Search

The objectives of this study were to evaluate survival in 141 patients with stage II-IV oral squamous cell carcinoma (OSCC) treated with preoperative intra-arterial chemotherapy with docetaxel, cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil (IADCPIVF) via the superficial temporal artery, and to clarify the prognostic factors. The study population included 59 patients with stage II OSCC, 34 with stage III, and 48 with stage IV. After IADCPIVF, 139 patients underwent surgery; minimally invasive surgeries (MIS) including excisional biopsy were performed on 96 patients with a remarkably good response to IADCPIVF. The primary tumour response rate was 99.3% (complete response rate 56.7%, good partial response rate 17.0%, fair partial response rate 25.5%). Additionally, there were no serious adverse events associated with IADCPIVF. The 5-year overall survival rate was 74.6% (stage II 83.6%, stage III 72.7%, stage IV 64.8%). In the multivariate analysis of survival, T classification and clinical tumour response were significant prognostic factors. Eight (8.3%) of the patients who received MIS had primary recurrence and six were salvaged. In conclusion, IADCPIVF is safe and efficacious for treating OSCC, and MIS could reduce the extent of primary tumour resection in the case of a remarkably good response.

The aim of this study was to evaluate the therapeutic efficacy and safety of proton beam therapy combined with retrograde intra-arterial infusion chemotherapy in elderly patients with locally advanced oral cancer. Between February 2009 and October 2019, 42 oral cancer patients aged ≥75 years were treated with this therapy. Median age was 80 years (range 75-90 years) and the median follow-up duration was 39 months (range 2-106 months). Of the 42 patients, 34 (81%) were diagnosed with stage IV cancer. The 3-year overall survival, local control, progression-free survival, and disease-specific survival rates were 56%, 69%, 32%, and 67%, respectively. Regarding acute toxicities, grade 3 neutropenia was observed in six patients (14%), anaemia in five (12%), acute kidney injury in one (2%), and oral mucositis in 18 (42%). Late toxicities of grade 3 were observed in seven patients: dysphagia in six (14%) and osteonecrosis of the jaw in one (2%). This study showed that proton beam therapy combined with retrograde intra-arterial infusion chemotherapy was effective for elderly patients with oral cancer, and toxicities were tolerable and manageable. The study findings suggest that this therapy is a potential treatment option for elderly oral cancer patients with difficulty in surgery and systemic chemotherapy.

The information presented herein extends our recent study of TTT (Trial for Triplet Antiemetic Therapy). One of our main clinical questions has been whether a 2nd generation serotonin receptor antagonist (5-HT3ra) would be superior to 1st generation 5-HT3ra when administering triplet antiemetic therapy for the prevention of chemotherapy induced nausea & vomiting (CINV), since a prior Japanese trial demonstrated palonosetron to be superior to granisetron for controlling the delayed phase of CINV induced by highly emetogenic chemotherapy (HEC) and to doublet antiemetic therapy including dexamethasone for anthracycline and cyclophosphamide containing regimens (AC). In this study, we assessed the efficacies of 1st and 2nd generation 5-HT3ra agents for use as triplet antiemetic therapy for AC, by monitoring CINV, focusing especially daily CR in the delayed phase. Between 2012 and 2015, 491 women with breast cancer receiving AC were recruited from 11 institutions in Japan, and randomly assigned to either single-dose palonosetron (0.75mg) or granisetron (40μg/kg) prior to chemotherapy on day 1, both with dexamethasone (9.9 mg intravenously) and aprepitant (125mg orally) on day 1 followed by additional doses (80mg orally) on days 2 and 3. Age, institution and habitual alcohol intake were used as stratification factors. The primary endpoint was a complete response (CR). Statistical analysis was done by Mantel-Haenszel Method. This trial was registered with UMIN000007882. All 491 patients were included in efficacy analyses (ITT): 246 patients in the palonosetron group and 245 in the granisetron group. We previously reported that the difference in CR during the delayed phase, i.e. 24 hours after the administration of AC, did not reach statistical significance (53.8% vs 58.5%) in MASCC 2016. However, daily CR in the palonosetron group was much higher than that in the granisetron group after 48 hours. Palonosetron showed better efficacy in controlling CINV during the late period of the delayed phase, i.e. 48 hours after AC administration, than granisetron as triplet antiemetic therapy for AC. The pattern of CINV reportedly shows two peaks including an acute phase caused by serotonin and a delayed phase caused by substance P, though the pattern of CINV with triplet antiemetic therapy administration might be different if the suppression of each of these peaks were to be achieved more efficiently. CINV may not be divided into two phases in the future, or the borderline area between the acute and delayed phases may require revision. The analysis of the late period of the delayed phase was ad hoc in this trial. However, when conducting studies related to CINV, it might be worthwhile to revise the borderline area between the two phases of CINV to facilitate elucidating the mechanisms underlying this potentially debilitating side effect of chemotherapy. Citation Format: Ogata H, Saito M, Tsuneizumi M, Kutomi G, Hosoya K, Kawai Y, Sugizaki K, Katsumata N, Senuma K, Kitabatake T, Suda M, Uomori T, Miura K, Kurata M, Nitta Y, Yonemoto N, Matsuoka J. Difference between 1st and 2nd generation serotonin receptor antagonists in triplet antiemetic therapy for highly emetogenic chemotherapy in breast cancer patients – according to recent multi-institutional double-blind randomized clinical research on the AC regimen [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-11-03.

