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Biomedical subjects

Y M Chen

Publications and source records attributed to Y M Chen.

At least 37 records · Page 2Linked to original sources

Interleukin-7 and interleukin-12 have different effects in rescue of depressed cellular immunity: comparison of malignant and tuberculous pleural effusions.

The present study attempts to determine the role of interleukin-7 (IL-7) and IL-12 in recovering the functions of the lymphocytes of malignant effusion, in terms of cytokine production, proliferation, and cytolytic activity, compared with lymphocytes from tuberculous pleural effusion. Effusion-associated lymphocytes (EAL) were isolated from tuberculous (tEAL) and malignant (mEAL) pleural effusions. The EAL proliferate response was measured after 3 days in culture. Interferon-gamma (IFN-gamma) production and cytotoxicity against K-562 cells or autologous tumor cells were assessed after 6 days in culture. It was found that the mEAL had depressed proliferation, IFN-gamma production, and cytolytic activity, as compared with tEAL. Stimulation with IL-12 plus IL-2, but not with IL-7 plus IL-2, fully restored the IFN-gamma production of mEAL to that of tEAL levels. In contrast, the proliferate response of mEAL was enhanced significantly more with IL-7 plus IL-2 than with IL-12 plus IL-2. Both the IL-7 plus IL-2 and IL-12 plus IL-2 stimulation of mEAL showed a significant increase in cytolytic activity against autologous tumor cells, although the cytolytic activity against K-562 cells did not increase. These results suggest that tEAL had a higher cellular activity than mEAL. This depressed cellular function of mEAL could be reversed with cytokines. However, different cytokines had different effects on mEAL; for example, IL-7 had a better effect in the stimulation of lymphocyte proliferation compared with IL-12, which had a better effect in driving the lymphocytes to the T helper 1 (TH1) pathway and a higher IFN-gamma production. Both IL-7 and IL-12, in the presence of IL-2, can restore the immunosuppressed cytolytic activity of the lymphocytes of malignant pleural effusion against autologous tumor.

Adjuvants, Immunologic↗

Expression and localization of human dopamine D2 and D4 receptor mRNA in the adrenal gland, aldosterone-producing adenoma, and pheochromocytoma.

Aldosterone secretion is evidently regulated by a dopaminergic inhibitory mechanism. Pharmacological characterization and autoradiographic studies revealed D2-like receptors in the adrenal cortex, especially in the zona glomerulosa. However, the subtype of the dopamine receptors involving this regulation has not been elucidated. To investigate which subtype of receptors expresses in the adrenal cortex, we examined the messages of D2-like receptors, D2, D3, and D4, by RT-PCR and in situ hybridization of adrenal glands and adrenal neoplasm. Both D2 and D4 receptors were expressed in normal adrenal glands, pheochromocytoma, and aldosterone-producing adenoma. However, the D2 receptors were not universally expressed, in contrast with the D4 receptors that were detected in all cases of aldosterone-producing adenoma and adrenal remnant. No D3 receptor message was detected by RT-PCR in any adrenal sample. Both D2 and D4 receptors were expressed in significant amounts in the adrenal medulla and pheochromocytoma. In the adrenal cortex, the expression of the D2 receptors was in the zona glomerulosa and zona reticularis, with no different signal intensities between the two zones. D4 receptors were mainly localized in the zona glomerulosa and, to a lesser extent, in the zona reticularis. Both receptors were expressed at low levels in the zona fasciculata. In aldosterone-producing adenoma, the expression of D2 and D4 was especially found in nonzona fasciculata-like cells. To elucidate which dopamine receptor regulates aldosterone secretion, the effects of specific D2 and D4 antagonists, raclopride and clozapine, respectively, were examined in cultured NCI-H295 cells. Dopamine further increased angiotensin II-induced aldosterone secretion by 20%. In the presence of 1 microM dopamine and angiotensin II, 10(-5)-10(-7) M clozapine decreased aldosterone levels by 40-55%. The decrease in aldosterone secretion by clozapine was completely reversed when raclopride was added simultaneously. These data suggest that dopamine exerts dual effects on aldosterone secretion in NCI-H295 cells. Activation of D4 receptors can increase aldosterone secretion, whereas an inhibitory effect is mediated via D2 receptors. In summary, we demonstrated the existence of both D2 and D4 receptors in the human adrenal gland and adrenal neoplasm. Both receptors play significant roles in the modulation of aldosterone secretion, but in opposite directions.

