PFS with capecitabine in overweight and obese patients compared to those receiving palbociclib plus ET. The impact of weight on the outcomes with fixed-dose oral drugs warrants further investigation in future studies. Table 1. Citation Format: Manuel Alva, Sara López-Tarruella, Christoph Zielinski, Manuel Ruíz - Borrego, Nicholas Turner, Eva Ciruelos, Montserrat Muñoz, Begoña Bermejo, Mireia Margelí, Antonio Antón, Zsuzsanna Kahan, Tibor Csöszi, Maribel Casas, Laura Murillo, Serafin Morales Murillo, Emilio Alba, Einav Nili-Gal Yam, Angel Guerrero, Lourdes Calvo, Juan de la Haba-Rodríguez, Manuel Ramos, Isabel Álvarez, Andrés García-Palomo, María Koehler, José Ángel García-Sáenz, J. Ignacio Chacón, Claire Swift, Christiane Thallinger, Miguel Gil-Gil, Miguel Martín. Body Mass Index and Treatment Efficacy in advanced Luminal Breast Cancer: Insights from the GEICAM/2013-02 (PEARL) trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-04-10.

Abstract CT158: A dose escalation and cohort expansion study of the CDK9 inhibitor KB-0742 in relapsed, refractory and transcriptionally addicted solid tumors

Abstract Background MYC transcriptional deregulation is a hallmark of cancer and is associated with poor clinical outcomes. MYC deregulated solid tumors including non-small cell (NSCLC), small cell lung cancer (SCLC), triple negative breast cancer (TNBC), and ovarian cancer are known for their aggressiveness and frequent relapse. Analysis of a real-world solid tumor cohort including NSCLC (n= 20,470), SCLC (n=1,517), TNBC (n=2,576) and ovarian cancer (n=1,667) demonstrated MYC family overexpression and/or genomic amplification in 47% to 87% of patients. Although MYC remains difficult to drug, targeting of its cofactors has emerged as an attractive strategy to inhibit MYC oncogenic activity. Cyclin-dependent kinase 9 (CDK9), a MYC cofactor, is a critical regulator of oncogenic MYC expression and activity. KB-0742 is a potent, selective, and orally bioavailable inhibitor of CDK9 with a long plasma half-life. KB-0742 is being evaluated in an ongoing Phase 1/2 study in advanced solid tumors (NCT04718675). Methods The Phase 1/2 study is being conducted in two parts: dose escalation and dose expansion. Part 1 dose escalation comprises patients with relapsed or refractory solid tumors. Part 2 dose expansion comprises patients with solid tumors that have a high prevalence of MYC overexpression including ovarian cancer, NSCLC, TNBC and SCLC. KB-0742 is dosed orally once daily for 3 consecutive days followed by 4 days off on a weekly basis in 28-day cycles until unacceptable toxicity or disease progression. Eligibility criteria include age > 18 years acceptable organ function and ECOG PS < 2. Up to 170 patients are planned to be enrolled in the study. Primary objectives include evaluation of pharmacokinetics (PK), pharmacodynamics (PD), safety, tolerability, and preliminary anti-tumor activity with the goal of identifying a maximum tolerated dose (MTD). Plasma PK measurements include Cmax, tmax, AUC0-last, accumulation ratio (Racc) and t1/2. Safety data will be evaluated per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. RP2D is informed by PD in peripheral blood mononuclear cells using assays to evaluate phosphorylation of the CDK9 substrate serine 2 on the RNA Polymerase II C-terminal domain (pSER2) and CDK9-responsive gene expression. Radiographic tumor response is assessed using RECIST 1.1 criteria. Exploratory objectives include assessment of KB-0742 PD in tumor tissue and profiling of treatment-related genomic, transcriptomic, and proteomic changes. The study is continuing as planned; the next data analysis will occur in 2024. Citation Format: Miguel Villalona Calero, Mark Agulnik, Monica Mita, Alain Mita, Noah Federman, Drew Rasco, David Spigel, Jia Luo, Glenn Hanna, Gregory Cote, Mohamad A. Salkeni, Rashmi Chugh, Natraj R. Ammakkanavar, Satish A. Shah, Amol Rao, Kamalesh Kumar Sankhala, Richard E. Cutler, Tressa Hood, Luis Carvajal, Crystal MacKenzie, Charles Lin, Jorge DiMartino, Elizabeth A. Olek, Brian Van Tine. A dose escalation and cohort expansion study of the CDK9 inhibitor KB-0742 in relapsed, refractory and transcriptionally addicted solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT158.

