The predictive value of pre-treatment inflammatory markers in advanced non-small-cell lung cancer.

BACKGROUND: Accurate prediction of outcome in advanced non-small-cell lung cancer (NSCLC) remains challenging. Even within the same stage and treatment group, survival and response to treatment vary. We set out to determine the predictive value of inflammatory markers C-reactive protein (CRP) and white blood cells (WBCS) in patients with advanced NSCLC. PATIENTS AND METHODS: Patients were assigned a prognostic index (PI): 0 for crp 10 mg/L or less and WBCS 11x109/L or less, 1 if one of the two markers was elevated, and 2 if both markers were elevated. We then used chest computed tomography (CT) imaging to evaluate response after 2 cycles of chemotherapy treatment. RESULTS: Of 134 patients, 46 had a PI of 0; 60, a PI of 1; and 28, a PI of 2. Disease progressed in 41 patients. Progression was significantly more frequent among patients with a PI of 2 (p = 0.008). Median survival was 20.0 months for the PI 0 group, 10.4 months for the PI 1 group, and 7.9 months for the PI 2 group (p < 0.001). The PI was the only significant prognostic factor for survival even after adjustment for performance status, smoking, and weight loss (hazard ratio: 1.57; 95% confidence interval: 1.2 to 2.14; p = 0.004). CONCLUSIONS: Inflammatory state correlates significantly with both chemotherapy response and survival in stage IV NSCLC. The PI may provide additional guidance for therapeutic decision-making.

Flexible modeling improves assessment of prognostic value of C-reactive protein in advanced non-small cell lung cancer.

BACKGROUND: C-reactive protein (CRP) is gaining credibility as a prognostic factor in different cancers. Cox's proportional hazard (PH) model is usually used to assess prognostic factors. However, this model imposes a priori assumptions, which are rarely tested, that (1) the hazard ratio associated with each prognostic factor remains constant across the follow-up (PH assumption) and (2) the relationship between a continuous predictor and the logarithm of the mortality hazard is linear (linearity assumption). METHODS: We tested these two assumptions of the Cox's PH model for CRP, using a flexible statistical model, while adjusting for other known prognostic factors, in a cohort of 269 patients newly diagnosed with non-small cell lung cancer (NSCLC). RESULTS: In the Cox's PH model, high CRP increased the risk of death (HR=1.11 per each doubling of CRP value, 95% CI: 1.03-1.20, P=0.008). However, both the PH assumption (P=0.033) and the linearity assumption (P=0.015) were rejected for CRP, measured at the initiation of chemotherapy, which kept its prognostic value for approximately 18 months. CONCLUSION: Our analysis shows that flexible modeling provides new insights regarding the value of CRP as a prognostic factor in NSCLC and that Cox's PH model underestimates early risks associated with high CRP.

Screening for depressive symptoms in patients with unresectable lung cancer.

INTRODUCTION: Early identification of psychological distress and depression is important to optimise the quality of life in patients with advanced non-small cell lung cancer (NSCLC). The prevalence of depression may vary, depending on the time since diagnosis of cancer, results of the treatment and the prognosis. The purpose of this study was to compare the efficacy of a self-administered screening tool (Hospital Anxiety and Depression Scale (HADS)) with a health professional administered tool (Montgomery-Asberg Depression Rating Scale (MADRS)) and to explore the variability of major affective symptoms in patients with unresectable lung cancer during the initial 7-8 weeks of chemotherapy treatment for their illness. MATERIAL AND METHODS: Patients with newly diagnosed unresectable lung cancer were screened on four occasions for anxiety and depressive symptoms simultaneously using the self-rated HADS and the MADRS administered by a psycho-oncologist or a trained research associate. The first assessment was done within 1 week of diagnosis and was repeated on 3 occasions during the initial 2 cycles of chemotherapy. RESULTS: Forty-nine patients, aged 38-82 years (median age 63 years) were enrolled. All patients had advanced NSCLC (stages 3A, 3B and 4) and 61% (30 patients) had an ECOG performance status (PS) of 1 or greater. The point prevalence of depression measured by an interviewer using the MADRS at visits 1-4 was 49%, 51%, 47%, and 41%, respectively. The point prevalence of self-reported depression (HADS) was significantly (p < 0.001) lower at each assessment point (18%, 20%, 6%, 12%) compared to health professional detected depression (MADRS). Although MADRS and HADS showed very strong (Pearson's correlation = 0.8) and significant (p < 0.001) correlation, the concordance rate in identifying the same cases of depression was only 54%. CLINICAL IMPLICATION AND CONCLUSION: The prevalence of depression among advanced lung cancer patients is high and varies very little during the first 2 cycles of chemotherapy. Among a variety of tools available for the screening of depression, a semi-structured interview is more effective at identifying clinically significant depression than a self-administered questionnaire.

