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Biomedical subjects

E Papadakis

Publications and source records attributed to E Papadakis.

At least 19 recordsLinked to original sources
PubMed2004

Psychophysical properties of a new F-speed intraoral film.

OBJECTIVES: To compare the psychophysical properties of the new Kodak InSight F-speed intraoral dental film with those for the E-speed Ektaspeed Plus film by means of the perceptibility curve (PC) test. METHODS: A specially designed test object was used. The test object was made of aluminium and was 10 mm thick. It contained ten holes, contrast details, with the same diameter of 1.5 mm but with different depths. The depths ranged from 0.03 mm to 0.30 mm in steps of 0.03 mm. The holes were placed randomly within a square area with a total of 16 possible positions. Radiographs of the test object were obtained over the full exposure ranges of the two films. A Combex DX-907 dental X-ray unit was used operating at 10 mA and two tube potentials, 70 kVp and 90 kVp. The focus-to-object distance was 50 cm. Ten observers evaluated the radiographs under uniform artificial lighting using a view box and stated the number of perceptible representations of contrast details. In order to construct perceptibility curves, absolute values of the reciprocal of the minimum perceptible logarithmic exposure differences, 1/(DeltalogE)min, were plotted as functions of the logarithm of exposures, logE, registered by the tested films. Comparisons between the two films were made separately for the two tube potentials, 70 kVp and 90 kVp. RESULTS: The results are presented graphically. PCs for the InSight film had higher peaks than those for the Ektaspeed Plus film. This indicates that the viewers were able to perceive smaller exposure differences in the former compared with the latter. PCs for the InSight film were shifted towards the left along the exposure axis relative to the PCs for the Ektaspeed Plus film indicating that the former film is more sensitive than the latter. The integrals of the PCs for InSight film were larger than those for Ektaspeed film indicating superior psychophysical properties of the InSight film. CONCLUSIONS: From the point of view of perception, the new InSight film has such psychophysical properties in comparison with Ektaspeed Plus film that it will be the more favourable of the two in clinical radiographic practice.

Absorptiometry, Photon↗
PubMed2001

Platinum-based and non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a randomised multicentre trial.

BACKGROUND: Docetaxel in combination with cisplatin or gemcitabine are active chemotherapy reigimes against non-small-cell lung cancer. We compared the efficacy and safety of a combination of cisplatin and docetaxel (group 1) with that of gemcitabine and docetaxel (group 2) in the treatment of advanced non-small-cell lung cancer in a prospective, randomised, multicentre trial. METHODS: Patients with stage IIIB or IV lung cancer who had not had prior chemotherapy were allocated either to group 1 and treated with docetaxel (100 mg/m(2), day 1) and cisplatin (80 mg/m(2), day 2) or to group 2 and treated with gemcitabine (1100 mg/m(2), days 1 and 8) and docetaxel (100 mg/m(2), day 8). All patients received recombinant human granulocyte colony-stimulating factor (150 mg/m(2)). All patients received recombinant human granulocyte colony-stimulating factor (150 mg/m(2)) had appropriate standard premedication. Response and toxicity were assessed using WHO criteria. Analysis was by intention to treat. FINDINGS: 441 patients were randomly assigned to receive docetaxel/cisplatin (group 1, n=219) or gemcitabine/docetaxel (group 2, n=222). 14 patients in group 1 and 21 patients in group 2 were not evaluable. Objective response rates were similar in the two groups: group 1, 32.4% (95% CI 26.2-38.6%; 1.4% complete response and 31% partial response); group 2, 30.2% (24.5-36.2%; 0.9% complete response and 29.3% partial response). The two groups did not differ in median duration of response, time to tumour progression, overall survival, or 1 year or 2 year survival rates. INTERPRETATION: Both drug combinations had comparable activity in patients with advanced cancer who had not previously had chemotherapy; however, gemcitabine and docetaxel had the most favourable toxicity profile.