Abstract B112: A dose escalation and cohort expansion study of the CDK9 inhibitor KB-0742 in relapsed, refractory ovarian cancer and transcriptionally addicted relapsed or refractory solid tumors

Abstract Ovarian cancer is responsible for more female cancer deaths than any other female reproductive malignancy. MYC deregulation is a hallmark of ovarian cancer and is associated with poor clinical outcome. In a real-world cohort (n=1,667), the MYC family of genes is overexpressed and/or genomically amplified in up to 87% of ovarian cancer. Although MYC remains undrugged, targeting of its cofactors has emerged as an attractive strategy to inhibit MYC oncogenic activity. Cyclin-dependent kinase 9 (CDK9) is a critical regulator of oncogenic MYC expression and activity. KB-0742 is an orally bioavailable, highly selective, long half-life (~24 hours) CDK9 inhibitor that demonstrates promising preclinical activity against ovarian cancer and is currently being evaluated in a phase 1/2 dose escalation and cohort expansion study in patients with ovarian cancer and other transcriptionally addicted tumors (NCT04718675). The phase 1/2 study is being conducted in two parts: dose escalation (part 1) and cohort expansion (part 2). Part 2 is comprised of cohort A (solid tumors with high prevalence of MYC overexpression including ovarian cancer, non-small cell lung cancer, and triple negative breast cancer) and cohort B (other transcriptionally addicted tumor types including sarcomas, adenoid cystic carcinoma, nut midline carcinoma and small cell lung cancer). KB-0742 is dosed orally once daily for 3 consecutive days, followed by 4 days off, on a weekly basis in 28-day cycles until unacceptable toxicity or disease progression. It is estimated that up to 170 patients will be enrolled in the study. Part 1 dose escalation is open to patients with relapsed or refractory solid tumors or non-Hodgkin’s lymphoma. Part 2 is defined by tumor indications as described in cohorts A and B. Eligibility criteria include age > 18 years (≥ 12 years old and with a body weight ≥ 40 kg in part 2, cohort B), acceptable organ function, and ECOG PS < 2. Primary objectives include evaluation of pharmacokinetics (PK), pharmacodynamics (PD), safety, tolerability, and preliminary anti-tumor activity, with the goal of identifying a maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Plasma PK measurements include Cmax, tmax, AUC0-last, accumulation ratio (Racc) and t1/2. Safety data will be evaluated per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. Dose escalation and MTD identification is guided by a Modified Continuous Reassessment Method (mCRM) (Goodman et al., Stat Med 1995). RP2D is informed by PD in peripheral blood mononuclear cells using assays to evaluate phosphorylation of the CDK9 substrate serine 2 on the RNA Polymerase II C-terminal domain (pSER2) and CDK9-responsive gene expression. Radiographic tumor response is assessed using RECIST 1.1 criteria. Exploratory objectives include assessment of KB-0742 PD in tumor tissue and profiling of treatment-related genomic, transcriptomic, and proteomic changes. Enrollment continues in the United States with sites in Spain, France, and UK expected to open. Citation Format: Miguel Villalona-Calero, Monica Mita, Alain Mita, Noah Federman, Drew Rasco, David Spigel, Jia Luo, Gregory M. Cote, Richard E. Cutler, Pavan Kumar, Crystal J. MacKenzie, Charles Lin, Jorge F. DiMartino, Elizabeth A. Olek, Brian Van Tine. A dose escalation and cohort expansion study of the CDK9 inhibitor KB-0742 in relapsed, refractory ovarian cancer and transcriptionally addicted relapsed or refractory solid tumors [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B112.

Gabapentin for Pain in Pediatric Palliative Care

ObjectiveGabapentin is commonly used to treat pain in children receiving pediatric palliative care. This study describes the real-world use of gabapentin and the associated benefits and adverse effects/events (AEs). MethodsA prospective, multicenter cohort of standardized data collection after a clinical decision was made to use gabapentin for managing neuropathic or nociplastic pain in children attended on by a pediatric palliative care service. It was conducted across 11 sites in seven countries including hospital, inpatient, and outpatient services. Clinical outcomes were graded using pain scales validated for age and cognitive ability and the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE) at baseline, 14 days, 28 days, six weeks and 12 weeks after initiation of gabapentin. Ad-hoc safety reporting continued throughout the study. ResultsData were collected from 127 children with a median age of 4.7 years (IQR 0.1–17.9); 61% had a neurological disorder, 21% advanced cancer and the cohort had a high level of disability (Lansky/Karnofsky performance score 37.1). Gabapentin was prescribed at standard pediatric doses. On average, 76% of children had a reduction in pain and 42% experienced a potential AE. The mean pain score decreased from 6.0 (SD 2.6) at baseline to 3.3 (SD 2.4) at 14 days and 1.8 (SD 1.8) after 12-weeks of gabapentin therapy. Ten percent had increased pain at each time point. AEs did not increase when individual changes over time were accounted for except for somnolence (7%). Serious AEs attributable to gabapentin were possible or probable in 3% of children. ConclusionsGabapentin prescribed at standard doses for advanced cancer and severe neurological injury in children under a pediatric palliative care service was associated with generally improved pain intensity at previously described levels of adverse effects.

