Parallel administration of nanoliposomal irinotecan and levo-leucovorin for pancreatic cancer.

BACKGROUND: Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU)/levo-leucovorin (Levo-LV) was approved for unresectable pancreatic cancer (UR-PC) in March 2020 in Japan. Levo-LV is administered by intravenous infusion over 120 min following 90 min intravenous infusion of nal-IRI (conventional method), causing a significant burden on both patients and the outpatient chemotherapy room owing to the prolonged administration time. Thus, from July 2021, we introduced the simultaneous intravenous administration of nal-IRI and Levo-LV (parallel method) with the approval of the institutional regimen committee. METHODS: We retrospectively reviewed the data of 69 patients with UR-PC who received nal-IRI plus 5-FU/Levo-LV at our hospital between June 2020 and October 2021. We examined the safety of the parallel method and compared the treatment outcomes and administration times between the two methods. RESULTS: The median age was 66 years (54%, male). Disease statuses were locally advanced, metastatic, and postoperative recurrence after pancreatectomy in 7, 50, and 12 patients, respectively. Nal-IRI plus 5-FU/Levo-LV treatment was second and third-line or later in 35 and 34 patients, respectively. No intravenous line problems were observed during the parallel administration of nal-IRI and Levo-LV. Although there were no significant differences in response rates and adverse events between the two methods, the administration time was significantly shorter in the parallel method than in the conventional method. CONCLUSION: The parallel administration of nal-IRI and Levo-LV is clinically safe and not inferior in efficacy. Moreover, parallel administration may offer convenience to patients and healthcare workers by reducing administration time.

A Questionnaire-based Assessment of the Anxiety, Satisfaction and Discomfort Experienced by Japanese Cancer Patients during the Use of Central Venous Ports.

Objective A significant number of Japanese cancer patients refuse to have central venous (CV) ports implanted. The aim of this study is to investigate the experiences of patients prior to and after CV port implantation, as well as their expectations regarding the use of CV ports. Methods This study was carried out at Osaka Medical Center for Cancer and Cardiovascular Diseases from October 20, 2014, to January 16, 2015. Data were collected using a questionnaire developed by the researchers, and various statistical analyses were performed. Results Among the 50 patients who participated in this study, the CV port was implanted due to poor venous access in 18 (36%). The proportion of patients who were anxious before the port implantation was significantly higher among the patients in whom CV ports were implanted due to poor venous access than among those in whom CV ports were implanted for other reasons. All patients exhibited high satisfaction levels, regardless of the reason for CV port implantation. CV port-related discomfort was most commonly associated with seat belts. Conclusion The patients exhibited high satisfaction levels regardless of the reason for CV port implantation. However, the patients that exhibited poor venous access often experienced anxiety before the implantation of the port, so it is important to provide such patients with sufficient information prior to port implantation. In order to improve the quality of life of patients with CV ports, medical staff should give special consideration to discomfort experienced by patients that are wearing seat belts.

Pretreatment with PKC inhibitor triggers TNF-alpha induced apoptosis in TNF-alpha-resistant B16 melanoma BL6 cells.

Tumor necrosis factor alpha (TNF-alpha) modulates various events through several different pathways. Many tumor cells are resistant to this cytokine. Pretreatment of these cells with actinomycin D enhances TNF-alpha-induced apoptosis. In the present study, we investigated the mechanism of this enhancement and whether or not the apoptosis of TNF-alpha-resistant cancer cells can be induced by the inhibition of Protein kinase C (PKC). When TNF-alpha was added after inhibition of PKC by H7, apoptosis was observed, and companied with the activation of nuclear factor kappa B (NF-kappaB). After the inhibition of protein kinase B (Akt) by LY294002 or p38 mitogen-activated protein kinase (p38MAPK) by SB203580, the addition of TNF-alpha did not cause apoptosis. However, after the inhibition of MAPK/extracellular signal-regulated kinase kinase 1/2 (MEK1/2) with U0126, apoptosis was observed when TNF-alpha was added. In the Western blotting analysis, phosphorylation of MEK1/2 occurred at 60 minutes after the addition of TNF-alpha. However, it was noted that after pretreatment with H7, a significant decrease in phosphorylated MEK1/2 was observed. The present findings suggest that MEK1/2 plays an important role in TNF-alpha-resistance in TNF-alpha-resistant B16 melanoma BL6 cells. Furthermore, it was found that MEK1/2 is more important than NF-kappaB, Akt, and p38MAPK in anti-apoptotic PKC signaling and that TNF-alpha-resistance can be overcome by inhibiting MEK1/2. These results suggest the possibility of development of a new anticancer drug treatment.