-
In Vivo (Athens, Greece) 2024Treatment options are limited, and the prognosis is poor for patients with platinum-resistant recurrent metastatic (R/M) head and neck squamous cell carcinoma (HNSCC)....
BACKGROUND
Treatment options are limited, and the prognosis is poor for patients with platinum-resistant recurrent metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). This study evaluated the efficacy and safety of a paclitaxel and ifosfamide (TI) regimen in patients with R/M HNSCC whose disease had progressed following platinum-based therapy.
PATIENTS AND METHODS
In this retrospective study, we included 53 patients with R/M HNSCC who underwent at least one cycle of TI-based therapy, post platinum failure, between February 2020 and August 2023. Some patients received the TI regimen in combination with immunotherapy and/or cetuximab. Key metrics assessed included the objective response rate (ORR), disease control rate, and progression-free as well as overall survival.
RESULTS
The study observed an ORR of 15.8% and a disease control rate of 36.8%. The median progression-free survival for the entire cohort was 3.3 months, and the median overall survival was 9.6 months. Notably, the combination of TI with immunotherapy yielded a higher ORR of 30.8%, compared to 14.3% with TI alone. The most prevalent grade 1-2 adverse events were anemia (81%), weight loss (68%) and hypernatremia (55%).
CONCLUSION
The TI-based regimen demonstrated favorable efficacy and safety profile in treating R/M HNSCC. Enhanced outcomes may be attainable when combining it with immunotherapy. This study suggests that TI-based therapy could serve as a potential salvage option for this specific patient group.
Topics: Humans; Male; Female; Middle Aged; Aged; Salvage Therapy; Head and Neck Neoplasms; Drug Resistance, Neoplasm; Paclitaxel; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Recurrence, Local; Adult; Ifosfamide; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Platinum; Neoplasm Metastasis; Aged, 80 and over; Treatment Outcome
PubMed: 38936932
DOI: 10.21873/invivo.13644 -
Gynecologic Oncology Jun 2024Chemotherapy-induced alopecia (CIA) is a common and emotionally-taxing side effect of chemotherapy, including taxane agents used frequently in treatment of gynecologic... (Review)
Review
BACKGROUND
Chemotherapy-induced alopecia (CIA) is a common and emotionally-taxing side effect of chemotherapy, including taxane agents used frequently in treatment of gynecologic cancers. Scalp hypothermia, also known as "cold caps", is a possible method to prevent severe CIA, studied primarily in the breast cancer population.
OBJECTIVES
To compile existing data on scalp hypothermia in cancer patients receiving taxane chemotherapy in order to investigate its application to the gynecologic cancer population.
SEARCH STRATEGY
MEDLINE, Embase, CINAHL, ClinicalTrials.gov, and Cochrane were searched through January 31, 2023.
SELECTION CRITERIA
Full-text manuscripts reporting on the results of scalp hypothermia in patients receiving taxane-based chemotherapy.
DATA COLLECTION AND ANALYSIS
Binomial proportions were summed, and random-effects meta-analyses performed.
MAIN RESULTS
From 1424 records, we included 31 studies, representing 14 different countries. Only 5 studies included gynecologic cancer patients. We extracted the outcome of the proportion of patients with <50% hair loss. Among 2179 included patients, 60.7% were reported to have <50% hair loss (meta-analysis: 60.6%, 95% confidence interval [CI] 54.9-66.1%). Among the 28 studies reporting only on taxane-based chemotherapy, the rate of <50% hair loss was 60.0% (meta-analysis: 60.9%, (95% CI: 54.9-66.7%). In comparative studies, hair loss was significantly less in patients who received scalp hypothermia versus those who did not (49.3% versus 0% with <50% hair loss; OR 40.3, 95% CI: 10.5-154.8). Scalp cooling achieved <50% hair loss in patients receiving paclitaxel (67.7%; meta-analysis 69.9%, 95% CI 64.1-75.4%) and docetaxel (57.1%; meta-analysis 60.5%, 95% CI 50.0-71.6%). Meta-analysis on patient satisfaction in regard to scalp cooling found a satisfaction rate of 78.9% (95% CI 69.1-87.4%).
