Therapeutic efficacy and safety of biweekly administration of enfortumab vedotin for urothelial carcinoma.

OBJECTIVES: Enfortumab vedotin (EV) is an established pharmacotherapy for metastatic urothelial carcinoma (mUC); however, its adverse events (AEs) cannot be overlooked. The study investigated the efficacy and safety of biweekly EV administration. METHODS: Patients with mUC who received EV at our institution were included in the study. Eligible patients were classified into two groups as follows: those who received EV on a standard schedule (standard group) and those who received EV on a biweekly schedule (biweekly group); the treatment outcomes and AEs between the two groups were compared. RESULTS: Nine and 19 patients were in the standard group and biweekly groups, respectively. The progression-free survival, overall survival, and overall response rate were not significantly different between the two groups. AEs following EV administration, such as decreased appetite (P < .01), pruritus (P < .01), rash maculopapular (P < .01), anemia (P = .04), and liver dysfunction (P = .04), were significantly more frequent in the standard group. Grade 3 or higher AEs, such as pruritus (P = .03) and rash maculopapular (P < .01), were significantly more frequent in the standard group. Furthermore, significantly more patients in the standard group had to be given a reduced dose due to adverse events (P = .02). CONCLUSIONS: Biweekly administration of EV may be safer without compromising therapeutic efficacy than the standard schedule.

Comparative Efficacy and Safety of Standard and Biweekly Trifluridine/Tipiracil Regimen in Patients With Colorectal Cancer.

BACKGROUND/AIM: Trifluridine/tipiracil (FTD/TPI) is used to treat metastatic colorectal cancer (mCRC). Since the standard regimen of FTD/TPI features a complex dosing schedule and frequently results in severe hematological toxicities, a simplified regimen has emerged, in which FTD/TPI is orally administered biweekly. However, the survival benefits and potential adverse events associated with the biweekly FTD/TPI regimen have not been fully evaluated in previous reports. Therefore, in this study, the differences in efficacy and safety between the standard and biweekly FTD/TPI regimens were retrospectively investigated in patients with mCRC. PATIENTS AND METHODS: Data from 90 patients who received FTD/TPI for mCRC were extracted from the electronic medical records at the Osaka University Hospital. According to the inclusion and exclusion criteria, 85 of the 90 patients were enrolled in the study. We compared patient characteristics, overall survival (OS), progression-free survival (PFS), and adverse events between the standard (n=56) and biweekly groups (n=29). RESULTS: The biweekly group exhibited prolonged OS and PFS compared to patients in the standard group. Multivariate analysis for OS and PFS demonstrated that the biweekly regimen was the only significant factor that affected OS, and not PFS (HR=0.561, p=0.049). Kaplan-Meier analysis indicated that neutropenia (grade ≥3) in the biweekly group was significantly prolonged compared to the standard group (p=0.012). However, there were no significant differences in adverse events between the two groups (p>0.999). CONCLUSION: The biweekly FTD/TPI regimen, compared to the standard regimen, should enhance both OS and PFS in patients with mCRC without escalating any adverse event.

Bi-Weekly Voice Therapy Versus Weekly Voice Therapy for Muscle Tension Dysphonia.

OBJECTIVES: To compare the outcomes of bi-weekly voice therapy (BWVT) with weekly voice therapy on perception, acoustics, and quality of life for individuals with muscle tension dysphonia (MTD). METHODS: Thirty participants with MTD were enrolled either BWVT (40 min/session, two sessions per week for 4 weeks) or weekly voice therapy (40 min/session, once a week for 8 weeks). Auditory perceptual ratings, acoustic parameters, and the Mandarin version of the voice-related quality of life questionnaire (MV-RQOL) scores were statistically analyzed before and after treatment. RESULTS: There were significant improvements in the voice qualities such as overall grade, roughness, asthenia, and strain in both groups after treatment. Acoustics analyses showed that fundamental frequency, speaking fundamental frequency, jitter, shimmer, and cepstral peak prominence significantly improved in both groups after treatment. For the MV-RQOL questionnaire scores, the result also demonstrated that both groups felt significant improvements in voice-related quality of life after treatment. However, there were no significant differences between the two groups of treatment effects. CONCLUSIONS: Patients with MTD can restore voice qualities and quality of life if they are able to complete a full course of voice therapy, regardless of the intensity of voice therapy. However, if they can receive the BWVT, they would be able to regain their voice faster. The results of this study can be provided as a reference for clinicians when treating patients with MTD.