Adenoma↗

Pyeloureteritis cystica: case report.

Pyeloureteritis cystica, characterized by multiple bubbly filling defects on urography and caused by inflammatory stimuli, is a rare disorder of the ureter. It commonly affects older people. Diagnosis is established by radiological studies. Antibiotics should be given if urinary tract infection is present. Up to now, no other specific treatment can be used to cure this disorder. We report a case of pyeloureteritis cystica associated with urinary tract infection and a ureteral stone in a young woman who presented with hematuria and bilateral flank pain. The pyeloureteritis cystica had a bead-like appearance on intravenous pyelogram and retrograde pyelogram as well as in magnetic resonance urography. The diagnosis and treatment of this disorder are discussed. Magnetic resonance urography can provide high-resolution of coronal images of the entire urinary tract without the use of contrast agents or ionizing radiation. However, the cost of the procedure is a major concern.

Adult↗

Clostridium bacteremia: emphasis on the poor prognosis in cirrhotic patients.

Bacteremic episodes caused by anaerobes are unusual and the clinical importance of Clostridium bacteremia remains unclear. This retrospective case study examined the risk factors among a group of patients who developed Clostridium bacteremia. Medical records from 73 episodes of clostridial bacteremia in 73 patients treated in a medical center during an 11-year period were reviewed. Of all episodes, 96% were community-acquired. Twelve percent of patients had polymicrobial bacteremia, with Escherichia coli being the most common accompanying bacterium. Diabetes mellitus (26%) and liver cirrhosis (25%) were the most common underlying diseases. The most common etiological organisms were Clostridium perfringens (77%), Clostridium bifermentans (9%), and Clostridium septicum (4%). Only one patient with C. septicum bacteremia had a histocytotoxic infection, which was a fatal gas gangrene. Univariate analysis of data from patients with monomicrobial Clostridium bacteremia revealed that younger age (age < 65 years), underlying liver cirrhosis, and presence of septic shock at initial presentation were associated with fatality; but only the latter two variables were independently associated with fatality in multivariate logistic regression analysis. Appropriate antimicrobial therapy for monomicrobial Clostridium bacteremia did not significantly affect clinical outcomes, which might suggest that Clostridium species in the bloodstream can be regarded as merely contaminants or transient bacteremia. This suggestion was not supported by the finding that seven of 13 cirrhotic patients with monomicrobial Clostridium bacteremia died of sepsis, of whom six had not receive appropriate antimicrobial therapy. Therefore, the clinical importance of Clostridium bacteremia should be interpreted with caution because of its high risk of mortality in susceptible hosts, particularly cirrhotic patients, who do not receive appropriate therapy timely.

Adult↗

Klebsiella pneumoniae psoas abscess: predominance in diabetic patients and grave prognosis in gas-forming cases.

Seven cases of psoas abscess caused by Klebsiella pneumoniae were observed at the National Cheng Kung University Hospital within a period of 4.5 years. These cases constituted 25% of a total 28 episodes of non-tuberculous psoas abscess, ranking second to those caused by Staphylococcus aureus (8 cases). Eight cases of psoas abscess caused by K. pneumoniae were identified from Medline, and 5 of which were reported from Taiwan. Of these 8 cases, 1 neonatal case was excluded, and the remaining 7 adult cases were combined with the 7 cases in this series for analysis. The mean age was 53.8 years, and diabetes mellitus was the most common underlying disease. Fever and pain on the flank and back area were the common findings. The interval between the onset of symptoms and diagnosis ranged from 1 to 60 days. The most common sites of concurrent infection were the urinary tract (6 cases; 43%) and bone (3 cases; 21%). All patients received percutaneous or surgical drainage in addition to antibiotic treatment. Gas formation was present in 5 of the 12 patients recorded, and 4 of them died during hospitalization. Only 1 patient had a metastatic infection with osteomyelitis of the left radius and right humerus; he had experienced 5 episodes of recurrent K. pneumoniae infections in different sites. We concluded that K. pneumoniae should be considered as an important endemic pathogen of psoas abscess in diabetics in Taiwan. The high mortality rate in the gas-forming cases should also be highlighted. Early recognition, empiric antimicrobial coverage for K. pneumoniae, and aggressive drainage or debridement are indicated in these patients.