Cellular membranes obtained from the 1321N1 and A172 astrocytoma cell lines were immobilized on a chromatographic phase to create cellular membrane affinity chromatography (CMAC) columns, CMAC(1321N1) and CMAC(A172). The columns were characterized using frontal affinity chromatography with [(3)H]-epibatidine as the marker ligand and epibatidine, nicotine, and methyllycaconitine as the displacers. The results indicated that the columns contained homomeric alpha7 nicotinic acetylcholine receptors (alpha7 nAChR) and heteromeric nicotinic acetylcholine receptors (alpha(x)beta(y) nAChRs), which was confirmed by the addition of subtype-specific inhibitors, alpha-bungarotoxin (alpha7 nAChR) and kappa-bungarotoxin (alpha(x)beta(y) nAChR) to the mobile phase. The presence of two additional ligand-gated ion channels (LGICs), gamma-aminobutyric acid (GABA(A)) and N-methyl-D-aspartic acid (NMDA), was established using frontal affinity chromatography with flunitrazepam and diazepam (GABA(A) receptor) and MK-801 and NMDA (NMDA receptor). The presence of the four LGICs was confirmed using confocal microscopy and flow cytometry. The results indicate that the CMAC(1321N1) and CMAC(A172) columns contain four independently functioning LGICs, that the columns can be used to characterize binding affinities of small molecules to each of the receptors, and that the CMAC approach can be used to probe the expression of endogenous membrane receptors.

Among the Japanese radiological technicans, four deaths from aplastic anemia have been reported after 1930. On the other hand, during the period from 1930 to 1960, the population of radiological technicians is estimated to be 74,400 man-years, in which 0.5 aplastic anemias are expected. However, actually three died from aplastic anemia. This difference is statistically significant at the 1% level. While, in the period from 1961 to 1973, the observed value is 1 against 0.7 expected. It is concluded that aplastic anemia had been induced frequently among the Japanese radiological technicians in the era when there was much exposure to occupational radiation.

A model of tumor regression during the course of radiotherapy is presented, which considered the lethal effect of radiation, the elimination of dying cells and the reproduction of surviving cells. The model was applied to multiple lung metastases in a woman, which were treated with different doses per fraction. The regression of tumor volume was measured from chest radiographs which were taken once a week during the treatment. Radiosensitivity of tumor cells estimated by the model was of D0=150 R and n=5. The half life of dying cells in the tumor was 15 days.