A phase I/II trial of neoadjuvant chemotherapy with cisplatin and vinorelbine followed by accelerated irradiation for patients with inoperable nonsmall cell lung carcinoma.

BACKGROUND: Both locoregional and distant disease control remains poor in the treatment of Stage III nonsmall cell lung carcinoma (NSCLC). This trial was conducted to evaluate the tolerance and responses of patients with NSCLC given a neoadjuvant regimen of cisplatin and vinorelbine chemotherapy followed by accelerated thoracic radiotherapy. METHODS: Forty-two patients with Stage IIIA and IIIB NSCLC were entered into the study. Treatment consisted of cisplatin 100 mg/m2 given on Days 1 and 29 and vinorelbine 30 mg/m2 given weekly for 5 weeks, with a planned 50% dose reduction to 15 mg/m2 planned for Week 2. This was followed by thoracic irradiation of 60 gray (Gy) in 30 fractions of 2 Gy over 4 weeks (once daily during Weeks 1 and 2 and twice daily during Weeks 3 and 4). RESULTS: With a median follow-up time of 12.2 months (27-65 months for survivors), the median survival was 12.2 months (16.6 months for patients with no prior weight loss and 7.8 months for those with prior weight loss). The response rate after induction chemotherapy was 46.1%, increasing to 74.4% after radiation therapy (8 complete responses and 21 partial responses). The rate of progression was 13 of 18 (72%) for those who responded to chemotherapy (4 distant, 9 local) and 18 of 21 (86%) for those who did not respond to chemotherapy (14 distant, 7 local). The most frequent acute Grade 3 toxicity was nausea (21.4%). CONCLUSIONS: Accelerated thoracic irradiation after induction chemotherapy is well tolerated and yields therapeutic results that compare favorably with those reported for other regimens of chemotherapy and standard fractionated radiotherapy. The data from this study suggest that the responses of patients with clinically apparent disease to induction chemotherapy might indicate a likelihood of controlling microscopic distant metastases.

Efficacy of inhaled steroids (beclomethasone dipropionate) for treatment of mild to moderately severe asthma in the emergency department: a randomized clinical trial.

STUDY OBJECTIVE: To examine the efficacy of an inhaled steroid, when added to a standard regimen of beta-agonist therapy, in the treatment of patients with mild to moderately severe asthma in the emergency department. METHODS: A convenience sample of adult patients with asthma (FEV1 % predicted 40% to 69%) presenting to the ED was randomly assigned in a double-blind fashion into 2 treatment groups. The first group received 2.5 mg nebulized salbutamol plus 1 mg (4 puffs) of beclomethasone dipropionate (BDP) at baseline, 30 minutes, and at 1, 2, and 4 hours, delivered by a metered-dose inhaler (MDI) attached to a spacer device (Vent-AH-aler, Glaxo). The second group was given the same salbutamol regimen plus MDI placebo through the Vent-AH-aler. The primary endpoint was improvement in FEV1 %predicted at 6 hours. RESULTS: Of 54 patients enrolled, 28 were assigned to the BDP group and 26 to the placebo group. Spirometry improved significantly in both groups over the 6 hours compared with baseline (ANOVA, P <.001). At 6 hours, the mean absolute improvement in FEV1 % predicted for BDP was 18% versus 17% for placebo (95% confidence interval for the absolute difference of 1% [-8% to 10%]). The proportion of patients in the BDP group who were hospitalized was 7% compared with 19% for patients in the placebo group (95% confidence interval for the difference of 12% [-6%, 30%]). CONCLUSION: In this group of patients with mild to moderately severe asthma, 5 mg BDP delivered by MDI during the initial 4 hours of an emergency visit was of no added benefit over standard therapy, as measured by improvement in FEV1 % predicted at 6 hours. However, a trend toward a difference in admission favoring BDP was observed. [Afilalo M, Guttman A, Colacone A, Dankoff J, Tselios C, Stern E, Wolkove N, Kreisman H: Efficacy of inhaled steroids (beclomethasone dipropionate) for treatment of mild to moderately severe asthma in the emergency department: A randomized clinical trial.