Adolescent↗

Preoperative diagnosis and localization of aldosterone-producing adenoma by adrenal venous sampling after administration of metoclopramide.

BACKGROUND AND PURPOSE: Adrenal venous sampling is the most reliable test to distinguish aldosterone-producing adenoma (APA) from idiopathic hyperaldosteronism (IHA). The diagnostic accuracy can be improved by administration of adrenocorticotropin to minimize pulsatile secretion of aldosterone. Metoclopramide (MCP), a dopamine antagonist, can increase aldosterone secretion promptly without affecting cortisol secretion. This study investigated the diagnostic accuracy of adrenal venous sampling after MCP injection for the preoperative diagnosis and localization of APA. METHODS: Prospective diagnosis and adrenalectomy was based on adrenal venous sampling in 23 patients with a diagnosis of primary aldosteronism. Plasma aldosterone concentrations from adrenal veins and the inferior vena cava were measured before and 30 minutes after intravenous administration of 10 mg MCP. The ratio of bilateral adrenal venous aldosterone concentrations after MCP was used for diagnosis as follows: a ratio greater than 5 indicated APA, less than 3 indicated IHA, and 3-5 indicated an intermediate diagnosis. RESULTS: Catheterization of the right adrenal vein was unsuccessful in three patients. Twelve of 13 patients with an aldosterone ratio greater than 5 after MCP underwent unilateral adrenalectomy, and APA was confirmed in 11 of these patients. One patient with an intermediate diagnosis also had surgically confirmed APA. Six patients had a ratio less than 3. Before MCP administration, 10 of 13 patients with APA had a ratio greater than 5, and three patients had a ratio between 3 and 5; one patient with IHA had a ratio greater than 5. MCP improved the diagnosis of APA to an accuracy of 92% (12/13). Correct diagnosis of APA based on computerized tomography (CT) was 85% (11/13). There was discordance between the findings of adrenal venous sampling and CT in four of 20 patients. CONCLUSIONS: Administration of MCP to stimulate aldosterone secretion during adrenal venous sampling can improve the accuracy of differential diagnosis between APA and IHA.

Adenoma↗

A model for the study of cystic endometrial hyperplasia in bitches.

The aims of this study were: (i) to establish a reliable model for the study of cystic endometrial hyperplasia in ovariectomized bitches; and (ii) to assess the roles of oestrogen and progesterone in the pathogenesis of irritant-induced cystic endometrial hyperplasia. Greyhound bitches (n = 15) were ovariectomized and divided into five groups (n = 3 per group). After 3-4 weeks, oestradiol benzoate (0.6-4.8 micrograms kg-1, i.m.) was administered twice a day for 12 days to the bitches in group 1, followed by progesterone (0.2-1.8 mg kg-1, i.m.) twice a day for 30-33 days. These dosages were chosen to mimic the plasma hormone concentrations of a normal oestrous cycle. A silk suture was inserted by laparotomy into the left uterine horn 12 days into the simulated dioestrus (determined by vaginal cytology) and necropsy was performed after a further 12 days. For groups 2-5, the silk suture was positioned at ovariectomy. After a further 3-4 weeks, these bitches were treated with progesterone (group 2: 1.8 mg kg-1 i.m. twice a day), oestradiol benzoate (group 3: 0.6-4.8 micrograms kg-1 i.m. twice a day), oestradiol benzoate and progesterone together (group 4: previous dosages) or vehicle (group 5). Necropsies were performed after 12-13 days of treatment. Cystic endometrial hyperplasia was induced in the suture-containing uterine horns of all bitches in groups 1 and 4, and in two bitches in group 2. Cystic endometrial hyperplasia did not develop in any control (no suture) uterine horns, or in either uterine horn of the bitches treated with either oestradiol only or vehicle. These results indicate that progesterone is necessary for the development of irritant-induced cystic endometrial hyperplasia and that oestradiol potentiates the effects of progesterone. The protocol used for bitches in group 1 would be a suitable model for further studies of the pathogenesis of cystic endometrial hyperplasia.

