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Topotecan is a semisynthetic derivative of camptothecin that specifically targets topoisomerase I. It has well-established antineoplastic properties and has been successfully combined with other antineoplastic agents with activity dependent on DNA disruption, such as cisplatin and etoposide. Topotecan is indicated for the treatment of small cell lung cancer (SCLC) sensitive disease after failure of first-line chemotherapy and metastatic ovarian carcinoma after failure of initial or subsequent chemotherapy. Since the approval of topotecan for the second-line treatment of SCLC, studies have been conducted in the first-line setting. Recent studies demonstrate the utility of i.v. topotecan in combination with cisplatin for untreated SCLC. Further, an oral formulation of topotecan is currently under investigation and may provide added convenience for patients. Oral topotecan has been studied in the first- and second-line settings for both SCLC and non-small cell lung cancer (NSCLC). Three recent phase III trials have demonstrated the activity of oral topotecan. In the first study of chemotherapy-naïve patients with extensive-disease SCLC, oral topotecan plus cisplatin provided efficacy and safety similar to those of etoposide plus cisplatin. In a second study of patients with relapsed SCLC, treatment with oral topotecan showed a statistically significant and clinically meaningful longer overall survival time and improvement in dyspnea and quality of life compared with best supportive care alone in all prognostic groups. Finally, in previously treated patients with NSCLC, single-agent oral topotecan was shown to be noninferior in 1-year survival rate relative to the current standard of i.v. docetaxel. In future studies, oral topotecan will represent a good candidate for combination therapy with other i.v. or oral chemotherapy agents, monoclonal antibodies, and small molecule tyrosine kinase inhibitors.

The ternary compound Co(6)Al(11-x)Si(6+x) (epsilon phase) was prepared from the elements by arc melting and subsequent heat treatment, and then characterized by single-crystal X-ray diffraction (XRD), electron-probe microanalysis (EPMA), differential thermal analysis (DTA) and transmission electron microscopy (TEM). This new structure type consists of planar layers with the composition [Co(6)Al(10)Si(4)], which are penetrated by perpendicular (Si-Si-Al) chains. While the layers are well described by an orthorhombic model (space group Pnma, Pearson symbol oP46), the chains exhibit doubled periodicity, thus yielding a superstructure. Two alternative ordering models (space group Cmc2(1), oC184, and space group P2(1)/c, mP92) are presented and discussed based on XRD and TEM results. The (Si-Si-Al) chains are located in pentagonal antiprismatic ;channels' which reveal the similarity of the Co(6)Al(11-x)Si(6+x) structure to Al-rich transition-metal compounds such as Co(4)Al(13), Co(2)Al(5), Fe(4)Al(13), V(7)Al(45), V(4)Al(23) and VAl(10), which also exhibit this type of pentagonal ;channels' in their crystal structures. The phase shows only a very small homogeneity range.

Background: C.E.R.A. (Continuous Erythropoietin Receptor Activator) is an innovative agent with unique erythropoietin receptor activity and prolonged half-life. This study evaluated C.E.R.A. once weekly (QW) or once every 3 weeks (Q3W) in patients with anemia and advanced non-small cell lung cancer (NSCLC) receiving chemotherapy., Methods: In this Phase II, randomized, open-label, multicenter, dose-finding study, patients (n = 218) with Stage IIIB or IV NSCLC and hemoglobin (Hb) or= 2 g/dL or achievement of Hb >or= 12 g/dL with no blood transfusion in the previous 28 days determined in two consecutive measurements within a 10-day interval) was also measured., Results: Dose-dependent Hb increases were observed, although the magnitude of increase was moderate. Hematopoietic response rate was also dose dependent, achieved by 51% and 62% of patients in the 4.2 and 6.3 microg/kg Q3W groups, and 63% of the 2.1 mug/kg QW group. In the Q3W group, the proportion of early responders (defined as >or= 1 g/dL increase in Hb from baseline during the first 22 days) increased with increasing C.E.R.A. dose, reaching 41% with the highest dose. In the 6.3 microg/kg Q3W group, 15% of patients received blood transfusion. There was an inclination for higher mean Hb increases and lower transfusion use in the Q3W groups than in the QW groups. C.E.R.A. was generally well tolerated., Conclusion: C.E.R.A. administered QW or Q3W showed clinical activity and safety in patients with NSCLC. There were dose-dependent increases in Hb responses. C.E.R.A. appeared to be more effective when the same dose over time was given Q3W than QW, with a suggestion that C.E.R.A. 6.3 microg/kg Q3W provided best efficacy in this study. However, further dose-finding studies using higher doses are required to determine the optimal C.E.R.A. dose regimen in cancer patients receiving chemotherapy.

