Bioequivalence of a hybrid pegylated liposomal doxorubicin hydrochloride injection and Caelyx®: A single-dose, randomized, multicenter, open-label, two-period crossover study in patients with advanced ovarian cancer.

OBJECTIVE: To evaluate the bioequivalence of a hybrid pegylated liposomal doxorubicin (PLD) hydrochloride injection with reference product Caelyx®. METHODS: This multicenter, open-label, balanced, randomized, two-treatment, two-period, two-sequence, single-dose, crossover, bioequivalence study was conducted in female patients aged ≥18 years and ≤75 years with ovarian cancer, whose disease progressed or recurred after platinum-based chemotherapy, and who were scheduled to start PLD therapy. Patients were intravenously infused drugs over 1 h at 50 mg/m2 dose two hours after breakfast on the first day of the chemotherapy cycle in period-I and crossed over to the other arm in period-II (day 29). Pharmacokinetic (PK) analyses were performed using two separate, validated liquid chromatography-mass spectrometry methods for encapsulated and unencapsulated doxorubicin. RESULTS: Both the test and reference formulations were well-tolerated and safe. The pharmacokinetic analysis for both encapsulated and unencapsulated doxorubicin was conducted in 50 patients and PK parameters were found to be comparable between test and reference products. The geometric mean ratios (90% confidence interval) of hybrid PLD/Caelyx® were; maximum measured plasma concentration (Cmax): 91.94-97.28%, area under the plasma concentration versus time from time 0 to t (AUC0-t): 95.19-103.67%, AUC from time 0 to ∞ (AUC0-∞): 95.13-103.66% for encapsulated doxorubicin and for unencapsulated doxorubicin Cmax: 92.08-116.46%, AUC0-t: 91.91-108.28%, AUC0-∞: 93.45-110.05%. CONCLUSION: The PLD formulation was found to be bioequivalent to Caelyx®.

Fixed dose combination of capecitabine and cyclophosphamide in metastatic breast cancer: Results from THE ENCLOSE phase 2/3 randomized multicenter study.

AIM: To evaluate pharmacokinetics, efficacy and safety of fixed-dose combination (FDC) of oral capecitabine + cyclophosphamide in metastatic breast cancer (MBC) patients progressing after anthracycline and/or taxane chemotherapy. METHODS: In this prospective, adaptive, phase-2/3, open-label study (CTRI/2014/12/005234), patients were randomized (1:1:1) to three FDC doses (doses/day: D1, capecitabine + cyclophosphamide 1400 mg + 60 mg; D2, 1800 mg + 80 mg; D3, 2200 mg + 100 mg) for 14 days, in 21-day cycles. In Part-I, multiple-dose pharmacokinetics and optimal dose(s) were evaluated with futility analysis. Group(s) with <3 responders based on best overall response rate (BOR, complete response [CR]+partial response [PR]), were discontinued. Efficacy (BOR, disease control rates [DCR; CR + PR + stable disease]) and safety of optimal dose(s) were evaluated in Part-II. RESULTS: Of 66 patients (n = 22/group) in Part-I, pharmacokinetics (D1 = 7/22, D2 = 9/22, D3 = 8/22) showed dose-proportionality for cyclophosphamide and greater than dose-proportionality for capecitabine. Modified intent-to-treat (mITT) analysis showed BOR of 7.14% (1/14) in D1 (discontinued), and 22.22% (4/18) each in D2 and D3, respectively. In Part-II, 50 additional patients were randomized in D2 and D3 (n = 144; total 72 [22 + 50] patients/group). mITT analysis in D2 (n = 54) and D3 (n = 58) showed BOR of 29.63% (16/54, 95%CI: 17.45-41.81%) and 22.41% (13/58, 95%CI: 11.68-33.15%), respectively. DCR in D2 and D3 were 87.04% (47/54, 95%CI: 78.08-96.00%) and 82.76% (48/58; 95%CI: 73.04-92.48%) after 3 and 57.41% (31/54; 95%CI: 52.41-79.50%) and 50.00% (29/58; 95%CI: 40.40-67.00%), after 6-cycles, respectively. Hand-foot syndrome (16.67%), vomiting (9.72%) in D2, and hand-foot syndrome (18.06%), asthenia (15.28%) in D3 were most-common adverse events. CONCLUSION: FDC of capecitabine + cyclophosphamide (1800 + 80 mg/day) showed high disease control rates and good safety profile in MBC patients.