Animals↗

[Second sampled survey on the distribution of human parasites in Zhejiang Province].

OBJECTIVE: Twenty-six species of human parasites were recorded in Zhejiang Province in 1987-1989 as a part of the national investigation on the distribution of human parasites, and the total prevalence was 80.2%. In order to find out possible changes on the composition of parasite species and decrease of prevalence after control intervention particularly mass chemotherapy in the past years and provide evidence for an improved control strategy, the second sampled survey was carried out from 1998 to 1999. METHODS: Ten counties were identified randomly out of 28 counties where the last survey was conducted following the same sampling method. Same technics were used for case detection and data processing. RESULTS: The total infection rate in a sample of 15,698 was 22.84% was 22.84% in 30 investigation spots in 10 counties, and 17 species of parasites were revealed. The overall prevalence was reduced by 71.51% in comparison to that of 1989, and the number of parasite species was 17, 9 less than that of the last investigation. CONCLUSIONS: The prevalence of human parasites has greatly declined in this province due to the socioeconomic development and adoption of comprehensive control measures focusing on mass chemotherapy in the past decade.

Adolescent↗

Genomic structure, expression, and chromosomal localization of the human glycine N-methyltransferase gene.

The glycine N-methyltransferase (GNMT) gene encodes a protein that not only acts as an enzyme to regulate the ratio of S-adenosylmethionine to S-adenosylhomocysteine, but also participates in the detoxification pathway in liver cells. Previously, we reported that the expression level of GNMT was diminished in human hepatocellular carcinoma. In this study, the human GNMT gene was cloned and characterized. It contains six exons and spans about 10 kb. Instead of a TATA box, it has a transcriptional initiator located 801 bp upstream from the translation start codon. The gene was localized to chromosome 6p12 using fluorescence in situ hybridization. Northern blot analysis of 16 tissues from different human organs showed that GNMT was expressed only in liver, pancreas, and prostate.

Adult↗

Activation of nuclear factor kappaB in hepatitis C virus infection: implications for pathogenesis and hepatocarcinogenesis.

The hepatitis C virus (HCV) core protein is a multifunctional protein. It may bind to the death domain of tumor necrosis factor receptor 1 (TNFR1) and to the cytoplasmic tail of lymphotoxin-beta receptor, implying that it may be involved in the apoptosis and anti-apoptosis signaling pathways. In vitro studies have been inconclusive regarding its ability to inhibit or enhance TNF-alpha-induced apoptosis. To address this issue, electrophoretic mobility shift assay (EMSA) and immunohistochemical studies were used to show the activation of nuclear factor kappaB (NF-kappaB) in HCV-infected liver tissues and in HCV core-transfected cells. The activation of NF-kappaB was correlated with the apoptosis assays. The results showed that NF-kappaB activation could be shown in HCV-infected livers and HCV core-transfected cells. The data of EMSA correlated with those of immunohistochemical studies, which revealed a higher frequency of NF-kappaB nuclear staining in HCV-infected than in normal livers. NF-kappaB activation conferred resistance to TNF-alpha-induced apoptosis in HCV core-transfected cells. Inhibition of NF-kappaB activation by pyrrolidine dithiocarbamate sensitized them to TNF-alpha-induced apoptosis. These findings suggest that HCV infection may cause anti-apoptosis by activation of NF-kappaB and implicate a mechanism by which HCV may evade the host's immune surveillance leading to viral persistence and possibly to hepatocarcinogenesis.

Adult↗

Usefulness of pig-tail catheter for palliative drainage of malignant pleural effusions in cancer patients.