Analysis of neuroendocrine markers, HER2 and CEA before and after chemotherapy in patients with stage IIIA non-small cell lung cancer: a Cancer and Leukemia Group B study.

Several studies have suggested that biochemical or molecular markers examined in non-small cell lung cancer carry prognostic or treatment response information. Non-small cell lung cancer patients whose tumors have neuroendocrine (NE) features may be more responsive to chemotherapy. In addition, increased expression of HER2 (c-erbB-2), a membrane-bound receptor with tyrosine kinase activity, has been associated with shortened survival. The Cancer and Leukemia Group B (CALGB) performed a study of patients with stage IIIA (N2 nodes positive) non-small cell lung cancer in which patients received initial chemotherapy followed by surgery, then post-operative therapy consisting of sequential chemotherapy and radiation therapy. Since all patients underwent mediastinoscopy, this provided an opportunity to compare pre- and post-chemotherapy tumor specimens to test the hypothesis that these proteins would predict treatment response. In particular, we hypothesized that the post-chemotherapy specimens would be enriched for NE marker negative cells because of the increased sensitivity of NE positive cells to chemotherapy. We performed immunohistochemical analysis for a panel of NE markers [neuron-specific enolase (NSE), Leu-7, chromogranin A (ChrA), synaptophysin (Syn)], HER2 and CEA to determine if there was an effect of therapy on the percentage of cells expressing these markers. Secondary endpoints were a correlation with chemotherapy response and survival. Slides were scored for intensity (0-4) and percentage of cells positive (0-4). Of 61 eligible patients, there were 38 with both pre- and post-chemotherapy specimens. When both intensity of staining and percentage of positive cells were considered, post-chemotherapy specimens had a higher percentage of positive NE markers compared with pre-chemotherapy. In addition, there was no correlation between NE marker, HER2 or CEA expression (prior to or post treatment) and response to chemotherapy or survival. These data do not support the hypothesis that NE positive tumor cells are preferentially killed by chemotherapy in patients with stage IIIA non-small cell lung cancer.

Meal-induced oxygen desaturation and dyspnea in chronic obstructive pulmonary disease.

OBJECTIVE: To study arterial oxygen saturation (SpO2) obtained by pulse oximetry and dyspnea during active eating (AE) and passive eating (PE) in patients with severe chronic obstructive pulmonary disease (COPD). DESIGN: Patients were studied on two consecutive days with AE and PE, which occurred in random order. SpO2 was recorded for 20 mins before and during eating, and dyspnea was recorded by the patient using a 10 cm visual analogue scale before and upon completion of eating. SETTING: Subjects were in-patients at an intermediate care facility who were hospitalized for pulmonary rehabilitation or for convalescence after an exacerbation of COPD. POPULATION STUDIED: Thirty-five patients with severe COPD (forced expiratory volume in 1 s [FEV1] less than 50% predicted, FEV1 to forced vital capacity ratio less than 65%) were studied. Mean age was 70.5 7.1 years. MAIN RESULTS: Mean SpO2 decreased significantly (P<0.05) from 91.7 3.4% to 90.1 4.0% during AE, and 91.7 3.2% to 90. 8 3.6% during PE. Mean lowest SpO2 was lower and percentage of time with SpO2 less than 90% was greater during eating compared with corresponding control periods during both AE and PE. Dyspnea increased significantly (P<0.05) from 1.4 1.2 to 3.3 2.3 cm during AE, and from 1.5 1.5 to 2.4 2.2 cm during PE. The increase in dyspnea was significantly greater during AE than PE. CONCLUSIONS: Eating is an activity that can adversely affect SpO2 and increase dyspnea in patients with severe COPD. Oxygen desaturation and particularly increased dyspnea may at least in part relate to the recruitment of upper extremity muscles during eating.