Small-cell lung cancer is characterized by an aggressive clinical course with high tendency for early dissemination. At presentation, patients are usually symptomatic and with hilar or mediastinal mass at radiography. Staging should be focused on identifying any evidence of distant spread. Chemotherapy including cisplatin and etoposide is a cornerstone of treatment for all patients. Limited-stage disease should be managed by chemotherapy combined with concurrent chest irradiation. All patients who achieve complete response should be considered for elective cranial irradiation. Surgical treatment may be used in highly selected patients with TNM stage I disease, and surgery should always be combined with chemotherapy. Extensive-stage disease should be managed by multi-agent chemotherapy alone. Long-term survivors should undergo careful monitoring for development of a second primary tumour.

The challenges associated with synthesizing expanded semiconductor frameworks with cage-like crystal structures continue to be of interest. Filled low-density germanium and silicon framework structures have distinct properties that address important issues in thermoelectric phonon glass-electron crystals, superconductivity and the possibility of Kondo insulators. Interest in empty framework structures of silicon and germanium is motivated by their predicted wide optical bandgaps of the same magnitude as quantum dots and porous silicon, making them and their alloys promising materials for silicon-based optoelectronic devices. Although almost-empty Na(1-x)Si136 has already been reported, the synthesis of guest-free germanium clathrate has so far been unsuccessful. Here we report the high-yield synthesis and characteristics of germanium with the empty clathrate-II structure through the oxidation of Zintl anions in ionic liquids under ambient conditions. The approach demonstrates the potential of ionic liquids as media for the reactions of polar intermetallic phases.

Background: Patients with advanced non-small cell lung cancer (NSCLC) do not have curative treatment options; therefore, treatments should prolong survival and improve quality of life (QoL). We compared the effect on QoL of two docetaxel-platinum regimens with vinorelbine-cisplatin., Methods: QoL was assessed by the Lung Cancer Symptom Scale (LCSS) and the general EuroQol five-dimensional questionnaire (EQ-5D) in 926 chemotherapy-naïve patients with stages IIIB to IV NSCLC. Patients were randomly assigned to receive: docetaxel 75 mg/m2 plus cisplatin 75 mg/m2, every 3 weeks (DC); docetaxel 75 mg/m2 and carboplatin 6 mg/ml min, every 3 weeks (DCb); or vinorelbine 25 mg/m2/week plus cisplatin 100 mg/m2, every 4 weeks (VC)., Results: Overall, patients treated with either docetaxel-containing regimen had better QoL than VC-treated patients (LCSS global item "QoL today": P=0.064 for DC and P=0.016 for DCb versus VC; EQ-5D global item "health state today": P=0.016 for DC and P<0.001 for DCb versus VC). DC-treated patients experienced improved pain relief compared with VC (P=0.033), whereas pain relief with DCb and VC was similar. Patients treated with either docetaxel regimen had more favorable changes in performance status (P=0.065 for DC and P<0.001 for DCb versus VC) and mean weight loss (0.06 kg, gain of 0.08 kg, and 2.27 kg for DC, DCb, and VC, respectively; P<0.001 for both DC versus VC and DCb versus VC)., Conclusion: The TAX 326 study shows that docetaxel-platinum regimens relieve symptoms and improve QoL in patients with advanced NSCLC. DCb and DC were superior to VC in all QoL outcomes assessed except for the difference between DC and VC in LCSS "QoL today", which was not significant.