Phase II trial of biweekly administration with eribulin after three cycles of induction therapy in hormone receptor-positive, HER2-negative metastatic breast cancer (JACCRO BC-03).

PURPOSE: Metastatic breast cancer (MBC) is usually incurable; treatment aims to maximize patients' function and quality of life (QOL). Eribulin is a standard treatment in patients with MBC pretreated with anthracycline and taxane; however, the best administration schedule is unknown. METHODS: In this prospective phase II trial of patients with luminal MBC, we administered biweekly eribulin to patients who completed a three-cycle induction treatment. RESULTS: Sixty patients with hormone-receptor-positive and HER2-negative MBC were enrolled; 40 obtained stable disease (SD) or better efficacy after induction therapy, after which they were switched to biweekly maintenance administration. The median progression-free survival (PFS) in patients who switched to maintenance therapy was 15.21 weeks (95% CI 9.71-22.14), starting on the first day of maintenance therapy. Overall survival (OS) in patients who switched to maintenance therapy was 21.39 months (95% CI 18.89-32.89). PFS and OS in the whole population starting from the registration date were 19.00 weeks (95% CI 17.00-25.00) and 21.52 months (95% CI 16.23-24.25), respectively. PFS from the enrollment date for patients who received maintenance therapy was 25.29 weeks (95% CI 19.14-32.14). Patients who achieved complete response or partial response during induction therapy had significantly longer PFS compared to patients with SD. CONCLUSION: The efficacy of biweekly administration of eribulin at maintenance was nonsignificant. However, less frequent visits are convenient, and reduced dose intensity improves safety. Biweekly administration, besides dose reduction, could be an acceptable option for patients who are unable to maintain a standard regimen.

Subcutaneous Immunoglobulin 16.5% (Cutaquig®) in Primary Immunodeficiency Disease: Safety, Tolerability, Efficacy, and Patient Experience with Enhanced Infusion Regimens.

PURPOSE: To achieve reductions in infusion time, infusion sites, and frequency, a prospective, open-label, multicenter, Phase 3 study evaluated the safety, efficacy, and tolerability of subcutaneous immunoglobulin (SCIG) 16.5% (Cutaquig®, Octapharma) at enhanced infusion regimens. METHODS: Three separate cohorts received SCIG 16.5% evaluating volume, rate, and frequency: Cohort 1) volume assessment/site: up to a maximum 100 mL/site; Cohort 2) infusion flow rate/site: up to a maximum of 100 mL/hr/site or the maximum flow rate achievable by the tubing; Cohort 3) infusion frequency: every other week at twice the patient's weekly dose. RESULTS: For Cohort 1 (n = 15), the maximum realized volume per site was 108 mL/site, exceeding the currently labeled (US) maximum (up to 40 mL/site for adults). In Cohort 2 (n = 15), the maximum realized infusion flow rate was 67.5 mL/hr/site which is also higher than the labeled (US) maximum (up to 52 mL/hr/site). In Cohort 3 (n = 34), the mean total trough levels for every other week dosing demonstrated equivalency to weekly dosing (p value = 0.0017). All regimens were well tolerated. There were no serious bacterial infections (SBIs). Most patients had mild (23.4%) or moderate (56.3%) adverse events. The majority of patients found the new infusion regimens to be better or somewhat better than their previous regimens and reported that switching to SCIG 16.5% was easy. CONCLUSIONS: SCIG 16.5% (Cutaquig®), infusions are efficacious, safe, and well tolerated with reduced infusion time, fewer infusion sites, and reduced frequency. Further, the majority of patients found the new infusion regimens to be better or somewhat better than their previous regimens.

A phase II study of daily encorafenib in combination with biweekly cetuximab in patients with BRAF V600E mutated metastatic colorectal cancer: the NEW BEACON study.

