Impact of Prior Platinum-Based Therapy on Patients Receiving Salvage Systemic Treatment for Advanced Urothelial Carcinoma.

BACKGROUND: Trials of salvage therapy for advanced urothelial carcinoma have required prior platinum-based therapy. This practice requires scrutiny because non-platinum-based first-line therapy may be offered to cisplatin-ineligible patients. PATIENTS AND METHODS: Data of patients receiving salvage systemic chemotherapy were collected. Data on prior first-line platinum exposure were required in addition to treatment-free interval, hemoglobin, Eastern Cooperative Oncology Group performance status, albumin, and liver metastasis status. Cox proportional hazard regression was used to evaluate their association with overall survival (OS) after accounting for salvage single-agent or combination chemotherapy. RESULTS: Data were obtained from 455 patients previously exposed to platinum-based therapy and 37 not exposed to platinum. In the group exposed to prior platinum therapy, salvage therapy consisted of a single-agent taxane (n = 184) or a taxane-containing combination chemotherapy (n = 271). In the group not exposed to prior platinum therapy, salvage therapy consisted of taxane or vinflunine (n = 20), 5-fluorouracil (n = 1), taxane-containing combination chemotherapy (n = 12), carboplatin-based combinations (n = 2), and cisplatin-based combinations (n = 2). The median OS for the prior platinum therapy group was 7.8 months (95% confidence interval, 7.0, 8.1), and for the group that had not received prior platinum therapy was 9.0 months (95% confidence interval, 6.0, 11.0; P = .50). In the multivariable analysis, prior platinum therapy versus no prior platinum exposure did not confer an independent impact on OS (hazard ratio, 1.10; 95% confidence interval, 0.75, 1.64; P = .62). CONCLUSION: Prior platinum- versus non-platinum-based chemotherapy did not have a prognostic impact on OS after accounting for major prognostic factors in patients receiving salvage systemic chemotherapy for advanced urothelial carcinoma. Lack of prior platinum therapy should not disqualify patients from inclusion onto trials of salvage therapy.

[Pain assessment in terminally-ill cancer patients on admission in hospice and its modification after the first three days of care. A monocentric experience]. / Il dolore nel paziente oncologico terminale: valutazione del sintomo all'ingresso in hospice e delle sue modifi cazioni nei primi tre giorni di assistenza. Esperienza monocentrica.

AIMS: Pain is among the most frequent and distressing symptoms in terminally-ill cancer and, to date, many patients still experience uncontrolled pain. In this paper we evaluated prevalence and intensity of pain on admission in our palliative care center and during the first three days of care. PATIENTS AND METHODS: From September 2009 to October 2009 we consecutively recruited 96 terminally-ill cancer patients : on admission more than 50% had severe pain and only 4% referred to be pain-free. 54% of patients was on treatment with strong opioids. RESULTS: After three days from admission in our palliative care unit only 7% of patients experienced severe pain, 25% reported absence of pain and 80% of patients was on treatment with strong opioids. CONCLUSIONS: The beginning of palliative care led to a meaningful and rapid reduction of pain in the vast majority of terminally-ill cancer patients evaluated in this study.

Weekly regimen of paclitaxel and carboplatin as first-line chemotherapy in elderly patients with stage IIIB-IV non small cell lung cancer (NSCLC): results of a phase II study.

Single-agent chemotherapy is the preferred treatment option in chemonaive elderly patients with advanced nonsmall-cell lung cancer (NSCLC). The role of combination chemotherapy in this setting is uncertain although several studies report satisfactory efficacy and safety using weekly paclitaxel and carboplatin (AUC=6) as first-line chemotherapy in elderly patients. It is still unclear which schedule of this regimen which could offer the best therapeutic index. The aim of this study was to evaluate the activity and tolerability of concomitant weekly administration of paclitaxel and carboplatin in untreated elderly patients with advanced NSCLC. From february 2005 to April 2008 36 consecutive elderly patients with advanced NSCLC were enrolled. Median age was 74 years (range, 70-83 years) and median ECOG PS was 1 (range, 0-1). patients received carboplatin (AUC=2) and paclitaxel 80 mg/m² on days 1,8 and 15 every 28 days. All patients were evaluable for efficacy and toxicity; a median of 4 cycles was administered. Twelve patients had partial response (33%; 95% C.I. 15,8-52,3%), 10 patients (28%) showed stable disease. The median time to progression (TTP) was 5.7 months (95% C.I. 3.1-8.6 months) with a median overall survival (MOS) of 9 months (95% C.I. 4.4-13.9 months). Toxicity was mild with no cases of febrile neutropenia; 5 patients (14%) developed grade 2 neuropathy. Our study confirms the substantial activity of weekly regimen of paclitaxel and carboplatin. Due to its favorable profile of toxicity this schedule could represent an interesting therapeutic option in selected chemonaive elderly patients with advanced NSCLC.

