scholarly journals Plinabulin Rapidly (within 24 Hours) Reverses Myelosuppression Induced By Chemotherapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2056-2056
Author(s):  
Douglas W. Blayney ◽  
Mengru Chang ◽  
Lan Huang ◽  
Ramon Mohanlal
Keyword(s):  
Breast Cancer ◽  
Blood Cell ◽  
Single Agent ◽  
Rapid Onset ◽  
Fixed Dose ◽  
Control Group ◽  
Blood Draw ◽  
Total N ◽  
Cell Counts ◽  
And Control

Abstract Introduction Plinabulin (Plin), a small molecule selective immune-enhancing microtubulin binding agent (SIMBA) has anti-cancer activity, and also prevents chemotherapy (Chemo) induced neutropenia (CIN). Plin has a rapid onset CIN prevention (1 st week) and G-CSF a delayed onset (2 nd week) of the cycle. Single agent Plin has non-inferior protection against CIN compared to Peg. Combining Plin with pegfilgrastim (Peg) has superior protection against CIN throughout the entire Chemo cycle (Blayney ASCO 2021). Plinabulin protected LSK cells in mice receiving myelosuppressive Chemo, which are cells equivalent to CD34+ in humans (Tonra Cancer Chemotherapy and Pharmacology. 2020). We evaluated the mechanism of Plin's rapid onset for CIN prevention in patients (pts). Methods Data from the CIN phase 2/3 Plin trials PROTECTIVE-1 (NCT03102606) with docetaxel 75 mg/m2 in pts with NSCLC, Breast Cancer, Prostate Cancer and PROTECTIVE-2 (NCT0329457) with docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 (TAC) in early stage Breast Cancer was analyzed for pts receiving either Plin (n=228) or Control (no Plin); n=172). Both studies 105 and 106 had patients randomized to either Plin or Pegfilgrastim, which latter was given on the next day of Chemo, on day (D)2. The safety blood draw, taken on D2 at predose Pegfilgrastim, served as a no-treatment Control on D2 in this blood cell analysis for comparison with Plin, which was given on D1. The Plin dose was 20 mg/m2 or 40 mg, and was given as a single dose per cycle, by 30 min IV infusion, 30 min after Chemo on day (D)1. The 40 mg fixed dose is equivalent to 20 mg/m2 Plin. Absolute neutrophil count (ANC), monocyte (M), eosinophil (E), basophil (B), lymphocyte (L), erythrocyte (RBC), and platelet (P) counts were obtained from peripheral blood draws and analyzed by Central Laboratory (Covance). The primary analysis was to compare cell counts between Plin and Control in blood draws taken 24 hour (hr)post-Chemo (thus D2). Separately, we also established Spearman correlation coefficients (r) of scatter plots between ANC and M,E,B,L,RBC, or P count on D2, in a broader dataset that also included Plin doses of 5,10 and 30 mg/m2 in addition to 0 and 20 mg/m2 (40 mg fixed) doses to allow for dose-response evaluation (total n=451). D2 cell counts were expressed as change from pre-dose D1, in absolute values. Results At predose D1 (baseline), counts of ANC, M,E,B,L,RBC, and P were similar between the Plin and Control groups (p=NS). On D2, at 24 hr post-Chemo, ANC, M,E and B ,had all significantly decreased compared to D1 in the Control group (indicating myelosuppression by Chemo), whereas significantly increased with Plin (suggesting reversal of this myelosuppression), albeit within normal range (Table below). At 24 hr post-Chemo, counts for L and RBC had significantly decreased compared to D1 with both Control and Plin, however this decrease was ~50% less with Plin compared to Control (P<0.001). No difference in P counts were observed between Plin and Control at 24 hr post Chemo (p=0.69). Correlative analyses showed that at 24 hr post-Chemo (D2), ANC was positively correlated with counts of M (r=+0.42; p<0.0001), E (r=+0.16; p=0.0008), B (r=+0.20; p<0.0001), L (r=+0.32; p<0.0001), RBC (r=+0.07; p=0.1187) and P (r=+0.18; p=0.0002). Thus, with larger increase in ANC counts on D2, the larger were the increase in the other blood cell types. The observed results were Plin dose-dependent, and consistent between pts receiving either docetaxel alone or TAC . Shown below are mean (SD) of absolute cell count on D2, expressed as change from predose D1. Conclusion Plin rapidly (within 24 hours) reversed myelosuppression induced by Chemo, by protecting granulocyte-monocyte-progenitor (GMP) stem cells (responsible for producing ANC, M, B and E cells) or progenitor cells further upstream in the hematopoietic lineage tree. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Effects of Cancer, Chemotherapy and Cytokines on Subjective and Objective Cognitive Functioning Among Patients with Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2576
Author(s):  
Vincent Chin-Hung Chen ◽  
Chin-Kuo Lin ◽  
Han-Pin Hsiao ◽  
Bor-Show Tzang ◽  
Yen-Hsuan Hsu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cognitive Function ◽  
Cognitive Abilities ◽  
Verbal Fluency ◽  
Control Group ◽  
Control Groups ◽  
Semantic Verbal Fluency ◽  
Cytokine Levels ◽  
Chemotherapy Patients ◽  
And Control

