Safety and efficacy of cabazitaxel in Japanese patients with castration-resistant prostate cancer.

BACKGROUND: Several studies have reported the efficacy of cabazitaxel in cancer therapy; however, investigations of its safety are few. The aim of this study was to retrospectively analyze the efficacy and safety of cabazitaxel based on treatment outcome data. METHODS: A questionnaire form on the use of cabazitaxel was mailed to hospitals associated with the Shinshu University. Responses were received from 11 institutions regarding 55 cases. RESULTS: Patients received a median of 4 courses of cabazitaxel treatment. Decreases in prostrate-specific antigen (PSA) were observed in 61.5% of cases with declines of 30%, 50%, and 90% in 36.5%, 23.0%, and 7.6% of cases, respectively. PSA progression-free survival was 5.0 months, and overall survival after the start of cabazitaxel was 13.0 months. Forty-five patients received postcabazitaxel treatment; 17 showed decreased PSA. Safety assessment indicated that white blood cell and neutrophil counts were significantly higher in the second than in the first course of treatment and Grade 3 to 4 leukopenia and neutropenia significantly decreased. Twenty-four subjects were aged ≥75 years; 79% of them had their doses reduced at the first administration. The mean dose was 20 mg/m2. However, there was no significant difference in the PSA progression-free survival between the ≥75-year-old and <75-year-old groups. Patients in the ≥75-year-old group, particularly those whose doses were not reduced, experienced several Grade 3 to 4 adverse effects. Ten patients discontinued treatment owing to adverse effects and systemic worsening. CONCLUSIONS: To use cabazitaxel effectively, starting administration as early as possible before disease progression is important, and even if Grade 3 to 4 leukopenia and neutropenia are observed during the first course, it is important to carefully maintain the dose. Even when treating elderly patients, reducing the dose does not reduce therapeutic efficacy. However, because this cohort experienced several ≥ Grade 3 adverse effects, a great deal of caution is required.

[THE EFFECT OF LOW-DOSE INTRAVESICAL BACILLUS CALMETTE-GUÉRIN (BCG) INFUSION THERAPY FOR NON-MUSCLE INVASIVE BLADDER CANCER].

(Objective) Bacillus Calmette-Guérin (BCG) intravesical infusion therapy plays an important role in the treatment of patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Our institute performs low-dose (40 mg) BCG intravesical infusion therapy (completed 8 times) to reduce side effects. We retrospectively investigated its efficacy and side effects. (Patients and methods) We analyzed the response, non-recurrence, and side effect rates by risk stratification in 179 patients who received low-dose BCG intravesical infusion therapy from September 2003 to November 2018 in Nagano Municipal Hospital. Complications were classified using the Common Terminology Criteria for Adverse Events version 4.0. (Results) The median age was 73 years, and the male/female ratio was 137:42. The median observation period was 32 months, and infusion was completed 8 times in 149 cases (83.2%). The overall response rate was 88.8%. The response rate was significantly higher in the low-grade pathology group than in the high-grade group. However, no significant differences in G1/G2/G3 side effects, sex, age, presence of carcinoma in situ (CIS), depth of invasion, purpose of administration, and grade of side effects were observed. The overall non-recurrence rates were 91.8%, 76.7%, and 71.3% at 1, 3, and 5 years, respectively. Nevertheless, there were no significant differences in the non-recurrence rates with respect to depth of penetration, the degree of dysmorphism, purpose of administration, presence of CIS, and completed of infusion. A total of 71 G2 side effects (39.7%) were identified, and 3 cases of G3 side effects required hospitalization. (Conclusion) In our institution, the completion rate of low-dose BCG intravesical infusion therapy was high, with few side effects. Furthermore, it demonstrated similar therapeutic effect to that reported with standard-dose administration. Low-dose BCG intravesical infusion therapy may be an effective treatment, particularly for pathologically low-grade NMIBC.

Oncological and renal outcomes of segmental ureterectomy vs. radical nephroureterectomy for upper tract urothelial carcinoma.

Segmental ureterectomy (SU) represents a promising alternative for the treatment of upper tract urothelial carcinomas (UTUCs) as it is a less invasive procedure and guarantees the preservation of renal units. The present study evaluated oncological outcomes and renal functions following SU when compared with radical nephroureterectomy (RNU). A total of 26 patients with UTUCs who underwent SU (n=12) or RNU (n=14) were retrospectively evaluated. SU was performed in patients with clinically unifocal disease. In the SU group, the following surgeries were carried out: 7 direct ureterocystoneostomy, 1 reimplantation on psoas hitch bladder, 1 reimplantation on Boari flap bladder, 2 ureteral end-to-end anastomosis and 1 subtotal ureterectomy. In the SU group, tumors were low grade urothelial carcinoma (UC) in 6 patients, high grade UC in 5 patients and high grade UC with squamous cell differentiation in 1 patient, as well as ≤pT1 in 5, ≥pT2 in 6 and pTis in 1 patient; 'p' refers to the pathological state. The 5-year overall, cancer-specific, recurrence free and metastasis free survival in the SU group were 77.8, 87.5, 34.4 and 80.8%, respectively, which all exhibited no significant differences when compared with those of the RNU group. With regard to renal function, postoperative estimated glomerular filtration rates were preserved in the SU group. The present study demonstrated that SU does not result in poorer cancer control when compared with RNU. Thus, SU is an acceptable alternative to RNU in selected cases, as it is less invasive and preserves renal functions.

[A Case Report of Splenic Metastasis of Renal Cell Carcinoma].

A 64-year-old female patient underwent radical left nephrectomy in 2005 after being diagnosed with renal cell carcinoma. The pathological diagnosis was pT2b pN0 M0 clear cell carcinoma. Three years postoperatively, metastatic recurrence in the para-aortic lymph node was noted, and the patient underwent retroperitoneal lymph node dissection in 2008. The pathological diagnosis was renal cell carcinoma (a combination of clear cell carcinoma and type 2 papillary cell carcinoma). Five years later, she exhibited splenic metastasis on computed tomography, but no other distant metastases were observed. She underwent splenectomy in 2013, and the pathological diagnosis was splenic metastasis of renal cell carcinoma (type 2 papillary cell carcinoma). Three months after the splenectomy, she developed multiple bone metastases but refused to undergo treatment with molecularly targeted drugs ; hence, she was transferred to palliative care services. Fourteen months after the splenectomy, she died of cancer. Most metastatic splenic tumors occur as part of multiple organ metastases in the terminal stage of renal cell carcinoma. If splenic metastasis of renal cell carcinoma is observed, further imaging studies should be performed, and splenectomy should only be considered if a definitive diagnosis of sporadic splenic metastasis is made.

[A Case Report of 2,8-Dihydroxyadenine Stone].

Here we report a case of a 2,8-dihydroxyadenine (2,8-DHA) stone. A 48-year-old woman arrived at our hospital with left flank pain. She was diagnosed with a left ureteral stone. Extracorporeal shock wave lithotripsy (ESWL) was tried, but the left ureteral stone was radiolucent and ESWL was not effective. Transurethral ureterolithotripsy (TUL) was successful. An analysis of the stone revealed 2,8-DHA. A 2,8-DHA stone is caused by adenine phosphoribosyltransferase (APRT) deficiency. By genetic tests, she was diagnosed with APRT deficiency.

[A case report of progressive penile necrosis].

The penis is provided with blood by multiple arteries. Penile necrosis is uncommon. Penile necrosis sporadically occurs in patients with progressive diabetes mellitus and/or end stage renal failure. Penile necrosis is often considered a poor prognostic feature. We present a case of penile necrosis in a patient with mild diabetes mellitus.