Impact of Long-Term Treatment with Belantamab Mafodotin on Safety and Efficacy Outcomes in Patients with Relapsed/Refractory Multiple Myeloma in DREAMM-3

Introduction: DREAMM-3 (NCT04162210) is a randomized study comparing single-agent belantamab mafodotin, a first-in-class antibody-drug conjugate targeting B-cell maturation antigen, to a standard-of-care regimen, pomalidomide plus dexamethasone (Pd). This post-hoc analysis from the DREAMM-3 trial evaluated the safety and efficacy of long-term treatment (≥52 weeks) with belantamab mafodotin compared with Pd, as well as the effects of dose modifications, in adult patients with relapsed/refractory multiple myeloma (RRMM) at third line of therapy or later. Methods: Patients were randomized (2:1) to belantamab mafodotin 2.5 mg/kg intravenously once every 3 weeks (Q3W; 21-day cycle) or pomalidomide 4 mg orally once daily (Days 1-21) and dexamethasone 40 mg (20 mg if >75 years) orally once weekly (28-day cycle). Belantamab mafodotin dose reductions or delays were permitted to manage treatment-related Grade 3-4 adverse events (AEs), or Grade 2 AEs that were worsening or had symptoms lasting >7 days. Following AE resolution to Grade ≤1, belantamab mafodotin treatment could resume with or without dose reduction (to 1.9 mg/kg). If no dose delays occurred, patients could receive a maximum of 17 cycles in 52 weeks, hence 17 cycles was used as a threshold to assess long term safety. Ocular exams were performed prior to dosing belantamab mafodotin Q3W up to Cycle 6, then every 3 months if no significant ocular events were reported. Treatment-related ocular AEs were graded per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5 and per the Keratopathy Visual Acuity (KVA) scale. The KVA scale incorporates corneal examination findings and changes in Snellen-equivalent best corrected visual acuity (BCVA) into a composite grade. Ocular AEs are reported as worst-case post-baseline. Efficacy responses (per 2016 International Myeloma Working Group criteria) were assessed Q3W, regardless of treatment delays. Results: As of September 12, 2022, 50/218 (23%) patients were treated with belantamab mafodotin for ≥52 weeks. AEs were reported in all patients treated with belantamab mafodotin for ≥52 weeks. Grade ≥3 AEs occurred in 82% (n=41); the most frequent were reduced visual acuity (24%), thrombocytopenia (18%), and neutropenia (16%). The majority of AEs reported occurred at or before cycle 17. For the most common (>40%) AEs (any grade), few additional events occurred after cycle 17 (1 new occurrence each of dry eye, reduced visual acuity, eye irritation, and thrombocytopenia after cycle 17). Few infections (any grade) occurred after cycle 17 (COVID-19, n=5; viral infection, n=1; pneumonia influenzal, n=1). No patients permanently discontinued treatment due to AEs considered related to belantamab mafodotin. Ocular AEs were reported in 94% (n=47) of patients treated with belantamab mafodotin for ≥52 weeks. The majority of ocular AEs (n=487) were of Grade 1 or 2 severity (88%) and no ocular AEs led to study treatment discontinuation. At the time of data cutoff, 95% (n=41) of patients experiencing Grade ≥2 KVA events had recovered prior to the end of study treatment exposure (defined as last dose + 20 days). Most patients had a dose modification, and no loss of efficacy was observed. The clinical benefit rate (≥minimal response) in these patients was 90% (45/50) and the median time to best response was 6.3 months (range 0.8-18.8). Median duration of response was not reached (NR; 95% CI 17.9, NR) in the subset of patients treated for ≥52 weeks. At the time of data cutoff, 94% (n=47) patients were alive. Conclusions: In patients who received long-term treatment (≥52 weeks), the safety profile of belantamab mafodotin was consistent with previous reports. Despite the need for belantamab mafodotin dose delays and reductions, no patients discontinued study treatment due to belantamab mafodotin-related AEs. During dose delays, clinical responses were maintained or deepened in most cases, demonstrating that management of AEs using dose modifications did not impact clinical activity. Together, this suggests that dose modifications are highly effective in the management of emerging AEs while allowing for sustained clinical benefit. Funding: GSK (207495). Drug linker technology licensed from Seagen Inc.; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.

Chidamide As Maintenance in Peripheral T-Cell Lymphoma for Patients in Response after Induction Therapy: A Single Center Retrospective Study

