Safety and pharmacokinetic evaluation of repeated intravenous administration of palonosetron 0.75 mg in patients receiving highly or moderately emetogenic chemotherapy.

PURPOSE: The aims of this study were to evaluate the safety, efficacy, and pharmacokinetics of repeated doses of palonosetron 0.75 mg on days 1 and 3 in Japanese patients who received highly or moderately emetogenic chemotherapy. METHODS: Twenty- six patients received palonosetron 0.75 mg intravenously before chemotherapy on days 1 and 3 plus dexamethasone (12-16 mg before chemotherapy on day 1 and 4-8 mg on days 2 and 3). The primary endpoints were safety and pharmacokinetics. Pharmacokinetics were evaluated in a subset of patients (n=6). Complete response and complete protection were evaluated as secondary endpoints. RESULTS: The accumulation ratios for C max and AUClast after the second dose on day 3 were 1.42 and 1.37, respectively. These values were consistent with the theoretical values expected from the half-life of palonosetron on day 1. Almost all of the patients had no nausea or vomiting in the acute phase (complete response (CR) rate, 96.2% [25/26]; CP rate, 92.3% [24/26]). In the delayed phase (24-192 h post-chemotherapy), the complete response and complete protection rates were 76.9% (20/26) and 61.5% (16/26), respectively. Treatment was well tolerated. CONCLUSIONS: This is the first study to report the pharmacokinetics of multiple doses of palonosetron 0.75 mg, given on days 1 and 3, in Japanese patients. Repeated treatment with palonosetron was safe and well tolerated by patients who received highly or moderately emetogenic anticancer chemotherapy.

Severe Hemorrhagic Cystitis Caused by Cyclophosphamide and Capecitabine Therapy in Breast Cancer Patients: Two Case Reports and Literature Review.

Combined oral cyclophosphamide and capecitabine (XC) chemotherapy is used for metastatic breast cancer (MBC) patients. We report herein two MBC patients who developed severe hemorrhagic cystitis after XC therapy. Case 1: A 67-year-old woman with MBC had received XC therapy for 2.5 years. After a sudden onset of lower abdominal pain and gross hematuria, cystoscopy revealed a urinary bladder mucosa showing diffuse dilation of the capillaries and a large blood clot. A total dose of 60.8 g cyclophosphamide had been given and the XC regimen was discontinued immediately. The patient experienced frequent episodes of bladder tamponade over 18 months and underwent continuous bladder irrigation and cystoscopic fulguration. Hyperbaric oxygen therapy (HBOT) provided only temporary relief and the patient subsequently developed hemorrhagic shock. A bilateral ureterostomy was eventually performed. Case 2: A 65-year-old woman with MBC was given XC for 3 years, but this was discontinued after she developed new lung lesions. The patient was given a total dose of 78.4 g of cyclophosphamide. A month later, the patient complained of intermittent gross hematuria, which progressed to persistent macroscopic hematuria for 1 week. She underwent continuous bladder irrigation with saline, without an improvement in her bladder tamponade. Subsequently, the bleeding ceased completely after HBOT. Some MBC cases can be controlled for a long time with XC therapy. For those cases, we need to realize that severe hemorrhagic cystitis may occur. Even at a low dose, requires testing periodically for occult blood in the urine to detect the early stages of cystitis.

Adenoid cystic carcinoma with high-grade transformation forming spindle cell component of the submandibular gland.

Adenoid cystic carcinoma (AdCC) with high-grade transformation (AdCC-HGT) is rare, and AdCC-HGT with spindle cell component is particularly rare. The patient was a 65-year-old man with a 5 cm sized swelling of the right submandibular gland. Submandibular sialoadenectomy was performed. Histopathological findings mainly showed conventional AdCC, and minorly showed two other components: (1) the pleomorphic component, a proliferation of atypical pleomorphic epithelial cells forming solid or small clusters and accompanied by necrosis; (2) the spindle cell component, containing atypical spindle cells invading the stroma. Postoperative chemoradiotherapy was performed. Multiple right lung nodular lesions were found on the contrast-enhanced chest CT one month after the surgery. Thoracoscopic pulmonary resection was performed. The lung tumors exhibited a proliferation of atypical spindle cells, accompanied by necrosis. We considered that the spindle cell component of the AdCC-HGT of the submandibular gland developed lung metastases. The patient died seven months after submandibular sialoadenectomy due to respiratory failure. Although rare, our case highlights the importance of recognising spindle cell components in conventional AdCC; even if the area is small, these high-grade transformation areas can metastasise and become prognostic factors.