Aged↗
PubMed2001

Use of an automated on-line SPE-HPLC method to monitor caffeine and selected aniline and phenol compounds in aquatic systems of Macedonia-Thrace, Greece.

Caffeine and selected aniline and phenol compounds have been monitored in the river, lake, and ground water of Northern Greece (Macedonia-Thrace) from September 1999 to December 2000 by means of a fully automated on-line SPE-HPLC method. Among the target aniline and phenol compounds the most abundant was 2,6-di-tert-butyl-4-methylphenol, which was found to be present in both surface and ground water samples. Caffeine was also very frequently present in river and ground water, although its presence in lake water was rare. Caffeine and 2,6-di-tert-butyl-4-methylphenol were also monitored by off-line SPE of water samples and GC-ion-trap MS analysis of extracts.

Aniline Compounds↗
PubMed2001

Mild or moderate chronic obstructive pulmonary disease risk in elective coronary artery bypass grafting surgery.

A history of chronic obstructive pulmonary disease (COPD) is considered a risk factor in patients undergoing coronary artery bypass grafting (CABG) surgery. The objective of this study was to examine the impact of history of mild or moderate COPD on outcome in patients undergoing elective CABG surgery. In this prospective, case-controlled study, we compared two groups of adult patients undergoing elective CABG surgery. In this prospective, case-controlled study, we compared two groups of adult patients undergoing elective CABG surgery. There were no statistically significant differences regarding early postoperative complications between the groups (p > 0.05). The median duration of mechanical ventilation and ICU length of stay were 0.4 and 1 days, respectively, in the two groups. The mean (+/- SD) hospital stay was 7.8 +/- 1.6 days in the COPD group and 7.5 +/- 1.3 days in the control group (p = 0.1). The mortality rate was found 1.4% in COPD patients and 0.7% in the control group (p = 0.5). We concluded that patients with a history of mild or moderate COPD undergoing elective CABG had morbidity and mortality rates comparable with those of controls (p > 0.05).

Adult↗
PubMed2001

Docetaxel in combination with gemcitabine plus rhG-CSF support as second-line treatment in non-small cell lung cancer. A multicenter phase II study.

BACKGROUND: Docetaxel in combination with gemcitabine is an active front-line chemotherapy regimen against non-small cell lung cancer (NSCLC) with acceptable toxicity. A multicenter phase II study was conducted in order to determine the toxicity and efficacy of this combination, as salvage treatment in patients progressing after a cisplatin-based front line regimens. PATIENTS AND METHODS: Thirty-two patients with histologically confirmed, bidimensionally measurable NSCLC, who failed prior cisplatin-based chemotherapy were enrolled. The patients' median age was 62.5 years, 29 (91%) were male, 23 (72%) had disease stage IV, and 22 (69%) had a performance status (WHO) 0-1. Gemcitabine (900 mg/m(2)) was administered on days 1 and 8 and docetaxel (100 mg/m(2)) on day 8, after appropriate premedication. rhG-CSF (150 microg/m(2)) was given prophylactically from day 9 to 15. Treatment was repeated on an outpatient basis every three weeks. RESULTS: A total of 127 chemotherapy cycles were administered. In an intention-to-treat analysis five patients (15.6%; 95% CI: 3.04-28.21%) achieved a partial response, 11 (34.4%) stable disease, and 16 (50%) progressive disease. The median duration of response was 9 months, the median TTP 7 months, and the overall median survival 6.5 months; the overall 1-year survival probability was 27.6%. Grade 3/4 neutropenia was observed in five (15.6%) patients and in two of them associated with fever. Grade 3 anemia and thrombocytopenia occurred in three (9%) and two (6.5%) patients, respectively. Non-hematologic toxicity was very mild with only one episode of grade 4 diarrhea and mucositis, respectively; two (6%) patients complained for grade 3 asthenia. CONCLUSION: The combination of gemcitabine and docetaxel with prophylactic use of rhG-CSF is a safe and well-tolerated regimen for the treatment of patients with advanced NSCLC, who failed front-line treatment with cisplatin-based regimens.

