A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer.

BACKGROUND: Capecitabine (Xeloda) is a novel, oral, selectively tumor-activated fluoropyrimidine with proven activity in the treatment of advanced colorectal cancer. This trial was conducted to evaluate the efficacy, safety and feasibility of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer, with a view to replacing 5-fluorouracil (5-FU) in such patients. PATIENTS AND METHODS: Forty-four patients received capecitabine 1250 mg/m2 twice daily (2500 mg/m2/day) for 14 days followed by 7 days of rest, for up to six cycles. RESULTS: Capecitabine produced an objective response rate of 34% (all partial responses) and stable disease in 14 patients (30%). The median time to disease progression (TTP) was 3.2 months [95% confidence interval (CI) 2.7-6.4 months] and median overall survival was 9.5 months (95% CI 6.9-13.2 months). Hand-foot syndrome (HFS), nausea, anorexia, diarrhea and vomiting were the most common adverse events. While HFS was the most frequent grade 3/4 toxicity (National Cancer Institute Common Toxicity Criteria), only 9% of patients experienced grade 3 HFS. Severe myelosuppression was not reported during the study. CONCLUSIONS: Capecitabine monotherapy is active and well tolerated as first-line therapy in patients with advanced/metastatic gastric cancer. Larger comparative trials investigating capecitabine-based combination regimens in patients with advanced gastric cancer are warranted.     

Lymphatic mapping and intraoperative lymphoscintigraphy for identifying the sentinel node in penile tumors

Lymph node mapping has become an integral part of the management of melanoma and breast cancer with regard to both staging and treatment. We report our technique for lymphatic mapping and intraoperative lymphoscintigraphy applied to a patient with penile melanoma. This technique may improve the sensitivity of identifying the sentinel lymph node in patients with malignant penile lesions.     

Expression of nm23 protein in human osteosarcoma in relationship with early metastasis

Nm23 protein expression was analyzed by immunohistochemical staining using formalin-fixed, paraffin-embedded sections from 39 cases with osteosarcomas and compared with the histologic findings and early metastasis for the purpose of detecting nm23 expression in osteosarcoma and elucidating the clinical significance of its expression. Immunoreactivity of nm23 protein was detected in 48.7% of the total cases. There was no statistical difference between nm23 expression and early metastasis, but there was a trend for cases with nm23 expression to progress to early metastasis within 1 year after operation. The role of nm23 as a tumor metastasis suppressor in osteosarcomas appeared less prominent.     

Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413.

PURPOSE: This trial tested the hypothesis that combined androgen suppression (CAS) and whole-pelvic (WP) radiotherapy (RT) followed by a boost to the prostate improves progression-free survival (PFS) by 10% compared with CAS and prostate-only (PO) RT. This trial also tested the hypothesis that neoadjuvant and concurrent hormonal therapy (NCHT) improves PFS compared with adjuvant hormonal therapy (AHT) by 10%. MATERIALS AND METHODS: Eligibility included localized prostate cancer with an elevated prostate-specific antigen (PSA) < or = 100 ng/mL and an estimated risk of lymph node (LN) involvement of 15%. Between April 1, 1995, and June 1, 1999, 1,323 patients were accrued. Patients were randomly assigned to WP + NCHT, PO + NCHT, WP + AHT, or PO + AHT. Failure for PFS was defined as the first occurrence of local, regional, or distant disease; PSA failure; or death for any cause. RESULTS: With a median follow-up of 59.5 months, WP RT was associated with a 4-year PFS of 54% compared with 47% in patients treated with PO RT (P =.022). Patients treated with NCHT experienced a 4-year PFS of 52% versus 49% for AHT (P =.56). When comparing all four arms, there was a progression-free difference among WP RT + NCHT, PO RT + NCHT, WP RT + AHT, and PO RT + AHT (60% v 44% v 49% v 50%, respectively; P =.008). No survival advantage has yet been seen. CONCLUSION: WP RT + NCHT improves PFS compared with PO RT and NCHT or PO RT and AHT, and compared with WP RT + AHT in patients with a risk of LN involvement of 15%.     

High glucose inhibits glucose uptake in renal proximal tubule cells by oxidative stress and protein kinase C

BACKGROUND: High glucose has been considered to play an important role in alteration of renal proximal tubule transporter's activity. This study examined the mechanism by which high glucose modulates alpha-methyl-D-glucopyranoside (alpha-MG) uptake in primary cultured rabbit renal proximal tubule cells (PTCs). METHODS: PTCs were incubated with 25 mmol/L glucose alone or combined with taurine, ascorbic acid, catalase, staurosporine, and bisindolylmaleimide I. Then alpha-MG uptake and lipid peroxide (LPO) formation were examined. RESULTS: Twenty-five mmol/L glucose from four hours, but not 25 mmol/L mannitol, inhibited alpha-MG uptake by 23% compared with 5 mmol/L glucose (control). In the study to examine the relationship of oxidative stress in the high-glucose-induced inhibition of alpha-MG uptake, 25 mmol/L glucose significantly increased LPO by 27% compared with control. However, 10 mmol/L glucose did not affect alpha-MG uptake and LPO formation. Taurine (2 mmol/L), ascorbic acid (1 mmol/L), endogenous antioxidants, or catalase (600 U/mL) significantly blocked 25 mmol/L glucose-induced increase of LPO formation and inhibition of alpha-MG uptake. In the experiment to examine the effects of protein kinase C on LPO formation, 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 ng/mL) increased LPO formation, and staurosporine (10(-7) mol/L) and bisindolylmaleimide I (10(-6) mol/L) totally blocked 25 mmol/L glucose-induced increase of LPO formation and inhibition of alpha-MG uptake. In addition, taurine reduced TPA-induced increase of LPO formation and inhibition of alpha-MG uptake. CONCLUSION: High glucose induces, in part, the inhibition of alpha-MG uptake through LPO formation, and activation of protein kinase C may play a role in high-glucose-induced LPO formation in the primary cultured rabbit renal PTCs.     

Actual half-life of alpha-fetoprotein as a prognostic tool in pediatric malignant tumors

In a retrospective study, the prognostic value of monitoring the decay of alpha-fetoprotein (AFP) was assessed. Serum AFP was determined serially in 18 children with malignant germ-cell or hepatic tumors: 7 endodermal sinus tumor, 3 embryonal carcinoma, 5 malignant teratoma, 2 hepatoblastomas, and 1 hepatocellular carcinoma. The actual half-life (AHL) of AFP was computed after surgical resection of the tumor. In group 1, which had complete resection and no recurrence during follow-up (n = 13), the AHL of AFP was 4.0 ± 0.9 days. In group 2, which had incomplete resection or recurrence during follow-up (n = 5), the AHL of AFP was 24.8 ± 20 days, significantly longer than that of group 1 (P = 0.0026). The increased AHL of AFP indicated residual active tumor after surgical resection. The AHL of AFP may be more sensitive than serial monitoring of AFP in detecting preclinical recurrence after surgical resection of AFP-secreting tumors. Treatment strategies can be based on AFP clearance, and prospective clinical trials are warranted.