Evaluation of right ventricular systolic pressure during incremental exercise by Doppler echocardiography in adults with atrial septal defect.

STUDY OBJECTIVES: Pulmonary hypertension is the most important complication in patients with atrial septal defect (ASD), but its role in limiting exercise has not been examined. This study sought to evaluate exercise performance in adults with ASD and determine the contribution of elevated pulmonary artery pressure in limiting exercise capacity. DESIGN: We used Doppler echocardiography during exercise in 10 adults (aged 34 to 70 years) with isolated ASD (New York Heart Association class I, II) and an equal number of matched control subjects. Incremental exercise was performed on an electrically braked upright cycle ergometer. Expired gases and VE were measured breath-by-breath. Two-dimensional and Doppler echocardiographic images were obtained at rest prior to exercise to determine ASD size, stroke volume (SV), shunt ratio (Qp:Qs), right ventricular outflow tract (RVOT) size, and right ventricular systolic pressure at rest (RVSPr). Doppler echocardiography was repeated at peak exercise to measure right ventricular systolic pressure during exercise (RVSPex). RESULTS: Resting echocardiography revealed that RVOT was larger (21+/-4 vs 35+/-8 mm, mean+/-SD; p=0.0009) and RVSPr tended to be higher (17+/-8 vs 31+/-8 mm Hg; p=0.08) in ASD; however, left ventricular SV was not different (64+/-23 vs 58+/-23 mL; p>0.05), compared with control subjects. Despite normal resting left ventricular function, ASD patients had a significant reduction in maximum oxygen uptake (VO2max) (22.9+/-5.4 vs 17.3+/-4.2 mL/kg/min; p=0.005). RVSPex was higher (19+/-8 vs 51+/-10 mm Hg; p=0.001) and the mean RVSP-VO2 slope (1+/-2 vs 18+/-3 mm Hg/L/min; p=0.003) and intercept (17+/-4 vs 27+/-4 mm Hg; p=0.05) were higher in the ASD group. VO2max correlated inversely with both RVSPr (r=-0.69; p=0.007) and RVSPex (r=-0.67; p=0.01). CONCLUSION: These findings suggest that adults with ASD have reduced exercise performance, which may be associated with an abnormal increase in pulmonary artery pressure during exercise.

International differences in epidemiology of lung adenocarcinoma.

In Europe, the squamous cell carcinoma is the most frequent non-small cell lung cancer (NSCLC) subtype and until now, no increase in incidence of lung adenocarcinoma (ADC) has been described (except in the Netherlands), in contrast to North America where ADC predominates. Our aim was to compare the percentage of ADC in Montreal (MTL), Canada, with that in Strasbourg (STBG), France. We prospectively identified patients with NSCLC in MTL and in STBG over an 8-month period and described the distribution of NSCLC by sex, age, subtype and smoking history. A total of 172 patients in MTL and 166 in STBG were identified. The male/female ratio was significantly different in STBG (12:1) and in MTL (2:1). The percentage of ADC was significantly higher in MTL (40%) than in STBG (30%). This difference is partly due to the higher number of women with NSCLC in Montreal combined with the predominance of ADC in women. The proportion of ADC decreased with age in STBG, but was similar in each age category in MTL. In STBG, most women with NSCLC had never smoked (69%), in contrast to MTL where only 16% of women had never smoked. In conclusion, ADC is more frequent in MTL than in STBG. This is partly due to the higher number of women with NSCLC in MTL combined with the predominance of ADC in women. The greatest proportion of ADC subtype in the youngest cohorts of men in STBG suggests that ADC may be on the rise in this city.