BACKGROUND: Patients with BRAF V600E mutated metastatic colorectal cancer (mCRC) have a poor prognosis. The introduction of BRAF targeted therapy with encorafenib and weekly administered cetuximab have shown improved survival with a median progression free survival (PFS) of 4.3 months. However, a regimen with cetuximab given every second week may have comparable efficacy and is more convenient for patients. While BRAF targeted therapy is a new standard therapy in pre-treated patients with BRAF V600E mutated mCRC, resistance invariably occurs and is an emerging challenge. The aim of this study is to investigate the efficacy and tolerability of cetuximab given every second week in combination with daily encorafenib and to explore the correlation between markers of resistance and outcome. METHODS: The study is an open label, single arm, phase II study, investigating the efficacy and tolerability of cetuximab given every second week in combination with encorafenib in patients with BRAF V600E mutated mCRC. Furthermore, we will be investigating mechanisms of response and resistance against BRAF targeted therapy though comprehensive genomic profiling on tumor tissue and blood for circulating tumor DNA analysis. A total of 53 patients (19 + 34 in two steps) will be included according to Simon's optimal two stage design. The primary end point of the study is 2 months PFS rate. DISCUSSION: By combining BRAF inhibitor with cetuximab given every second week we can halve the number of visits in the hospital compared to the currently approved regimen with weekly cetuximab. This seems particularly relevant in a group of patients with a median overall survival of 9.3 months. Resistance after initial response to targeted therapy can be either adaptive (e.g., epigenetic, or transcriptomic alterations) or acquired (selective genetic alterations - e.g., activating de novo mutations) resistance. It is of great importance to untangle these complex mechanisms of resistance in patients with BRAF V600E mutated mCRC to improve treatment strategies in the future potentially even further. TRIAL REGISTRATION: EU Clinical Trial Register, Eudract no. 2020-003283-10 . Registered on 11 November 2020.

Vaccination Rate and Incidence of COVID-19 and Case Fatality Rate (CFR): A Correlational Study Using Data From 2019 to 2021.

INTRODUCTION:  COVID-19 has infected over 300 million people and killed almost five million people worldwide. The rapid development and deployment of vaccines almost a year after the initial outbreak was poised to contain the pandemic and enable the mobilization of the people and the economy. Vaccine deployment and containment of the pandemic have been far from uniform across the world. There is a lack of a clear understanding of the correlation between the COVID-19 vaccination rates and the incidence of the COVID-19 disease and COVID-19 mortality. AIM:  The study aims to determine the correlation between the COVID-19 vaccination rate and the bi-weekly incidence rate of the COVID-19 disease to better understand the correlation between the vaccination rate and the COVID-19-related fatality in various countries. MATERIALS AND METHODS:  Data from vaccination and the case fatality rate were abstracted until September 15, 2021, and from October 15 to October 31, respectively, for the various countries categorized based on their income levels. The bi-weekly COVID-19 incidence rate per million population and the case fatality rate was analyzed using SPSS version 27 (IBM Corp., Armonk, NY), followed by frequencies and percentages. Spearman rank correlation was used to determine the relationship between the variables. RESULTS:  A total of 191 countries were included in the study. The vaccination rate ranged from 0.03% to 82.1%, CFR from 0.14% to 32.1%, and the bi-weekly incidence rate ranged from zero to 1,283 per million population. A positive correlation was observed between vaccination rate and bi-weekly incidence rate (+0.57), whereas a negative correlation was observed between vaccination rate and CFR (-0.34). The results indicate a moderate positive correlation between vaccination rate and bi-weekly incidence rate and a weak negative correlation between vaccination rate and case fatality rate. DISCUSSION AND CONCLUSION:  Our study is interesting for the observation that the bi-weekly incidence rate of COVID-19 positively correlated with the rate of vaccination. In contrast, the vaccination rate correlated negatively with the case fatality rate. Although several factors may have contributed to the increased incidence rates for COVID-19, these observations refute the myth that COVID-19 vaccination offers complete protection from reinfection, especially in the backdrop of easing pandemic containment measures by some countries. An increase in the vaccination rate is certainly a positive contributor to the decreasing case fatality observed.

Biweekly administration of cetuximab in Japanese patients with recurrent or metastatic head and neck cancer.