Adult↗
PubMed2001

Second-line treatment with vinorelbine and carboplatin in patients with advanced non-small cell lung cancer. A multicenter phase II study.

OBJECTIVE: A phase II study was conducted to evaluate the efficacy and toxicity of vinorelbine-carboplatin (VNB-C) combination as a salvage treatment in patients with advanced non-small cell lung cancer (NSCLC) progressing after or failing previous non-platinum, taxane-based treatment. PATIENTS AND METHODS: Thirty-seven patients with cytologically or histologically confirmed NSCLC were enrolled. VNB 30 mg/m(2) was administered on days 1 and 8 and C 300 mg/m(2) on day 1 every 28 days. G-CSF (5 microg/kg per day s.c.) was used prophylactically on days 10-15 in case of grade 3-4 neutropenia or febrile neutropenia after the first cycle. RESULTS: Twenty-nine patients were evaluable for response and all were evaluable for toxicity. In an intention-to-treat analysis, two (5%) complete and four (11%) partial responses were documented for an overall response rate of 16% (95% CI, 4.49-28.84%). Eleven (30%) patients experienced disease stabilisation and 20 (54%) disease progression. The median duration of response was 7.5 months, the median TTP was 9 months, and the median survival was 8.5 months. Patients with objective remission and stable disease had a statistically significant survival benefit over patients with disease progression. Grade 3 and 4 neutropenia occurred in three (8%) and ten (27%) patients, respectively, and six cases (16%) were complicated with fever. Grade 4 thrombocytopenia was documented in one (3%) patient. Non-hematological toxicity was mild, with grade 2 and 3 asthenia reported in 18 (48%) patients. No treatment-related deaths occurred. CONCLUSION: VNB-C combination is well tolerated and retains a notable degree of activity in NSCLC patients progressing after previous non-platinum, taxane-based treatment. Moreover, it confers tumour growth control in a significant proportion of patients, and this seems to be associated with a survival benefit for them.

Adult↗
PubMed2001

Comparison of docetaxel/cisplatin to docetaxel/gemcitabine as first-line treatment of advanced non-small cell lung cancer: early results of a randomized trial.

The study compares docetaxel plus cisplatin (DC) and docetaxel plus gemcitabine (DG) regimens for the treatment of advanced non-small cell lung cancer (NSCLC). Patients were randomized to receive either the DC or the DG combination. They were stratified according to age, performance status (PS) and stage of disease. Three hundred seventeen patients entered the study. Of them, 162 received the DC regimen and 155 the DG regimen. There were no differences in the patients' characteristics between the two study arms. Preliminary analysis included 132 evaluable patients in the DC arm and 114 in the DG arm. Three complete responses (CR) (2.3%) and 39 partial responses (PR) (30%) were documented in the DC arm (response rate (RR) 32.3%; 95% CI 23.87-39.76%), whereas 1 CR (0.9%) and 38 PR (33%) were documented in the DG arm (RR: 33.9%; 95% CI 25.5-42.92%). No differences in the RR, response duration, time to tumor progression, overall survival and 1-year survival were observed between the two groups. Regarding toxicity, there were no significant differences in grade 3-4 anaemia and thrombocytopenia between the two arms. However, grade 3-4 neutropenia occurred in 40 patients (33%) treated with the DC regimen and in 31 patients (22%) treated with the DG regimen (P=0.01). Twenty-four (16%) patients in the DC arm and 20 (14%) in the DG arm developed febrile neutropenia. There was one death due to sepsis in each arm. Non-haematological toxicity was mild and equal in the two arms, with the exception of grade 3-4 nausea and diarrhoea, which were more frequent in the DC arm. In conclusion, preliminary results showed that the DG regimen was as effective as the DC regimen. The toxicity profile of the DG combination was relatively milder. Hence, cisplatin cannot be considered longer as a mandatory component of chemotherapy against NSCLC.