The effects of combined intravenous and inhaled steroids (beclomethasone dipropionate) for the emergency treatment of acute asthma. The Asthma ED Study Group.

OBJECTIVE: To compare the efficacy of high-dose inhaled steroids in conjunction with IV steroids with that of IV steroids alone in the emergency treatment for acute asthma. METHODS: A double-blind, placebo-controlled, randomized trial was conducted on 60 ED patients presenting with acute asthma. All patients received nebulized salbutamol, and IV methylprednisolone, 80 mg at baseline and 40 mg at 6 hours. In addition to the above therapy, the experimental group received beclomethasone dipropionate (BDP) 7 mg over 8 hours via a metered-dose inhaler (MDI) attached to a holding chamber, while the control group received a placebo administered in the same fashion. Patients were treated on the protocol for 12 hours with the primary outcome measure being the change in % predicted FEV1. RESULTS: Of 60 patients, 30 were randomized to BDP (age: 42 +/- 16 years; FEV1: 0.97 +/- 0.42 L) and 30 were randomized to placebo (age: 37 +/- 18 years; FEV1: 0.98 +/- 0.35 L). Spirometry and dyspnea measured by the Borg Scale improved significantly in both groups compared with baseline (p < 0.001). Changes in spirometry measures, dyspnea, and vital signs did not differ between treatment groups over the 12 hours of study (p > 0.05). CONCLUSION: Inhaled BDP added to the standard regimen of IV methylprednisolone, and beta-agonist did not further improve flow rates or dyspnea scores measured for up to 12 hours after presentation to the ED.

The increasing incidence of lung adenocarcinoma: reality or artefact? A review of the epidemiology of lung adenocarcinoma.

Lung adenocarcinoma is the most common cell type in females (smokers or non-smokers) and in non-smoking males. Its incidence has been increasing in younger cohorts of males and females until very recent years. Changes in classification and in pathological techniques account for some of this increase. In females and non-smoker males, the increase could be partly due to a detection bias in former studies. Nevertheless, successive cohorts over time seem more likely to develop adenocarcinoma and less likely to develop squamous cell carcinoma. These differences between birth cohorts suggest that the increasing incidence of adenocarcinoma is not only due to changes in pathological diagnosis. Geographical differences are also observed: in Europe, the squamous cell type still predominates and an increase in incidence of adenocarcinoma has only been reported in the Netherlands. In Asia, in the 1960s and 1970s, the proportion of adenocarcinoma was higher than in North America or Europe and seems to be increasing. To what extent these differences are due to differences. In establishing diagnosis remains unknown. Despite these biases in temporal and geographical trends detailed in this review, there has probably been a true increase in incidence of adenocarcinoma. An explanation for this should be sought in studies on detailed smoking history and passive smoking exposure, occupational exposure, diet and cooking, pollution and other environmental factors.

The impact of Filgrastim schedule variation on hematopoietic recovery post-chemotherapy.

BACKGROUND: A phase 2 trial was done to study effects of varying treatment schedule of Filgrastim (r-metHuG-CSF) on hematologic recovery following chemotherapy. PATIENTS AND METHODS: Forty-six patients with extensive small-cell carcinoma of the lung were randomized to receive one of three Filgrastim schedules following cyclophosphamide, doxorubicin, and etoposide (CAE) chemotherapy for up to six cycles of treatment. Chemotherapy was delivered on days 1-3 of each 21-day cycle with Filgrastim initiated at 5 micrograms/kg/day subcutaneously (SC) beginning on day 4, day 6, or day 8 and continuing until post-nadir neutrophil recovery. RESULTS: During the first cycle of chemotherapy, the duration of neutropenia was similar for all three schedules; however, the pattern of absolute neutrophil count (ANC) recovery differed. In subsequent cycles of treatment, an improvement in the severity of neutropenia occurred in patients on the day-4 and day-6 schedules compared with the first cycle of chemotherapy. By contrast, patients on the day-8 schedule continued to experience neutropenia similar to that seen in cycle one. Patients on the day-8 schedule also experienced a greater magnitude of grade IV thrombocytopenia in later cycles of treatment. CONCLUSION: Timing of Filgrastim administration post-chemotherapy has profound effects on hematologic recovery. Delay of Filgrastim until day 8 was associated with suboptimal hematologic recovery compared with administration of Filgrastim on day 4 or day 6. Initiation of Filgrastim on day 4 or day 6 showed a similar pattern of hematologic recovery. Beginning Filgrastim on day 6 is associated with a decrease in the total dose of Filgrastim administered.