We retrospectively collected data from patients enrolled between 1996 and 1997, to evaluate the efficacy of sono-guided pig-tail-catheter drainage in cancer patients with large, symptomatic, amounts of malignant effusion and to evaluate the hemodynamic change after effusion drainage. A total of 477 pig-tail catheter drainage procedures were performed on 342 cancer patients. Sonographic findings, volume drained within 36 h after pig-tail insertion, heart rate and respiratory rate 24 h before and after drainage, and dyspnea sensations were recorded. We found that unilateral right-side effusion was the most frequent presentation. The mean amount of effusion drained within 36 h was 1,747 ml in cancer patients. The decreases in heart rate (from 97/min to 91/min) and in respiratory rate (from 23/min to 21/min) were both statistically significant. There was no significant correlation between the amount of effusion before drainage and the heart rate or respiratory rate. The amount drained within 36 h was correlated significantly with the changes in heart and respiratory rates. Dyspnea sensations decreased or subsided in 91% of the patients within this time period. There were few complications with the pig-tail drainage procedure. Sono-guided pig-tail drainage is a safe and convenient method of effusion drainage in cancer patients. It not only provides temporary relief of symptoms from massive pleural effusions, but can also be used for pleurodesis if needed.

Adolescent↗

Phase II study with gemcitabine, ifosfamide and cisplatin in advanced non-small cell lung cancer.

The aim of the present study was to determine the clinical activity and toxicity of a novel chemotherapy combination regimen of gemcitabine, ifosfamide and cisplatin (GIP), administered every 3 weeks, in patients with inoperable non-small cell lung cancer (NSCLC). From October 1998 to July 1999, 18 previously untreated stages IIIb (4) and IV (14) patients were enrolled into the study. Gemcitabine and ifosfamide (with mesna as uroprotection) was administered on days 1 and 6, at a dose of 1000 and 1500 mg/m2, respectively; and cisplatin was given on day 1 at a dose of 60 mg/m2, every 3 weeks. All 18 patients were evaluable for response and toxicity profiles. One patient achieved a complete response, and II patients achieved a partial response, with an overall response rate of 66.7% (95%, CI, 45-89%). The main toxicity was hematological, a NCI grade 3-4 neutropenia in 16 patients (88.9%) during the treatment course. Febrile neutropenia occurred in three patients (16.6%). Grade 3 anemia occurred in eight patients (44.41%) and grade 3-4 thrombocytopenia occurred in 11 patients (61.1%). Non-hematological toxicity was mild and tolerable. No toxic death occurred. The median survival was 12.7 months and 1 year survival was 58.4%. The GIP combination chemotherapy produced a high response rate in advanced NSCLC; however, there was a relatively high percentage of hematological toxicity that still could be tolerated. A randomized trial comparing GIP to a two-drug combination of gemcitabine and cisplatin is planned.

Adult↗

Pentoxifylline inhibits human peritoneal mesothelial cell growth and collagen synthesis: effects on TGF-beta.

BACKGROUND: Prevention or treatment of peritoneal fibrosing syndrome has become an important issue in patients on continuous ambulatory peritoneal dialysis (CAPD). Recent evidence has suggested that mesothelial stem cell proliferation and matrix over-production predispose the development of peritoneal fibrosis. We investigated whether pentoxifylline (PTX) affects human peritoneal mesothelial cell (HPMC) growth and collagen synthesis. METHODS: HPMC was cultured from human omentum by an enzymic disaggregation method. Cell proliferation was assayed using a methyltetrazolium uptake method. Cell cycle analysis was performed by flow cytometry. Collagen synthesis was measured by 3H-proline incorporation into pepsin-resistant, salt-precipitated collagen. Prostaglandins and cAMP were determined by enzyme immunoassay. Northern blot analysis was used to determine mRNA expression. RESULTS: Our data show that PTX inhibited serum-stimulated HPMC growth and collagen synthesis in a dose-dependent manner. Cell cycle analysis showed that PTX arrested the HPMCs in the G1 phase. PTX decreased the procollagen alpha1 (I) mRNA expression either stimulated by serum or transforming growth factor-beta (TGF-beta). PTX did not alter prostaglandins synthesis but dose-dependently increased intracellular cAMP level. PTX, the same as 3-isobutyl-l-methylxanthine, could potentiate prostaglandin E1 (PGE1) increased cAMP levels of HPMC. The antimitogenic and antifibrogenic effects of PTX on HPMC were reversed by N-[2]-((p-Bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide (H-89). Therefore, the mechanism of these effects may be due to the phospodiesterase inhibitory property of PTX. CONCLUSIONS: These data suggest that PTX may have a role in treating peritoneal fibrosing syndrome.

