scholarly journals Effect of Scalp Cooling on the Pharmacokinetics of Paclitaxel

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3915
Author(s):  
Leni van Doorn ◽  
Mandy M. van Rosmalen ◽  
Wendy M. van der Deure ◽  
Esther Oomen-de Hoop ◽  
Robert Porrazzo ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Side Effect ◽  
Chemotherapeutic Agent ◽  
Relative Difference ◽  
High Impact ◽  
Scalp Cooling ◽  
Weekly Dose ◽  
Geometric Means ◽  
Blood Samples ◽  
Paclitaxel Treatment

Chemotherapy-induced alopecia (CIA), a side effect with high impact, can be prevented by cooling the scalp during the administration of some cytotoxic drugs. However, the effects of this prolonged scalp cooling on the pharmacokinetics of chemotherapy have never been investigated. In this study, we compared the pharmacokinetics of the widely used chemotherapeutic agent paclitaxel (weekly dose of 80–100 mg/m2) in female patients with solid tumors using concomitant scalp cooling (n = 14) or not (n = 24). Blood samples were collected in all patients for pharmacokinetic analyses up to 6 h after one course of paclitaxel administration. The primary endpoint was the clearance (L/h) of paclitaxel. Paclitaxel clearance—expressed as relative difference in geometric means—was 6.8% (90% CI: −16.7% to 4.4%) lower when paclitaxel was administered with concomitant scalp cooling versus paclitaxel infusions without scalp cooling. Within the subgroup of patients using scalp cooling, paclitaxel clearance was not statistically significantly different between patients with CIA (alopecia grade 1 or 2) and those without CIA. Hence, scalp cooling did not negatively influence the clearance of paclitaxel treatment.

Putative Blood Somatic Mutations in Post-Traumatic Stress Disorder-Symptomatic Soldiers: High Impact of Cytoskeletal and Inflammatory Proteins

2021 ◽  
Vol 79 (4) ◽  
pp. 1723-1734
Author(s):  
Shlomo Sragovich ◽  
Michael Gershovits ◽  
Jacqueline C.K. Lam ◽  
Victor O.K. Li ◽  
Illana Gozes
Keyword(s):  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Somatic Mutations ◽  
Stress Disorder ◽  
Ptsd Symptom ◽  
High Impact ◽  
Post Traumatic Stress ◽  
Blood Samples ◽  
Post Traumatic ◽  
The Brain

Background: We recently discovered autism/intellectual disability somatic mutations in postmortem brains, presenting higher frequency in Alzheimer’s disease subjects, compared with the controls. We further revealed high impact cytoskeletal gene mutations, coupled with potential cytoskeleton-targeted repair mechanisms. Objective: The current study was aimed at further discerning if somatic mutations in brain diseases are presented only in the most affected tissue (the brain), or if blood samples phenocopy the brain, toward potential diagnostics. Methods: Variant calling analyses on an RNA-seq database including peripheral blood samples from 85 soldiers (58 controls and 27 with symptoms of post-traumatic stress disorder, PTSD) was performed. Results: High (e.g., protein truncating) as well as moderate impact (e.g., single amino acid change) germline and putative somatic mutations in thousands of genes were found. Further crossing the mutated genes with autism, intellectual disability, cytoskeleton, inflammation, and DNA repair databases, identified the highest number of cytoskeletal-mutated genes (187 high and 442 moderate impact). Most of the mutated genes were shared and only when crossed with the inflammation database, more putative high impact mutated genes specific to the PTSD-symptom cohorts versus the controls (14 versus 13) were revealed, highlighting tumor necrosis factor specifically in the PTSD-symptom cohorts. Conclusion: With microtubules and neuro-immune interactions playing essential roles in brain neuroprotection and Alzheimer-related neurodegeneration, the current mutation discoveries contribute to mechanistic understanding of PTSD and brain protection, as well as provide future diagnostics toward personalized military deployment strategies and drug design.

Skin and mucosal alterations

2007 ◽  
pp. 635-652
Keyword(s):  
Body Image ◽  
Cancer Treatment ◽  
Advanced Cancer ◽  
Oral Mucositis ◽  
Hair Loss ◽  
Side Effect ◽  
Oral Care ◽  
Scalp Cooling ◽  
It Impacts ◽  
Scalp Hypothermia

Hair loss (alopecia) 636 Scalp cooling (scalp hypothermia) 638 Oral mucositis and related problems 640 Oral mucositis: managing the process and symptoms 644 Oesophagitis 646 Oral care in advanced cancer 647 Malignant wounds 648 Lymphoedema 650 Hair loss can be a distressing side effect of cancer treatment; it impacts on body image and feelings of attractiveness, creates anxiety and causes a visual reminder of the disease and treatment. Alopecia is not a major side effect for most people, but a small group of patients will become extremely distressed by it....