Adult↗
PubMed2001

A multicenter randomized clinical trial comparing paclitaxel-cisplatin-etoposide versus cisplatin-etoposide as first-line treatment in patients with small-cell lung cancer.

BACKGROUND: Previous phase I-II studies have shown that the combination of paclitaxel-cisplatin-etoposide (TEP) is very active and well tolerated in patients with small-cell lung cancer (SCLC). In order to compare the TEP combination to cisplatin etoposide (EP) regimen as front-line treatment in patients with SCLC, we conducted a randomised multicenter study. PATIENTS AND METHODS: One hundred thirty-three chemotherapy-naïve patients with histologically proven limited or extensive stage SCLC were randomised to receive either paclitaxel 175 mg/m2 i.v. three-hour infusion on day 1 and cisplatin 80 mg/m2 i.v. on day 2 and etoposide 80 mg/m2 i.v. on days 2-4 with G-CSF support (5 mcg/kg s.c. days 5-15) or cisplatin 80 mg/m2 i.v. on day 1 and etoposide 120 mg/m2 i.v. on days 1-3 in cycles every twenty-eight days. RESULTS: Due to excessive toxicity and mortality observed in the TEP arm, an early interim analysis was performed and the study was closed. Sixty-two patients received two hundred sixty-one cycles of TEP and seventy-one patients three hundred twenty-three cycles of EP The two patient groups were well balanced for age, sex, performance status, stage of disease and the presence of abnormal LDH at diagnosis. In an intention-to-treat overall analysis both regimens were equally active with a complete and partial response rate of 50% (95% confidence interval (CI): 37.5%-62.4%) for TEP and 48% (95%) CI: 36.2%-59.5%) for EP (P = 0.8). The median time to disease progression was 11 months for TEP and 9 months for EP (P = 0.02). The duration of response, one-year survival and overall survival were similar in the two arms. Similarly, in an intention-to-treat subgroup analysis of patients with limited or extensive stage disease, there was no difference in the activity between the two regimens except of a longer median time to disease progression in the extensive stage in favour of the TEP regimen, eight versus six months (P = 0.04). However, there were eight toxic deaths in the TEP arm versus none in the EP arm (P = 0.001). Moreover, the TEP regimen was associated with more severe toxicity than the EP regimen in terms of grade 4 neutropenia (P = 0.04), grade 3-4 thrombocytopenia (P = 0.02), febrile neutropenia (P = 0.08), grade 3-4 diarrhea (P = 0.01), grade 3-4 asthenia (P = 0.05) and grade 3 neurotoxicity (P = 0.06). CONCLUSIONS: In this early terminated study, the TEP regimen was significantly more toxic than the EP regimen. The TEP regimen is associated with significant toxicity and mortality, and should not be used outside of a protocol setting. For future investigations, dose and schedule modifications are necessary to reduce toxicity.

Adult↗
PubMed2001

Vinorelbine-based regimens as salvage treatment in patients with advanced non-small cell lung cancer: two parallel multicenter phase II trials.