CONCLUSION
Scalp hypothermia may be an effective method to reduce some cases of CIA due to taxane chemotherapy, especially paclitaxel. More trials need to be done to determine the precise effects of scalp hypothermia in gynecologic cancer patients.
PubMed: 38936283
DOI: 10.1016/j.ygyno.2024.06.012 -
Gynecologic Oncology Jun 2024Ovarian cancer, a leading cause of cancer-related deaths in women, remains a formidable challenge, especially in the context of platinum-resistant disease. This study...
OBJECTIVE
Ovarian cancer, a leading cause of cancer-related deaths in women, remains a formidable challenge, especially in the context of platinum-resistant disease. This study investigated the potential of the benzimidazole derivative BNZ-111 as a novel treatment strategy for platinum-resistant ovarian cancer.
METHODS
The human EOC cell lines A2780, HeyA8, SKOV3ip1, A2780-CP20, HeyA8-MDR, and SKOV3-TR were treated with BNZ-111, and cell proliferation, apoptosis, and cell cycle were assessed.
RESULTS
It demonstrated strong cytotoxicity in both chemo-sensitive and chemo-resistant epithelial ovarian cancer cell lines, inducing apoptosis and G2/M cell cycle arrest. In vivo experiments using orthotopic and patient-derived xenograft models showed significant tumor growth inhibition without apparent toxicity to vital organs. Unlike paclitaxel, BNZ-111 proved effective in paclitaxel-resistant cells, potentially by bypassing interaction with MDR1 and modulating β-3 tubulin expression to suppress microtubule dynamics.
CONCLUSION
BNZ-111, with favorable drug-like properties, holds promise as a therapeutic option for platinum-resistant ovarian cancer, addressing a critical clinical need in gynecologic oncology.
PubMed: 38936282
DOI: 10.1016/j.ygyno.2024.06.011 -
Journal of Clinical Oncology : Official... Jun 2024Long-term outcomes of patients with stage I human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving adjuvant trastuzumab emtansine (T-DM1)...
Adjuvant Trastuzumab Emtansine Versus Paclitaxel Plus Trastuzumab for Stage I Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 5-Year Results and Correlative Analyses From ATEMPT.
PURPOSE
Long-term outcomes of patients with stage I human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving adjuvant trastuzumab emtansine (T-DM1) remain undefined, and prognostic predictors represent an unmet need.
METHODS
In the ATEMPT phase II trial, patients with stage I centrally confirmed HER2-positive breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for 1 year or paclitaxel plus trastuzumab (TH). Coprimary objectives were to compare the incidence of clinically relevant toxicities between arms and to evaluate invasive disease-free survival (iDFS) with T-DM1. Correlative analyses included the HER2DX genomic tool, multiomic evaluations of HER2 heterogeneity, and predictors of thrombocytopenia.
RESULTS
After a median follow-up of 5.8 years, 11 iDFS events were observed in the T-DM1 arm, consistent with a 5-year iDFS of 97.0% (95% CI, 95.2 to 98.7). At 5 years, the recurrence-free interval (RFI) was 98.3% (95% CI, 97.0 to 99.7), the overall survival was 97.8% (95% CI, 96.3 to 99.3), and the breast cancer-specific survival was 99.4% (95% CI, 98.6 to 100). Comparable iDFS was observed with T-DM1 irrespective of tumor size, hormone receptor status, centrally determined HER2 immunohistochemical score, and receipt of T-DM1 for more or less than 6 months. Although ATEMPT was not powered for this end point, the 5-year iDFS in the TH arm was 91.1%. Among patients with sufficient tissue for HER2DX testing (n = 187), 5-year outcomes significantly differed according to HER2DX risk score, with better RFI (98.1% 81.8%, hazard ratio [HR], 0.10, = .01) and iDFS (96.3% 81.8%, HR, 0.20, = .047) among patients with HER2DX low-risk versus high-risk tumors, respectively.