Cell Division↗

Minor salivary gland secretion in the elderly.

OBJECTIVE: Very little information exists on minor salivary gland output (MSGO) in health and disease. We investigated the minor salivary gland output of elderly subjects with different medical backgrounds and the relationship of that output with life practices, demographic variables, complaints of dry mouth, medication usage, functional status, medical treatments, and dental and medical variables. STUDY DESIGN: MSGO was measured with a special moisture-detecting paper on the lip, cheek, and palate, which comprised the total MSGO. A parsimonious linear regression model was developed to determine which of the many measured variables influenced the MSGO. RESULTS: There were significant differences in MSGO between the recruitment sites, with the non-Veteran Affairs (VA) Independent Living participants having significantly lower MSGO than the VA groups. A secretion rate for MSGO based on median values from all subjects of <4.6 microL/min was categorized as being low, whereas a secretion rate for MSGO >/=4.6 microL/min was categorized as high. A regression model was used to examine variables that could be associated with MSGO variability. The results show that being older, a woman, a current smoker, and having a complaint of dry mouth were associated with lower MSGO rates. CONCLUSIONS: An association between subjective complaints of dry mouth and a decrease in MSGO measured objectively was demonstrated in this elderly population. Furthermore, age and sex effects on MSGO were also demonstrated.

Activities of Daily Living↗

Restoration of cytotoxic T lymphocyte function in malignant pleural effusion: interleukin-15 vs. interleukin-2.

The present study attempts to define the role of interleukin-15 (IL-15), as compared with IL-2, in generating cytotoxic T lymphocytes (CTL) from the malignant effusions of cancer patients. Effusion-associated lymphocytes (EAL) from malignant effusion were incubated with IL-15 or IL-2 with or without alphaCD3. Proliferation and cytotoxicity assays were performed. IL-15 was found to have at least an equivalent, if not higher, activity to IL-2 in terms of lymphocyte proliferation and generation of CTL from EAL. The proliferative response of EAL, cocultured with IL-15, with or without alphaCD3, was partly inhibited by pretreatment with an anti-IL2 receptor beta chain monoclonal antibody (mAb). The proliferative response of EAL, cocultured with alphaCD3, IL-2, or both, was partly inhibited by pretreatment with an anti-IL-2 receptor alpha chain mAb. Overnight [5lCr] release assays against K562, Daudi, and the patients' autologous tumor cells were done to evaluate EAL's cytolytic activity. MHC class I Ab blocked the stimulated cytolytic activity of EAL against autologous tumors. An mAb depletion assay showed that the phenotype of the restored EAL was CD16-CD4-CD8+; thus, the restored activity of EAL was CTL activity. The results suggest that both IL-15 and IL-2 can restore CTL activity from EAL in the presence of T cell receptor (TCR)-CD3 engagement, but the effect of IL-15 was superior.

Adenocarcinoma↗

A phase II study of single-agent docetaxel chemotherapy for non-small cell lung cancer.

BACKGROUND: Docetaxel is an active agent used in the treatment of non-small cell lung cancer (NSCLC). METHODS: A phase II trial of single-agent docetaxel chemotherapy was conducted in Chinese patients with NSCLC, as either a first- or second-line treatment, to assess response and toxicity. The treatment scheme was docetaxel 75 mg/m2 intravenous infusion for 1 h every 3 weeks for up to nine cycles. Dexamethasone was routinely given for 3 days, beginning 1 day before chemotherapy. RESULTS: From August 1996 to December 1997, 48 patients were enrolled, including 34 chemo-naive patients and 14 patients previously treated with one chemotherapeutic regimen. All patients were evaluable for toxicity profiles and 47 patients were evaluable for response rate. As expected, the major toxicity was myelosuppression. Grade 3 or 4 neutropenia occurred in 41 of 48 (85.5%) patients during treatment. Twenty patients (41.7%) experienced febrile neutropenia and accounted for two toxic deaths. Only one patient suffered from grade 3 thrombocytopenia and two patients from grade 3 anemia. Moderate or severe asthenia occurred in 30 patients (62.5%). Moderate fluid retention (peripheral edema) was observed in five patients (10.4%) and severe fluid retention in three; all were reversible. No grade 3 or 4 neurosensory toxicity was observed. After two cycles of treatment, 14 of 47 evaluable patients attained a partial response (29.8%, 95% CI 16.7-42.9%), including 30.3% (95% CI 14.6-46%) of those in first-line treatment and 28.6% (95% CI 4.9-52.3%) of those in second-line treatment. The median time to disease progression was 13 weeks in first-line patients and 19 weeks in second-line patients. Median survival time was 7.1 and 11.7 months in first- and second-line patients, respectively. CONCLUSION: Docetaxel is active and has an acceptable toxicity profile, in both first- and second-line treatments, in Chinese patients with inoperable NSCLC.

