Polycyclic Aromatic Hydrocarbons: Are They a Problem in Processed Oil Shales?

Organic residues from processed oil shales were characterisized with specific attention to polycyclic aromatic hydrocarbons (PAH). Oil shale development in the White River Basin (Utah and Colorado) was projected and hydrological and geological parameters pertinent to estimations of polycyclic aromatic hydrocarbons (PAH) flux were focused. Oil shale samples from the Union B, Paraho, and Tosco II processes were extracted by using organic solvents in a soxhlet apparatus and by mixing shale samples with water (characterization i

Gemcitabine and docetaxel as first-line treatment for advanced urothelial carcinoma: a phase II study

The purpose of the study was to investigate the toxicity and efficacy of the combination of gemcitabine and docetaxel in untreated advanced urothelial carcinoma. Patients with previously untreated, locally advanced/recurrent or metastatic urothelial carcinoma stage-IV disease were eligible. Patients with Performance status: PS ECOG >3 or age >75 years or creatinine clearance <50 ml min−1 were excluded. Study treatment consisted of docetaxel 75 mg m−2 (day 8) and gemcitabine 1000 mg m−2 (days 1+8), every 21 days for a total of six to nine cycles. A total of 31 patients with urothelial bladder cancer, 25 men and six women, aged 42–74 (median 64) years were enrolled. The majority of patients had a good PS (51.6%; PS 0). In all, 15 (48.3%) patients had locally advanced or recurrent disease only and 16 (54.8%) presented with distant metastatic spread, with multiple site involvement in 22.5%. Toxicity was primarily haematologic, and the most frequent grade 3–4 toxicities were anaemia 11 (6.7%) thrombocytopenia eight (4.9%), and neutropenia 45 (27.6%), with 10 (6.1%) episodes of febrile neutropenia. No toxic deaths occurred. A number of patients had some cardiovascular morbidity (38.7%). Nonhaematological toxicities except alopecia (29 patients) were mild. Overall response rate was 51.6%, including four complete responses (12.9%) and 12 partial responses (38.7%), while a further five patients had disease stabilisation (s.d. 16.1%). The median time to progression was 8 months (95% CI 5.1–9.2 months) and the median overall survival was 15 months (95% CI 11.2–18.5 months), with 1-year survival rate of 60%. In conclusion, this schedule of gemcitabine and docetaxel is very active and well tolerated as a first-line treatment for advanced/relapsing or metastatic urothelial carcinoma. Although its relative efficacy and tolerance as compared to classic MVAC should be assessed in a phase III setting, the favourable toxicity profile of this regimen may offer an interesting alternative, particularly in patients with compromised renal function or cardiovascular disease

A phase II trial of gemcitabine plus carboplatin in advanced transitional cell carcinoma of the urothelium

<p>Abstract</p> <p>Background</p> <p>Recent studies have demonstrated the effectiveness of cisplatin-based combinations in patients with advanced transitional cell carcinoma(TCC) of the urothelium. Concern over cisplatin toxicity instigated a search for alternative regimens. The aim of the study was to evaluate the activity and tolerability of gemcitabine plus carboplatin combination as first-line treatment in patients with advanced transitional cell carcinoma of the urothelium.</p> <p>Methods</p> <p>Patients with advanced TCC were treated with gemcitabine 1200 mg/m²on days 1 and 8 and carboplatin area under the concentration-time curve(AUC) 5 on day 1 every 21 days.</p> <p>Results</p> <p>Out of 41 patients, thirty-nine were evaluable for efficacy and 41 for toxicity. A median of 5 cycles (range 1–6) was administered. Overall response rate was 46.2% (95% confidence interval: 32–65%) including 10.3% complete responses and 35.9% partial responses. The median time to progression and median overall survival were 7.5 months (95% confidence interval: 6.6–8.4 months) and 13.6 months (95% confidence interval: 10.2–17.0 months), respectively. Grade 3/4 neutropenia, anemia and thrombocytopenia were observed in 36.6%, 26.8, and 24.4% of patients, respectively. Non-hematological toxicity was generally mild. Grade 3 vomiting occurred in 1 (2.4%) patients.</p> <p>Conclusion</p> <p>The gemcitabine plus carboplatin combination is active in advanced TCC with acceptable toxicity and needs to be evaluated further and compared with other non-cisplatin-containing regimens.</p> <p>Trial registration</p> <p>ISRCTN88259320</p