CONCLUSION
Adjuvant T-DM1 for 1 year leads to outstanding long-term outcomes for patients with stage I HER2-positive breast cancer. A high HER2DX risk score predicted a higher risk of recurrence in ATEMPT.
PubMed: 38935923
DOI: 10.1200/JCO.23.02170 -
PloS One 2024Mucosal-delivered drugs have to pass through the mucus layer before absorption through the epithelial cell membrane. Although there has been increasing interest in...
Mucosal-delivered drugs have to pass through the mucus layer before absorption through the epithelial cell membrane. Although there has been increasing interest in polymeric mucins, a major structural component of mucus, potentially acting as important physiological regulators of mucosal drug absorption, there are no reports that have systematically evaluated the interaction between mucins and drugs. In this study, we assessed the potential interaction between human polymeric mucins (MUC2, MUC5B, and MUC5AC) and various drugs with different chemical profiles by simple centrifugal method and fluorescence analysis. We found that paclitaxel, rifampicin, and theophylline likely induce the aggregation of MUC5B and/or MUC2. In addition, we showed that the binding affinity of drugs for polymeric mucins varied, not only between individual drugs but also among mucin subtypes. Furthermore, we demonstrated that deletion of MUC5AC and MUC5B in A549 cells increased the cytotoxic effects of cyclosporin A and paclitaxel, likely due to loss of mucin-drug interaction. In conclusion, our results indicate the necessity to determine the binding of drugs to mucins and their potential impact on the mucin network property.
Topics: Humans; Paclitaxel; Mucin 5AC; A549 Cells; Drug Interactions; Mucin-5B; Mucins; Mucin-2; Rifampin; Cyclosporine; Protein Binding
PubMed: 38935605
DOI: 10.1371/journal.pone.0306058 -
JAMA Oncology Jun 2024The optimal radiotherapy technique for unresectable locally advanced non-small cell lung cancer (NSCLC) is controversial, so evaluating long-term prospective outcomes of...
IMPORTANCE
The optimal radiotherapy technique for unresectable locally advanced non-small cell lung cancer (NSCLC) is controversial, so evaluating long-term prospective outcomes of intensity-modulated radiotherapy (IMRT) is important.
OBJECTIVE
To compare long-term prospective outcomes of patients receiving IMRT and 3-dimensional conformal radiotherapy (3D-CRT) with concurrent carboplatin/paclitaxel for locally advanced NSCLC.
DESIGN, SETTING, AND PARTICIPANTS
A secondary analysis of a prospective phase 3 randomized clinical trial NRG Oncology-RTOG 0617 assessed 483 patients receiving chemoradiotherapy (3D-CRT vs IMRT) for locally advanced NSCLC based on stratification.
MAIN OUTCOMES AND MEASURES
Long-term outcomes were analyzed, including overall survival (OS), progression-free survival (PFS), time to local failure, development of second cancers, and severe grade 3 or higher adverse events (AEs) per Common Terminology Criteria for Adverse Events, version 3. The percentage of an organ volume (V) receiving a specified amount of radiation in units of Gy is reported as V(radiation dose).
RESULTS
Of 483 patients (median [IQR] age, 64 [57-70] years; 194 [40.2%] female), 228 (47.2%) received IMRT, and 255 (52.8%) received 3D-CRT (median [IQR] follow-up, 5.2 [4.8-6.0] years). IMRT was associated with a 2-fold reduction in grade 3 or higher pneumonitis AEs compared with 3D-CRT (8 [3.5%] vs 21 [8.2%]; P = .03). On univariate analysis, heart V20, V40, and V60 were associated with worse OS (hazard ratios, 1.06 [95% CI, 1.04-1.09]; 1.09 [95% CI, 1.05-1.13]; 1.16 [95% CI, 1.09-1.24], respectively; all P < .001). IMRT significantly reduced heart V40 compared to 3D-CRT (16.5% vs 20.5%; P < .001). Heart V40 (<20%) had better OS than V40 (≥20%) (median [IQR], 2.5 [2.1-3.1] years vs 1.7 [1.5-2.0] years; P < .001). On multivariable analysis, heart V40 (≥20%), was associated with worse OS (hazard ratio, 1.34 [95% CI, 1.06-1.70]; P = .01), whereas lung V5 and age had no association with OS. Patients receiving IMRT and 3D-CRT had similar rates of developing secondary cancers (15 [6.6%] vs 14 [5.5%]) with long-term follow-up.
