ABSTRACT
BACKGROUND: To ascertain the anti-tumor effect of zoledronic acid (ZOL) treatment on clinical outcomes in patients with bone metastatic prostate cancer, we examined the effect of ZOL started simultaneously with hormonal therapy as initial treatment in these patients. METHODS: Forty-seven patients with bone-metastatic prostate cancer who received a luteinizing hormone releasing-hormone (LHRH) analogue and an anti-androgen [maximal androgen blockade (MAB)] were assigned to receive ZOL (4 mg intravenous administration every month for 2 years). The time to progression (TTP) of the prostate-specific antigen (PSA), the overall survival (OS), and the rate of PSA decrease in patients with MAB and ZOL treatment (ZOL group) were compared with these parameters in patients who received only MAB at one institute as a control group (non-ZOL group). RESULTS: Although the nadir PSA level and the rate of PSA normalization showed no significant differences between the ZOL and non-ZOL groups, the time to nadir PSA in the ZOL group was significantly shorter than that in the non-ZOL group (P < 0.05, Mann-Whitney U-test). There was a significant difference in TTP (P = 0.017, log-rank test) between the ZOL and non-ZOL groups, and statistically significant differences in TTP and OS between the ZOL and non-ZOL groups (P = 0.044 and 0.035, log-rank test) were recognized particularly in patients with advanced disease (extension of disease, grade 3 and 4). CONCLUSIONS: Simultaneous administration of ZOL and MAB as initial treatment delayed TTP in bone-metastatic prostate cancer patients. Initial treatment with ZOL has the possibility of anti-tumor activity to delay disease progression.
Subject(s)
Bone Neoplasms/drug therapy , Diphosphonates/administration & dosage , Imidazoles/administration & dosage , Prostate-Specific Antigen/blood , Prostatic Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bone Neoplasms/pathology , Bone Neoplasms/secondary , Disease-Free Survival , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Zoledronic AcidABSTRACT
We report a case of pancreatic metastasis from renal cell carcinoma detected 25 years after radical nephrectomy. A 74-year-old man, who had undergone radical nephrectomy for renal cell carcinoma at age 49, was found by computed tomography to have a strongly enhanced mass on the pancreatic head. The patient underwent pancreaticoduodenectomy and the pathological diagnosis was metastatic renal cell carcinoma. This was evidently a slow growing tumor because the metastatic pancreas tumor was well demarcated and the metastasis was found 25 years after the primary operation. Aggressive surgical treatment of isolated metastatic lesions offers a chance of long-term survival. Patients with a history of RCC should undergo a long-term follow-up to detect and evaluate metastasis to pancreas as well as other organs.
Subject(s)
Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Nephrectomy , Pancreatic Neoplasms/secondary , Aged , Humans , Male , Time FactorsABSTRACT
2-Deoxy-beta-D-ribose 1-phosphate (1) was synthesized in a stereoselective manner and isolated with no detectable contamination by its alpha-isomer (4). Explicit configuration of 4 was first determined by NMR comparison with 1 judging from NOE results and their coupling constants. Natural purine nucleoside phosphorylase (PNPase) did not recognize 1 and gave no products such as alpha- or beta-deoxynucleosides.
Subject(s)
Purine-Nucleoside Phosphorylase/metabolism , Ribosemonophosphates/chemical synthesis , Ribosemonophosphates/metabolism , Deoxyribonucleosides/chemistry , Deoxyribonucleosides/metabolism , Magnetic Resonance Spectroscopy , Molecular Conformation , Ribosemonophosphates/chemistry , Stereoisomerism , Substrate SpecificityABSTRACT
A chemo-enzymatic method for preparations of natural and unnatural deoxynucleosides was developed. The method consists of chemical synthesis of natural and unnatural deoxyribose 1-phosphates and their enzymatic conversion to deoxynucleosides. A highly stereoselective synthesis of 2-deoxyribose 1-phosphate was first achieved by an unprecedented application of crystallization-induced asymmetric transformation. Additionally, we first discovered a 2'-deoxycytidine producing enzyme. The discovery and the development of a scalable synthetic process of 2-deoxyribose 1-phosphate enabled us to manufacture all four natural 2'-deoxynucleosides practically. The methodology was applied to the synthesis of 2',3'-dideoxy-3'-fluoroguanosine via synthetic 2,3-dideoxy-3-fluororibose 1-phosphate.
Subject(s)
Nucleosides/chemical synthesis , Chromatography, High Pressure Liquid , Nucleosides/chemistryABSTRACT
Between June 1998 and August 2000, five patients with germ cell tumor were treated with high-dose CEI: carboplatin (1,250 mg/m2), etoposide (1,500 mg/m2), and ifosfamide (7.5 g/m2), followed by peripheral blood stem cell transplantation (PBSCT) at Yokohama City University Hospital. All patients were classified into either poor risk group of International Germ Cell Consensus Classification or advanced extent of Indiana University stage, and received one cycle of high-dose CEI after 4-6 cycles of standard PEB (cisplatin, bleomycin, vinblastin) therapy. Three of the patients achieved complete response, one achieved partial response and one achieved no change after whole treatment. There were no fatal complications and no treatment-related deaths.