Efficacy and safety of nanosomal docetaxel lipid suspension based chemotherapy in metastatic ovarian carcinoma: A retrospective study.

The aim of the current study was to assess the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS) based chemotherapy in patients with metastatic epithelial ovarian carcinoma. In the present multicenter study, the medical records of patients who received NDLS (60-75 mg/m2; 3-weekly cycles) based chemotherapy for metastatic epithelial ovarian cancer in routine clinical care were retrospectively evaluated. Patients were followed-up from September 2014 until September 2018. The efficacy endpoints were the overall response rate (ORR) and disease control rate measured in accordance with the Response Evaluation Criteria in Solid Tumours 1.1. Overall survival (OS) and safety were also evaluated. Of the 13 patients evaluated, 46.2% (6/13) received NDLS-based first-line chemotherapy and 53.8% (7/13) patients received second-line chemotherapy [platinum-sensitive, 57.1% (4/7); platinum-resistant, 42.9% (3/7)]. The ORRs were 60.0% (3/5) and 57.1% (4/7) for patients receiving first- and second-line chemotherapy, respectively. The estimated median OS for patients receiving NDLS-based first-line chemotherapy was 17.4 months (follow-up duration, 4.3-49.4 months). The estimated median OS was 26.1 months (follow-up duration, 5.1-37.5 months) in patients with platinum-sensitive disease, whereas the OS was 14.8 months (follow-up duration, 3.5-14.8 months) in patients with platinum-resistant disease. No grade III/IV adverse events (AEs) were observed; ≥1 AE in grade I-II was reported in 84.6% (11/13) of patients. Overall, NDLS-based chemotherapy was efficacious and well-tolerated in the management of metastatic epithelial ovarian carcinoma.

Hyperimmune anti-COVID-19 IVIG (C-IVIG) treatment in severe and critical COVID-19 patients: A phase I/II randomized control trial.

BACKGROUND: Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG) is an unexplored therapy amidst the rapidly evolving spectrum of medical therapies for COVID-19 and is expected to counter the three most life-threatening consequences of COVID-19 including lung injury by the virus, cytokine storm and sepsis. METHODS: A single center, phase I/II, randomized controlled, single-blinded trial was conducted at Dow University of Health Sciences, Karachi, Pakistan. Participants were COVID-19 infected individuals, classified as either severely or critically ill with Acute Respiratory Distress Syndrome (ARDS). Participants were randomized through parallel-group design with sequential assignment in a 4:1 allocation to either intervention group with four C-IVIG dosage arms (0.15, 0.20, 0.25, 0.30 g/kg), or control group receiving standard of care only (n = 10). Primary outcomes were 28-day mortality, patient's clinical status on ordinal scale and Horowitz index (HI), and were analysed in all randomized participants that completed the follow-up period (intention-to-treat population). The trial was registered at clinicaltrials.gov (NCT04521309). FINDINGS: Fifty participants were enrolled in the study from June 19, 2020 to February 3, 2021 with a mean age of 56.54±13.2 years of which 22 patients (44%) had severe and 28 patients (56%) had critical COVID-19. Mortality occurred in ten of 40 participants (25%) in intervention group compared to six of ten (60%) in control group, with relative risk reduction in intervention arm I (RR, 0.333; 95% CI, 0.087-1.272), arm II (RR, 0.5; 95% CI, 0.171-1.463), arm III (RR, 0.167; 95% CI, 0.024-1.145), and arm IV (RR, 0.667; 95% CI, 0.268-1.660). In intervention group, median HI significantly improved to 359 mmHg [interquartile range (IQR) 127-400, P = 0.009)] by outcome day, while the clinical status of intervention group also improved as compared to control group, with around 15 patients (37.5%) being discharged by 7th day with complete recovery. Additionally, resolution of chest X-rays and restoration of biomarkers to normal levels were also seen in intervention groups. No drug-related adverse events were reported during the study. INTERPRETATION: Administration of C-IVIG in severe and critical COVID-19 patients was safe, increased the chance of survival and reduced the risk of disease progression. FUNDING: Higher Education Commission (HEC), Pakistan (Ref no. 20-RRG-134/RGM/R&D/HEC/2020).