Background Peripheral T-cell lymphoma (PTCL) is a set of heterogeneous mature T- and natural killer cell neoplasms, most of which are associated with poor prognosis. PTCL patients usually experience frequent relapses. To improve the poor clinical outcomes of PTCL, novel agents that target various pathways have been studied and developed. Histone deacetylase (HDAC) inhibitors are among the most significant improvements made in recent years. Chidamide, a novel benzamide class of HDAC inhibitor, showed significant efficacy in relapsed/refractory PTCL patients in previous studies. But the role chidamide of as a maintenance therapy in PTCL patients after first-line therapy is still unknown. Methods In this retrospective, single-center, single-arm study, a total of 342 newly diagnosed PTCL patients were reviewed in the First Affiliated Hospital, Zhejiang University School of Medicine (Zhejiang, China) from August 2014 to May 2022. Patients with natural killer/T-cell lymphoma, mycosis fungoides were not enrolled. After excluding patients with insufficient clinical data, with other concurrent tumor, received other anti-tumor agents during maintenance therapy, or underwent sequential transplantation, there were 35 PTCL patients achieved objective response after first-line therapy, and received chidamide as maintenance therapy. The primary endpoint of this study was progress-free survival (PFS), overall survival (OS), and adverse events (AEs). Response and progression data were evaluated according to the 2016 Lugano Classification lymphoma response criteria. Adverse events were evaluated according to the National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) version 4.0. Survival outcomes were assessed with Kaplan-Meier method. Results 35 PTCL patients were enrolled, including angioimmunoblastic T-cell lymphoma (AITL) (13, 37.1%), anaplastic large-cell lymphoma (ALCL) (2, 5.7%), PTCL-NOS (20, 57.1%). There were 22 (62.9%) males and 13 (37.1%) females, 16 (45.7%) patients were over 65 years old, 32 patients (91.4%) had clinical stage III-IV, 9 patients (25.7%) had B symptoms, 8 patients (22.9%) had ECOG score ≥2, 15 patients (42.9%) with IPI score ≥3-5, 18 (51.4%) achieved complete remission (CR) and 17 (48.6%) achieved partial remission (PR) after induction chemotherapy. The median follow-up time was 35.2 months (range 13.0 to 107.7). The median duration of chidamide maintenance therapy was 17.7 months (range 2.4 to 98.0). 22 (62.9%) patients received 20mg chidamide twice a week and 13 (37.1%) used 30mg twice a week . The median PFS and median OS were not reached. The 3-year PFS and OS were 64.9% and 89.2%. Patients who achieved CR after induction chemotherapy had a better prognosis trend. Among the 18 patients who received maintenance therapy after CR, there was no death and the 3-year PFS was 76.4%. Patients with B symptoms had a worse prognosis (P<0.05), the median PFS was 22.5 months, the median OS was not reached, and the 3-year overall survival rate was 75%. The 3-year PFS and OS of the remaining 26 patients without B symptoms were 78.5% and 94.1%, respectively. The most common grade 3-4 AEs were hematological toxicities, including neutropenia(20.0%), anemia(8.6%), thrombocytopenia(5.7%), mainly in 30mg group, as detailed in Table 1. Adverse events usually occurred during the first 6 weeks, most of with were manageable by supportive care and dose modification, none of the adverse reactions leaded to death. There was no statistical difference in PFS and OS between the 30mg and 20mg groups under current sample size. Conclusions Chidamide maintenance is effective and may prolong the PFS and OS for PTCL patients with manageable safety profile. It is an appropriate therapeutic option as up-front consolidation therapy for PTCL patients with complete or partial response after first-line therapy. Larger-sample, prospective, multicenter cohort study is still needed to further confirm the conclusion.

Efficacy of metformin in prevention of paclitaxel-induced peripheral neuropathy in breast cancer patients: a randomized controlled trial.

Background: Paclitaxel-induced peripheral neuropathy (PN) is a serious clinical problem with no approved drug for prevention. This study aimed to examine the neuroprotective effect of metformin against paclitaxel-induced PN in breast cancer patients. Methods: Patients with confirmed breast cancer diagnosis who were planned to receive paclitaxel were randomized to receive either metformin or placebo. Both groups received the standard chemotherapy protocol for breast cancer. Patients started metformin/placebo 1week before paclitaxel initiation and continued study interventions thereafter for nine consecutive weeks. The primary outcome was the incidence of development of grade two or more paclitaxel-induced sensory PN. The PN was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Patients' quality of life (QoL) was assessed by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACTGOG-Ntx) subscale. Pain severity was measured by the Brief Pain Inventory Short Form (BPI-SF). Serum levels of nerve growth factor (NGF) and neurotensin (NT) were measured at baseline and at the end paclitaxel treatment. Results: A total of 73 patients (36 in the metformin arm and 37 in the control arm) were evaluated. The cumulative incidence of development of grade two or more PN was significantly lower in the metformin arm (14 (38.9%) than the control arm (28 (75.7%); p = 0.001). At the end of paclitaxel treatment, patients' QoL was significantly better in the metformin arm [median (IQR) FACTGOG-Ntx subscale of (24.0 (20.5-26.5)] compared to the control arm (21.0 (18.0-24.0); p = 0.003). The metformin arm showed lower "average" and "worst" pain scores than those detected in the control arm. At the end of the paclitaxel treatment, there was a significant difference in the median serum NGF levels between the two arms, favoring metformin (p < 0.05), while NT serum levels were deemed comparable between the two study arms (p = 0.09). Conclusion: The use of metformin in breast cancer patients offered a marked protection against paclitaxel-induced PN, which translated to better patient QoL. Clinical Trial Registration: https://classic.clinicaltrials.gov/ct2/show/NCT05351021, identifier NCT05351021.