Background: We aimed to investigate the associations of breast cancer (BC) and cancer-related chemotherapies with cytokine levels, and cognitive function. Methods: We evaluated subjective and objective cognitive function in BC patients before chemotherapy and 3~9 months after the completion of chemotherapy. Healthy volunteers without cancer were also compared as control group. Interleukins (IL) 2, 4, 5, 6, 10, 12p70, 13, 17A, 1β, IFNγ, and TNFα were measured. Associations of cancer status, chemotherapy and cytokine levels with subjective and objective cognitive impairments were analyzed using a regression model, adjusting for covariates, including IQ and psychological distress. Results: After adjustment, poorer performance in semantic verbal fluency was found in the post-chemotherapy subgroup compared to controls (p = 0.011, η2 = 0.070); whereas pre-chemotherapy patients scored higher in subjective cognitive perception. Higher IL-13 was associated with lower semantic verbal fluency in the post-chemotherapy subgroup. Higher IL-10 was associated with better perceived cognitive abilities in the pre-chemotherapy and control groups; while IL-5 and IL-13 were associated with lower perceived cognitive abilities in pre-chemotherapy and control groups. Our findings from mediation analysis further suggest that verbal fluency might be affected by cancer status, although mediated by anxiety. Conclusions: Our findings suggest that verbal fluency might be affected by cancer status, although mediated by anxiety. Different cytokines and their interactions may have different roles of neuroinflammation or neuroprotection that need further research.

Toxicopathological effects of lambda-cyhalothrin in female rabbits (Oryctolagus cuniculus)

2010 ◽  
Vol 30 (7) ◽  
pp. 591-602 ◽  
Author(s):  
Abdul Basir ◽  
Ahrar Khan ◽  
Riaz Mustafa ◽  
Muhammad Zargham Khan ◽  
Farzana Rizvi ◽  
...  
Keyword(s):  
Blood Cell ◽  
Oryctolagus Cuniculus ◽  
Hemoglobin Concentration ◽  
Control Group ◽  
Mean Corpuscular Hemoglobin ◽  
Dependent Manner ◽  
Cell Counts ◽  
Lambda Cyhalothrin ◽  
Group A ◽  
Dose Dependent

