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Pharmacies are currently unable to stock proper oral dosage forms for pediatric populations. This leads to manipulation of medications or the need to compound specialized medications, which can be a time-consuming process. Using Semisolid Extrusion (SSE) additive manufacturing (AM), specialized medications can be produced in an expedited process from off-the shelf medication in a hospital or outpatient pharmacy setting. In this study, tablets with a desired dose of 5 mg of metoprolol tartrate derived from commercial Seloken™ 50 mg tablets were 3D printed in a hospital setting. Validation testing was done on five batches, highlighting tablets with a high uniformity in mass and dimension, drug content, acceptable microbial assays, and prolonged release during in-vitro analysis. The average drug content found for the tablets was within ±6% of 5 mg for all batches produced. Comparisons were done between the SSE tablets and capsules produced in an external compounding facility, highlighting several positive aspects of SSE-produced tablets beyond simply shortening the production timeline. The SSE tablets printed in this study are characterized by their smaller size, enhanced prolonged release properties, and more uniform drug content across the tested samples. Additionally, interviews with pharmaceutical professionals were conducted to determine the positive aspects of SSE and further improvements to bring this technique as seamlessly as possible into the pharmacy. This study underscores the feasibility of employing SSE in the production of specialized medications within a hospital environment. Furthermore, it highlights the methodological advantages SSE offers over existing production standards, demonstrating its potential to improve pharmaceutical manufacturing in healthcare settings.

Abstract Aim To investigate the outcomes of cabozantinib in patients with unresectable hepatocellular carcinoma (uHCC), focusing on dose setting and modification. Methods We retrospectively analyzed 34 Japanese patients who received cabozantinib for uHCC. Trough concentrations (Ctrough) of cabozantinib were also measured weekly for 6 weeks in the 18 patients. Results Sixteen patients received ≥40 mg (high‐dose group), and 18 patients received 20 mg (low‐dose group). Dose escalations were performed in 27.8% of the patients in the low‐dose group. Although median duration of the first dose reduction or interruption in the low‐dose group was twice that in the high‐dose group (28 vs. 14 days, p

Abstract Background Palbociclib improves outcomes for women with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (HR+/HER2− ABC). Dose reductions are recommended for the management of hematologic toxicities. A previous pooled analysis from the PALOMA clinical trials showed that 36.9% of patients required dose reduction, predominantly during the first 6 months of treatment and with decreasing frequency during subsequent 28-day treatment cycles (C). Previous data have shown that palbociclib dose reductions do not affect efficacy. This pooled, post hoc analysis evaluated the frequency of hematologic adverse events (AEs) before and after palbociclib dose reduction in PALOMA-1, PALOMA-2, and PALOMA-3. Methods This analysis evaluated the frequency of hematologic AEs 30 days before dose reduction and during each subsequent treatment from C1 to C6 among patients who required palbociclib dose reduction. Data were pooled from 3 randomized studies. PALOMA-1 was a phase 2, open-label study of postmenopausal patients untreated for ABC receiving palbociclib plus letrozole or letrozole alone. PALOMA-2 was a phase 3, double-blind study of postmenopausal patients untreated for ABC receiving palbociclib plus letrozole or placebo plus letrozole. PALOMA-3 was a phase 3, double-blind study of pre/perimenopausal or postmenopausal patients, whose disease progressed on prior endocrine therapy, receiving palbociclib plus fulvestrant or placebo plus fulvestrant. Results A total of 311 (35.5%) patients with HR+/HER2− ABC required a palbociclib dose reduction (93.6% due to AEs) from 125 to 100 mg. Mean patient age was 59.9 years, and 46.9% of patients had visceral disease. Median time to dose reduction was 70 days. The majority of dose reductions occurred within 3 months of starting palbociclib treatment. Incidences of all-grade and grades 3/4 hematologic AEs were lower following dose reduction. Conclusions A decrease in frequency and severity of hematologic AEs, including febrile neutropenia, following palbociclib dose reduction was observed, supporting the recommended use of dose reduction in AE management. Trial registration These studies were sponsored by Pfizer. ClinicalTrials.gov: NCT00721409 ; registration date July 24, 2008. ClinicalTrials.gov: NCT01740427 ; registration date December 4, 2012. ClinicalTrials.gov: NCT01942135 ; registration date September 13, 2013.