Purpose: This open-label, randomized, multicenter, phase III study compared oral topotecan versus intravenous (IV) docetaxel in patients with previously treated non-small-cell lung cancer (NSCLC)., Patients and Methods: Patients with stage III or IV NSCLC, performance status < or = 2, who had received only one prior chemotherapy regimen, were randomly assigned to treatment with oral topotecan 2.3 mg/m2/d on days 1 to 5 or IV docetaxel 75 mg/m2 day 1 every 21 days., Results: A total of 829 patients were randomly assigned. In intent-to-treat analysis, 1-year survival rates were 25.1% with topotecan and 28.7% with docetaxel. The difference of -3.6% (95% CI, -9.59% to 2.48%) met the predefined criteria for noninferiority of topotecan relative to docetaxel because the lower limit of the 95% CI was above -10%. Median survival was 27.9 weeks with topotecan and 30.7 weeks with docetaxel. Although not statistically significant (log-rank P = .057), the higher survival rate with docetaxel was maintained across the entire treatment period. The median time to progression was 11.3 weeks with topotecan versus 13.1 weeks with docetaxel (log-rank P = .02). The overall response rate was 5% in each group. Grade 3/4 neutropenia occurred more frequently with docetaxel (60% v 50%). Grade 3/4 anemia and thrombocytopenia occurred more frequently with topotecan (26% v 10% and 26% v 7%, respectively)., Conclusion: Oral topotecan provides activity in the treatment of relapsed, locally advanced, unresectable NSCLC. Both regimens were well tolerated with differing safety profiles. Topotecan may provide an option for patients who desire an orally available treatment after relapse.

Purpose: The primary objective of this randomized phase III study was to show significant difference in median time to progression (TTP) in patients with advanced NSCLC treated with single-agent gemcitabine maintenance therapy versus best supportive care following gemcitabine plus cisplatin initial first-line therapy., Patients and Methods: Chemonaive patients with stage IIIB/IV NSCLC received gemcitabine 1,250 mg/m(2) (days 1 and 8) plus cisplatin 80 mg/m(2) (day 1) every 21 days. Patients achieving objective response or disease stabilization following initial gemcitabine plus cisplatin therapy were randomized (2:1 fashion) to receive maintenance gemcitabine (1,250 mg/m(2) on days 1 and 8 every 21 days) plus best supportive care (GEM arm), or best supportive care only (BSC arm)., Results: Between November 1999 and November 2002, we enrolled 352 patients (median age: 57 years; stage IV disease: 74%; Karnofsky performance status (KPS) >80: 41%). Following initial therapy, 206 patients were randomized and treated with gemcitabine (138) or best supportive care (68). TTP throughout the study period was 6.6 and 5 months for GEM and BSC arms, respectively, while values for the maintenance period were 3.6 and 2.0 months (for p < 0.001 for both). Median overall survival (OS) throughout study was 13.0 months for GEM and 11.0 months for BSC arms (p = 0.195). The toxicity profile was mild, with neutropenia being most common grade 3/4 toxicities., Conclusion: Maintenance therapy with gemcitabine, following initial therapy with gemcitabine plus cisplatin, was feasible, and produced significantly longer TTP compared to best supportive care alone. Further studies are warranted to establish the place of maintenance chemotherapy in patients with advanced NSCLC.