BACKGROUND: Cetuximab (Cmab) plays an important role in the treatment for recurrent or metastatic head and neck cancer (R/M HNC). To date, however, no safety data on biweekly administration of cetuximab at a dose of 500 mg/m2 (biweekly Cmab) for Japanese HNC patients have been available. METHODS: We retrospectively reviewed the clinical records of five R/M HNC patients who received biweekly Cmab in our institute between January 2016 and September 2021 and compared the safety profile between two phases of weekly 250 mg/m2 and biweekly 500 mg/m2 Cmab in the identical patients. RESULTS: All patients initially received Cmab in combination with chemotherapy. Chemotherapy consisted of paclitaxel plus carboplatin in two patients, cisplatin + 5-FU in one patient, and paclitaxel in two patients. Three patients switched treatment schedule from weekly Cmab to biweekly Cmab, while two patients received biweekly Cmab after completion of chemotherapy. The main reason for switching to biweekly Cmab was an unacceptably long commuting time to the hospital. The median duration of Cmab was 217 days (49-321) during weekly Cmab with or without chemotherapy and 42 days (28-175) during biweekly Cmab. Median dose of biweekly Cmab was 4 (3-12). During biweekly Cmab, worsened (Grade ≥ 2) toxicities were observed in two patients: one with grade 2 dry skin and the second with grade 2 skin infection. None developed grade ≥ 3 adverse events or discontinued treatment due to Cmab-related adverse events. CONCLUSION: Biweekly Cmab was well tolerated and did not demonstrate severe toxicities related to Cmab for R/M HNC.

Efficacy and Safety of Cetuximab Dosing (biweekly vs weekly) in Patients with KRAS Wild-type Metastatic Colorectal Cancer: A Meta-analysis.

BACKGROUND: Cetuximab 500 mg/m2 biweekly (Q2W) plus chemotherapy is commonly used and recommended by NCCN guidelines. This meta-analysis compares efficacy and safety between Q2W versus weekly (Q1W) cetuximab dosing. METHODS: A systematic literature review was performed on Pubmed and RightFind (2007-2017) for patients with KRAS wild-type mCRC who received Q2W or Q1W cetuximab and other treatments. Observational studies and case reports were excluded. Randomized trials comparing Q2W and Q1W dosing, and single-arm trials with only Q2W schedule were included. CRYSTAL, a phase 3 randomized study with Q1W cetuximab dosing was paired with each single-arm study with a Q2W schedule and reweighted to achieve similar demographic/baseline characteristics. Overall survival (OS) and progression-free survival (PFS) with hazard ratios (HR), overall response rate (ORR) with odds ratios, and risk difference of adverse events of special interest (AESI) between Q2W versus Q1W cetuximab were analyzed. RESULTS: Five phase 2 studies with cetuximab Q2W/Q1W dosing schedules were identified: CECOG (phase 2; Q2W, n = 77; Q1W, n = 75), NORDIC 7.5 (phase 2; Q2W, n = 152) and NORDIC 7 (arm C of phase 3; Q1W, n = 109), CELINE (n = 60), OPTIMIX (n = 99), and APEC (n = 289) all phase 2, Q2W, single-arm studies paired with CRYSTAL Q1W dosing (n = 303). Efficacy was similar between Q2W versus Q1W administration; OS HR = 0.96, 95% confidence interval (CI) [0.89, 1.04]; PFS HR = 0.96, 95% CI [0.87, 1.05]; ORR odds ratio 1.16, 95% CI [0.96, 1.41]. Mean differences (Q2W-Q1W) across AESI rates were not clinically meaningful with no obvious directionality. CONCLUSION: This meta-analysis demonstrated no significant differences in efficacy and safety between Q2W versus Q1W cetuximab administration in mCRC patients.

Intraperitoneal perforation through lymph node metastases in a patient with esophageal squamous cell carcinoma during intensive chemotherapy: A case report with literature review.

INTRODUCTION: Esophageal fistula after treatment is a critical and fatal complication of esophageal cancer. A fistula forming from lower thoracic esophageal cancer to the peritoneum through lymph node metastases following chemotherapy has not been reported. We report a case of peritonitis due to lymph node perforation through the tumor ulcer after induction of biweekly docetaxel, cisplatin, and 5FU combined chemotherapy (Bi-DCF) for advanced esophageal squamous cell carcinoma (ESCC). PRESENTATION OF CASE: A 48-year-old woman was referred to us with a diagnosis of lower thoracic ESCC and thoracoabdominal aortic aneurysm. Esophagogastroduodenoscopy showed a circumferential type 3 tumor with stenosis in the lower thoracic esophagus. Contrast-enhanced computed tomography (CT) showed a thoracoabdominal aortic aneurysm and wall thickening of the lower thoracic esophagus that was suspicious of esophageal cancer. Lymph node metastases dumpling from around the tumor to abdominal cavity were also observed. The initial diagnosis was ESCC T3 N3 M1 (para-aortic lymph nodes and liver) Stage IVB. She was started on Bi-DCF (docetaxel 35 mg/m2 days 1/15, cisplatin 40 mg/m2 days 1/15, 5FU 400 mg/m2 days 1-5, 15-19) as the first-line regimen. The third day after starting chemotherapy, she felt strong abdominal pain, and internal necrosis of lymph nodes around the primary lesion and free air in the abdominal cavity were found. Peritonitis was diagnosed due to a fistula formed from the lower thoracic ESCC to the peritoneum through lymph node metastases. She underwent emergency laparoscopic drainage, omental filling, and jejunostomy. Postoperatively, her general condition and inflammatory findings improved within 10 days, and she could continue intensive chemotherapy as scheduled. DISCUSSION: Because of the risk of perforation and fistula in regimens that are expected to cause tumor shrinkage, careful observation may be required after starting chemotherapy. CONCLUSION: We report the first case of peritonitis caused by perforation through lymph node metastasis of thoracic esophageal cancer.