CONCLUSIONS AND RELEVANCE
These findings support the standard use of IMRT for locally advanced NSCLC. IMRT should aim to minimize lung V20 and heart V20 to V60, rather than constraining low-dose radiation bath. Lung V5 and age were not associated with survival and should not be considered a contraindication for chemoradiotherapy.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT00533949.
PubMed: 38935373
DOI: 10.1001/jamaoncol.2024.1841 -
Nanomedicine (London, England) Jun 2024Paclitaxel and imatinib mesylate are drugs used in the treatment of breast cancer. Conventional drug-delivery systems have limitations in the effective treatment of...
Paclitaxel and imatinib mesylate are drugs used in the treatment of breast cancer. Conventional drug-delivery systems have limitations in the effective treatment of breast cancer using the drugs. Combination index studies were used to identify the optimum ratio of both drugs showing maximum synergistic effect. Using a systematic quality-by-design approach, protamine-coated PLGA nanoparticles co-loaded with paclitaxel and imatinib mesylate were formulated. Further characterization and cell line evaluations were performed. Encapsulation efficiency obtained was 92.54% for paclitaxel and 75.12% for imatinib mesylate. A sustained (24 h) and controlled zero-order drug release was obtained. Formulated nanoparticles had a low IC value and enhanced cellular uptake.
PubMed: 38934510
DOI: 10.1080/17435889.2024.2353557 -
Scandinavian Journal of Clinical and... Jun 2024Neoadjuvant chemotherapy (NAC) is the preferred treatment option in locally advanced breast cancer (BC). The administration of NAC is associated with a wide range of...
Neoadjuvant chemotherapy (NAC) is the preferred treatment option in locally advanced breast cancer (BC). The administration of NAC is associated with a wide range of adverse effects. This pilot observational prospective study examined the effect of NAC using anthracycline + cyclophosphamide (AC) followed by paclitaxel (PTx) on a portfolio of 22 plasma and urinary amino acids, plasma proteins (albumin, prealbumin, transferrin), and products of nitrogen metabolism (urea, creatinine, uric acid) in plasma and urine. Plasma and 24-h urine samples were obtained from ten patients with early breast cancer (N1-3 N0-2 M0), at the following time points: before the start of NAC and during the AC/PTx treatment period (a total of 8 measurements at three-weekly intervals). Amino acids were analyzed using ion exchange chromatography. There were no significant differences in the measured parameters in plasma and urine between pre-NAC and during AC- and PTx-treatment. No trend was detected. A significant difference in the portfolio of plasma and urinary amino acids was found only in the pre-treatment period compared to the control group. Levels of eight plasma amino acids (8/22) were significantly reduced and those of nine urine amino acids were increased (9/22). Nitrogenous catabolites in plasma and urine were not indicative of increased protein catabolism during the anthracycline and taxane treatment periods. A slightly positive nitrogen balance was accompanied by an average weight gain of 3.3 kg (range 0-6 kg). The AC/PTx treatment regimen did not cause significant changes in the monitored laboratory parameters.
PubMed: 38934425
DOI: 10.1080/00365513.2024.2369982 -
Oncology Letters Aug 2024Adjuvant chemotherapy is usually not considered for pT1a pN0 human epidermal growth factor receptor 2 (HER2)-positive breast cancer due to its low recurrence rate. The...