Preliminary evidence of activity of pralatrexate in relapsed/refractory ovarian cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15557-e15557
Author(s):  
Nashat Y. Gabrail ◽  
Carrie L. Smith
Keyword(s):  
Ovarian Cancer ◽  
Renal Impairment ◽  
Renal Insufficiency ◽  
Solid Tumors ◽  
Hematological Malignancies ◽  
Folate Receptor ◽  
Ca 125 ◽  
Clinical Activity ◽  
Weekly Dose ◽  
The Impact

e15557 Background: Pralatrexate, a novel antifolate, is approved in the US for the treatment of relapsed/refractory peripheral T-cell lymphoma at a dose of 30mg/m2 weekly for 6 weeks of a 7-week cycle. Previous studies in solid tumors have focused on a q2w schedule at 190mg/m2. As pralatrexate is 30-40% renally excreted, an ongoing renal impairment study is investigating the impact of mild, moderate and severe renal impairment on pralatrexate distribution in patients with hematological malignancies and solid tumors. As folate receptor alpha is frequently overexpressed in epithelial ovarian cancers, we hypothesized that ovarian cancer may be a target for pralatrexate treatment and therefore have included a number of ovarian cancer patients in this trial. Methods: Patients with solid tumors and hematological malignancies were enrolled in a phase I clinical trial. Patients are treated in cohorts depending on renal function normal, mild renal insufficiency, moderate renal insufficiency and severe non-dialysis dependent renal failure. This analysis is limited to 6 patients with refractory ovarian cancer. The dose of pralatrexate is 30mg/m2 weekly for 6 weeks of a 7-week cycle, with dose adjustment depending on toxicity. Results: The 6 patients, all with stage 4 refractory ovarian cancer had received 4 or more prior chemotherapy regimens and had refractory disease, defined as, nonresponsive to the last chemotherapy regimen or progression within 3 months of the last dose of chemotherapy. Of the 6 patients, 2 experienced objective responses lasting 9 months and 4 months respectively. Disease response was assessed by CA- 125 and RECIST criteria. Two patients experienced stable disease for 4 months and 5 months respectively. One patient had grade 5 mucositis after the second weekly dose and one patient had progressive disease after disease stabilization for 3 months. Conclusions: Pralatrexate given at a dose of 30mg/m2 to patients with refractory ovarian cancer has demonstrable activity that needs to be confirmed in well-designed efficacy trials. Importantly, this is the first demonstration of clinical activity in a solid tumor at the currently approved dose.

CTC enumeration and characterization as a pharmacodynamic marker in the phase I clinical study of APX3330, an APE1/Ref-1 inhibitor, in patients with advanced solid tumors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14531-e14531 ◽  
Author(s):  
Lincy Chu ◽  
Amanda K. L. Anderson ◽  
Mark Andrew Landers ◽  
Yipeng Wang ◽  
Mark R. Kelley ◽  
...  
Keyword(s):  
Clinical Study ◽  
Phase I ◽  
Solid Tumors ◽  
Dual Function ◽  
Protective Function ◽  
Blood Samples ◽  
Steady State Serum ◽  
Downstream Analysis ◽  
Cancer Cell Signaling ◽  
Tumor Agent

e14531 Background: APE1/Ref-1 is a dual-function protein with a pleiotropic role in regulating transcription factors involved in cancer cell signaling via redox control, as well as responding to oxidative and base DNA damage. APX3330 is a highly selective inhibitor of the Ref-1 mediated redox function in tumors, while enhancing the neuronal protective function of APE1. APX3330 is undergoing clinical development as an anti-tumor agent that also protects and reverses oxidative damage to neurons. We now report on the CTC analysis conducted as part of the study (NCT0337508). Results of the clinical study are reported in a separate abstract. Methods: A total of 19 patients with 10 various solid tumors, including rectal, pancreatic, colon, endometrial, gall bladder, hepatocellular, prostate, melanoma, bladder, and ovarian cancers received APX3330 in escalating divided daily doses of 240, 360, 480, 600, and 720mg. Blood samples were collected from all patients prior to receiving APX3330 and after achieving steady-state serum concentrations of the drug. Samples were sent to Epic Sciences to analyze circulating tumor cells (CTCs) in peripheral blood via their CTC Platform. Results: Cumulatively, 37 samples from 19 patients were received. 35/37 (95%) samples passed technical quality control and were feasible for downstream analysis. 9/17 (53%) baseline samples (BL) had CTCs detected, while 9/18 (50%) on-treatment (OTx) draws had CTCs detected. 16 patients had BL and OTx samples that were further evaluated with the longitudinal analysis. Of these, 7/16 (44%), 6/16 (38%), and 3/16 (19%) patients showed a reduction trend, an increase trend, and no change in all CTC populations (delta greater than or equal to 0 CTC/ml), respectively. Patient follow-up is ongoing and the correlation of CTC biomarkers with clinical outcomes is pending. Conclusions: APX3330 is undergoing clinical evaluation as an anti-tumor agent that protects against and reverses CIPN. In this phase I study, 44% of evaluable blood samples showed a reduction in CTCs after initiation of treatment with APX3330. Additional studies are now being planned. Clinical trial information: NCT0337508.