Biweekly cetuximab in combination with capecitabine and oxaliplatin (XELOX) or irinotecan (XELIRI) in the first-line and second-line treatment of patients with RAS wild-type metastatic colorectal cancer.

Background: Oral capecitabine in combination with intravenous oxaliplatin (XELOX) or irinotecan (XELIRI) are acceptable substitutions to fully intravenous regimens. Biweekly (as opposed to weekly) cetuximab is more convenient when combined with biweekly chemotherapy. Here, we report the tolerability and efficacy of biweekly cetuximab in combination with biweekly XELOX or XELIRI in patients with RAS wild-type metastatic colorectal cancer (RAS-WT mCRC). Methods: Clinical data of consecutive patients with mCRC who received biweekly cetuximab (500 mg/m2) in combination with XELOX or XELIRI between January 2009 and May 2019 in the first- or second-line settings was extracted. Dosage of XEL (Capecitabine/XELODA) was 1,000 mg/m2 twice daily for 9 days, plus on day 1 oxaliplatin 85 mg/m2 or irinotecan 180 mg/m2. Treatment dose reduction and delay for ≥7 days was analysed as surrogates for toxicity. Extended RAS testing was performed in the context of this study for patients who received treatment based on limited KRAS-WT genotype. Results: Sixty one patients with RAS-WT mCRC fulfilled the eligibility criteria. XELOX was administered to 26 (42.6%) and XELIRI to 35 (57.4%) of patients. For all patients in the first-line setting, the objective response rate (ORR), median progression free survival (PFS) and median overall survival (OS) were 54%, 8 months and 25 months, respectively. The corresponding outcomes for the subgroup of patients who received first-line XELOX were 68%, 10 months and not reached, respectively. For all patients in the second-line setting, the ORR, PFS and OS were 50%, 7 months and 20 months, respectively. Chemotherapy components dose reduction and delays were observed in 18 (29.5%) and 25 (41%) patients, respectively. The corresponding frequencies for cetuximab were 3 (5%) and 31 (50.8%). Conclusion: Biweekly cetuximab in combination with XELOX or XELIRI is tolerable and effective. The addition of cetuximab to capecitabine and oxaliplatin is associated with favourable outcome.

Association of weekly or biweekly use of 50 000 IU vitamin D3 with hypervitaminosis D.

Since the beginning of the COVID-19 pandemic, many Iranian people have been taking 50 000 IU of vitamin D3 on weekly or biweekly bases in order to enhance their immune system function. This cross-sectional study was conducted on the patients of endocrinology clinic to compare 25(OH)D levels of weekly or biweekly consumption with the monthly users of vitamin D3 50 000 IU. The level >100 ng/mL of 25(OH)D was defined as hypervitaminosis D. In total, 211 patients (108 and 103 patients in monthly and weekly/biweekly groups, respectively) were studied. In the subgroups of weekly and biweekly users, the rates of hypervitaminosis were 18.9% and 4.5%, respectively. In contrast, only 0.9% of monthly users had hypervitaminosis D. The highest vitamin D value of 185 ng/mL was detected in a patient who had consumed 50 000 IU vitamin D3 weekly for 6 years. No hypercalcaemia was detected in patients with hypervitaminosis D.

Cost-minimization analysis of biweekly dosing of cetuximab and FOLFIRI compared with panitumumab and FOLFOX for first-line treatment of patients with KRAS wild-type metastatic colorectal cancer in the United States.

