Phase II clinical trial of sorafenib plus interferon-alpha treatment for patients with metastatic renal cell carcinoma in Japan.

BACKGROUND: To improve antitumor effects against metastatic renal cell carcinoma (mRCC), use of molecular target-based drugs in sequential or combination therapy has been advocated. In combination therapy, interferon (IFN)-α amplified the effect of sorafenib in our murine model (J Urol 184:2549, 2010), and cytokine-treated mRCC patients in Japan had good prognoses (Eur Urol 57:317, 2010). We thus conducted a phase II clinical trial of sorafenib plus IFN-α for untreated mRCC patients in Japan. METHODS: In this multicenter, prospective study, provisionally registered patients with histologically confirmed metastatic clear cell RCC received natural IFN-α (3 dosages of 3 million U per week) for 2 weeks. Only IFN-α-tolerant patients were registered to this trial, and treated additionally with oral sorafenib (400 mg, bid). The primary end point of the study was rate of response (CR + PR) to sorafenib plus IFN-α treatment assessed using RECIST v1.0. The secondary end points were disease control rate (CR + PR + SD), progression free survival (PFS), overall survival (OS), and safety of the combined treatment. PFS and OS curves were plotted using the Kaplan-Meier method. RESULTS: From July 2009 to July 2012, a total of 53 untreated patients were provisionally registered, and 51 patients were finally registered. Rate of Response to the combined therapy of sorafenib plus IFN-α was 26.2 % (11/42) (CR 1, PR 10). The median PFS was 10.1 months (95 % CI, 6.4 to 18.5 months), and the median OS has not been reached yet. The combined therapy increased neither the incidence of adverse effects (AE) nor the incidence of unexpected AE. A limitation was that a relatively high number of patients (9 patients) were excluded for eligibility criteria violations. CONCLUSION: Our data have demonstrated that sorafenib plus IFN-α treatment is safe and effective for untreated mRCC patients. TRIAL REGISTRATION: UMIN000002466 , 9(th) September, 2009.

Quality of life improvements among cancer patients in remission following the consumption of Agaricus blazei Murill mushroom extract.

OBJECTIVES: The aim of this preliminary clinical study was to assess if the daily intake of Agaricus blazei Murill (ABM) granulated powder (SSI Co., Ltd., Tokyo, Japan) for 6 months improved the quality of life (QOL) in cancer patients in remission. DESIGN: Open study. SETTING: Subjects diurnally took 1 (1.8 g; N=23), 2 (3.6 g; N=22), or 3 (5.4 g; N=22) packs/day orally for 6 months. MAIN OUTCOME MEASURES: The SF-8 Health Survey questionnaire was used to evaluate the QOL. The differences between the SF-8 baseline scores at the time of entry and 6-months after ABM treatment were evaluated. RESULTS: The results showed a significant improvement in QOL in both physical and mental components. More specifically, QOL effects of ABM in different genders showed males improved physical components, while females improved only mental components. QOL effects in the different age groups showed that ages 65 and under improved mental components, while ages 66 and older improved physical components. Furthermore, with respect to optimal dose effects of ABM with respect to QOL improvement, two packs per day for 6 months showed improvements in both physical and mental components. CONCLUSION: This preliminary longitudinal clinical study demonstrated that daily intake of ABM appears to improve both physical and mental components based on SF-8 qualimetric analysis.

Phase I Clinical Study of the Dietary Supplement, Agaricus blazei Murill, in Cancer Patients in Remission.

Although many cancer patients use complementary and alternative medicine, including Agaricus blazei Murill (ABM), safety is not yet well understood. Cancer survivors took 1.8, 3.6, or 5.4 g ABM granulated powder (Kyowa Wellness Co., Ltd., Tokyo, Japan) per day orally for 6 months. Adverse events were defined by subjective/objective symptoms and laboratory data according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI-CTCAE v3.0). Seventy-eight patients were assessed for safety of ABM (30/24/24 subjects at 1/2/3 packs per day, resp.). Adverse events were observed in 9 patients (12%). Most were digestive in nature such as nausea and diarrhea, and one patient developed a liver dysfunction-related food allergy, drug lymphocyte product. However, none of these adverse events occurred in a dose-dependent manner. This study shows that ABM does not cause problems in most patients within laboratory parameters at the dosages tested over 6 months. This trial supports previous evidence that the ABM product is generally safe, excluding possible allergic reaction.

Dietary administration of mushroom mycelium extracts in patients with early stage prostate cancers managed expectantly: a phase II study.

OBJECTIVE: To assess the efficacy and safety of dietary supplements in patients with early stage prostate cancers who are managed expectantly. METHODS: Seventy-four patients with early prostate cancer, who were treated with expectant management, enrolled in the study. A mushroom mycelium extract was given at a dose of 4.5 g/day for 6 months. The primary endpoint was the proportion of patients in which the prostate specific antigen level decreased by 50% or more following treatment. The adverse events, change of prostate specific antigen value and quality of life were also evaluated. RESULTS: In only one of 74 patients (1.4%), the prostate specific antigen value decreased more than 50%. Grade 2 diarrhea and grade 1 itching were observed in one patient, and patient ingestion compliance was maintained near 100%. The alternation of prostate specific antigen values was stable before and after treatment. In subjects with strong anxiety prior to supplement ingestion, these feelings were significantly alleviated (state anxiety, P = 0.0018; trait anxiety, P = 0.0099). CONCLUSIONS: In this phase II study of early prostate cancer patients who were managed expectantly, a mushroom mycelium extract was an ineffective treatment for reducing 50% or more the patient prostate specific antigen values.

[Primary urothelial carcinoma of the prostate: a case of spread along ducts and into seminal vesicles].

A 75-year-old man was referred to our department with prostate cancer. When our pathologist reviewed the biopsy specimen, he was diagnosed as intraductal urothelial carcinoma. Transurethral random biopsy showed the urothelial carcinoma in the prostate ducts but no cancer in the bladder. He was diagnosed as primary urothelial carcinoma of the prostate ducts (cTis pd cN0 M0), and radical cystoprostatectomy were performed. Histopathological examination showed urothelial carcinoma in situ spread along ducts and ejaculatory ducts and into seminal vesicles but there was not invasion of prostatic stroma. (pTis pd pN0 M0 Urothelial carcinoma G3 pL0 pV0) He had no adjuvant therapy, he is alive without any evidence of tumor recurrence after surgery.