Effectiveness of scalp cooling in reducing chemotherapy-induced alopecia: A single center prospective study in Lebanon.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12075-e12075
Author(s):  
Nour Haidar ◽  
Lewis Nasr ◽  
Fadi Nasr
Keyword(s):  
Breast Cancer ◽  
Prospective Study ◽  
Hair Loss ◽  
Side Effect ◽  
Chemotherapy Regimen ◽  
Stage I ◽  
P Value ◽  
Scalp Cooling ◽  
Multiple Cycles ◽  
The One

e12075 Background: Hair loss (alopecia) is recognized as one of the most common and distressing side effects of chemotherapy. The scalp cooler first used in 1970s against the Chemotherapy CIA (chemotherapy induced alopecia). This study aimed at assessing the effectiveness of scalp cooling (PAXMAN Cooler ORBIS II SCALP COOLER) in reducing chemotherapy-induced alopecia. Methods: This prospective study was conducted at the Mount-Lebanon Hospital in the one day chemotherapy between 01 January 2017 and 31 December 2018. 109 women diagnosed with breast cancer with stage I or II undergoing neoadjuvant, and adjuvant chemotherapy were enrolled. Patients with scalp cooling 54.1% (n=59), control 45.9 % (n=50). Scalp cooling done by using the scalp cooling device. The primary end point was to assess the hair loss using the dean’s scale after multiple cycles of chemotherapy. The clinical assessment and alopecia evaluation were done after each chemotherapy cycle. The secondary endpoint was the side effect of the scalp cooler such as headache. Results: The Mean age was 55.73 ± 11.9 years. 82.56 %received Anthracycline-based chemotherapy regimen with Docetaxel, and 14.69 % Anthracycline-based chemotherapy regimen with Paclitaxel and 2.75 % took only anthracycline with cyclophosphamide. The effectiveness of hair preservation was successfully reported as 62.7% grade 0, 22.01 % grade 1 and 15.29% grade 2. There were highly significant differences between patients underwent scalp cooling and patients without scalp cooling with different regimens of chemotherapy (P value <0.0001). The major side effect, the headache where was reported in 25.7% from the total (P value <0.0001). Conclusions: Hair preservation in stage I , II breast cancer undergoing multiple regimens of chemotherapy was significantly more effective in the scalp cooling group.

scholarly journals Phase I study of DFP-11207, a novel chemotherapeutic agent, in patients with solid tumors by reasonable dose escalation

2016 ◽  
Vol 27 ◽  
pp. vii88
Author(s):  
Jaffer A. Ajani ◽  
Cathy Eng ◽  
Milind Javle ◽  
Katrina Hernandez ◽  
Barry D. Anderson ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Phase I Study ◽  
Chemotherapeutic Agent

385 A first-in-human study of lemzoparlimab, a differentiated anti-CD47 antibody, in subjects with relapsed/refractory malignancy: initial monotherapy results

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A410-A410 ◽  
Author(s):  
Jordan Berlin ◽  
Wael Harb ◽  
Alex Adjei ◽  
Yan Xing ◽  
Paul Swiecicki ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Dose Escalation ◽  
Phase 1 ◽  
Human Study ◽  
Evaluation Criteria ◽  
Receptor Occupancy ◽  
High Dose ◽  
Weekly Dose ◽  
Response Data ◽  
Good Laboratory