The Effect of Metformin on Chemotherapy-Induced Toxicities in Non-diabetic Breast Cancer Patients: A Randomised Controlled Study

Breast cancer patients treated with adriamycin-cyclophosphamide plus paclitaxel (AC-T) are often challenged with serious adverse effects for which no effective therapies are available. Here, we investigated whether metformin, an antidiabetic drug with additional pleiotropic effects could favourably offset AC-T induced toxicities. Seventy non-diabetic breast cancer patients were randomised to receive either AC-T (adriamycin 60 mg/m2 + cyclophosphamide 600 mg/m2 × 4 cycles Q21 days, followed by weekly paclitaxel 80 mg/m2 × 12 cycles) alone or AC-T plus metformin (1700 mg/day). Patients were assessed regularly after each cycle to record the incidence and severity of adverse events based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. Moreover, baseline echocardiography and ultrasonography were done and repeated after the end of neoadjuvant therapy. Addition of metformin to AC-T resulted in significantly less incidence and severity of peripheral neuropathy, oral mucositis, and fatigue (p < 0.05) compared to control arm. Moreover, the left ventricular ejection fraction (LVEF%) in the control arm dropped from a mean of 66.69 ± 4.57 to 62.2 ± 5.22% (p = 0.0004) versus a preserved cardiac function in the metformin arm (64.87 ± 4.84to65.94 ± 3.44%, p = 0.2667). Furthermore, fatty liver incidence was significantly lower in metformin compared with control arm (8.33% vs 51.85%, p = 0.001). By contrast, haematological disturbances caused by AC-T were preserved after concurrent metformin administration (p > 0.05). Metformin offers a therapeutic opportunity for controlling toxicities caused by neoadjuvant chemotherapy in non-diabetic breast cancer patients. This randomised controlled trial was registered on November 20, 2019 in ClinicalTrials.gov under registration number: NCT04170465.

Vincristine induced peripheral neuropathy in children undergoing chemotherapy for acute lymphoblastic leukaemia during induction

Background: Vincristine is an anticancer agent administered to all children with acute lymphoblastic leukemia (ALL), and peripheral neuropathy is the major dose-limiting toxicity of this therapy. As cure rates of childhood ALL exceeds 80%, therefore treatment-related toxicities need to be reduced. Thus, the aim of this study was to determine the prevalence and risk factors of vincristine-induced peripheral neuropathy (VIPN) in children with ALL undergoing induction chemotherapy. Methods: A case-control study was conducted from September 2017 to August 2018 in the Department of Paediatric Haematology and Oncology at Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. Eighty newly diagnosed ALL and 35 acute myeloid leukemia (AML) cases aged 5 to 17 years with no pre-existing neurological abnormality were recruited. To assess the peripheral neuropathy, we used pediatric-modified total neuropathy score and National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE), version-04 grade. Results: Among ALL patients, 29.2% developed peripheral neuropathy compared to 10% in AML control group (P=0.04). Higher proportion (57.1%) of peripheral neuropathy was found in age below 10 years (P&lt;0.001). There was no significant association of peripheral neuropathy with sex and body mass index of the patients. Conclusion: Almost 3 in 10 patients developed VIPN during the induction therapy which is significantly higher in age below 10 years compared to ≥ 10 years. Bangabandhu Sheikh Mujib Medical University Journal 2023;16(1): 02-07

Outcomes of PD-1 Inhibitors Treatment of Chronic Active Epstein Barr Virus Infection : A Single Center Retrospective Analysis

INTRODUCTION Chronic active Epstein-Barr virus (CAEBV) disease is a high-mortality disease, which is characterized by persistent infectious mononucleosis-like symptoms. There is no standard treatment of CAEBV and allogeneic hematopoietic stem cell transplantation (HSCT) was considered as an only potentially therapeutic approach. PD-1 inhibitors have achieved high response in many Epstein-Barr virus-related diseases. In this single-center retrospective analysis, we report the outcomes of PD-1 inhibitors treatment of CAEBV. METHODS Sixteen CAEBV patients were treated with PD-1 inhibitors between 6/1/2017 and 12/31/2021. Hemophagocytic lymphohistiocytosis (HLH) was excluded. Patients received Nivolumab or Sindilizumab therapy every 3 to 4 weeks, 100 to 200 mg intravenously. Clinical and laboratory assessments were performed on patients before each infusion during treatment. Adverse events were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. RESULTS Among the sixteen patients with a median age at onset of 33 years (range, 11-67 years), twelve patients responded to PD-1 inhibitors, and their median duration of relapse-free survival (RFS) was 10.3 months (range, 1.0-54.8 months). Three of them achieved clinical complete response (clinical CR), as well as molecular CR, and nine patients achieved partial response (PR) (Figure 1). Four of the nine PR patients converted from PR to no response (NR), and five remained in PR. The remaining four patients did not respond to PD-1 inhibitor therapy. One patient eventually died from a severe lung infection and one patient died of severe liver failure. The median time and cycles from the first application of PD-1 inhibitor to clinical CR in three patients with clinical CR were 43 days (range, 30-72 days) and 3 cycles (range, 2-4 cycles). Patient 14 suffered immune-related pancreatitis (Grade 2, CTCAE 5.0) after 6 cycles of PD-1 inhibitor therapy. Four patients developed persistent or intermittent high fever after the first infusion of PD-1 inhibitors. Other than that, no treatment-related adverse events have been observed. There was no correlation of treatment outcome with blood count, aspartate aminotransferase (AST) level, alanine aminotransferase (ALT) level, LDH level, cytokine level or ferritin level. Comparing the NK cell function of responders and non-responders, the test results showed higher numbers of patients with defective NK cell function among non-responders. The immunohistochemical analysis showed that patients with high PD-L1 expression in tumor tissue may have a more significant response to PD-1 inhibitors. Genetic testing indicated that, except for 1 patient without gene sequencing and 8 patients with no related gene mutation detected, the other 7 patients were detected with potentially pathogenic or susceptibility mutations. CONCLUSION In patients with CAEBV, PD-1 inhibitors have tolerable toxicity and comparable outcomes while improving quality of life and financial toxicity. Larger prospective studies and longer follow-up time is needed to be conducted. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Functional imaging-guided carbon ion irradiation with simultaneous integrated boost for localized prostate cancer: study protocol for a phase II randomized controlled clinical trial

