A weekly regimen of cisplatin, paclitaxel and topotecan with granulocyte-colony stimulating factor support for patients with extensive disease small cell lung cancer: a phase II study

The present study was aimed at defining the antitumour activity of the cisplatin-paclitaxel-topotecan (CPT) weekly administration with G-CSF support in chemo-naive SCLC patients with extensive disease (ED-SCLC). Chemonaive ED-SCLC patients received cisplatin 40 mg/m2, paclitaxel 85 mg/m2, and topotecan 2.25 mg/m2weekly, with G-CSF (5 μg/kg days 3–5) support, for a maximum of 12 weeks. 37 patients were treated, for a total of 348 cycles delivered. 8 complete responses (22%) and 22 partial responses (59%) were recorded, giving an 81% [95% CI = 65–92%] ORR. At a 13-month (range, 4–26) median follow-up, median progression-free and overall survival were 8 months and 12.5 months, with 1-year and 2-year projected survivals of 55% and 21%, respectively. No toxic deaths occurred. Grade 4 neutropenia and thrombocytopenia occurred in 6 and 3 patients, respectively. Only one case of neutropenic sepsis was recorded, while haemorrhagic thrombocytopenia was never observed. Diarrhoea, paraesthesias and fatigue were the main nonhaematologic toxicities being severe in 6, 2 and 10 patients, respectively. The weekly CPT combination with G-CSF support represents a well tolerated therapeutic approach in chemo-naive ED-SCLC patients. The activity rate seems at least similar to that achievable with the standard front-line approaches. © 2001 Cancer Research Campaign http://www.bjcancer.co

Multiparametric advanced research tool for meteo satellites data interfacing with space observation of ultra high energy cosmic rays

To approach the study of the cosmic rays in the energy range E > 1020 eV, the upper end of the spectrum observed to date, with a large statistical significance (103 events/year), and hence address the solution of several astrophysical and cosmological problems related to their existence and behaviour, a new generation of experiments will probably have to be conceived and realised. They will be based on the observation and measurements of cosmic rays from space. The extremely low rate of these events (∼ 1 event/(century × km2 × sr)) imposes a very large effective area to be monitored, of the order of 105 km2, as an observational requirement to meet the target statistics. The Extreme Universe Space Observatory (EUSO)mission has been proposed as the precursor of this new generation of experiments. Its approach consists in fact in looking downwards to the Earth atmosphere by means of a large field-of-view telescope accommodated aboard an orbiting satellite. The fluorescence strike produced by a cosmic ray through the atmosphere will be recorded by the detector, which will reconstruct the kinematical and dynamical features of the primary cosmic ray. The atmosphere acts therefore as an active target for the detectable event. A strategic tool for the success of EUSO as well as for all the experiments of its category will be a correct and detailed atmospheric sounding system, in order to monitor the atmospheric parameters within the field-of-view of the telescope. Beside an on-board measurement by means of dedicated devices such an infrared camera (IR)and possibly a LIDAR (LIght Detection And Ranging)coupled to the main instrument, the Atmosphere Sounding will take advantage from the continuous observation of the atmospheric parameters given by the orbiting meteorological satellites. Their databases have thus to be interfaced to the experimental data and used picking-up the relevant data according to the space and time coordinates corresponding to each triggered event. The present work outlines a software module (MARVIN-Multiparametric Advanced Research tool for Visualisation In the Network) able to build-up such an interface, and shows a preliminary implementation of it, using a sample of existing satellites and ISCCP meteorological data collection. It has been developed during the phase A study of the EUSO mission but is general enough to be adapted to different missions observing the Earth atmosphere from space

A phase II study of sequential chemotherapy with docetaxel after the weekly PELF regimen in advanced gastric cancer. A report from the Italian group for the study of digestive tract cancer