Multiple metastases of human epidermal growth factor receptor 2‑positive, hormone receptor‑positive, pT1a pN0 breast cancer within 1 year after surgery: A case report.
Adjuvant chemotherapy is usually not considered for pT1a pN0 human epidermal growth factor receptor 2 (HER2)-positive breast cancer due to its low recurrence rate. The present report describes a case of pT1a hormone receptor-positive HER2-positive breast cancer with multiple recurrences in the axillary lymph nodes and liver within 1 year after radical surgery. A 58-year-old woman underwent left total mastectomy and sentinel lymph node biopsy for left breast cancer with pathological stage IA (pT1a pN0). The subtype corresponded to luminal B-like breast cancer with a nuclear grade of 3 and a Ki-67 labeling index of 37%. An aromatase inhibitor (letrozole) was planned to be administered for 5 years after surgery, but the patient was diagnosed with multiple liver and axillary lymph node metastases 11 months after surgery. After 1 year of chemotherapy (paclitaxel) in combination with anti-HER2 therapy (pertuzumab and trastuzumab), liver metastases resolved. A complete response of the liver lesion has been maintained 4 years after the anti-HER2 therapy initiation. The present case exhibited two poor prognostic factors: High Ki-67 labeling index and nuclear grade 3. Based on the 'Predict' tool, the present case would be expected to have a cancer-related mortality rate of 6% 10 years after surgery with adjuvant endocrine therapy. Although this value may be controversial for postoperative anti-HER2 therapy, the present case should not be considered to be a low-risk case. When the identification of high-risk pT1a pN0 HER2-positive breast cancer is possible, postoperative anti-HER2 therapy plus chemotherapy would be effective in decreasing the rate of recurrence.
PubMed: 38933808
DOI: 10.3892/ol.2024.14498 -
Frontiers in Pharmacology 2024Chemotherapy-induced peripheral neuropathy (CIPN) is a shared burden for 68.1% of oncological patients undergoing chemotherapy with Paclitaxel (PTX). The symptoms are...
Chemotherapy-induced peripheral neuropathy (CIPN) is a shared burden for 68.1% of oncological patients undergoing chemotherapy with Paclitaxel (PTX). The symptoms are intense and troublesome, patients reporting paresthesia, loss of sensation, and dysesthetic pain. While current medications focus on decreasing the symptom intensity, often ineffective, no medication is yet recommended by the guidelines for the prevention of CIPN. Cannabinoids are an attractive option, as their neuroprotective features have already been demonstrated in neuropathies with other etiologies, by offering the peripheral neurons protection against toxic effects, which promotes analgesia. We aim to screen several new cannabinoids for their potential use as neuroprotective agents for CIPN by investigating the cellular toxicity profile and by assessing the potential neuroprotective features against PTX using a primary dorsal root ganglion neuronal culture. Our study showed that synthetic cannabinoids JWH-007, AM-694 and MAB-CHMINACA and phytocannabinoids Cannabixir Medium dried flowers (NC1) and Cannabixir THC full extract (NC2) preserve the viability of fibroblasts and primary cultured neurons, in most of the tested dosages and time-points. The combination between the cannabinoids and PTX conducted to a cell viability of 70%-89% compared to 40% when PTX was administered alone for 48 h. When assessing the efficacy for neuroprotection, the combination between cannabinoids and PTX led to better preservation of neurite length at all tested time-points compared to controls, highly drug and exposure-time dependent. By comparison, the combination of the cannabinoids and PTX administered for 24 h conducted to axonal shortening between 23% and 44%, as opposed to PTX only, which shortened the axons by 63% compared to their baseline values. Cannabinoids could be potential new candidates for the treatment of paclitaxel-induced peripheral neuropathy; however, our findings need to be followed by additional tests to understand the exact mechanism of action, which would support the translation of the cannabinoids in the oncological clinical practice.
PubMed: 38933665
DOI: 10.3389/fphar.2024.1395951