BackgroundDue to the physical dose distribution characteristic of “Bragg peak” and the biological effect as a kind of high linear energy transfer ray, heavy ion therapy has advantages over conventional photon therapy in both efficacy and safety. Based on the evidence that prostate cancer lesions before treatment are the most common sites of tumor residual or recurrence after treatment, simultaneous integrated boost radiation therapy for prostate cancer has been proven to have the advantage of improving efficacy without increasing toxicities.MethodsThis study is a prospective phase II randomized controlled clinical trial evaluating the efficacy and safety of functional imaging-guided carbon ion irradiation with simultaneous integrated boost for localized prostate cancer. One hundred and forty patients with localized prostate cancer will be randomized into carbon ion radiotherapy group and simultaneous integrated boost carbon ion radiotherapy group at a 1:1 ratio. The primary endpoint is to compare the incidence of treatment-related grade 2 and higher acute toxicities between the two groups according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. Secondary endpoints are late toxicities, biochemical relapse-free survival, overall survival, progression-free survival, and quality of life.DiscussionThis study adopts functional imaging-guided simultaneous integrated boost of carbon ion radiotherapy for localized prostate cancer, aiming to evaluate the differences in the severity and incidence of acute toxicities in patients with localized prostate cancer treated with carbon ion radiotherapy and simultaneous integrated boost carbon ion radiotherapy, in order to optimize the carbon ion treatment strategy for localized prostate cancer.Trial registrationClinicalTrials.gov NCT05010343. Retrospectively registered on 18 August 2021

One-Year Treatment-Related Side Effects and Quality of Life After Chemoradiotherapy in Squamous Cell Carcinoma of the Anus

Patient-reported outcome (PRO) and National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) data for patients with squamous cell carcinoma of the anus (SCCA) treated with modern radiation therapy (RT) are lacking. The primary aim of this study was to report bowel and bladder PRO and NCI-CTCAE for patients with SCCA 1 year after RT. From 2015 to 2020, we included patients in a prospective Danish national study. Data were collected before treatment (PT) and 1 year after treatment (1Y) using NCI-CTCAE version 4.0, as well as European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and CR29. We evaluated the combined PRO scores according to the European Organisation for Research and Treatment of Cancer scoring guidelines, and classified changes according to score difference from PT to 1Y as no change (0-5), minor (5-10), moderate (11-20), and major (>20). Raw scores were reported as frequencies of each of the scores: Not at all, a little, quite a bit, and very much. Of the 270 patients, 81% had complete data sets, including PT and 1Y answers. Functional mean scores were equal to a matched normal population cohort at PT and 1Y. From PT to 1Y, C30 scores were stable despite minor improvements in global health status/quality of life (7.3), emotional functioning (9.3), insomnia (8.0), and appetite loss (7.8). For questionnaire CR29, bowel and bladder symptoms and sore skin improved with minor change (6.2), and buttocks, anal, or rectal pain improved with moderate change (18.3). Flatulence worsened moderately (12.6), and fecal incontinence had minor worsening (7.8). Agreement between PROs and NCI-CTCAE was generally only fair to moderate, especially for quantitative symptoms, such as pain (κ=0.25). For patients with SCCA who underwent definitive RT, only a few patients had high scores (indicating quite a bit or very much frequency of bother) regarding bowel and bladder symptoms.

Incidence of oxaliplatin hypersensitivity reaction among colorectal cancer patients: A 5-year retrospective study.

Background:Oxaliplatin is a third-generation platinum compound that has efficacy against colorectal cancer. Hypersensitivity reactions during oxaliplatin infusion are a key problem during its use, with the varying incidences and deficiencies of clearly identified risk factors.Objective:To determine the incidence, severity and risk factors of oxaliplatin-related hypersensitivity reaction (HSR).Method:This retrospective study investigated 245 colorectal cancer patients (1,690 treatment cycles) receiving care at King Chulalongkorn Memorial Hospital, Thai Red Cross society between January 1, 2015 and December 31, 2019. The patients’ demographic data, laboratory data and clinical features suggesting hypersensitivity reactions to oxaliplatin were reviewed. The Fisher’s Exact test and unpaired t-test were used to determine the differences among patients with and without oxaliplatin HSR. The potential risk factors for oxaliplatin HSR were analyzed for statistical significance by logistic regression.Results:A total of 245 colorectal cancer patients (1,690 treatment cycles) were included in this study. The incidence of oxaliplatin HSR was 37.96%, according to the US National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (NTCAE) version 5.0, grade 1, grade 2 and higher grades were 27.35% (67 patients), 6.53% (16 patients) and 4.08% (10 patients), respectively. The proportion of male patients and patients with a history of prior exposure to platinum-based chemotherapy were statistically higher in the HSR group. The eosinophil count and serum creatinine level were also significantly greater in the HSR group. On the contrary, the total lymphocyte count and serum albumin level were significantly lower in the HSR group. The multivariate logistic regression found 5 risk factors with a significant difference. Male gender, prior exposure to platinum-based chemotherapy and elevated eosinophil count were associated with increased risk of oxaliplatin HSR, whereas elevated monocyte count and elevated serum albumin were protective factors for the development of oxaliplatin HSR.Conclusion:Colorectal cancer patients treated with an oxaliplatin-based regimen with male gender, prior exposure to platinum-based chemotherapy and elevated eosinophil count have a greater risk of oxaliplatin related hypersensitivity reactions.