The aim of this study was to investigate effects of lambda-cyhalothrin (LCT) on clinical, hematological, biochemical and pathological alterations in rabbits (Oryctolagus cuniculus). New Zealand white female rabbits (n = 24) of 4-5 months age having 997.92 ± 32.83 g weight were divided into four equal groups. Group A (control) received normal saline intraperitoneally (ip). Animals in groups B, C and D were treated with LCT 1.0, 4.0 and 8.0 mg/kg bw ip. Each group received seven consecutive doses at an interval of 48 hours. Blood and serum samples were collected at an interval of 96 hours. Blood analysis revealed a significant (p < 0.05) decrease in red blood cell and white blood cell counts, hemoglobin concentration and lymphocytes, while mean corpuscular hemoglobin concentration, mean corpuscular volume, neutrophils, monocytes and eosinophils were increased. Serum biochemical analysis revealed significant (p < 0.05) decrease in serum total proteins and serum albumin, while an increase was seen in serum alanine aminotransferase and aspartate aminotransferase activities compared with the control group. Serum globulin values varied non-significantly in all treatment groups as compared to control group. A dose-dependent increase in the incidence of micronucleated polychromatic erythrocyte was observed. All gross and histopathological lesions observed in LCT-treated rabbits were dose-dependent. Liver of the treated rabbits exhibited extensive perihepatitis, hyperplasia of bile duct, necrosis, hemorrhages and congestion. In lungs, there were hemorrhages, thickened alveolar walls, congestion, emphysema, collapsed alveoli and accumulation of extensive inflammatory cells. Kidneys were congested and hemorrhagic whereas renal parenchyma and stroma were normal. Microscopically, heart showed congestion of blood vessels and nuclear pyknosis, myodegeneration. It was concluded from the study that LCT produced toxicopathological alterations in rabbits in a dose-dependent manner. On the basis of the results, it can be suggested that overdosing of LCT be avoided while treating animals for ectoparasites.

Phase I study of BJ-001, a tumor-targeting interleukin-15 fusion protein, in patients with solid tumor.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14545-e14545
Author(s):  
Ki Y. Chung ◽  
Haeseong Park ◽  
Raghad Muhsin Abdul-Karim ◽  
Deborah Blythe Doroshow ◽  
Jorge Chaves ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Tumor Targeting ◽  
Single Agent ◽  
Adult Patients ◽  
Fixed Dose ◽  
Cell Counts ◽  
Phase 1B ◽  
Interleukin 15

e14545 Background: BJ-001 is the first tumor-targeting Interleukin-15 (IL-15) fusion protein, composed of an integrin-binding Arg-Gly-Asp (RGD)-4C motif, linked with a human IgG1 Fc, and then a modified sushi domain of human IL-15Rα unit and a human IL-15. Tumor-targeting is achieved with RGD-4C motif which binds to αvβ3, αvβ5, and αvβ6 integrins, commonly overexpressed in solid tumors. The molecule has shown an ability to activate Natural Killer (NK) and T cells in vitro and in pre-clinical in vivo studies. Methods: This first in-human (FIH) study has 2 phases: Phase 1a and Phase 1b. Phase 1a consists of 3 parts. In all 3 parts patients receive escalating doses of BJ-001 as a once weekly subcutaneous injection for 4 weeks in 6-week cycles. Part 1 utilizes an accelerated dose escalation design with single patient cohort for the first 3 dose levels. Part 2 uses a 3+3 dose escalation design. Part 3 uses a 3+3 dose escalation of BJ-001 but in combination with a fixed-dose PD-(L)1 inhibitor. Dose escalation will proceed based on clinical safety and tolerability data observed during the Dose Limiting Toxicity (DLT) period, i.e., Cycle 1 Days 1 through 28 for Part 1 and Cycle 1 Days 1 through 42 for Parts 2 and 3. Adult patients (ECOG PS ≤ 2) with locally advanced or metastatic solid tumors refractory to or intolerant of all existing therapies are eligible for Phase 1a. Phase 1b will enroll cohorts of adult patients with selected solid tumors known to have high levels of integrin expression at the Maximum Tolerated Dose or Recommended Phase 2 Dose of BJ-001 in combination with a PD-(L)1 inhibitor, as identified in Phase 1a, Part 3. Results: As of Jan 31, 2021, 9 patients have received BJ-001 dosing as a single agent at 0.21 µg/kg (n = 1), 0.9 µg/kg (n = 1), 3 µg/kg (n = 1), 6 µg/kg (n = 3), or 10 µg/kg (n = 3) in Phase 1a Parts 1 and 2, wherein 7 patients, including 1 patient in the 10 µg/kg cohort, have completed the DLT period. Among these 7 patients, 2 (1 in 3 µg/kg and 1 in 6 µg/kg cohorts) have stable disease and are still receiving BJ-001 treatment beyond Cycle 1. The longest duration in the study, to date, is approximately 4 cycles (over 5 months). Treatment Emergent Adverse Events (TRAEs) include injection site reactions (6/7, Grade 1-2), anorexia (2/7, Grade 1-2), cytokine release syndrome (1/7, Grade 1, resolved in 1 day), and temporal wasting (1/7, Grade 1). The AEs did not result in dose interruption or dose level adjustment. No DLTs observed to date. With escalating doses, a trend of increased post-dose NK cell counts observed, whereas Regulatory T cell (Treg) counts remained stable. Conclusions: To date, BJ-001 is well tolerated up to 6 µg/kg. The safety evaluation for 10 µg/kg is ongoing. The observed NK and Treg cell profiles are consistent with known IL-15 biology. Clinical trial information: NCT04294576.