Lung cancer is the main cause of cancer deaths around the world. At 12% of all cancer incidents, lung cancer is the most frequent single cause of death, of both males and females. In 2002 among male population in Poland, lung cancer was the second, following heart failure, cause of death, ranging at 8% of deaths in general. It was third cause of death among females ranging at 2.3% in general. Considering cancer deaths in 2002 in Wielkopolska, lung cancer was most frequent cause of death among males (30%) and second frequent among females (10.4%). The last 25 years the number of deaths decreased among younger generation of males (first in the age group 20-44, later in the middle age group) and this phenomenon has dominated the general picture of cancer among males. However the increase of mortality rates in the older age group might be still observed. The constant increase of mortality has been observed among females, especially in the middle age group (45-64). It should be highlighted that the level of mortality has been equalled in both genders in the youngest age group (20-44), which means suddenly growing risk among young population of women in Wielkopolska.

Tobacco smoking is the cause of 30% of deaths among men and 7% among women in Poland. Such data call for detailed analysis. Previous researche on frequency of smoking was focused on the analysis of all-Poland population. The following research was aimed at the description of tobacco smoke exposure in population of Wielkopolska in the late 1990s. Smoking habits in Wielkopolska is more prevalent in men than women and this prevalence is sustained in time. The smoking habit among men decreased during the last 5 years of the 20th century, however it is higher among women (1996: 47.5% men and 27.7% women, 2000: 41.9% men and 29.9% women). The positive fact is the raising percentage of both men and women who give up smoking. The results show that the level of education is a strong predictor of smoking among men: the higher education, the lower percentage of smokers. This relation does not seem to be that obvious in women. The place of living is another factor influencing the percentage of smoking people--the prevalence is lower in cities, especially among men. Presented results show that there are similar changes in smoking habits in Wielkopolska as observed nationwide. The difference concerns slightly lower percentage of tobacco users among men and higher among women in Wielkopolska than in nationwide population. Distribution of involvement of subsequent categories (i.e. gender, age, education and place of living) follow the pattern observed in general population. The knowledge about smoking habits in Wielkopolska forms the ground for actions within the frame of evidence based medicine, systematic assessment of frequency of smoking would allow taking up appropriate preventive actions such as youth education and therapeutic (treatment of smoking habit) actions.

The aim of the study was to assess the early and late results of extended pneumonectomies in lung cancer patients with T3 and T4 disease. Between Jan. 1995 and Dec. 1999--445 pneumonectomies were performed in patients with lung cancer. In 37 patients without preoperative N2 involvement a standard pneumonectomy was extended to include the following additional resections: chest wall (10), pericardium (9), diaphragm (5), VCS (3), descending aorta (2), left atrium (5), esophagus (1) and tracheal bifurcation (2). The effect of various factors on general mortality and morbidity was analyzed with the use of binary logistic regression. There were two early postoperative deaths (6.8%). Major complications occurred in 10 patients (29%). Overall survival rates at 1, 2, and 3 years were 43, 30 and 24%, respectively. The survival rates for the subgroup with chest involvement only were 50, 42 and 30%, respectively. Eight patients survived beyond the 36 month follow-up. The only factor significantly affecting mortality was incomplete resection, as revealed by postoperative microscopic examination (R1, p<0.05). Extended operations are justified by a relatively low mortality rate and low number of severe postoperative complications, specially in patients with chest wall involvement only. The result of this treatment predominantly depends upon the completeness of the resection.