UNLABELLED: Two parallel phase II trials were conducted in order to evaluate the efficacy and toxicity of vinorelbine-ifosfamide (VNB-IFX) and vinorelbine-carboplatin (VNB-C) combinations as salvage treatment in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients failing platinum-based front-line chemotherapy were enrolled in the VNB-IFX trial while patients failing non-platinum-containing chemotherapy were treated with VNB-C. Twenty-nine patients were treated with VNB-IFX [median age: 59 years; performance status, PS (WHO) 0--1: 72% and disease stage IV: 79%] and 37 with VNB-C [median age: 61 years; PS (WHO) 0--1: 51% and stage IV: 84%]. Patients received vinorelbine 25 mg/m(2) i.v. on days 1 and 8 and ifosfamide 1.6 g/m(2) i.v. on days 8--10 with uroprotective mesna, in cycles of 28 days. G-CSF (5 microg/kg/day s.c.) was administered prophylactically on days 11--16 or until hematological recovery. The VNB-C regimen consisted of carboplatin 300 mg/m(2) on day 1 and vinorelbine 30 mg/m(2) on days 1 and 8 every 28 days. RESULTS: Twenty-six patients were evaluable for response in the VNB-IFX trial and 29 in the VNB-C. Overall response rates (intent-to-treat analysis) were 3% (1 patient; duration of response: 3 months) for the VNB-IFX and 16% (median duration of response: 7.5 months) for the VNB-C combination. The median time to progression and survival for patients receiving VNB-IFX were 4.5 and 6 months (1-year survival: 19%), respectively; the corresponding values for VNB-C were 9.0 and 8.5 months (1-year survival: 38%). The median survival of patients achieving stable disease was 10 (VNB-IFX) and 14.5 (VNB-C) months. Grade 3--4 neutropenia occurred in 4 (13%) of the patients treated with VNB-IFX; all cases were complicated with fever. Grade 3--4 neutropenia was documented in 13 (35%) patients in the VNB-C trial; 6 (16%) developed neutropenic fever. There were no treatment-related deaths. Non-hematologic toxicity for the VNB-IFX and VNB-C regimens was mild with grade 2--3 peripheral neurotoxicity occurring in 3 (10%) and 7 (19%) patients, and grade 2--3 asthenia in 11 (38%) and 18 (48%) patients, respectively. CONCLUSION: Both combinations were associated with a tolerable toxicity profile. VNB-C demonstrated notable activity in patients previously treated with a taxane-based regimen, whilst VNB-IFX failed to produce a significant response rate in patients treated with platinum-containing chemotherapy. Stabilization of disease was associated with a favorable survival in both studies.

Adolescent↗
PubMed1999

Docetaxel and granulocyte colony-stimulating factor in patients with advanced non-small-cell lung cancer previously treated with platinum-based chemotherapy: a multicenter phase II trial.

PURPOSE: To investigate the activity of docetaxel and granulocyte colony-stimulating factor support (G-CSF) in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with cisplatin. PATIENTS AND METHODS: A total of 60 patients with locoregional and metastatic NSCLC who had relapsed or progressed after first-line treatment with cisplatin-based regimens were enrolled into the trial. Docetaxel at 100 mg/m2 was given as a 1-h infusion with G-CSF (rhG-CSF given s.c. at 150 microg/m2) support from day 2 to day 8 every 3 weeks; all patients received premedication with corticosteroids. RESULTS: In all, 1 (1.6%) and 14 (23.3%) patients achieved a complete response (CR) and a partial response (PR), respectively, for an overall response rate of 25% (95% CI 14.0-35.9%); stable disease (SD) and progressive disease (PD) were documented in 18 (30%) and 27 (45%) patients, respectively. The median duration of response was 20 weeks and the median time to tumor progression was 28 weeks. The median overall survival was 32 weeks and the 1-year survival rate was 23%. A total of 263 courses were given at a median of 3 cycles/patient. Grade 3 and 4 neutropenia occurred in 11 (18%) and 14 (23%) patients, respectively, with 18 (30%) patients requiring hospitalization for neutropenic fever; 1 patient died of sepsis. Grade 2 peripheral neuropathy occurred in 9 patients (15%) and grade 3 asthenia, in 4 (7%). Other toxicities were mild. CONCLUSIONS: Docetaxel has considerable single-agent activity in patients with NSCLC who have relapsed or progressed after first-line chemotherapy with cisplatin-based regimens.

Adult↗
PubMed1999

Formoterol and beclomethasone versus higher dose beclomethasone as maintenance therapy in adult asthma.