Abstract Background Oxaliplatin, irinotecan, 5-fluorouracil, and l-leucovorin (FOLFIRINOX) has become one of the first-line treatment options for advanced pancreatic cancer (PC). However, the relatively high rate of grade 3 or 4 adverse events associated with the standard dosage of FOLFIRINOX limits its widespread use in clinical practice. In this study, we were to evaluate the efficacy and safety of a modified FOLFIRINOX regimen as a first-line chemotherapy for Chinese patients with metastatic PC. Methods Patients with histologically confirmed primary metastatic pancreatic adenocarcinoma with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0–2 were recruited to receive the modified FOLFIRINOX regimen (intravenous infusion of oxaliplatin, 65 mg/m2; irinotecan, 150 mg/m2; l-leucovorin, 200 mg/m2; and 5-fluorouracil, 2400 mg/m2, repeated every 2 weeks). The treatment was continued for 12 cycles unless the patient had progressive disease (PD), stable disease (SD) with symptom deterioration, unacceptable adverse events, or requested to terminate the treatment prematurely. The primary endpoint was objective response rate (ORR). Results Sixty-five patients were enrolled from July 2012 to April 2017 in three institutions, and they all received at least one cycle of chemotherapy, with a median of 8 cycles (range 1–12 cycles). No complete response was observed. Twenty-one (32.3%) patients had partial responses, and 27 (41.5%) had SD. The ORR and disease control rate of the study cohort was 32.3% and 73.8%. The estimated median overall survival and progression-free survival were 11.60 (95% confidence interval [CI] 8.76–14.44) and 5.77 (95% CI 5.00–6.54) months. Major grade 3 or 4 adverse events included neutropenia (12.3%) and diarrhea (6.2%). No treatment-related death was observed. Conclusions Modified FOLFIRINOX was well-tolerated and might be a promising option as first-line therapy for Chinese patients with metastatic PC. Trial registration ClinicalTrials.gov, NCT02028806. Registered 7 January 2014, https://clinicaltrials.gov/ct2/show/NCT02028806

Background: FOLFIRINOX chemotherapy displays significant survival improvements in patients with pancreatic cancer. However, toxicities have hampered enthusiasm for the use of FOLFIRINOX in full dose. In order to increase the tolerability, many researchers focused on the modification of FOLFIRINOX. On the other hand, hyperthermia (HT) has been considered as an effective ancillary treatment for cancer therapy. Up to now, there is no report evaluating combining deep regional hyperthermia (DRHT) with modified-FOLFIRINOX for pancreatic cancer patients. Methods: In this study, we conducted a retrospective review of pancreatic cancer patients treated with the combination of new form modified-FOLFIRINOX and DRHT (BSD2000). Patients underwent chemotherapy that included low-dose irinotecan (70–130 mg/m2), oxaliplatin (65–70 mg/m2) on day 1 and 5-FU (2400 mg/m2 as a 46 h continuous infusion, no bolus) or capecitabine (CAP) (1000 mg/m2 twice daily on days 1–10) or tegafur, gimeracil and oteracil potassium (TS-1) (80–120 mg/d twice daily on days 1–10), 2-week schedule. Generally, DRHT treatment was performed weekly, 45 min for each time during chemotherapy. Results: The patients receiving mFOLFIRINOX as the first line chemotherapy combining with DRHT, obtained an improvement in OS and PFS, 17 months (95% CI 1.97–32.03 months) and 4 months (95% CI 0–8.29 months) respectively. Overall, this combination regimen was safe; 17.6% patients suffered from grade 3/4 toxicities. Conclusions: In conclusion, we conducted a retrospective study combining mFOLFIRINOX and DRHT, which was well tolerated. The efficacy in the treatment of pancreatic cancer was encouraging, but further studies would be required to prove its merit, compared with conventional treatment.