The purpose of this study was to determine the benefit of high dose rate endotracheal brachytherapy as an exclusive palliative treatment of obstructive tracheal cancer. Thirty-five patients with advanced tracheal carcinoma were treated between May 1999 and March 2001 in Greatpoland Cancer Center. They were qualified for brachytherapy due to life-threatening situations. Fourteen patients were irradiated using three fractions 7.5 Gy each one every week, six patients received three fractions 10 Gy each one every week and fifteen patients received one fraction of 10 Gy. Survival time was compared with chosen clinical factors (age, sex, Karnofsky status, tumor location, lymph nodes involvement and percent of obturation) and prescribed dose. The median survival (Kaplan-Meier) for all patients was 6.6 months. Patients with an endoscopically controlled complete remission 4 weeks after the treatment had a significantly better survival in comparison to patients with a partial remission or no change of tumor size (p=0.0003). Univariate analysis revealed significant difference between patients with Karnofsky score equal with 60 or lower (28/35, 80%) and higher than 60 (7/35, 20.0%) (p=0.005). Difference between the grade of tumor obturation (more than 60% of tracheal lumen (27/35, 77.1%), 60% or lower (8/35, 22.9%) was found in univariate analysis (p=0.04). In multivariate analysis statistically important prognostic factor for survival was Karnofsky score (p=0.04). Statistical analysis revealed no differences in survival according to sex and age (p=0.43 for age, p=0.19 for sex), tumor localization (p=0.13), lymph node involvement (p=0.48) or fractionation scheme (p=0.62). Exclusive HDR brachytherapy of advanced tracheal carcinoma was a safe palliative method of treatment and caused in many patients prolonged survival and improved quality of life. Most important prognostic factor for survival, confirmed in both univariate and multivariate analysis, was Karnofsky score.

Background: A phase II trial of alternating i.v. and oral vinorelbine in combination with cisplatin was designed to determine the response rate, safety profile, progression-free survival, overall survival and quality of life (QoL) in advanced non-small-cell lung cancer (NSCLC)., Patients and Methods: Fifty-six chemotherapy-naïve patients received cisplatin 100 mg/m(2) and i.v. vinorelbine 25 mg/m(2) on day 1, followed by oral vinorelbine 60 mg/m(2) on days 8, 15 and 22, every 28 days., Results: After an independent review, the response rate was 33% [95% confidence interval (CI) 20% to 46%]. Median progression-free and overall survival were 5.5 months (95% CI 3.7-6.4) and 8.9 months (95% CI 8.8-11.7), respectively. The most frequent hematological toxicities were neutropenia (grade 3-4 in 73% of patients) and anemia (grade 3-4 in 11% of patients). Grade 3-4 infections and non-hematological toxicities occurred occasionally. QoL for lung cancer related symptoms was stable or improved., Conclusions: The efficacy and safety of the alternating vinorelbine schedule (i.v. on day 1, oral on days 8, 15 and 22) in combination with cisplatin in advanced NSCLC are similar to those of the standard regimen using exclusively i.v. vinorelbine, whereas ease of administration and patient comfort may favor the novel approach.

Purpose: To investigate whether docetaxel plus platinum regimens improve survival and affect quality of life (QoL) in advanced non-small-cell lung cancer (NSCLC) compared with vinorelbine plus cisplatin as first-line chemotherapy., Patients and Methods: Patients (n = 1,218) with stage IIIB to IV NSCLC were randomly assigned to receive docetaxel 75 mg/m2 and cisplatin 75 mg/m2 every 3 weeks (DC); docetaxel 75 mg/m2 and carboplatin area under the curve of 6 mg/mL * min every 3 weeks (DCb); or vinorelbine 25 mg/m2/wk and cisplatin 100 mg/m2 every 4 weeks (VC)., Results: Patients treated with DC had a median survival of 11.3 v 10.1 months for VC-treated patients (P =.044; hazard ratio, 1.183 [97.2% confidence interval, 0.989 to 1.416]). The 2-year survival rate was 21% for DC-treated patients and 14% for VC-treated patients. Overall response rate was 31.6% for DC-treated patients v 24.5% for VC-treated patients (P =.029). Median survival (9.4 v 9.9 months [for VC]; P =.657; hazard ratio, 1.048 [97.2 confidence interval, 0.877 to 1.253]) and response (23.9%) with DCb were similar to those results for VC. Neutropenia, thrombocytopenia, infection, and febrile neutropenia were similar with all three regimens. Grade 3 to 4 anemia, nausea, and vomiting were more common (P <.01) with VC than with DC or DCb. Patients treated with either docetaxel regimen had consistently improved QoL compared with VC-treated patients, who experienced deterioration in QoL., Conclusion: DC resulted in a more favorable overall response and survival rate than VC. Both DC and DCb were better tolerated and provided patients with consistently improved QoL compared with VC. These findings demonstrate that a docetaxel plus platinum combination is an effective treatment option with a favorable therapeutic index for first-line treatment of advanced or metastatic NSCLC.