Biweekly DoceAqualip in mCRPC patients beyond 20 cycles: A case series.

INTRODUCTION: Docetaxel 75 mg/m2 every 3 weeks for up to 10 cycles is an accepted standard regimen in metastatic castration-resistant prostate cancer (mCRPC). We report our experience with >20 cycles of biweekly nanosomal docetaxel lipid suspension (NDLS) treatment in patients with mCRPC. CASE REPORTS: Cases with long-term treatment of NDLS treatment in mCRPC patients were identified from the medical records of Jawaharlal Nehru Cancer Hospital & Research Centre Bhopal, India. A total of three cases with >20 cycles of NDLS are presented here. MANAGEMENT AND OUTCOMES: Overall, the 3 patients received biweekly NDLS at a dose of 45 mg/m2 for 22, 36, and 40 cycles, respectively, except for one patient where NDLS was initiated at 50 mg/m2 and later reduced to 45 mg/m2. All the 3 patients reported prostate-specific antigen (PSA) response (>50% decline in PSA levels from baseline). The time to treatment failure (TTF) was 14.8, 18.2, and 20.6 months in these 3 patients, respectively. PSA nadir occurred after 14, 6 and 13 cycles, respectively. The OS was 21.6, 22.2 and 25.8 months, respectively. Anemia, lymphopenia, and neutropenia were the most common adverse events. NDLS treatment was overall well-tolerated without any new safety concerns. CONCLUSIONS: Biweekly NDLS for >20 cycles was effective and well-tolerated in patients with mCRPC. NDLS can potentially be used for long-term management, which may be a requirement for most patients with mCRPC.

Thymoquinone with Metformin Decreases Fasting, Post Prandial Glucose, and HbA1c in Type 2 Diabetic Patients.

OBJECTIVE: Antihyperglycemic activity of Thymoquinone (TQ) was evaluated in diabetic mouse model and patients. METHODS: TQ (50 mg/kg) was orally administered daily for 21 days in combination with metformin in diabetic mice and a reduction on blood glucose level was monitored. In human, a 90-day randomized study was carried out in 60 Type 2 Diabetes mellitus patients to evaluate safety and efficacy of TQ administration with metformin in a 3-arm study. Patients in arm 1 (T1) received 1 tablet of metformin SR 1000 mg and 1 tablet of TQ 50 mg once daily. The second arm (T2) patients received 1 tablet of metformin SR 1000 mg and 2 tablets of TQ 50 mg once daily. Patients in arm 3 (R) received 1 tablet of metformin SR 1000 mg only. RESULTS: The diabetic mice treated with combination of TQ and metformin showed significant decrease in blood sugar compared to those treated with only metformin. In patients who completed the study, the glycated hemoglobin (HbA1c) values in T1, T2 and R decreased after 3 months from 7.2, 7.2 and 7.3 to 6.7, 6.8, and 7.1, respectively. A greater reduction in Fasting Blood Glucose and Post Prandial Blood Glucose was also observed in T1 and T2 arms compared to R. CONCLUSION: At dose levels of 50 and 100 mg of TQ combined with a daily dose of 1000 mg Metformin demonstrated a reduction in the levels of HbA1c and blood glucose compared to the standard treatment of diabetic patients with metformin alone.

Production of hyperimmune anti-SARS-CoV-2 intravenous immunoglobulin from pooled COVID-19 convalescent plasma.

Background: This study assesses the feasibility of producing hyperimmune anti-COVID-19 intravenously administrable immunoglobulin (C-IVIG) from pooled convalescent plasma (PCP) to provide a safe and effective passive immunization treatment option for COVID-19. Materials & methods: PCP was fractionated by modified caprylic acid precipitation followed by ultrafiltration/diafiltration to produce hyperimmune C-IVIG. Results: In C-IVIG, the mean SARS-CoV-2 antibody level was found to be threefold (104 ± 30 cut-off index) that of the PCP (36 ± 8.5 cut-off index) and mean protein concentration was found to be 46 ± 3.7 g/l, comprised of 89.5% immunoglobulins. Conclusion: The current method of producing C-IVIG is feasible as it uses locally available PCP and simpler technology and yields a high titer of SARS-CoV-2 antibody. The safety and efficacy of C-IVIG will be evaluated in a registered clinical trial (NCT04521309).

