Phase I/II trial of docetaxel and concurrent radiation therapy in localized high risk prostate cancer (AGUSG 03-10).

PURPOSE: A Phase I/II trial was conducted to assess the radiosensitizer docetaxel administered weekly (20 mg/m(2)) with concurrent intensity modulated radiation therapy (72 Gy at 1.8 Gy/fraction) in high risk prostate cancer. PATIENTS AND METHODS: Patients with high risk prostate cancer (clinical stage > or = T3; Gleason score 8, 9, or 10; Gleason score 7 and PSA > 10) received IMRT (Clinac 600 CD with 6 MV photons and sliding window technique) and concurrent weekly docetaxel (20 mg/m(2)) as a continuous 30 minute infusion for 8 weeks. Patients desirous of concurrent androgen suppression were not excluded. RESULTS: Twenty men (median age: 64 years; range, 50-78 years) were enrolled in the chemoradiation protocol. Three patients experienced treatment interruptions: dehydration requiring inpatient hydration (n = 2); NSAID induced GI bleed (n = 1). An additional patient required outpatient hydration (<24 hours) with no treatment interruption. Overall, the most frequently observed toxicities were grade 2 diarrhea (40%), grade 2 fatigue (40%), grade 2 urinary frequency (35%), taste aversion (20%), grade 2 constipation (20%), and rectal bleeding (15%). No significant hematologic toxicity (grades 2-4) was encountered among the 20 patients. Although the follow-up interval was relatively short, no significant subacute gastrointestinal toxicities have been observed. At a median follow-up duration of 11.7 months, 17 patients were free of biochemical disease recurrence, and all patients are alive. CONCLUSION: The radiosensitizer docetaxel administered weekly (20 mg/m(2)) with concurrent IMRT is well tolerated with acceptable toxicity. Early oncologic outcomes in this challenging patient cohort are encouraging.

Does laparoscopy beget underuse of partial nephrectomy for T(1) renal masses? Competing treatment decision pathways may influence utilization.

BACKGROUND AND PURPOSE: It has been suggested that renal laparoscopy has resulted in an underuse of partial nephrectomy (PN) for small renal masses in the U.S. In the absence of evidence-based medicine (EBM) guide-lines, multiple-perspective reasoning is required where complete v partial nephrectomy and the laparoscopic v the open surgical approach must be considered. We report on the PN rate in a contemporary laparoscopicera series of patients with T(1) renal masses and examine the potential influence of the management decision tree on the PN rate. PATIENTS AND METHODS: An actively managed database of referred patients with T(1) renal masses was utilized retrospectively. All patients were evaluated by a single fellowship-trained urologic oncologist with formal laparoscopic training. Patients were presented with a management decision tree in which PN v total nephrectomy (TN) was the first decision node, laparoscopy v open surgery was the second decision node, and the actual PN rate was reported. We then constructed a hypothetical decision tree in which the first and second decision nodes were reversed and the criteria for performing laparoscopic nephrectomy remained constant. RESULTS: Seventy consecutive patients were entered during a 36-month period (July 2002-June 2005). The actual PN rate was 60%: 91% for lesions <2.0 cm, 68% for lesions 2.1 to 4.0 cm, and 33% for lesions 4.1 to 7.0 cm; and 62% of patients were treated laparoscopically. When the first and second decision nodes were reversed and this hypothetical model was applied to the study cohort, the projected PN rate was 23%, and 96% of the patients were treated laparoscopically. In the hypothetical model, the PN rate fell when patients who chose laparoscopy at the first decision node were excluded from PN at the second decision node if the criteria for laparoscopic PN were not met. CONCLUSION: Laparoscopy did not appear to result in underuse of PN. We explain this by suggesting that the PN rate may be influenced by variation in the decision tree itself. Such variation is inherent in complex clinical decision making where EBM guidelines are lacking.

Exogenous expression of caspase-14 induces tumor suppression in human salivary cancer cells by inhibiting tumor vascularization.

BACKGROUND: Current therapeutic approaches to salivary gland cancer are often associated with severe disfigurement and loss of glandular function, which are traumatic to the patients. Exploration of novel treatment approaches, such as gene therapy, is needed. MATERIALS AND METHODS: The human salivary gland cancer cell line HSG was transiently transfected with full length human caspase-14 cDNA. Photomicroscopy, BrdU assay, cell counting, MTT assay, and TUNEL assay were applied. To determine the tumorigenicity, tumor volume, tumor pathology and vascularization were analyzed in vivo. RESULTS: Cell growth and viability were inhibited significantly by transient caspase-14 expression. Caspase-14 expression resulted in a significant reduction of tumorigenicity. Importantly, a significant decrease in tumor blood vessel formation was observed. CONCLUSION: Salivary gland cancer cells underwent growth inhibition, cell death, and reduced tumorigenicity in vivo when exogenous caspase-14 was expressed, which could be due, in part, to an inhibitory effect of caspase-14 on tumor vascularization.