In advanced gastric cancer, we investigated feasibility and activity of sequential chemotherapy with docetaxel after an intensive weekly regimen consisting of cisplatin, epidoxorubicin, fluorouracil, leucovorin (PELF) plus filgrastim. Chemotherapy-naive patients with relapsed or metastatic gastric cancer received 8 weekly administrations of chemotherapy with cisplatin 40 mg/m2, fluorouracil 500 mg/m2,epi-doxorubicin 35 mg/m2, 6S-steroisomer of leucovorin 250 mg/m2and glutathione 1.5 g/m2. On the other days filgrastim 5 μg kg–1was administered by subcutanous injection. Subsequently, patients with partial response or stable disease received 3 cycles of docetaxel 100 mg/m2every 3 weeks. 40 patients have been enrolled and they are evaluable for response and toxicity. After the PELF regimen, 3 patients achieved complete response, 13 patients showed partial response, 21 patients had stable disease and 3 patients progressed (40% response rate; 95% CI 25% to 55%). After docetaxel, 9 out 34 patients improved the outcome (26.5%); 7 patients with stable disease achieved partial response and 2 patients with partial response achieved complete response. The overall response rate in the 40 patients was 57.5% (95% CI, 42.5% to 72.5%). The PELF regimen did not cause any grade IV toxicity, the most frequent grade III acute side-effects were thrombocytopenia and vomiting which occurred in the 10% of 320 PELF cycles. Docetaxel caused grade III–IV neutropenia and thrombocytopenia in the 10% and the 19% of cycles respectively. Fatigue was a frequent side-effect during both PELF and docetaxel chemotherapy. The sequential application of docetaxel after PELF chemotherapy gained major objective responses with manageable toxicity. This strategy is worth of further investigation in the setting of palliative or neoadjuvant chemotherapy. © 2001 Cancer Research Campaign http://www.bjcancer.co

Oxaliplatin plus raltitrexed and leucovorin-modulated 5-fluorouracil i.v. bolus: a salvage regimen for colorectal cancer patients

The aim of the present study was to define the activity and tolerability of a triplet regimen including oxaliplatin 130 mg m−2 (2 h i.v. infusion) and raltitrexed 3.0 mg m−2 (15 min i.v. infusion) given on day 1, followed by levo-folinic acid 250 mg m−2 (2 h i.v. infusion) and 5-fluorouracil 1050 mg m−2 i.v. bolus on day 2, every 2 weeks, in pretreated colorectal cancer patients. From April 1999 to December 2000, 50 patients were enrolled: 26 were males and 24 females, their median age was 63 (range, 43–79) years; ECOG performance status was 0 in 26 patients, ⩾1 in 24 patients; 26 patients had received previous adjuvant chemotherapy, 40 patients had been exposed to one or two lines of palliative chemotherapy (including irinotecan in 31 cases); 18 patients were considered chemo-refractory. A total of 288 cycles were administered, with a median number of 6 (range 1–12) courses per patient. A complete response was obtained in three patients, and a partial response in nine patients, giving a major response rate of 24% (95% confidence interval, 13–38%), while 15 further patients showed a stable disease, for an overall control of tumour growth in 60% of patients. Three complete responses and three partial responses were obtained in patients pretreated with irinotecan (response rate, 19%); among refractory patients, three achieved partial responses (response rate, 13%). After a median follow-up of 18 (range, 10–30) months, 40 patients showed a progression of disease: the growth modulation index ranged between 0.2 and 2.5: it was ⩾1.33 (showing a significant delay of tumour growth) in 16 (40%) patients. Actuarial median progression-free survival time was 7.6 months, and median survival time was 13.6 months: estimated probability of survival was 55% at 1 year. Main severe toxicity was neutropenia: World Health Organisation grade 4 affected 32% of patients; non-haematological toxicity was mild: World Health Organisation grade 3 diarrhoea was complained of by 8%, and grade 3 stomatitis by 4% of patients; neurotoxicity (according to Lévi scale) was scored as grade 3 in 8% of patients. In conclusion, this regimen was manageable and active as salvage treatment of advanced colorectal cancer patients; it showed incomplete cross-resistance with irinotecan-based treatments, and proved to delay the progression of disease in a relevant proportion of treated patients

Concomitant MPZ and MFN2 Gene Variants and Charcot Marie Tooth Disease in a Boy: Clinical and Genetic Analysis-Literature Review