Endoxifen: A new, protein kinase C inhibitor to treat acute and mixed mania associated with bipolar I disorder.

OBJECTIVES: Endoxifen is a protein kinase C inhibitor. The objective of the present phase III study was to demonstrate the safety and efficacy of endoxifen in treating bipolar I disorder (BPD I) patients. METHODS: A multicenter, double-blind, active-controlled study was conducted using a daily dose of 8 mg endoxifen compared to 1000 mg divalproex, the current standard treatment, in patients with BPD I acute manic episodes with/without mixed features. The primary endpoint of our study was the mean change in total Young Mania Rating Scale (YMRS) score at day 21. RESULTS: Endoxifen (n = 116) significantly (p < 0.0001) reduced total YMRS score (from 33.1 to 17.8. A significant (p < 0.001) improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) score was observed for endoxifen (4.8 to 2.5). Early time to remission of the disease was observed with endoxifen compared to divalproex. None of the patients required rescue medication and there was no drug-associated withdrawals. Changes in Clinical Global Impressions-Bipolar Disorder and Clinical Global Impression-Severity of Illness scores showed that treatment with endoxifen was well-tolerated. CONCLUSIONS: Endoxifen at a low daily dose of 8 mg was as efficacious and safe in patients with BPD I acute manic episodes with/without mixed features.

A Multicentric, Retrospective Efficacy and Safety Study of Nanosomal Docetaxel Lipid Suspension in Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: To evaluate the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS, DoceAqualip) in patients with metastatic castration-resistant prostate cancer (mCRPC). MATERIALS AND METHODS: In this multicenter, retrospective study, we analyzed the medical charts of mCRPC patients, who were treated with NDLS administered as 2-weekly (50 mg/m2) or 3-weekly regimens (75 mg/m2). The study endpoints were prostate-specific antigen (PSA) response (>50% PSA decline from baseline), PSA progression (PSA increase from baseline beyond 12 weeks: ≥25% and ≥2 ng/mL), median PSA decline, and time-to-treatment failure (TTF). Overall survival (OS) and safety were also evaluated. RESULTS: Data of 24 patients with mCRPC were analyzed in this study. NDLS was administered as a 2-weekly regimen in 37.5% (9/24; all first-line) patients and as a 3-weekly regimen in 62.5% patients (15/24; first-line: 20% (3/15), second-line: 80% (12/15)). Overall, PSA response was reported in 66.7% (16/24) patients. The PSA response was 77.8% (7/9 patients) in the 2-weekly group and 60% (9/15 patients) in the 3-weekly group. The median decline in PSA was 96.31% in the 2-weekly group and 83.29% in the 3-weekly group; the median TTF was 6.7 and 6.5 months in the 2 weekly group and 3-weekly group, respectively. The median OS was 14.6 months (follow-up: 5.5-25.8 months) in the 2-weekly group whereas it was not reached in the 3-weekly group (follow-up: 7.9-15.6 months). The most common hematological AEs were anemia, lymphopenia, thrombocytopenia, and neutropenia whereas nausea, weakness, constipation, vomiting, and diarrhea were the most common (≥10%) nonhematological AEs. Overall, NDLS treatment was well tolerated without any new safety concerns. CONCLUSIONS: Nanosomal docetaxel lipid suspension (2-weekly or 3-weekly) was effective and well tolerated in patients with metastatic castration-resistant prostate cancer.