A placebo-controlled, crossover comparison of salmeterol and salbutamol in patients with asthma.

We compared the effects of salmeterol (Sm) (50 micrograms twice daily) with that of salbutamol (Sb) (200 micrograms four times daily) and placebo (P) in patients with mild-to-moderate asthma with asthma symptoms and related the effectiveness of these therapies between patients who used concurrent inhaled corticosteroids (ICS) and those who did not. The study was a 12-wk, multicenter, double-blind, placebo-controlled crossover trial with 367 adult asthmatics randomized to each trial medication for 4 wk. Inhaled Sb was provided as rescue medication to all patients throughout the trial. Only 80% of patients, albeit the majority, were receiving maintenance treatment with ICS throughout this trial; this reflects practice current in early 1990. Each study day, patients recorded their morning and evening peak expiratory flows (PEF), assessment of asthma symptoms, and use of rescue medication. Both morning and evening PEF were greater during treatment with Sm than with Sb (mean differences between the treatments of 29.8 and 14.3 L/min, respectively) or P (27.7 and 20.3 L/min, respectively) (p < 0.0001). Sm was also more effective than Sb or P in lowering diurnal variation in PEF and increasing the percentage of symptom-free days and rescue-free days and nights with no sleep disturbance (p < or = 0.0004). Sb was more effective than P in increasing evening PEF and the percentage of symptom-free days (p < 0.05) and rescue-free days (p < 0.0001). The same clinical superiority of Sm compared with Sb and P was observed in those patients using ICS (p < 0.001 for all treatment comparisons), and to a greater extent than in those patients not using ICS (i.e., Sm was more effective than Sb and P in just six of the 20 treatment comparisons; p < 0.05). In conclusion, Sm 50 micrograms twice daily is effective in the management of mild-to-moderate asthma and it further improves asthma control in patients already using ICS.

Treatment of small cell lung carcinoma in the elderly.

BACKGROUND: The number of elderly people with small cell lung carcinoma (SCLC) is increasing and currently nearly 25% are older than 70 years. Elderly patients may not tolerate intensive therapy and, therefore, often do not receive such treatment. Additionally, age may be an independent predictor for response and survival. We compared the investigation, staging procedure, and management of patients less than 60 years, 60 to 69, and older than 70 years who were diagnosed with SCLC between 1985 and 1991. We hypothesized that elderly patients were investigated and treated less aggressively, and that their outcome was poorer than that of younger patients with SCLC. METHODS: Information on weight loss, performance status, coexisting disease, staging investigations, and treatment was recorded. Treatment was categorized as optimal or suboptimal using predetermined criteria, and correlated with patient age. Toxicity grade, response to treatment, and survival were noted. RESULTS: There were no differences among the 3 age groups with respect to disease stage, and weight loss, although poorer performance status and comorbidity were more common in those patients older than 70 years. Elderly patients were investigated and treated less aggressively than the 2 younger patient groups. The oldest group received smaller chemotherapy dosage, fewer cycles, and had more dose reductions compared to the younger patients. Only 1 of 81 elderly patients was enrolled on an experimental protocol as compared with 19% and 28% of the younger patient groups. Furthermore, elderly patients had the highest frequency of supportive care alone. There was a significant relationship between advanced age and suboptimal treatment, with those older than 70 years having an odds ratio (OR) of 0.30 (95% confidence interval (CI) 0.15-0.61), for having received optimal treatment. Despite this, survival was similar for younger and older groups of patients (OR 0.89, CI 0.6-1.3). CONCLUSIONS: Elderly patients had poorer pre-treatment performance status, greater comorbidity, were more likely to have suboptimal therapy and were almost never entered into clinical trials. Despite this their survival did not differ from that of younger patients with SCLC. Randomized trials of treatment, with assessment of quality of life, are necessary to determine the effect of modified regimens for elderly patients with SCLC.