: Charcot- Marie- Tooth (CMT) disease includes a group of clinically and genetically heterogeneous neuropathic disorders with an estimated frequency of 1 on 2.500 individuals. CMTs are differently classified according to the age of onset, type of inheritance, and type of inheritance plus clinical features. For these disorders, more than 100 genes have been implicated as causal factors, with mutations in the PMP22 being one of the most common. The demyelinating type (CMT1) affects more than 30% of the CMTs patients and manifests with motor and sensory dysfunctions of the peripheral nervous system mainly starting with slow progressive weakness of the lower extremities. We report here a 12 year- old boy presenting with typical features of CMT1 type, hearing impairment, and inguinal hernia who at the next-generation sequence analysis displayed a concomitant presence of two variants: the c.233 C>T p.Ser 78Leu of the MPZ gene (NM_000530.6) characterized as pathogenetic and the c.1403 G>A p.Arg 468His of the MFN2 gene (NM_014874.3) characterized as VUS. Concomitant variant mutations in CMTs have been uncommonly reported. The role of these gene mutations on the clinical expression and a literature review on this topic is discussed

Randomised trial comparing biweekly oxaliplatin plus oral capecitabine versus oxaliplatin plus i.v. bolus fluorouracil/leucovorin in metastatic colorectal cancer patients: results of the Southern Italy Cooperative Oncology study 0401

Oxaliplatin combined with either fluorouracil/leucovorin (OXAFAFU) or capecitabine (OXXEL) has a demonstrated activity in metastatic colorectal cancer patients. We aimed at comparing these two regimens in terms of response rate (RR), safety, progression-free survival (PFS), and quality of life (QoL) of patients

Robust Model Predictive Control of An Input Delayed Functional Electrical Stimulation

Functional electrical stimulation (FES) is an external application of low-level currents to elicit muscle contractions that can potentially restore limb function in persons with spinal cord injury. However, FES often leads to the rapid onset of muscle fatigue, which limits performance of FES-based devices due to reduction in force generation capability. Fatigue is caused by unnatural muscle recruitment and synchronous and repetitive recruitment of muscle fibers. In this situation, overstimulation of the muscle fibers further aggravates the muscle fatigue. Therefore, a motivation exists to use optimal controls that minimize muscle stimulation while providing a desired performance. Model predictive controller (MPC) is one such optimal control method. However, the traditional MPC is dependent on exact model knowledge of the musculoskeletal dynamics and cannot handle modeling uncertainties. Motivated to address modeling uncertainties, robust MPC approach is used to control FES. Moreover, two new robust MPC techniques are studied to address electromechanical delay (EMD) during FES, which often causes performance issues and stability problems. This thesis compares two types of robust MPCs: a Lyapunov-based MPC and a tube- based MPC for controlling knee extension elicited through FES. Lyapunov-based MPC incorporated a contractive constraint that bounds the Lyapunov function of the MPC with a Lyapunov function that was used to derive an EMD compensation control law. The Lyapunov-based MPC was simulated to validate its performance. In the tube-based MPC, the EMD compensation controller was chosen to be the tube that eliminated output of the nominal MPC and the output of the real system. Regulation experiments were performed for the tube-based MPC on a leg extension machine and the controller showed robust performance despite modeling uncertainties

\u201cWeekly docetaxel and gemcitabine as first line treatment for metastatic breast cancer: results of a multicenter phase II study\u201d

Objectives: We conducted a multicenter phase II study to evaluate the clinical effi cacy, toxicity, and dose intensity of a new weekly schedule of docetaxel and gemcitabine as fi rst-line treatment of metastatic breast cancer patients. Methods: We enrolled 58 patients, 52% of whom had received a previous anthracycline-containing chemotherapy. The treatment schedule was: docetaxel 35 mg/m 2 and gemcitabine 800 mg/m 2 i.v. on days 1, 8,15 every 28 days. Results: All patients were assessable for toxicity and 56 for effi cacy. Overall response rate was 64.3% with 16.1% of complete responses and 48.2% of partial responses. Median survival was 22.10 months (95% CI: 15.53\u201328.67) and median time to tumor progression was 13.6 months (95% CI: 10.71\u201316.49). The most common hematological toxicity was neutropenia (no febrile neutropenia), which occurred in 28 patients (48.3%) but grade 3\u20134 in only 8 patients (14%). Alopecia, the most common nonhematological toxicity, occurred in 20 (34.5%) patients, but only 5 patients (8.6%) experienced grade 3 alopecia. Conclusion: The activity of docetaxel and gemcitabine in metastatic breast cancer is confirmed. The promising results of the employed schedule,in agreement with other published studies, need to be further confirmed within a phase III study