Hyperimmune anti-COVID-19 IVIG (C-IVIG) Therapy for Passive Immunization of Severe and Critically Ill COVID-19 Patients: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The aim of this trial is to investigate the safety and clinical efficacy of passive immunization therapy through Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG: 5% liquid formulation), on severe and critically ill patients with COVID-19. TRIAL DESIGN: This is a phase I/II single centre, randomised controlled, single-blinded, superiority trial, through parallel-group design with sequential assignment. Participants will be randomised either to receive both C-IVIG and standard care or only standard care (4:1). PARTICIPANTS: The study is mono-centric with the participants including COVID19 infected individuals (positive SARS-CoV-2 PCR on nasopharyngeal and/or oropharyngeal swabs) admitted in institute affiliated with Dow University Hospital, Dow University of Health Sciences, Karachi, Pakistan. Consenting patients above 18 years that are classified by the treating physician as severely ill i.e. showing symptoms of COVID-19 pneumonia; dyspnea, respiratory rate ≥30/min, blood oxygen saturation ≤93%, PaO2/FiO2 <300, and lung infiltrates >50% on CXR; or critically ill i.e. respiratory failure, septic shock, and multiple organ dysfunction or failure. Patients with reported IgA deficiency, autoimmune disorder, thromboembolic disorder, and allergic reaction to immunoglobulin treatment were excluded from study. Similarly, pregnant females, patients requiring two or more inotropic agents to maintain blood pressure and patients with acute or chronic kidney injury/failure, were also excluded from the study. INTERVENTION AND COMPARATOR: The study consists of four interventions and one comparator arm. All participants receive standard hospital care which includes airway support, anti-viral medication, antibiotics, fluid resuscitation, hemodynamic support, steroids, painkillers, and anti-pyretics. Randomised test patients will receive single dose of C-IVIG in following four dosage groups: Group 1: 0.15g/Kg with standard hospital care Group 2: 0.2g/Kg with standard hospital care Group 3: 0.25g/Kg with standard hospital care Group 4: 0.3g/Kg with standard hospital care Group 5 (comparator) will receive standard hospital care only MAIN OUTCOMES: The primary outcomes are assessment and follow-up of participants to observe 28-day mortality and, • the level and duration of assisted ventilation during hospital stay, • number of days to step down (shifting from ICU to isolation ward), • number of days to hospital discharge, • adverse events (Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)) during hospital stay, • change in C-Reactive Protein (CRP) levels, • change in neutrophil lymphocyte ratio to monitor inflammation. RANDOMISATION: Consenting participants who fulfill the criteria are allocated to either intervention or comparator arm with a ratio of 4:1, using sequentially numbered opaque sealed envelope simple randomization method. The participant allocated for intervention will be sequentially assigned dosage group 1-4 in ascending order. Participants will not be recruited in the next dosage group before a set number of participants in one group (10) are achieved. BLINDING (MASKING): Single blinded study, with participants blinded to allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Total 50 patients are randomised. The intervention arms consist of 40 participants divided in four groups of 10 participants while the comparator group consists of 10 patients. TRIAL STATUS: Current version of the protocol is "Version 2" dated 29th September, 2020. Participants are being recruited. Recruitment started on June, 2020 and is estimated to primarily end on January, 2021. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov, NCT04521309 on 20 August 2020 and is retrospectively registered. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1).

Efficacy and safety of nanosomal docetaxel lipid suspension-based chemotherapy in squamous cell carcinoma of the head and neck: A multicenter retrospective study.

Squamous cell carcinoma of the head and neck (SCCHN) is the most common cancer in Indian men. Docetaxel alone or in combination with other chemotherapeutic agents is recommended for the management of SCCHN. The present multicenter, retrospective study was conducted to evaluate the efficacy and safety of a novel docetaxel formulation 'nanosomal docetaxel lipid suspension (NDLS)'-based chemotherapy in SCCHN. The medical records of patients with SCCHN, who were treated with NDLS-based chemotherapy and followed up between August 2014 and September 2018, were reviewed. The efficacy endpoints were overall response rate [ORR; complete response (CR) + partial response (PR)] and disease control rate (DCR; CR + PR + stable disease) for patients receiving NDLS-based induction or palliative chemotherapy. Overall survival (OS) and safety were also evaluated. Efficacy evaluation was available in 30/34 patients (induction, 20/23; palliative, 10/11). NDLS-based induction chemotherapy showed an ORR and DCR of 95% and a median OS of 43.5 months (follow-up duration, 0.6-80.3 months). For NDLS-based palliative chemotherapy, the ORR and DCR were 50% and the median OS time was 4.6 months (follow-up duration, 1.8 to 14.3 months). At least one adverse event was reported in 82.6% patients. No new safety concerns were reported. Overall, NDLS-based chemotherapy was effective and well tolerated in the treatment of SCCHN.