A total of 132 adult asthmatics who were symptomatic on 500 microg x day(-1) inhaled beclomethasone dipropionate (BDP) were studied in an open-label randomized, parallel group, 12 week, clinical trial. The addition of 12 microg formoterol fumarate solution aerosol (pressurized metered dose inhaler) b.i.d. to BDP at a dose of 500 microg x day(-1) was compared with a higher dose of 1,000 microg x day(-1) BDP. Mean morning premedication peak expiratory flow rate (PEF) during the final week of treatment (primary end-point) increased in both groups compared to baseline. The estimated treatment difference of 20.4 L x min(-1) (95% confidence interval 3.2-37.6) after 12 weeks of treatment was statistically significant (p<0.05) in favour of the formoterol/BDP group. The overall mean morning premedication PEF for the entire treatment period was higher in the formotero/BDP group (p=0.002). The overall number of puffs of rescue medication and asthma symptom scores were less in the formotero/BDP group (p<0.01). Safety and tolerability evaluations were satisfactory in both groups. In conclusion, the results suggest that the addition of formoterol fumarate to the existing dose of an inhaled corticosteroid should be considered as an alternative to increasing the dose of inhaled corticosteroid in the inadequately controlled asthmatic.

Administration, Inhalation↗
PubMed1999

Front-line treatment of advanced non-small-cell lung cancer with docetaxel and gemcitabine: a multicenter phase II trial.

PURPOSE: To evaluate the tolerance and efficacy of the combination of docetaxel and gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-one chemotherapy-naive patients with NSCLC were treated with gemcitabine 900 mg/m2 intravenously on days 1 and 8 and docetaxel 100 mg/m2 intravenously on day 8 with granulocyte colony-stimulating factor (150 microg/m2, subcutaneously) support from day 9 to day 15. Treatment was repeated every 3 weeks. RESULTS: The patients' median age was 64 years. The World Health Organization performance status was 0 to 1 in 39 patients and 2 in 12 patients. Fifteen patients (29%) had stage IIIB disease, and 36 (71%) had stage IV; histology was mainly squamous cell carcinoma (59%). A partial response was achieved in 19 patients (37.5%; 95% confidence interval, 24% to 50%); stable disease and progressive disease were each observed in 16 patients (31.4%). The median duration of response and the time to tumor progression were 5 and 6 months, respectively. The median survival was 13 months, and the actuarial 1-year survival was 50.7%. Grade 4 anemia and thrombocytopenia were rare (2%). Four patients (8%) developed grade 3 or 4 neutropenia, and all were complicated with fever; there was no treatment-related death. Grade 3 or 4 diarrhea occurred in three patients (6%), grade 2 or 3 neurotoxicity in four patients (8%), grade 2 or 3 asthenia in 10 patients (20%), and grade 2 or 3 edema in 10 patients (20%). CONCLUSION: The combination of docetaxel/gemcitabine is well tolerated, can be used for outpatients, and is active for the treatment of advanced NSCLC. This treatment merits further comparison with other cisplatin- or carboplatin-based combinations.

Adult↗
PubMed1998

First-line treatment of advanced non-small-cell lung cancer with docetaxel and cisplatin: a multicenter phase II study.

PURPOSE: To evaluate the efficacy and safety of the docetaxel-cisplatin combination in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naïve patients with histologically confirmed, measurable stage IIIB or IV NSCLC, a World Health Organization (WHO) performance status of 0-2 and adequate bone marrow, renal, hepatic and cardiac function were eligible for the study. Patients received docetaxel (100 mg/m2) as an one-hour infusion on day 1 and cisplatin (80 mg/m2) as a 30-min infusion with appropriate hydration on day 2. Granulocyte colony-stimulating factor (G-CSF; 150 micrograms/m2, SC) was given on days 3 to 13. Treatment was repeated every three weeks. RESULTS: Fifty-three patients were enrolled (28 with stage IIIB and 25 with stage IV). One complete and 23 partial responses were observed (overall response rate (OR): 45%; 95% CI: 34.1%-61.8%). The response rate was 57% and 32% in patients with stages IIIB and IV disease (P = NS). The median time to progression was 36 weeks and the median survival 48 weeks; the one-year survival was 48%. Grade 3-4 neutropenia occurred in 23 patients, 15 of whom were hospitalized for neutropenic fever; two patients died of sepsis. Grade 2 neurotoxicity was observed in six patients and grade 3 in five patients; grade 3 fatigue occurred in seven patients, grade 3-4 mucositis in four patients and grade 3-4 diarrhea in six patients. Mild allergic reactions and oedema were observed in five and four patients, respectively. The median dose intensity was 30 mg/m2/week for docetaxel and 24 mg/m2/week for cisplatin, corresponding to 91% and 89% of the specified protocol doses, respectively. CONCLUSIONS: The docetaxel-cisplatin combination is an active regimen in advanced NSCLC, but hematologic toxicity remains high despite the prophylactic use of G-CSF.