scholarly journals Effect of immunoadjuvants on the disease course in patients with operable breast cancer

2019 ◽  
Vol 14 (4) ◽  
pp. 20-23
Author(s):  
M. M. Vasilyeva ◽  
I. P. Moshurov ◽  
L. Yu. Grivtsova ◽  
N. N. Tupitsyn ◽  
N. A. Kozlov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Tissue ◽  
Radical Mastectomy ◽  
Control Group ◽  
Cancer Management ◽  
New Strategy ◽  
Breast Cancer Management ◽  
Grade Ii ◽  
And Control

Background. A new strategy of breast cancer management is required for effective disease prevention and control. Immunotherapy is one of promising options.Objective: to evaluate the effect of immunoadjuvant polyoxidonium on pathmorphological changes in breast tumors.Materials and methods. The study was performed in 75 patients with breast cancer: 50 patients received polyoxidonium in a neoadjuvant regimen (main group), 25 patients did not receive polyoxidonium (control group). Polyoxidonium at a dose of 12 mg was administered intramuscularly 1 time per day on the days 1, 2, 3, 5 and 7 before surgery; on the day 8, radical mastectomy was performed in patients of both groups, followed by histological examination and determination of the grade of therapeutic pathomorphosis of the tumor.Results. The proportion of cases with grade I therapeutic pathomorphosis was 58 %, grade II therapeutic pathomorphosis – 6 %. Pathomorphosis in metastatic lymph nodes was observed in 22.7 % of cases.Conclusion. The anti-tumor effect of polyoxidonium was confirmed on the basis of the induction of pathomorphosis of the tumor tissue of breast cancer.

scholarly journals Effect of Self-care Training on Upper Limb Function and Pain After Breast Cancer Surgery

2021 ◽  
Vol 10 (2) ◽  
Author(s):  
Somyye Noura ◽  
Fatemeh Kiani ◽  
Nezarali Moulaei ◽  
Mojtaba Tasbandi ◽  
Ebrahim Ebrahimi Tabas
Keyword(s):  
Breast Cancer ◽  
Upper Limb ◽  
Intervention Group ◽  
Self Care ◽  
Control Group ◽  
Limb Function ◽  
Upper Limb Function ◽  
Care Training ◽  
The Mean ◽  
And Control

Background: Breast cancer patients who undergo mastectomy encounter numerous problems, the most annoying of which is lymphedema followed by pain and decreased function in the affected limb. Objectives: This study examined the effect of self-care training on upper limb function and pain after breast surgery. Methods: This quasi-experimental study was performed on two groups of 60 patients with breast cancer in the Oncology Ward of Zahedan University of Medical Sciences in 2021. The patients were selected based on the inclusion criteria and through convenience sampling and were then randomly divided into intervention and control groups. The patients in the intervention group attended self-care training and exercise programs implemented in five sessions in addition to the routine care. One and three months after the intervention, upper limb function and pain were measured with DASH and McGill pain questionnaires. The repeated measures analysis of variance (ANOVA) and Bonferroni test were used to compare the pre-, and post-intervention mean scores and mean differences in the two groups. Results: The mean scores of upper limb function one and three months after the training program in the intervention group were lower than the mean scores of the control group. In other words, the quality of upper limb function was not significantly different despite the changes in the first month, but upper limb function significantly improved three months after the intervention (P < 0.001 vs. P = 0.06). The mean pain scores before, one month, and three months after the intervention in the intervention group were 10.4, 35.7, and 6.26, respectively, and the corresponding values in the control group were 10.8, 41.7, and 21.1, respectively, showing significant differences between the two groups, with the intervention group having lower pain scores than the control group (P = 0.001). Conclusions: Since lymphedema and its consequences, including decreased upper limb function and pain, are very serious issues, medical staff can give priority to this training program and implement it to prevent and control these complications.