Adenocarcinoma↗

A phase II trial of tamoxifen, ifosfamide, epirubicin, and cisplatin combination chemotherapy for inoperable non-small-cell lung cancer.

A phase II trial of tamoxifen, ifosfamide, epirubicin, and cisplatin (TIEP) chemotherapy was conducted in patients with chemonaive inoperable non-small-cell lung cancer (NSCLC) to assess response and toxicity. From October 1997 to August 1998, 19 patients were treated. The treatment schema included tamoxifen 60 mg twice daily by mouth on days 1 to 3, ifosfamide 3 g/m2 intravenous infusion (IV) 60 minutes with mesna on day 2, epirubicin 50 mg/m2 IV bolus on day 2, and cisplatin 60 mg/m2 IV 60 minutes on day 2 every 4 weeks for up to six cycles. All patients were evaluable for response and toxicity. The major toxicity was myelosuppression; grade 3 or 4 leukopenia or neutropenia occurred in 14 of 19 (73.7%) patients during treatment, and 6 patients (31.6%) experienced fever in association with the neutropenia; no toxic deaths occurred. Grade 3 anemia occurred in six patients (31.6%) during the treatment. Grade 3 or 4 nausea/vomiting occurred in only one patient. Toxicities other than neutropenia and anemia were minimal. After two cycles of treatment, 9 of 19 patients attained a partial response (47.4%, 95% confidence interval 24.9%-69.9%) in this study. The median time to disease progression was 6 months and median survival time was 12 months. We conclude that TIEP is an active combination regimen with an acceptable toxicity profile in Chinese patients with inoperable NSCLC.

Aged↗

A phase II trial of vinorelbine and cisplatin in previously untreated inoperable non--small-cell lung cancer.

Weekly vinorelbine injection with cisplatin had been used in treatment of non-small-cell lung cancer. We performed a phase II trial to evaluate the efficacy and toxicity of a new schedule of vinorelbine and cisplatin in patients with previously untreated, inoperable (stage IIIB or stage IV) non-small-cell lung cancer. From April 1996 to May 1997, 52 patients were enrolled for study, and 50 patients were eligible and evaluable for both response and toxicity assessment. Therapy consisted of vinorelbine, 30 mg/m2, intravenously on days 1 and 5 of a 21-day cycle, and cisplatin 100 mg/m2 (reduced to 80 mg/m2 after the first seven patients) given on day 1. A total of 211 treatment courses were administered; the median number of cycles administered per patient was 4.5 (range: 1-6), the median dose intensity for vinorelbine was 16.9 mg/m2/week (84.4%), whereas that of cisplatin was 22.8 mg/m2/week (84.7%). Twenty-five patients responded to therapy for an overall response rate of 50%; one patient attained a complete response (2%). The main toxicities were vomiting, myelosuppression, and diarrhea, which included World Health Organization grade 3 or 4 nausea/vomiting (58% patients), anemia (41% patients), neutropenia (12% patients), and diarrhea (14%). The median duration of responses was 9 months. The median time to disease progression was 6.8 months (range 0.4-18.1 months). Median survival was 13 months, and 54% of patients were alive at 1 year. We conclude that this new schedule of vinorelbine and cisplatin achieves a high response with acceptable toxicity profile in patients with advanced non-small-cell lung cancer.

Adult↗