Adult↗
PubMed1998

Salvage treatment with paclitaxel and gemcitabine for patients with non-small-cell lung cancer after cisplatin- or docetaxel-based chemotherapy: a multicenter phase II study.

BACKGROUND: To evaluate the tolerance and efficacy of the combination of paclitaxel and gemcitabine as salvage treatment in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-nine patients with measurable NSCLC (PS 0-1: 80%; stage IV: 84%) who progressed or failed first-line chemotherapy were enrolled. Prior chemotherapy was cisplatin-based with (n = 20) or without (n = 22) docetaxel and docetaxel-vinorelbine (n = 7). Patients received gemcitabine (900 mg/m2 i.v.; days 1 and 8) and paclitaxel (175 mg/m2; day 8) every three weeks: G-CSF (150 micrograms/m2/day s.c.; days 9-15) was given prophylactically to all patients. RESULTS: One (2%) complete and eight (16%) partial responses were achieved (overall response 18%; 95% CI: 4%-24%); 14 patients (29%) had stable disease and 26 (53%) progressive disease. Six responses were observed in 17 patients who responded to first-line chemotherapy. The median duration of response was seven months, the median TTP eight months and the median survival 11 months. The one-year survival rate was 37%. Grade 3-4 neutropenia occured in six (12%) patients, grade 2-3 neurotoxicity in 16 (32%) and grade 2-3 asthenia in 25 (51%). Other toxicities were mild. CONCLUSIONS: The paclitaxel-gemcitabine combination is a well-tolerated and relatively active salvage regimen in patients with NSCLC and it merits further investigation.

Adult↗
PubMed1997

Second-line treatment of advanced non-small cell lung cancer with paclitaxel and gemcitabine: a preliminary report on an active regimen.

A phase II study of combination paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)/gemcitabine was conducted in patients with non-small cell lung cancer (NSCLC) who had failed first-line docetaxel- or cisplatin-based chemotherapy. Eligibility criteria included histologically confirmed measurable stage IIIB or IV NSCLC and previous exposure to docetaxel- or cisplatin-based regimens, World Health Organization performance status between 0 and 2, adequate hematologic parameters, and adequate hepatic, renal, and cardiac function. Gemcitabine (900 mg/m2) was given on days 1 and 8 as a 30-minute infusion; paclitaxel (175 mg/m2) was administered on day 8 as a 3-hour infusion after appropriate premedication. Granulocyte colony-stimulating factor (150 microg/m2 subcutaneously) was given on days 9 to 15. Treatment was repeated every 3 weeks until patients experienced disease progression. From October 1995 to December 1996, 26 patients with advanced NSCLC were enrolled (three stage IIIB, 23 stage IV). All 26 patients were assessable for toxicity, and 24 were evaluable for response. Two complete (8%) and five partial (21%) responses were observed, for an overall response rate of 29% (95% confidence interval, 11% to 47%). The median duration of response was 2.5 months and the median survival was 8 months. A median of three courses per patient was administered, and the median interval between courses was 21 days. The median delivered dose was 579 mg/m2/wk gemcitabine and 54.5 mg/m2/wk paclitaxel, corresponding to a relative dose intensity of 0.97 and 0.96, respectively. Grade 3/4 neutropenia occurred in two patients (8%). Grade 3 conjunctivitis occurred in one (4%) patient and grade 2/3 neurotoxicity in eight (31%) patients. Grade 3/4 and grade 2 fatigue occurred in four (15%) and eight (31%) patients, respectively. Other toxicities were mild to moderate. These preliminary results suggest that the paclitaxel/gemcitabine combination is an active and well-tolerated salvage regimen in patients with NSCLC previously treated with docetaxel- or cisplatin-based chemotherapy. The paclitaxel/gemcitabine combination merits further evaluation as first-line treatment.