A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen

A multicentre phase II trial to determine the efficacy of vinflunine as second-line therapy in patients with advanced transitional cell carcinoma (TCC) of the bladder; secondary objectives were to assess duration of response, progression-free survival (PFS) and overall survival (OS), and to evaluate the toxicity associated with this treatment. Patients had tumours that failed or progressed after first-line platinum-containing regimens for advanced or metastatic disease, or had progressive disease after platinum-containing chemotherapy given with adjuvant or neoadjuvant intent. Response and adverse events were assessed according to WHO criteria and NCI-CTC (version 2), respectively. Out of 51 patients treated with 320 mg m−2 of vinflunine, nine patients responded to the therapy yielding an overall response rate of 18% (95% CI: 8.4–30.9%), and 67% (95%CI: 52.1–79.3%) achieved disease control (PR+SD). Of note, responses were seen in patients with relatively poor prognostic factors such as a short (<12 months) interval from prior platinum therapy (19%, including an 11% response rate in those progressing <3 months after platinum treatment), prior treatment for metastatic disease (24%), prior treatment with vinca alkaloids (14%) and visceral involvement (20%). The median duration of response was 9.1 months (95% CI: 4.2–15.0) and the median PFS was 3.0 months (95% CI: 2.4–3.8). The median OS was 6.6 months (95% CI: 4.8–7.6). The main haematological toxicity was grade 3–4 neutropenia, observed in 67% of patients (42% of cycles). Febrile neutropenia was observed in five patients (10%) and among them two were fatal. Constipation was frequently observed (but was manageable and noncumulative) and was grade 3–4 in only 8% of patients. The incidence of grade 3 nausea and vomiting was very low (4 and 6% of patients, respectively). Neither grade 3–4 sensory neuropathy nor severe venous irritation was observed. Moreover, and of importance in this particular study population, no grade 3–4 renal function impairment was observed. Vinflunine is an active agent for the treatment of platinum-pretreated bladder cancer, and these results warrant further investigation in phase III trials, either as monotherapy or in combination with other agents as treatment of advanced/metastatic TCC of the bladder

Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival

The aim of the present study was to analyse lymphocyte subsets in consecutive peripheral blood samples and consecutive tumour tissue core needle biopsies performed before and during interleukin-2 based immunotherapy, and to correlate the findings with objective response and survival. Twenty-six patients with metastatic renal cell carcinoma were treated with low dose s.c. interleukin-2, interferon-α and histamine. A total of 250 blood samples and 62 core needle biopsies from 23 and 19 of these patients, respectively, were analysed. After 2 weeks of treatment, a significant positive correlation between absolute number of peripheral blood lymphocytes (P=0.028), CD3 (P=0.017), CD57 (P=0.041) and objective response was demonstrated. There was no correlation between any peripheral blood leukocyte subsets and survival. Cytotoxicity of peripheral blood mononuclear cells was not correlated to objective response or survival. Within the tumour tissue at baseline, a significant positive correlation between CD4 (P=0.027), CD8 (P=0.028), CD57 (P=0.007) and objective response was demonstrated. After one month of immunotherapy, a significant positive correlation between intratumoral CD3 (P=0.026), CD8 (P=0.015), CD57 (P=0.009) and objective response was demonstrated. A significant positive correlation between intratumoral baseline CD4 (P=0.047), baseline CD57 (P=0.035), CD3 at one month (P=0.049) and survival was demonstrated. These data provide novel in vivo evidence of the possible contribution of lymphocyte subsets in the tumour reduction in responding patients during interleukin-2 based immunotherapy. Confirmation of the results requires further studies including a larger number of patients