Efficacy and safety of nanosomal docetaxel lipid suspension based chemotherapy in gastric and gastroesophageal junction adenocarcinoma.

The current retrospective multicenter study evaluated the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS; DoceAqualip) based chemotherapy in patients with gastric and gastroesophageal junction (GEJ) adenocarcinoma. The medical charts of patients with gastric and GEJ adenocarcinoma, who were treated with NDLS (50-75 mg/m2; 3 weekly cycles) based chemotherapy and followed-up from April 2014 to September 2018, were analyzed. The study endpoints included overall response rate (ORR) and disease control rate (DCR) in neoadjuvant and metastatic settings. Overall survival (OS) and safety were also evaluated. Of the 43 patients with gastric (n=39) and GEJ (n=4) adenocarcinoma, efficacy evaluation was available in 35 (neoadjuvant, 17/18 patients; metastatic, 18/25 patients). In the neoadjuvant setting, an ORR of 58.82% and a DCR of 94.11% were observed, whereas in the metastatic setting, the ORR was 77.77% and the DCR was 83.33%. In the neoadjuvant setting, at a follow-up ranging from 0.7 to 41.2 months, the median OS was not reached. In the metastatic setting, the median OS was 31.9 months at a follow-up ranging from 0.2 to 50.3 months. At least one adverse event (AE) was reported in 24 patients. Anemia, lymphopenia and thrombocytopenia were the most common hematological AEs, while nausea, vomiting and weakness were the most common non-hematological AEs. NDLS based treatment was well-tolerated without any new safety concerns. Overall, NDLS-based chemotherapy was effective and well-tolerated in the management of gastric and GEJ adenocarcinoma.

A Multicenter, Retrospective Study (RE-ENACT 2) on Razumab™ (World's First Biosimilar Ranibizumab) in Retinal Vein Occlusion.

PURPOSE: The REal life assessmENt of safety And effeCTiveness of Razumab 2 (RE-ENACT 2) study evaluated the long-term effectiveness of biosimilar ranibizumab. We present the subgroup analysis of patients with retinal vein occlusion (RVO). METHODS: Data of patients who received pro re nata (PRN) biosimilar ranibizumab (November 2015 to December 2018, 17 centers) were analyzed. Endpoints were change from baseline in best corrected visual acuity (BCVA, Snellen's/logMAR), central subfield thickness (CSFT), intraocular pressure (IOP), and proportions of patients having intraretinal fluid (IRF) and subretinal fluid (SRF) at weeks 4, 8, 12, 16, 20, 24, 30, 36, and 48. RESULTS: Of 101 patients, 48.51% were men, and the majority (79.21%) were treatment naïve and had received 3 (range 1-5) injections (53.5%). Significant improvements (P < 0.05) were observed from baseline to all timepoints for BCVA [baseline, 0.89 ± 0.06 (n = 94); week 48, 0.41 ± 0.08 (n = 14)] and CSFT [baseline, 527.58 ± 19.9 (n = 85); week 48, 307.47 ± 16.4 (n = 15)]. Changes in IOP (mmHg) were non-significant [baseline, 15.38 ± 0.4 (n = 94); week 48, 13.94 ± 0.6 (n = 16); P = 0.5575). Proportions of patients having IRF [baseline, 71.3% (n = 84) vs week 48, 0% (n = 15)] and SRF [baseline, 52.5% (n = 83) vs week 48, 0% (n = 15)] were decreased. Similar results for BCVA, CSFT, IOP, IRF, and SRF were observed for BRVO and CRVO subgroups. There were no new safety concerns. CONCLUSIONS: Biosimilar ranibizumab demonstrated improvements in visual acuity and disease outcomes up to 48 weeks in patients with RVO without any new safety concerns.

Nanosomal Docetaxel Lipid Suspension-Based Chemotherapy in Breast Cancer: Results from a Multicenter Retrospective Study.