scholarly journals BLOOD INDICES OF AFRICAN CATFISH (CLARIAS GARIEPINUS) FOLLOWING DIETARY ADMINISTRATION OF TALINUM TRIANGULARE

2019 ◽  
Vol 7 (4) ◽  
pp. 185-198 ◽  
Author(s):  
Tina Porwal
Keyword(s):  
Blood Cell ◽  
Clarias Gariepinus ◽  
Control Group ◽  
African Catfish ◽  
Animal Blood ◽  
Blood Indices ◽  
Cell Counts ◽  
Blood Cell Counts ◽  
Leaf Powder ◽  
Talinum Triangulare

The effects of Talinum triangulare on the haematological indices of Clarias gariepinus was investigated. T. triangulare leaf powder at 0, 0.5, 1.0, and 3.0% concentrations were fed to Clarias gariepinus juveniles (n=84; 117.3 ± 1.57 g; 26.70 ± 0.26 cm) as feed additive for a period of six (6) weeks.  The packed cell volume (PCV) and Haemoglobin (Hb) concentration values, 34.67 ± 0.67%, 12.03 ± 0.26g/dl, respectively observed in the group fed with 1.0% were significantly higher (P<0.05) compare with the control group. Red blood cell counts (RBCs), white blood cell counts (WBCs), lymphocytes, MCV, MCH and MCHC recorded were marginally different (P>0.05) among the groups, were within standard for Clarias gariepinus, therefore adjudged not to indicate a negative physiological effect on the experimental fish. Blood indices values observed revealed that the varying additive levels of T. triangulare used had no negative physiological stress on the health status of the fish studied and haematological values observed were seen to be best in the group fed 1.0% T. triangulare. It could be recommended that 10g/kg of Talinum triangulare leaf powder be included in the diet of Clarias gariepinus for boosting of the animal blood and treatment of disease conditions such as anaemia.

scholarly journals Moxibustion as a Therapy for Breast Cancer–Related Lymphedema in Female Adults: A Preliminary Randomized Controlled Trial

2019 ◽  
Vol 18 ◽  
pp. 153473541986691 ◽  
Author(s):  
Chunhui Wang ◽  
Ming Yang ◽  
Yingyi Fan ◽  
Xiaohua Pei
Keyword(s):  
Breast Cancer ◽  
Scale Score ◽  
Controlled Trial ◽  
Visual Analog Scale Score ◽  
Control Group ◽  
Analog Scale ◽  
Randomized Controlled ◽  
Arm Circumference ◽  
Breast Cancer Related Lymphedema ◽  
And Control

Objective: To evaluate the effect of moxibustion on relieving breast cancer–related lymphedema. Materials and Methods: A randomized controlled trial was conducted in our institution from March 2016 to March 2017. All patients (N = 48) with cancer-related lymphedema were allocated to 2 groups: a treatment group, in which moxibustion was performed, and a control group, in which pneumatic circulation was performed with compression garments worn every day. Therapeutic efficacy was evaluated by measuring arm circumference (wrist crease, 10 cm proximal to wrist crease, elbow crease, and 10 cm proximal to elbow crease) and determining the Revised Piper Fatigue Scale score and Visual Analog Scale score for swelling before and after treatment. Results: All patients were treated for 4 consecutive weeks. Compared with 0 week after treatment, the affected-side arm circumference after 4 weeks’ treatment decreased in both treatment and control groups; the difference value in the treatment group was superior to that in the control group. Compared with the controls, moxibustion resulted in a lower Visual Analog Scale score. The Revised Piper Fatigue total scores were improved in both the moxibustion and control group, and there was no significant difference between the 2 groups. Moxibustion reduced the behavioral, sensory, emotional, and cognitive Revised Piper Fatigue scores, but only the behavioral and sensory scores improved in the control group. Conclusion: Moxibustion has potential effect on breast cancer–related lymphedema. We present promising preliminary data for larger randomized trials to enable accurate evaluation of moxibustion as a lymphedema treatment.