BackgroundCD47 blockade using SIRPα-Fc or anti-CD47 antibodies results in inhibition of the ‘do not eat’ signal and activation of phagocytosis and has emerged as a promising cancer treatment strategy. However, targeting CD47 leads to various hematological toxicities, particularly anemia and thrombocytopenia. Lemzoparlimab (also known as TJ011133 or TJC4) is a fully human, anti-CD47 IgG4 antibody that is endowed with a red blood cell (RBC) sparing property and unique binding epitope, potentially differentiating itself from other CD47 axis targeting therapies.MethodsThis phase 1 study (NCT03934814) is comprised of 2 parts. Part 1 consists of lemzoparlimab monotherapy dose escalation and 2 separate dose escalations of combination therapy with pembrolizumab or rituximab. The study is a standard 3+3 design. Part 2 is a dose expansion study. During monotherapy dose escalation, patients with relapsed/refractory solid tumors were administered an intravenous weekly dose (1 to 30 mg/kg) of lemzoparlimab to determine tolerability, safety, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity based on Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and iRECIST. Preliminary data from fully enrolled monotherapy cohorts in Part 1 are reported as of 17 July 2020.ResultsTwenty patients with relapsed/refractory solid tumors were enrolled to monotherapy dose escalation cohorts (1, 3, 10, 20 and 30 mg/kg). Lemzoparlimab toxicity was manageable up to 30 mg/kg without a dose-limiting toxicity (DLT) observed. The most common treatment-related adverse events (TRAEs) were anemia (30.0%, n=6), fatigue (25.0%, n=5), infusion-related reactions (20.0%, n=4), and diarrhea (15.0%, n=3). All TRAEs were Grade 1 or 2. A transient, non-dose-dependent average reduction of 1.5 mg/dL (range: 0.4–2.6 mg/dL) in hemoglobin during the first cycle was observed across all cohorts consistent with the results of pre-clinical good laboratory practice toxicity studies. Laboratory or clinical evidence of hemolysis was not observed in any cohort. Preliminary results indicate the PK of lemzoparlimab appears to be linear at mid- to high dose levels following a single dose. CD47 receptor occupancy shows complete saturation on peripheral T cells at peak concentrations of 20 mg/kg and above.ConclusionsLemzoparlimab appears safe up to 30 mg/kg with favorable PK and PD characteristics in patients with relapsed/refractory solid tumors to date. No TRAEs greater than Grade 2 have been observed. Results will be updated at presentation including available tumor response data.Trial RegistrationNCT03934814Ethics ApprovalThe study was approved by IRB, approval number 20190733.

scholarly journals Cell-free DNA profiling of metastatic prostate cancer reveals microsatellite instability, structural rearrangements and clonal hematopoiesis

2018 ◽  
Author(s):  
Markus Mayrhofer ◽  
Bram De Laere ◽  
Tom Whitington ◽  
Peter Van Oyen ◽  
Christophe Ghysel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Microsatellite Instability ◽  
Metastatic Prostate Cancer ◽  
Structural Variation ◽  
Predictive Biomarkers ◽  
High Impact ◽  
Blood Samples ◽  
Clonal Hematopoiesis ◽  
Free Dna

AbstractBackgroundThere are multiple existing and emerging therapeutic avenues for metastatic prostate cancer, with a common denominator, which is the need for predictive biomarkers. Circulating tumor DNA (ctDNA) has the potential to cost-efficiently accelerate precision medicine trials to improve clinical efficacy and diminish costs and toxicity. However, comprehensive ctDNA profiling in metastatic prostate cancer to date has been limited.MethodsA combination of targeted- and low-pass whole genome sequencing was performed on plasma cell-free DNA and matched white blood cell germline DNA in 364 blood samples from 217 metastatic prostate cancer patients.ResultsctDNA was detected in 85.9% of baseline samples, correlated to line of therapy and was mirrored by circulating tumor cell enumeration of synchronous blood samples. Comprehensive profiling of the androgen receptor (AR) revealed a continuous increase in the fraction of patients with intra-ARstructural variation, from 15.4% during first line mCRPC therapy to 45.2% in fourth line, indicating a continuous evolution of AR during the course of the disease. Patients displayed frequent alterations in DNA repair deficiency genes (18.0%). Additionally, the microsatellite instability phenotype was identified in 3.81% of eligible samples (≥0.1 ctDNA fraction). Sequencing of non-repetitive intronic- and exonic regions ofPTEN, RB1andTP53detected biallelic inactivation in 47.5%, 20.3% and 44.1% of samples with ≥0.2 ctDNA fraction, respectively. Only one patient carried a clonal high-impact variant without a detectable second hit. Intronic high-impact structural variation was twice as common as exonic mutations inPTENand RB1. Finally, 14.6% of patients presented false positive variants due to clonal hematopoiesis, commonly ignored in commercially available assays.ConclusionsctDNA profiles appear to mirror the genomic landscape of metastatic prostate cancer tissue and may cost-efficiently provide somatic information in clinical trials designed to identify predictive biomarkers. However, intronic sequencing of the interrogated tumor suppressors challenge the ubiquitous focus on coding regions and is vital, together with profiling of synchronous white blood cells, to minimize erroneous assignments which in turn may confound results and impede true associations in clinical trials.

Sign in / Sign up

Export Citation Format

Share Document