PURPOSE: The purpose of this study was to evaluate the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS, DoceAqualip)-based chemotherapy in breast cancer. METHODS: Medical charts of patients with breast cancer, who were treated and followed up with NDLS (75-100 mg/m2; 3-week cycle)-based chemotherapy from August 2014 to September 2018, were analyzed in this multicenter, retrospective study. The study endpoints were overall response rate (ORR: complete response [CR]+partial response [PR]) and disease control rate (DCR: CR+PR+stable disease [SD]) in neoadjuvant and metastatic settings. Overall survival (OS) and safety were evaluated for all settings. RESULTS: Of 91 patients (neoadjuvant: 12, adjuvant: 61, metastatic: 18), efficacy evaluation in 29 patients (neoadjuvant: 12/12, metastatic: 17/18) demonstrated an ORR and DCR of 100%, respectively, in the neoadjuvant setting, and an ORR of 64.7% and DCR of 70.6%, respectively, in the metastatic setting. At a median follow-up of 21.6 months (range: 2.1 to 49.9 months), median OS was not reached in neoadjuvant and adjuvant settings, and it was 30.4 months in metastatic settings. At least one adverse event (AE) was reported in 59.3% of patients. Anemia, thrombocytopenia, lymphopenia, and neutropenia were the most common hematological AEs reported while hyperglycemia and alteration in liver function tests were the most common non-hematological AEs. NDLS-based treatment was well tolerated without any new safety concerns. CONCLUSION: Nanosomal docetaxel lipid suspension-based chemotherapy was efficacious and well tolerated in the treatment of breast cancer. Further, NDLS is being evaluated prospectively in patients with triple-negative breast cancer (ClinicalTrials.gov: NCT03671044).

Probiotic potential of Saccharomyces strains isolated from Litchi chinensis (Lychee fruit).

Recently, probiotic yeasts have become an interesting topic of research all over the world. Saccharomyces cerevisiae is well proven probiotic yeast against several gastrointestinal diseases. Current study aimed to explore the probiotic potential and antibacterial properties of Saccharomyces strains isolated from fresh lychee fruits available in local markets of Karachi, Pakistan. Probiotic potential and antibacterial activity of locally isolated probiotic yeast strains (named as S. cerevisiae BEL 1 and S. cerevisiae BEL 9) was studied against gastrointestinal pathogens using standard in vitro screening methods. Comparative analysis was also carried out with commercially available S. boulardii probiotic preparations. Furthermore, for probiotic potential, all the studied yeast strains were exposed to various stress conditions inherent of gastrointestinal tract i.e., thermo tolerance, pH tolerance, bile salts survivability and osmo-tolerance. Isolated strains (BEL 1 and BEL 9) were able to tolerate at the temperatures (40oC and 45oC), moreover survived in the presence of gastric juices, extreme bile salt concentrations (range 0.5%-2%) and different osmotic stress conditions (1M and 1.5 M NaCl). Optimal growth was observed at 37oC. Similar growth pattern and viability of BEL 1 and 9 was found for most of the stress conditions, when compared with the commercially available strains of S. boulardii. Therefore, isolated yeast strains BEL 1 and 9 will be considered as a potential bio-therapeutic agent because of the promising probiotic potential.

A Multicenter, Retrospective Study (RE-ENACT 2) on the Use of Razumab™ (World's First Biosimilar Ranibizumab) in Wet Age-Related Macular Degeneration.