Photobiomodulation: a promising innovative approach for preventing oral mucositis in patients undergoing hematopoietic stem cell transplantation.

This single-center retrospective study aims to assess the feasibility, safety, and tolerability of CareMin650, a new photobiomodulation device, for both preventing oral mucositis (OM) and reducing its severity in the setting of hematopoietic stem cell transplantation (HCT). Patients who underwent autologous HCT for hematological malignancies between November 2020 and October 2021 could be included. Prophylactic photobiomodulation (PBM) was used daily from day 1 of conditioning until the day of neutrophil recovery at a dose of 3J/cm2. Curative PBM was started at a dose of 6J/cm2 when at least one grade 1 OM had occurred. For each OM case, time of onset, National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 grade for OM, analgesic dose, and time to resolution were reported. Twenty-five consecutive patients were included. The median age was 58years (range, 39-74) and 14 (56%) were male. Twenty-one patients (84%) received a high-dose melphalan conditioning regimen for multiple myeloma, and 4 (16%) patients received BEAM conditioning for aggressive lymphoma. A total of 178 CareMin650 sessions were performed, with a median of 7days of application (range, 4-12), with no device-related adverse events (AEs). According to the NCI-CTCAE v5.0 scale, 76% (19 of 25) of patients presented grade 0 or 1 mucositis (no ulcers), five patients (20%) developed small ulcers (grade 2), and only one patient developed grade 4 mucositis. Satisfaction rates were high among patients and users. Photobiomodulation provides excellent safety and tolerance, as well as promising efficacy, both as a preventive and curative strategy, in patients undergoing autologous HCT.

The Comparative Safety of Epirubicin and Cyclophosphamide versus Docetaxel and Cyclophosphamide in Lymph Node-Negative, HR-Positive, HER2-Negative Breast Cancer (ELEGANT): A Randomized Trial.

Simple SummaryAnthracycline and taxane-based chemotherapy are the cornerstone of adjuvant therapy for early breast cancer. In recent years, several trials explored the efficacy of the anthracycline-free regimens, especially for HER2-negative breast cancer patients, which turned out to be a feasible alternative. However, there is no comparison between epirubicin and cyclophosphamide versus docetaxel and cyclophosphamide about their safety and efficacy to date. ELEGANT is the first phase III randomized trial comparing the safety and efficacy of EC versus TC, and it reports comprehensive safety profiles of both regimens with a primary endpoint of grade 3 to 4 neutropenia rate.Background: In adjuvant settings, epirubicin and cyclophosphamide (EC) and docetaxel and cyclophosphamide (TC) are both optional chemotherapy regimens for lymph node-negative, hormone receptor (HR)-positive, human epidermal receptor 2 (HER2)-negative breast cancer patients. Neutropenia is one of the most common adverse events (AEs) of these regimens. The rate of grade 3–4 neutropenia varies in different studies, and direct comparisons of safety profiles between EC and TC are lacking. Method: ELEGANT (NCT02549677) is a prospective, randomized, open-label, noninferior hematological safety trial. Eligible patients with lymph node-negative HR+/HER2-tumors (1:1) were randomly assigned to received four cycles of EC (90/600 mg/m2) or TC (75/600 mg/m2) every three weeks as adjuvant chemotherapy. The primary endpoint was the incidence of grade 3 or 4 neutropenia defined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 on an intention-to-treat basis. Noninferiority was defined as an upper 95% CI less than a noninferiority margin of 15%. Results: In the intention-to-treat population, 140 and 135 patients were randomized into the EC and TC arms, respectively. For the primary endpoint, the rate of grade 3 or 4 neutropenia is 50.71% (95% CI: 42.18%, 59.21%) in the EC arm and 48.15% (95% CI: 39.53%, 56.87%) in the TC arm (95%CI risk difference: −0.100, 0.151), showing the noninferiority of the EC arm. For secondary endpoints, the rate of all-grade anemia is higher in the EC arm (EC 42.86% versus TC 22.96%, p = 0.0007), and more patients suffer from nausea/vomiting, hair loss, and nail changes (p < 0.01) in the EC arm. No statistically different disease-free survival was observed between the two arms (p = 0.13). Conclusion: EC is not inferior to TC in the rate of grade 3 or 4 neutropenia, but more other AEs were observed in the EC group.