scholarly journals Impact of Islam-Based Caring Intervention on Spiritual Well-Being in Muslim Women with Breast Cancer Undergoing Chemotherapy

Religions ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 361
Author(s):  
Maria Komariah ◽  
Urai Hatthakit ◽  
Nongnut Boonyoung
Keyword(s):  
Breast Cancer ◽  
Muslim Women ◽  
Well Being ◽  
Control Group ◽  
Religion And Spirituality ◽  
Peace Of Mind ◽  
Chronic Illness Therapy ◽  
Spiritual Well Being ◽  
And Control ◽  
The Impact

This research emphasizes the nurse’s role in incorporating Islamic teaching through the care practices provided in order to promote spiritual well-being in Muslim women with breast cancer undergoing chemotherapy. In addition, religion and spirituality have been recognized as the primary resources for coping. The aim of the study, therefore, was to explore the impact of an Islam-based caring intervention on the spiritual well-being of Muslim women with cancer. Furthermore, data were collected using a questionnaire and, also, the Functional Assessment of Chronic Illness Therapy-Spiritual well-being (FACIT-Sp) on baseline (Time 1), days 3 (Time 2), 23 (Time 3), and 44 (Time 4). The results showed the significant impact of an Islam-based caring intervention on the participants’ level of spiritual well-being. In addition, the mean scores varied between the intervention and control group over time. Based on the reflection, participants stipulated feeling peace of mind, closer to God, spirit for further life, and healthier.

Evaluation of high-dose versus standard FAC chemotherapy for advanced breast cancer in protected environment units: a prospective randomized study.

1987 ◽  
Vol 5 (3) ◽  
pp. 354-364 ◽  
Author(s):  
G N Hortobagyi ◽  
G P Bodey ◽  
A U Buzdar ◽  
D Frye ◽  
S S Legha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Response Rate ◽  
Metastatic Breast ◽  
Ambulatory Setting ◽  
Survival Duration ◽  
Control Group ◽  
High Dose ◽  
Control Groups ◽  
Median Response ◽  
And Control

Fifty-nine evaluable patients under 65 years of age with measurable metastatic breast cancer and without prior chemotherapy were randomly assigned to treatment with fluorouracil, Adriamycin (Adria Laboratories, Columbus, OH), and cyclophosphamide (FAC) at standard or high doses (100% to 260% higher than standard FAC) following a dose escalation schedule. Patients randomized to the high-dose FAC received the first three cycles of therapy within a protected environment. Subsequent cycles for this group were administered at standard doses of FAC in an ambulatory setting, the same as for the control group. After reaching 450 mg/m2 of Adriamycin, patients in both groups continued treatment with cyclophosphamide, methotrexate, and fluorouracil until there was disease progression. Analysis of pretreatment patient characteristics showed an even distribution for most known pretreatment factors, although the control group had slightly (but nonsignificantly) more favorable prognostic characteristics. Fourteen patients (24%) achieved a complete remission (CR) and 32 (54%) achieved a partial remission (PR), for an overall major response rate of 78%. There were no differences in overall, CR, or PR rates between the high-dose FAC and control groups. The median response durations were 11 and 10 months for the protected environment and control groups, respectively, and the median survival was 20 months for both groups. Hematologic, gastrointestinal (GI), and infection-related complications were significantly more frequent and severe in the group treated with high-dose chemotherapy. Stomatitis, diarrhea, and skin toxicity were dose-limiting. However, there were no treatment-related deaths. High-dose induction combination chemotherapy with the agents used in this study failed to increase the response rate or survival duration, and resulted in a substantial increase in toxicity.

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