Adult↗
PubMed1997

Docetaxel (Taxotere) and vinorelbine in the treatment of non-small cell lung cancer.

The efficacy and safety of a combination of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) and vinorelbine were evaluated in two phase II studies including 46 and 39 chemotherapy-naive patients with non-small cell lung cancer, respectively. In the first study, vinorelbine 25 mg/m2 was given on day 1 and docetaxel 100 mg/m2 on day 2, with recombinant human granulocyte colony-stimulating factor support from day 5 until day 12, every 3 weeks. In the second study, docetaxel 75 mg/m2 was given on day 1 and vinorelbine 20 to 25 mg/m2 on days 1 and 5 in a 3-week schedule. Grade 3/4 neutropenia was the most severe toxicity, occurring in 46% to 85% of patients, while febrile neutropenia was observed in 25% to 41% of patients. Two treatment-related deaths occurred in each study. Patients with a poor performance status were at an increased risk of infection. The objective response rates were 36.6% and 27%, respectively (mean, 32%). In two subsequent studies, the efficacy and safety of a triple-drug combination of docetaxel, vinorelbine, and cisplatin was evaluated. In the first study, 14 patients were treated with vinorelbine 25 mg/m2 and cisplatin 80 mg/m2 on day 1 and docetaxel 100 mg/m2 and vinorelbine 20 mg/m2 on day 8, every 3 weeks. In the second study, 46 patients received docetaxel 100 mg/m2 on day 1, cisplatin 100 mg/m2 and vinorelbine 30 mg/m2 on day 21, and vinorelbine 30 mg/m2 on days 28 and 35, every 6 weeks. The main toxicity was also grade 3/4 neutropenia (57% and 80% of patients, respectively). Febrile neutropenia developed in 50% and 15% of the patients in the first and second study, respectively. The overall response rates were 33% and 39%, respectively. It is concluded that combination therapy with docetaxel/ vinorelbine or with docetaxel/vinorelbine/cisplatin has antitumor activity in the treatment of non-small cell lung cancer. Granulocytopenia and febrile neutropenia are the most severe toxicities that limit the usefulness of these regimens.

Adult↗
PubMed1996

Ciclazindol inhibits ATP-sensitive K+ channels and stimulates insulin secretion in CR1-G1 insulin-secreting cells.

Ciclazindol, an anorectic drug, was shown to inhibit ATP-sensitive K+ (K(ATP)) channel currents and stimulate insulin secretion from CRI-G1 insulin-secreting cells. In contrast, the structurally related anorectic agent mazindol and the amphetamine-based anorectic compounds diethylpropion, fenfluramine, and phentermine had no effect on K(ATP) channel activity in this cell line. Similarly, cicliazindol elicited insulin secretion from CRI-G1 cells, whereas mazindol had no secretagogue action. The mechanism by which ciclazindol acts to inhibit K(ATP) channel activity is different than that of the sulfonylureas as ciclazindol is effective after procedures that decouple the sulfonylurea receptor from the K(ATP) channel. In agreement with this finding, ciclazindol failed to displace [3H]glibenclamide from CRI-G1 microsomal membranes. Further experiments demonstrated that ciclazindol has no significant effect on voltage-activated currents in this cell line.

Adenosine Triphosphate↗