Community-acquired Disseminated Exophiala dermatitidis Mycosis with Necrotizing Fasciitis in Chronic Graft-versus-host Disease.

We herein report a case of systemic phaeohyphomycosis by Exophiala dermatitidis (E. dermatitidis) with chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). The patient had been taking oral corticosteroids for years to control the GVHD. Yeast-like fungi were identified in a blood culture, so treatment with micafungin (150 mg/day) was begun, with no improvement. The patient passed away on hospital Day 12. A sequence analysis of rRNA revealed the isolate to be E. dermatitidis. This report brings attention to an emerging mycosis of community-acquired Exophiala species infection in the very-late phase after allogenic HSCT in patients with chronic GVHD.

Retrospective analysis of the efficacy and safety of eribulin therapy for metastatic breast cancer in daily practice.

BACKGROUND: Evidence of eribulin therapy for metastatic breast cancer (MBC) in clinical practice is not well documented. METHODS: We retrospectively analyzed the safety and efficacy of eribulin in 29 MBC patients from 2011 to 2016 at Fukuoka University Hospital. RESULTS: The median patient age, number of courses, total dose, and relative dose intensity were as follows: 65 years, five courses, 8.6 mg/m2 , and 75%, respectively. One patient achieved a complete response, (CR) six a partial response (PR), eight stable disease (SD) and 14 patients exhibited progressive disease. The objective response rate (ORR: CR + PR) was 24.1%, and the clinical benefit rate (CBR: CR + PR + SD) was 51.7%. The median progression-free survival was 90 days (95% confidence interval [CI] 67-126) and median overall survival was 264 days (95% CI 198-357). In patients who previously received 2-4 regimens, the ORR was 28.5% and the CBR was 57.1%. In patients who received 5-12 regimens, the ORR was 20% and the CBR was 45%. Chemotherapy was administered to 20 patients (69%) after eribulin administration, and the median overall survival rate of cases that achieved greater than a PR was 1088 days. The most frequent treatment-related grade 3/4 adverse events were neutropenia (55.2%), and febrile neutropenia (20.1%). Grade 3 peripheral neuropathy occurred in 13.8% of patients, but was not exacerbated even if present before treatment. CONCLUSION: Eribulin is effective for MBC patients who have received multiple chemotherapies. Neutropenia and febrile neutropenia may develop after heavy prior therapy.

Colitis mimicking graft-versus-host disease during treatment with the anti-CCR4 monoclonal antibody, mogamulizumab.

A 57-year-old male with acute-type adult T cell leukemia-lymphoma (ATL) developed persistent watery, non-bloody diarrhea at a volume of 2-3 L/day following the administration of the anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, mogamulizumab. An extensive examination revealed the absence of any pathogenic bacteria or parasites in his stool. Biopsied specimens from the colonic mucosa contained many small nests of apoptotic bodies in the colonic glands, which mimicked acute-colonic graft-versus-host disease. Activation of the auto-reactive immune system due to the depletion of regulatory T-cells by mogamulizumab was suspected as causative. Special attention should be paid to the risk of unique immune-related adverse events induced by mogamulizumab.

Osteosarcoma of the patella mimicking giant cell tumor: imaging features with histopathological correlation.

Patellar tumors represent an uncommon etiology of anterior knee pain and their diagnosis is often delayed. We present an unusual case of conventional osteosarcoma arising in the patella of a 47-year-old man. The patient presented with a 1-year history of increasing anterior knee pain and swelling. Plain radiographs revealed a multi-locular lytic lesion in the inferolateral side of the patella. Computed tomography scans demonstrated an intraosseous lytic lesion with cortical thinning/breakthrough anteriorly. On magnetic resonance imaging, the lesion exhibited low signal intensity on T1-weighted images and heterogeneous high signal intensity on T2-weighted images. Fluid-fluid levels were also observed on T2-weighted images. Contrast-enhanced fat-suppressed T1-weighted images demonstrated strong enhancement of the lesion. These imaging features were suggestive of a benign condition; however, the diagnosis of osteosarcoma was confirmed by histopathology. After neoadjuvant chemotherapy, a wide resection with a free anterolateral thigh flap was performed. The patient subsequently underwent adjuvant chemotherapy and had no evidence of local recurrence or distant metastasis six months after surgery. Our case highlights the difficulty in the diagnosis of patellar osteosarcoma and the importance of performing a biopsy before definitive treatment.