AIM: To compare the cost of biweekly regimens of first-line (1L) treatments of cetuximab-folinic acid, fluorouracil, and irinotecan (FOLFIRI) versus panitumumab-folinic acid, fluorouracil, and oxaliplatin (FOLFOX) in patients with Kirsten's rat sarcoma wild type (KRAS WT) metastatic colorectal cancer (mCRC) in the United States, across varying weights and body surface areas (BSAs). MATERIALS AND METHODS: Cost-minimization analysis (CMA) was performed to estimate per-patient cost differences of cetuximab-FOLFIRI versus panitumumab-FOLFOX. The CMA estimated the costs of RAS testing, premedication, drug acquisition, treating infusion reactions (IRs), supportive therapy, and biweekly administration of chemotherapy, cetuximab (500 mg/m2), and panitumumab (6 mg/kg) over 43 weeks (median progression-free survival). To calculate dose and cost, weight and height data were gathered from an electronic health record-derived de-identified database (n = 7,669; January 2013-October 2020). Base case analysis utilized mean weight/BSA of the overall cohort (82.04 kg/1.92 m2), and alternate scenarios were based on 88.18 kg/2.03 m2 (men, n = 4,477) and 73.43 kg/1.76 m2 (women, n = 3,192). RESULTS: For the base case, total treatment costs were $167,853 for cetuximab-FOLFIRI and $168,254 for panitumumab-FOLFOX; cost savings per patient receiving cetuximab-FOLFIRI was $400. Cost savings in alternate scenarios (men, $15,138; women, $15,004) resulted from lower drug acquisition costs for cetuximab (men, $14,833; women $14,854) and administration cost ($440) versus panitumumab. Cost savings of cetuximab-FOLFIRI in treating IR ($353) were similar across all scenarios. LIMITATIONS: With no head-to-head clinical trial data in the 1L setting, assumptions of similarity in efficacy and safety of cetuximab versus panitumumab were based on published network meta-analysis and the ASPECCT trial. This model did not consider a lifetime horizon. Costs of managing all adverse events (except IR) were not included. CONCLUSIONS: Biweekly cetuximab-FOLFIRI offers cost savings compared with panitumumab-FOLFOX for 1L therapy of patients with KRAS WT mCRC in the United States. These cost differences were observed for the overall population and across different BSA and weights for men and women.

Extracted features of national and continental daily biweekly growth rates of confirmed COVID-19 cases and deaths via Fourier analysis.

AIMS: By associating features with orthonormal bases, we analyse the values of the extracted features for the daily biweekly growth rates of COVID-19 confirmed cases and deaths on national and continental levels. METHODS: By adopting the concept of Fourier coefficients, we analyse the inner products with respect to temporal and spatial frequencies on national and continental levels. The input data are the global time series data with 117 countries over 109 days on a national level; and 6 continents over 447 days on a continental level. Next, we calculate the Euclidean distance matrices and their average variabilities, which measure the average discrepancy between one feature vector and all others. Then we analyse the temporal and spatial variabilities on a national level. By calculating the temporal inner products on a continental level, we derive and analyse the similarities between the continents. RESULTS: On the national level, the daily biweekly growth rates bear higher similarities in the time dimension than the ones in the space dimension. Furthermore, there exists a strong concurrency between the features for biweekly growth rates of cases and deaths. As far as the trends of the features are concerned, the features are stabler on the continental level, and less predictive on the national level. In addition, there are very high similarities between all the continents, except Asia. CONCLUSIONS: The features for daily biweekly growth rates of cases and deaths are extracted via orthonormal frequencies. By tracking the inner products for the input data and the orthonormal features, we could decompose the evolutionary results of COVID-19 into some fundamental frequencies. Though the frequency-based techniques are applied, the interpretation of the features should resort to other methods. By analysing the spectrum of the frequencies, we reveal hidden patterns of the COVID-19 pandemic. This would provide some preliminary research merits for further insightful investigations. It could also be used to predict future trends of daily biweekly growth rates of COVID-19 cases and deaths.

Mifepristone in Fibroids: Comparative Study of Safety and Efficacy of Biweekly Dosage Vs Daily Dosage Schedule.