Cisplatin-associated ototoxicity: perspectives from a single institution cervical cancer cohort and implications for developing a locally responsive monitoring programme in a public healthcare setting

BackgroundOtotoxicity monitoring is uncommon in South Africa, despite the increased use of ototoxic medication to manage the burden of disease in the country. The successful implementation of such a protocol requires cognisance of contextual realities and multiple dimensions for consideration from both patients and service providers. As part of an ongoing cohort study on cisplatin-associated ototoxicity and efforts to better inform the implementation of such programmes, the perspectives of cervical cancer patients and healthcare workers towards ototoxicity monitoring were assessed.MethodsThis concurrent-triangulation mixed-methods study was conducted at a tertiary hospital in South Africa. Self-reported questionnaires from patients (n = 80) and healthcare personnel comprising clinicians, oncology nurses, pharmacists, and radiotherapists (n = 32), results of audiological evaluations, researcher field notes, and estimated patient and service provider costs contributed to data for this study. Data analysis included descriptive statistics, comparison of test characteristics and deductive thematic analysis.ResultsThe ototoxicity monitoring programme was positively received by the participants, with 90.6% of healthcare personnel and 89% of patients reporting it to be beneficial. The clinicians (76.6%) were identified as the main providers of information on the effects of chemotherapy medication and made the necessary referrals for audiological evaluation. The approximate cost of setting up such a programme included purchase of equipment (US56 700) and the appointment of an audiologist (US 26 250). The approximate costs to patients included transport costs (US$ 38) and the loss of income for the day (US 60), calculated at the minimum wage per hour, if employed. Creative appointment scheduling, easy facility access and detailed locally comprehensible couselling improved patient compliance to the programme. Whilst the sequential use of American Speech-Language-Hearing Association (ASHA) and National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria aided in an evidence-informed approach to aural rehabilitation, DPOAEs and speech discrimination displayed low sensitivity (range 1.45% – 22.39%) but high specificity (range 77.78% – 100%) when identifying ototoxic change.ConclusionThis novel study, through a ‘real-world’ experience, has revealed that an ototoxicity monitoring programme is feasible in South Africa, through meaningful engagements with- and considerations from- patients and service providers regarding planning, delineation of responsibilities and cost implications. The findings can potentially serve as a roadmap for other limited resource environments.

A Case Report of Hypopharyngeal Cancer Improved with Chemotherapy and Korean Medicine Therapy

This study examined the clinical effects of Korean medicine therapy in a patient with hypopharyngeal cancer treated with chemotherapy. A 53-year-old male patient suffering from hypopharyngeal cancer was treated with docetaxel as well as acupuncture and herbal medicine. Tumor size was measured by computed tomography (CT) and adverse events were evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. After two months of combined treatment, the size of the tumor mass was reduced at the left side of the neck, posterior to the CCA and at the lymph node in the left retropharyngeal area and medial aspect of the carotid sheath. The adverse events of chemotherapy also improved. This study indicates that Korean medicine therapy, such as acupuncture and herbal medicine, may lessen the side effects of chemotherapy and may be effective in the treatment of hypopharyngeal cancer.

Characteristics and Clinical Implication of UGT1A1 Heterozygous Mutation in Tumor.

BackgroundThe literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear.MethodsA total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization.ResultsThere were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P < 0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not.ConclusionIn clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.

Проспективная комплексная оценка химиоиндуцированной периферической нейропатии у пациенток с раком молочной железы

Introduction. Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-dependent side effect of anticancer therapy that affects the patient’s quality of life. Currently, the problem of effective and reliable diagnostics for CIPN remains unresolved. Therefore, it is critically important to develop recommendations for a comprehensive assessment of peripheral neuropathy based on simple tests for vibration, tactile, pain sensitivity together with questionnaires. Aim. A prospective comprehensive assessment of the incidence and severity of CIPN using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) and the Patient Neurotoxicity Questionnaire (PNQ) in patients with breast cancer treated with taxanes. Materials and methods. Symptoms of CIPN were prospectively assessed in 60 patients using the PNQ, the NCI-CTCAE and the Eastern Cooperative Oncology Group (ECOG) Performance Status scores at baseline, 1 week after and 13 weeks after the start of chemotherapy. Results. The CIPN scores according to the PNQ were widely distributed among patients compared to the NCI-CTCAE scores for both sensory and motor neuropathy. There was a marked increase in symptoms of motor neuropathy in patients who were identified only on the basis of PNQ data. The PNQ was used to formally assess the impact of neuropathy on the patient’s activities of daily living. Conclusion. A comprehensive methodology based on a neurological examination together with the NCI-CTCAE and the PNQ will allow a more detailed assessment of the severity of СIPN, and in the future will provide an opportunity to develop a more effective patient management plan. The PNQ has shown itself to be a more sensitive tool compared to the NCI-STCAE, especially in assessing sensory neuropathy. Thus, it is reasonable to include patient-reported data in the evaluation of СIPN in order to provide a more accurate identification of the frequency and severity of neuropathy.