Coupling pH-stat and DO-stat titration to monitor degradation of organic substrates.

A combined titration methodology at constant pH and dissolved oxygen concentration to monitor the degradation of organics as carbon dioxide evolution rate (CER) and oxygen uptake rate (OUR) is presented. Equations necessary to assess CER from alkali titration rates and the instrument used to test the technique are described. Experiments were performed on samples of activated sludge from a domestic wastewater treatment plant using glucose and ethanol as substrates. OUR and CER were calculated for both substrates, as well as the respiratory quotient RQ = CER/OUR and biomass to substrate yields coefficients. RQ data for ethanol compared better with corresponding stoichiometric values than those for glucose.

Feasibility study to upgrade a textile wastewater treatment plant by a hollow fibre membrane bioreactor for effluent reuse.

A pilot plant membrane bioreactor has been tested in parallel with a full-scale activated sludge wastewater treatment plant fed on the wastewater from a textile factory. The possibility to upgrade the final effluent for internal reuse was investigated. The pilot and full-scale plants are located in a textile factory (Boselli & C., Olgiate Comasco, North Italy) which manufactures and finishes polyester fabric. The activated sludge wastewater treatment plant (WWTP) is an extended aeration system. The MBR pilot plant is a ZW-10 bench hollow fibre module (membrane surface area: 0.93 m2) submerged in a 200 L tank. Performance and operation of the membrane bioreactor (MBR) were evaluated in terms of permeate characteristics and variability (COD, colour, total N and P, microbiological counts), of membrane specific flux (l m(-2) h(-1) bar(-1)) and other operational parameters (sludge growth and yield).

Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial.

BACKGROUND: Continuous research into new strategies and chemotherapy agents for the treatment of malignant high-grade gliomas have led to the synthesis of a new chemotherapy drug, temozolomide (TMZ), with a lower toxicity profile compared to conventional chemotherapy agents, such as nitrosoureas. Temozolomide is an oral alkylating chemotherapy agent licensed for the treatment of recurrent high-grade gliomas, anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM). Because of its favorable pharmacokinetic and pharmacodynamic properties and improved tolerability, TMZ is now under investigation for concomitant use with radiotherapy in patients with newly-diagnosed GBM. We present a phase II clinical trial investigating the efficacy and safety of radio-chemotherapy combined treatment using TMZ, followed by six cycles of adjuvant chemotherapy with TMZ, in patients with newly-diagnosed GBM who have undergone debulking surgery or biopsy only. PATIENTS AND METHODS: Twenty-one patients with newly histologically-diagnosed GBM were enrolled into this phase II clinical trial. In phase I of the study, TMZ (75 mg/m2/day per 7 days/wk for 6 weeks) was orally administered to patients concomitantly with radiotherapy (RT) (2 Gy per fraction once daily, per 5 days/wk for 6 weeks). In phase II of the study, four weeks after completion of RT, a monochemotherapy using TMZ was administered at the dosage of 200 mg/m2/day per 5 days every 28 days for 6 cycles. Primary end-points were the safety and tolerability profile of this two-phase combined treatment and secondary end-points were the objective response and survival rates at twelve months and eighteen months from study entry. RESULTS: The one-year survival rate of patients treated with the investigated multimodality treatment was 58% and median survival time was 15.7 months. Concomitant RT plus TMZ (phase I) followed by adjuvant TMZ (phase 2) were well-tolerated; indeed, nonhematological adverse events were rare and mild to moderate in severity; grade 3 and 4 neutropenia and thrombocytopenia were the major-related hematological side-effects observed in only 2 and 3 of all patients in phase I and 4 patients in phase II. We found that the combination of radio- and chemo-therapy, in phase I of the study did not significantly increase the incidence and severity of hematological toxicity caused by the adjuvant TMZ-based chemotherapy administered in phase II of the study. CONCLUSION: The investigated multimodality treatment regimen was well-tolerated and prolonged survival while improving patients' quality of life.