BACKGROUND: Leiomyomas are the most prevalent benign tumors of the uterus and are seen more with increasing age. 50 mg biweekly dose was compared with 25 mg daily dose in terms of efficacy and safety in symptomatic women as the biweekly dose maybe an economically better alternative. Two different dosages of mifepristone for medical management of fibroids were compared in terms of efficacy and safety in symptomatic women. MATERIALS AND METHODS: Ninety-two women were recruited who fulfilled the criteria after informed consent and were randomized in two groups. Sample size was calculated on the basis of earlier literature, for response in terms of reduction in fibroid volume, assuming 1% level of significance and 95 % power of study, the optimum sample size came out to be minimum 27 in each group. Assuming loss to follow up of few patients, we took 45 patients in group 1 and 47 patients in group 2. Group 1 was given mifepristone in a dose of 25 mg once a day and Group 2 was given mifepristone 50 mg biweekly for 3 months. Fibroid volume, uterine volume, endometrial thickness, pictorial blood loss assessment chart score, hemoglobin levels, and liver transaminases were recorded at the beginning and at the end of treatment. Side effects were noted at the end of the treatment. RESULTS: Both the dosages lead to improvement in symptoms of the patients. Mifepristone significantly reduced fibroid volume in both the groups, but the difference between the groups was not significant (P = 0.99). Mifepristone treatment significantly reduced bleeding and increased hemoglobin levels in both the groups. The side effects were mild and tolerable. CONCLUSION: Mifepristone in both dosages is highly efficacious in causing amenorrhea, improving anemia, and enhancing the quality of life, and hence 50 mg biweekly dosage shows potential for being cost efficient.

Prophylactic pegfilgrastim to prevent febrile neutropenia among patients receiving biweekly (Q2W) chemotherapy regimens: a systematic review of efficacy, effectiveness and safety.

BACKGROUND: Pegfilgrastim, a long-acting granulocyte colony-stimulating factor (G-CSF), is commonly used to prevent febrile neutropenia (FN), a potentially life-threatening complication, following myelosuppressive chemotherapy. The FDA label for pegfilgrastim specifies that it should not be administered 14 days before or within 24 h of administration of myelosuppressive chemotherapy, precluding the use of pegfilgrastim in biweekly (Q2W) regimens. The National Comprehensive Cancer Network and the European Organisation for Research and Treatment of Cancer guidelines support the use of prophylactic pegfilgrastim in patients receiving Q2W regimens. The objective of this study was to systematically review evidence from randomized clinical trials (RCTs) and observational studies that describe the effectiveness and safety of prophylactic pegfilgrastim in preventing FN among patients receiving Q2W regimens. METHODS: An Ovid MEDLINE, Embase, and Cochrane Library literature search was conducted to evaluate the evidence regarding efficacy, effectiveness, and safety of prophylactic pegfilgrastim versus no prophylactic pegfilgrastim or prophylaxis with other G-CSF in patients who were receiving Q2W chemotherapy regimens with high (> 20%) or intermediate (10-20%) risk of FN for a non-myeloid malignancy. Studies that addressed absolute or relative risk of FN, grade 1-4 neutropenia, all-cause or any hospitalization, dose delays or dose reductions, adverse events, or mortality were included. Studies where the comparator was a Q3W chemotherapy regimen with primary prophylactic pegfilgrastim were also included. RESULTS: The initial literature search identified 2258 publications. Thirteen publications met the eligibility criteria, including eight retrospective, one prospective, one phase 1 dose escalation study, and three RCTs. In nine of the 13 studies reporting incidence of FN, and in seven of the nine studies reporting incidence of neutropenia, administration of prophylactic pegfilgrastim in patients receiving Q2W regimens resulted in decreased or comparable rates of FN or neutropenia compared with patients receiving filgrastim, no G-CSF, lipefilgrastim or pegfilgrastim in Q3W regimens. In six of the nine studies reporting safety data, lower or comparable safety profiles were observed between pegfilgrastim and comparators. CONCLUSIONS: In a variety of non-myeloid malignancies, administration of prophylactic pegfilgrastim was efficacious in reducing the risk of FN in patients receiving high- or intermediate-risk Q2W regimens, with an acceptable safety profile. TRIAL REGISTRATION: PROSPERO registration no: CRD42019155572 .

The Record-breaking Mei-yu in 2020 and Associated Atmospheric Circulation and Tropical SST Anomalies.