Purpose: To analyze treatment results of palliative HDR brachytherapy in patients with advanced lung cancer treated previously on another cancer. From May 1999 to May 2001 24 patients with diagnosis of lung cancer were treated with HDR brachytherapy in Greatpoland Cancer Center. All patients were treated for another cancer in the past. All patients became disqualified from surgical treatment and radical radiotherapy due to advance stage of diseases. High dose brachytherapy of 22.5 Gy counted in distances 1 cm from tube axis was used. Control group consisted of 56 lung cancer patients without past history of another malignancy treated with brachytherapy in the same period. Patients were observed during a period of 12 months in terms of local remission rates and survival time depends on chosen clinical factors. Median survival time in the first group of patients was 5.6 months and 8.9 months in the control group. Patients with the history of prior cancer lived shorter (log-rank test, p = 0.003). Significant correlation was observed between survival rate and remission rate achieved in 1th month after the end of treatment (log-rank test, p = 0.001)., Conclusions: 1. Past history of cancer decreases survival of patients with advanced lung cancer treated palliatively with HDR brachytherapy. 2. HDR brachytherapy of advanced lung cancer provides improvement of dyspnoea in most of patients. 3. The most important prognostic factor for survival was remission achieved within 1th month after the end of brachytherapy.

Unlabelled: Proliferating cell nuclear antigen (PCNA) is a DNA polymerase delta accessory protein, and is an indicator of the proliferative state of the cell. Nucleolar organizer regions (NORs) are loops of DNA that carry the ribosomal RNA (rRNA) genes and are markers of aggressiveness for certain tumors., Patients and Methods: This study tested the correlation between plasma cell morphology and PCNA and NOR expression in 50 multiple myeloma (MM) patients prior to therapy. 50 MM bone marrow trephine biopsies were studied using the monoclonal antibody PC-10 and the colloid silver nitrate method for identification of PCNA and AgNors, respectively., Results: PCNA positive cells ranged from 2% to 100%, higher PCNA expression was observed in patients with immature type of MM (mean 29.5%, SD = 5.5), the highest expression was seen in plasmablastic type MM (mean 60.5%, SD = 22.6). The AgNOR count was also higher in MM with plasmablasts in the bone marrow (p < 0.001). In addition, the localization of AgNOR changed according to the type of MM: in 84% of mature and intermediate MM NORs were present in the central nucleus whereas in immature and plasmablastic MM NORs were dispersed or near the membrane. Elevated PCNA expression and AgNOR counts was also seen in MM patients with hyperviscosity coma as well as in patients with renal failure., Conclusion: PCNA expression and AgNOR count in myeloma indicates the myeloma's proliferative activity and correlates positively with the cytomorphology of plasma cells and clinical outcome.

In patients with thrombocytosis normal to increased serum thrombopoietin (TPO) levels have been reported. The aim of this study was to investigate the relationship between serum TPO concentration, platelet number and plasma levels of fibrinogen in patients with reactive thrombocytosis (RT) due to lung cancer and in patients with essential (primary) thrombocythemia (ET). A total of 70 newly diagnosed patients with RT or ET (platelet counts >600 G/l) were studied: 45 with RT due to lung cancer (25 with non-small cell lung cancer, NSCLC and 20 with small cell lung cancer, SCLC), and 25 with ET. Twenty normal volunteers were used as controls. TPO was measured by immunoassay technique (ELISA). Mean serum TPO values in patients with RT due to lung cancer were statistically significantly higher than those in patients with ET or in controls. The highest platelet count was seen in patients with ET, and mean plasma fibrinogen levels were the highest in RT patients. In NSCLC patients mean serum TPO concentrations were higher (not statistically significant) than in SCLC, and a statistically significant relationship between TPO serum concentration and fibrinogen level was observed. No correlations between platelet counts and TPO serum concentrations were found. Our results indicate increased serum TPO levels in patients with thrombocytosis in lung cancer which may be related to the activity of neoplasms. In addition, it is postulated that the relatively low TPO values in patients with ET may result from a dysregulation of the feedback loop involved in platelet production.