INTRODUCTION: The REal life assessmENt of safety And effeCTiveness of Razumab (RE-ENACT) and long-term RE-ENACT 2 retrospective studies have evaluated the use of Razumab™ (world's first biosimilar ranibizumab) in retinal disorders in Indian patients. This report presents the subgroup analysis from the RE-ENACT 2 study in patients with wet age-related macular degeneration (wet AMD). METHODS: Medical charts of patients administered biosimilar ranibizumab injections as PRN treatment regimen between September 2015 and June 2018, at 17 centers across India, were reviewed. Changes from baseline in best-corrected visual acuity (BCVA, based on Snellen's or logMAR chart), central subfield thickness (CSFT), intraocular pressure (IOP), and proportions of patients having intraretinal fluid (IRF) and subretinal fluid (SRF) at weeks 4, 8, 12, 16, 20, 24, 30, 36, and 48 were evaluated. RESULTS: Of 103 patients with wet AMD, 62.1% were men and the majority (74.8%) were treatment naïve. The majority (57.9%) of the patients had received 3 (range 1-5) injections. Significant improvements were observed from baseline to all timepoints for BCVA (baseline, 0.92 ± 0.6 [n = 94]; week 48, 0.51 ± 0.4 [n = 14]; P = 0.0014) and CSFT (baseline, 430.83 ± 14.4 [n = 85]; week 48, 301.26 ± 11.6 [n = 15]; P < 0.0001). Changes in IOP from baseline to 48 weeks were minimal and not significant (14.92 ± 3.2 [n = 94] vs. 14.50 ± 2.1 [n = 18]; P = 0.9068). A decrease in proportions of patients having IRF (baseline, 63.6% [n = 99] vs. week 48, 15% [n = 20]) and SRF (baseline, 82.3% [n = 96] vs. week 48, 5% [n = 20]) were also observed. Similar results were observed for occult and classic subgroups. There were no new safety concerns. CONCLUSION: Razumab (biosimilar ranibizumab) demonstrated improvements in visual acuity and disease outcomes in patients with wet age-related macular degeneration without new safety issues.

Efficacy and Safety of Nanosomal Docetaxel Lipid Suspension-Based Chemotherapy in Sarcoma: A Multicenter, Retrospective Study.

OBJECTIVE: To evaluate the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS, DoceAqualip) based chemotherapy in patients with sarcoma. METHODS: In this retrospective, multicenter (6 centers), observational study, we analyzed the medical charts of adult patients of either sex, who were treated with NDLS (75 mg/m2 in 3-weekly cycles) based chemotherapy for the treatment of sarcoma. The efficacy outcomes were overall response rate (ORR: complete response (CR) + partial response (PR)) and disease control rate (DCR: CR + PR + stable disease (SD)) in patients who received NDLS-based chemotherapy in neoadjuvant and metastatic settings. Overall survival (OS) and safety were evaluated for all settings. RESULTS: Of 11 patients (neoadjuvant: 1, adjuvant: 3, and metastatic: 7) in this study, majority had leiomyosarcoma (63.6%, 7/11) followed by extraskeletal myxoid chondrosarcoma (EMC), high grade pleomorphic sarcoma of mandible, malignant fibrous histiocytoma of right thigh, and osteosarcoma of femur (9.1% each, 1/11 each). NDLS plus gemcitabine combination was used in 10 patients (90.9%), and NDLS plus cyclophosphamide was used in one patient with EMC (9.1%). Efficacy evaluation was performed for 7 patients (neoadjuvant: 1/1; metastatic: 6/7). Complete response was reported in one patient (soft tissue sarcoma of mandible) treated in neoadjuvant setting. In metastatic setting, ORR was 50% and DCR was 66.7% (CR: 16.7% (1/6), PR: 33.3% (2/6), SD: 16.7% (1/6)). At a median follow-up of 6.5 months (range: 0.06-20.2 months), median OS was not reached in neoadjuvant and adjuvant settings, but it was 15.8 months in metastatic setting. At least 1 AE was reported in 7 (63.6%) patients. Neutropenia, thrombocytopenia, lymphopenia, and anemia were the hematological AEs, whereas nausea, vomiting, and diarrhea were the most common nonhematological AEs. NDLS treatment was well tolerated without any new safety concerns. CONCLUSION: Nanosomal docetaxel lipid suspension-based chemotherapy was efficacious and well tolerated in the treatment of sarcoma. Further prospective trials are needed to confirm the data.

Nanosomal docetaxel lipid suspension based chemotherapy in a pregnant MBC patient - a case report.

The current report presents a case of a pregnant woman with breast cancer metastasized to liver and lungs. The standard of care for breast cancer in pregnancy is anthracycline/taxane-based chemotherapy regimens. Docetaxel has shown a favorable toxicity profile during the second and third trimesters of pregnancy. A novel nanosomal docetaxel lipid suspension (NDLS) (DoceAqualip), with a proven efficacy and tolerability profile, has been approved in India for the treatment of advanced solid tumors since 2013. We present here a case of a pregnant woman with metastatic breast cancer managed with NDLS based TAC regimen showing a partial response after six cycles. The patient delivered a healthy male child with normal Apgar score and weight at the 32nd week of gestation.