The record-breaking mei-yu in the Yangtze-Huaihe River valley (YHRV) in 2020 was characterized by an early onset, a delayed retreat, a long duration, a wide meridional rainbelt, abundant precipitation, and frequent heavy rainstorm processes. It is noted that the East Asian monsoon circulation system presented a significant quasi-biweekly oscillation (QBWO) during the mei-yu season of 2020 that was associated with the onset and retreat of mei-yu, a northward shift and stagnation of the rainbelt, and the occurrence and persistence of heavy rainstorm processes. Correspondingly, during the mei-yu season, the monsoon circulation subsystems, including the western Pacific subtropical high (WPSH), the upper-level East Asian westerly jet, and the low-level southwesterly jet, experienced periodic oscillations linked with the QBWO. Most notably, the repeated establishment of a large southerly center, with relatively stable latitude, led to moisture convergence and ascent which was observed to develop repeatedly. This was accompanied by a long-term duration of the mei-yu rainfall in the YHRV and frequent occurrences of rainstorm processes. Moreover, two blocking highs were present in the middle to high latitudes over Eurasia, and a trough along the East Asian coast was also active, which allowed cold air intrusions to move southward through the northwestern and/or northeastern paths. The cold air frequently merged with the warm and moist air from the low latitudes resulting in low-level convergence over the YHRV. The persistent warming in the tropical Indian Ocean is found to be an important external contributor to an EAP/PJ-like teleconnection pattern over East Asia along with an intensified and southerly displaced WPSH, which was observed to be favorable for excessive rainfall over YHRV.

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.

Prospective Multicenter Phase II Study of Biweekly TAS-102 and Bevacizumab for Metastatic Colorectal Cancer.

BACKGROUND: This study assessed the efficacy and safety of biweekly trifluridine and tipiracil hydrochloride (TAS-102) with bevacizumab combination therapy for patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: We included 19 patients with mCRC who received TAS-102 and bevacizumab combination therapy biweekly as third-line chemotherapy. The primary endpoint was progression-free survival. RESULTS: Patients had a median age of 73 years and most (73.4%) were men. The median progression-free and overall survival were 5.6 and 11.5 months, respectively. Five (26.3%) patients achieved a response and the disease control rate was 12/19 (63.1%). One patient (5.2%) experienced neutropenia grade 3 or more. The median time from baseline performance status 0/1 to worsening to 2 or more was 10.3 months. CONCLUSION: Biweekly TAS-102 plus bevacizumab facilitates tumor shrinkage by reducing the incidence of grade 3 or more neutropenia, improving survival, and maintaining performance status. This combination may represent a treatment option for patients with late-stage mCRC receiving third- or later-line therapy.

Cetuximab plus irinotecan administered biweekly with reduced infusion time to heavily pretreated patients with metastatic colorectal cancer and related RAS and BRAF mutation status.

Metastatic colorectal cancer (mCRC) is treated with cetuximab 250 mg/m2 administered weekly over 1 hour or biweekly (q2w) over 3.5 hours when combined with irinotecan. This prospective study investigated cetuximab 500 mg/m2 plus irinotecan 180 mg/m2 administered q2w over 1.5 hours independent of RAS or BRAF mutation status in mCRC patients in a third-line setting. The intention-to-treat population included 181 patients. No patients had complete response, 18% had partial responses (PR) and 48% stable disease (SD). For cetuximab, a relative dose intensity of ≥90% was reached in 78% and for irinotecan in 67% of the patients. Grade 3 to 4 toxicities were pain (17%), fatigue (9%), neutropenia (8%), diarrhea (8%), rash (8%), infection (7%) and hypersensitivity (3%). No deaths occurred. Next-generation sequencing in 96.7% of the patients revealed that 50.3% had RAS and BRAFV600E wild type (WT), with a mutation type (MT) in 45.1% of the RAS and 4.4% of the BRAFV600E genes. In patients with RAS-WT and RAS-MT tumors, a PR was obtained in 32% and 4% (P = .000003) and an SD in 43% and 53%, respectively, with a superior PFS (6.2 vs 3.7 months; hazard ratio [HR] 2.12, P = .00001) and OS (12.9 vs 8.8 months; HR 1.71, P = .0008). Treatment efficacy was poor in 7.4% of patients with an RAS mutation outside KRAS exon 2 and in 38% of patients with KRAS exon 2 mutations. Administration of cetuximab and irinotecan q2w, shortening treatment time from 3.5 to 1.5 hours, is recommended as standard therapy.