Denitrifying activity measurements using an anoxic titration (pHstat) bioassay.

An anoxic titrimetric test was investigated for measuring denitrifying activity in an activated sludge system. The method measures the amount of acid that is required to maintain the pH set-point value in a batch denitrification experiment. An iterative algorithm was implemented to extract nitrate uptake rate (NUR) data from titration data, since the accumulation and depletion (stripping) of reaction by-products HCO3- and CO2 affects the direct calculation of denitrifying activity from titration data. This method was performed using an automatic pH-stat acid dosing system, and the data were analysed using the simulation software package, AQUASIM.

Influence of pulsation on start-up of UASB reactors.

The aim of this work is to study the influence of pulsation on the start-up of lab-scale UASB reactors. Pulsation was produced by an Elastic Membrane Pulsator (EMP). The application of this device in previous works improved the performance of continuous fixed-bed fermentors and reduced the formation of preferential pathways, the retention of gas metabolites within the bed and the resistance to mass transfer. These characteristics seem to be suitable for feeding UASB reactors. In this work, the influence of pulsation frequency was studied in two pulsed UASB reactors operated in parallel with a non-pulsed one. One of them (P1) operated at high frequencies (periods of 50 and 200 s between each pulsation) and the other (P2) at low frequencies (periods of 3600 and 900 s between each pulsation). An important improvement of the removal efficiency for pulsed reactors with respect to the non-pulsed one was obtained. The structure of the biomass was observed at the end of the process by scanning electron microscopy. In general, granulation of biomass was improved when operating in pulsing form.

The IWA Anaerobic Digestion Model No 1 (ADM1).

The IWA Anaerobic Digestion Modelling Task Group was established in 1997 at the 8th World Congress on Anaerobic Digestion (Sendai, Japan) with the goal of developing a generalised anaerobic digestion model. The structured model includes multiple steps describing biochemical as well as physicochemical processes. The biochemical steps include disintegration from homogeneous particulates to carbohydrates, proteins and lipids; extracellular hydrolysis of these particulate substrates to sugars, amino acids, and long chain fatty acids (LCFA), respectively; acidogenesis from sugars and amino acids to volatile fatty acids (VFAs) and hydrogen; acetogenesis of LCFA and VFAs to acetate; and separate methanogenesis steps from acetate and hydrogen/CO2. The physico-chemical equations describe ion association and dissociation, and gas-liquid transfer. Implemented as a differential and algebraic equation (DAE) set, there are 26 dynamic state concentration variables, and 8 implicit algebraic variables per reactor vessel or element. Implemented as differential equations (DE) only, there are 32 dynamic concentration state variables.

Anaerobic removal of linear alcohol ethoxylates.

The present paper deals with a laboratory-scale study of anaerobic treatment of two commercial mixtures (LS2, LT7) of alcohol ethoxylates with 8-14 carbon atoms and 2 and 7 ethoxy groups. Tests were carried out in batch, with a 2 g l(-1) single dose, and in semibatch, with daily 0.2 g l(-1) doses. The behaviour of the tested mixtures was different: anaerobic sludge adsorption was the main removal process for LS2, while adsorption was less significant and biodegradation was more important for LT7. These differences appeared to be mainly related to the ethoxy portion length determining the extent of biodegradability and adsorption.

Methanogenic activity measurements by the MAIA biosensor: instructions guide.

The MAIA (Methanogenic Activity and Inhibition Analyser) is a titration (pH-stat) biosensor designed to determine the activity and inhibition related to acetoclastic methanogens. The main operational problems encountered in using this instrument are described.

Inhibiting effects of chloroform on anaerobic microbial consortia as monitored by the Rantox biosensor.