The aim of this study was to assess prospectively the occurrence of p53 and p16 mutations (considered separately and together) in NSCLC in terms of their clinical and prognostic relevance. Study group included 87 patients who underwent pulmonary resection for cure. p53 and p16 mutations were found in 22 (25%) and 14 (16%) cases, respectively. In eight patients (9%) both mutations were present, and the tendency for their common occurrence was significant (p = 0.02). There was no relation between mutation and clinical characteristics. Median survival in the entire group was 17 months and the 3-year survival probability--41%. There was no correlation between the occurrence of any mutation (considered separately or together) and survival. These results indicate that p53 and p16 gene mutations tend to occur together in NSCLC, however these alterations seem not to have noteworthy clinical and prognostic significance.

The aim of the study was to assess the frequency of serum Ab-anti-p53 in 39 patients with advanced NSCLC and to evaluate the predictive value of the test. Antibodies were present in 10 (25.6%) of patients. There was no correlation between Ab-anti-p53 and clinical characteristics including age, gender, and histological type of tumor. In 17 patients response to chemotherapy (CT) was obtained (in one patient--complete, and in 16--partial response). The percentage of patients responding to CT in group with and without serum antibodies did not differ significantly (33% and 48%, respectively; p = 0.48). The results of the study indicate that serum Ab-anti-p53 are relatively often present in advanced NSCLC patients, however the clinical value of this test needs further evaluation.

Background: Patient preference as well as concerns and difficulties with intravenous access and pharmaco-economic issues have driven the development of oral vinorelbine., Patients and Methods: Four phase II studies were conducted in chemotherapy-naive non-small-cell lung cancer (NSCLC) and as first-line chemotherapy of advanced breast cancer (ABC). As recommended in the phase I dose-finding study, the first step used a weekly dose of 80 mg/m2. This regimen was associated with an excessive rate of early deaths (10%) due to complicated neutropenia and led to discontinuation of the first two studies. In a second step, the dose of 60 mg/m2/week was given for the first three courses and subsequently increased to 80 mg/m2/week, in the absence of severe neutropenia., Results: One hundred and thirty eight patients (76 with NSCLC and 62 with ABC) received this regimen, of whom only five were unable to undergo dose escalation. The incidence of febrile neutropenia and neutropenic sepsis were low (2.9 and 3.6%, respectively). Although severe events were uncommon, nausea/vomiting and diarrhoea were frequent and primary prophylaxis with antiemetics should be recommended., Conclusions: Overall, the safety profile of oral vinorelbine at 60 mg/m2/week for the first three courses with escalation to 80 mg/m2 is qualitatively comparable to that of i.v. vinorelbine at standard doses. Similarly to i.v. chemotherapy, close haematological monitoring is necessary.

Purpose: A randomized phase II trial of oral vs. intravenous (i.v.) vinorelbine was designed to determine the efficacy and safety of oral vinorelbine with an intrapatient dose escalation in previously untreated patients with advanced non-small-cell lung cancer (NSCLC)., Patients and Methods: Between December 1997 and April 1999, 115 patients with stage IIIB or IV NSCLC were randomized (2 to 1) to receive either oral vinorelbine at a dose of 60 mg/m2/week for the first three administrations and then increased to 80 mg/m2/week in the absence of severe neutropenia, or i.v. vinorelbine at 30 mg/m2/week., Results: One hundred and fourteen patients (76 in the oral arm and 38 in the i.v. arm) were treated. Ninety-eight patients (86%) were eligible and assessable. The two treatment arms were well-balanced for demographic and prognostic features. After external panel review, the response rates in evaluable patients were 14%, in the oral arm and 12% in the i.v. arm. The median progression-free survival with oral and i.v. vinorelbine was 3.2 months and 2.1 months, respectively, and the median survival 9.3 and 7.9 months, respectively. The most common hematological toxicity was neutropenia, which was severe (grade 3-4) in 46% of patients and for 7% of administrations in the oral arm, and in 62% of patients and for 25% of administrations in the i.v. arm. Non-hematological toxicities including nausea, vomiting, anorexia, weight loss, diarrhea .and constipation were generally mild to moderate., Conclusion: The activity of oral and i.v. vinorelbine in advanced NSCLC appears to be comparable. The safety profiles of both formulations look qualitatively similar. Oral vinorelbine can therefore be considered a good alternative to i.v. administration.