The Rantox biosensor was designed for anaerobic wastewater treatment process control, and detects modifications of the feed based on the response of the acetoclastic methanogens contained in the sensor to periodic pulses of a concentrated organic substrate. The biosensor was tested under various operating conditions at the laboratory scale, in parallel with a digester under control fed on the same substrate. The aim was to evaluate the response of the biosensor in the presence of an incoming organic toxic compound (CHCl3). The experimental set-up, i.e. the biosensor and the digester, was connected to an automated control system developed under LabVIEW environment for data acquisition and operational sequence programming (the Rantox Virtual Instrument). Biomasses with different activities were used as inocula, and inhibition was induced by dosing chloroform according to two different procedures. The results showed good sensitivity and rapid response of the biosensor to feed intoxication. The presence of chloroform was detected by the Rantox with a rapid and visible response, and well in advance with respect to the digester.

Monitoring toxicity in anaerobic digesters by the rantox biosensor: theoretical background.

Process control of anaerobic reactors is difficult due to the complexity of the methabolic pathways in the microbial consortium and to the difficulty of detecting and monitoring process instability in short time, before the biomass is poisoned by incoming toxicants. Process control based on the Rantox biosensor is based on the following principle: the wastewater that can potentially induce an overload or contains a toxicant is first tested on a small "upstream" digester (the Rantox). This reactor makes possible to detect the potential instability and, if necessary, to divert the concentrated and/or contaminated wastewater to a buffer tank and consequently to protect the active biomass of the full-scale reactor. It is generally accepted that methanogens are the most sensitive microorganisms in anaerobic digestion. Among these bacteria, the acetoclastic methanogens are of primary importance because some 70% of the converted chemical oxyen demand (COD) mass flow passes through acetic acid. Therefore the first objective in the development of the Rantox biosensor has been to monitor the metabolism of acetoclastic methanogens in the presence of toxicants. This article presents the theoretical background required to evaluate the toxicity effects by determining the kinetic constants of the considered microorganisms from experimental data. The results of two series of calibration tests, performed in order to obtain a preliminary evaluation of the biosensor response to overload and toxicity conditions, are reported. In a second article, calibration tests will be described which refer to two prototypes of the biosensor tested in different operating conditions. The crucial point related to the Rantox, i.e., its comparison with a "normal" laboratory-scale digester to simulate a full-scale plant, will be the subject of the third (and last) article, which is planned to describe the development of this instrument.

Characterization of a prototype industrial on-line analyzer for bicarbonate/carbonate monitoring.

In many biological reactors bicarbonate is the major species determining pH buffering capacity, or alkalinity. In anaerobic digesters bicarbonate levels should be within 10 to 50 mM for stable operation. Bicarbonate alkalinity in wastewater treatment processes in routinely measured off-line titrimetrically. Recently we have described the principle of a novel on-line method of measuring bicarbonate alkalinity. In the prototype device described here, a continuous stream (15 cm(3) min(-1)) of the substrate to be monitored was saturated with gaseous CO2, acidified by the addition of excess acid, and the rate of carbon dioxide evolution, proportional to the concentration of bicarbonate/carbonate in the liquid flow, continuously measured by a sensitive gas meter. The instrument was robust and its response was satisfactory for wastewater treatment process control applications, with linearity in the range 5 to 50 mM HCO3(-), a response time in the order of 30 min, and accuracy of the order of 7% in the concentration range 5 to 50 mM sodium bicarbonate. The device was not affected by interference from volatile fatty acids, does not make use of pH probes which in many wastes are subject to fouling, and may form the basis of a digester control strategy.

Computation of physicochemical parameters, namely pH, in complex (bio)chemical systems: extension to gas-liquid systems.

The first model has been proposed to compute, in complex liquid (bio)chemical systems, a number of physicochemical parameters, namely pH, concentration of one of any chemical species, partition between acid-base forms, global charge, or ionic strength, assuming the physicochemical equilibrium state. The extension of the present model, described here, permits moreover the computation of gas-liquid distributions, specific gas volumes, or total pressures. The model solely requires the knowledge of existing thermodynamic constants and of the concentration of every chemical species other than the species under examination. The model elicits a unique equilibrium state. Computed values agreed with experimental measurements, thereby validating the model. Digital computer programs were prepared to use the proposed algorithms.