Purpose: To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non-small-cell lung cancer who had previously been treated with platinum-based chemotherapy. Secondary end points included assessment of response (docetaxel arm only), toxicity, and quality of life., Patients and Methods: Patients with performance statuses of 0 to 2 and stage IIIB/IV non-small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters. They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel. Patients were stratified by performance status and best response to cisplatin chemotherapy and were then randomized to treatment with docetaxel 100 mg/m(2) (49 patients) or 75 mg/m(2) (55 patients) or best supportive care. Patients in both arms were assessed every 3 weeks., Results: One hundred four patients (103 of whom were eligible for entry onto the study) were well balanced for prognostic factors. Of 84 patients with measurable lesions, six (7. 1%) achieved partial responses (three patients at each dose level). Time to progression was longer for docetaxel patients than for best supportive care patients (10.6 v 6.7 weeks, respectively; P <.001), as was median survival (7.0 v 4.6 months; log-rank test, P =.047). The difference was more significant for docetaxel 75 mg/m(2) patients, compared with corresponding best supportive care patients (7.5 v 4.6 months; log-rank test, P =.010; 1-year survival, 37% v 11%; chi(2) test, P =.003). Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m(2), three of whom died, and in one patient treated with docetaxel 75 mg/m(2). Grade 3 or 4 nonhematologic toxicity, with the exception of diarrhea, occurred at a similar rate in both the docetaxel and best supportive care groups., Conclusion: Treatment with docetaxel is associated with significant prolongation of survival, and at a dose of 75 mg/m(2), the benefits of docetaxel therapy outweigh the risks.

The structure of a new modification of Ti2Se, the beta-phase, and several related inorganic crystal structures containing elements with atomic numbers between 16 and 40 have been solved by quasi-automatic direct methods from single-crystal electron diffraction patterns of nanometre-size crystals, using the kinematical approximation. The crystals were several thousand times smaller than the minimum size required for single-crystal X-ray diffraction. Atomic coordinates were found with an average accuracy of 0.2 A or better. Experimental data were obtained by standardized techniques for recording and quantifying electron diffraction patterns. The SIR97 program for solving crystal structures from three-dimensional X-ray diffraction data by direct methods was modified to work also with two-dimensional electron diffraction data.

An attempt was made to undertake a randomized clinical trial of weight reduction in obese postmenopausal breast cancer patients as an adjuvant to primary surgical and radiotherapeutic treatment. The rationale was to improve prognosis which has been shown to be worse in the obese (probably because of its effect on extra-ovarian oestrogen production). Difficulties in recruiting a sufficient number of patients and the introduction of tamoxifen as anti-oestrogenic adjuvant therapy led to the decision to modify the aim of the study by limiting it to a feasibility study in 102 patients. In three hospitals in The Netherlands and in two hospitals in Poznan, Poland these patients were randomized in intervention and control groups according to a 3:2 ratio. Weight reduction in the intervention group was achieved by dietary means, ie caloric restriction was adapted to personal needs and behaviour of the patients. After 1 year a median weight loss of 6 kg was reached in both countries. In the Netherlands further follow-up indicated that this result could be maintained for another 2 years.