Cyfra 21-1 as a biologic marker of non-small cell lung cancer. Evaluation of sensitivity, specificity, and prognostic role.

BACKGROUND: Cytokeratins are epithelial markers whose expression is not lost during malignant transformation. Cyfra 21-1 is a cytokeratin-19 fragment that is soluble in serum and may be a useful circulating tumor marker. STUDY OBJECTIVE: The aims of this study were (1) to confirm sensitivity and specificity of Cyfra 21-1 in detecting non-small cell lung cancer (NSCLC) and especially the squamous cell subtype, (2) to assess the potential relationship between Cyfra 21-1 and disease stage of the disease in NSCLC, and (3) to evaluate prognostic effect of Cyfra 21-1 in NSCLC. METHODS: An immunoradiometric assay of serum Cyfra 21-1 was performed in 161 patients with lung cancers and 71 others with benign lung diseases. The ability of Cyfra 21-1 to detect different histologic subtypes of lung cancer vs benign lung diseases was assessed through receiver operating characteristic (ROC) curves and comparisons with other tumor markers such as carcinoembryonic antigen, neuron-specific enolase, and squamous cell carcinoma antigen. Comparisons of Cyfra 21-1 levels according to histologic subtype and disease stage were done using Kruskal-Wallis test. Independent prognostic value of Cyfra 21-1 was studied with a multivariate analysis of survival (Cox's model). RESULTS: Using a threshold of 3.3 ng/mL for Cyfra 21-1, sensitivity and specificity were, respectively, 0.59 and 0.94 in NSCLC, 0.68 and 0.94 in the subgroup of the squamous cell carcinoma, and 0.19 and 0.94 in small cell lung cancer. Cyfra 21-1 levels were significantly higher in advanced NSCLC than in early-stage disease. All 29 patients with serum concentrations > 32 ng/mL had stage IIIB-IV and only one of 14 patients with stage I-II disease had Cyfra 21-1 level > 18 ng/mL. In the multivariate analysis of survival, Cyfra 21-1 was an independent prognostic factor along with performance status and disease stage in NSCLC. CONCLUSIONS: Cyfra 21-1 is a sensitive and specific tumor marker of NSCLC, especially of squamous cell subtype. It also reflects the extent of the disease and has an independent prognostic role along with performance status and disease stage in NSCLC. IMPLICATIONS: A high level of Cyfra 21-1 in apparently early-stage NSCLC should be an indication for more extensive workup before thoracotomy. The independent prognostic role of Cyfra 21-1 level may be useful in stratifying populations with advanced NSCLC or early-stage resected NSCLC as elevated Cyfra 21-1 levels might identify those patients at high risk for treatment failure.

Fatal pulmonary toxicity following oral etoposide therapy.

Oral etoposide has considerable activity in small cell lung cancer and the low risk of toxicity has resulted in the frequent prescription of this agent in elderly or infirmed patients. We describe a case of fatal pulmonary toxicity following the administration of oral etoposide. This is the first report of biopsy-proven pulmonary toxicity associated with this agent.

Efficacy of Uniphyl, salbutamol, and their combination in asthmatic patients on high-dose inhaled steroids.

A group of 32 patients with moderately severe, chronic asthma (mean FEV1 55% of predicted), maintained on moderately high doses of inhaled corticosteroids (mean dose 1,100 micrograms/d), participated in this double-blind, placebo-controlled crossover study. The effect on pulmonary function of adding theophylline (U, once daily Uniphyl), inhaled salbutamol (S, 200 micrograms four times per day), and their combination (C) or placebo (P) was assessed on Day 14 of each treatment phase. Patients recorded peak expiratory flow, asthma symptom severity (morning and evening), and use of rescue salbutamol inhaler in daily diaries. Mean FEV1 between 0730 and 1800 h and maximum FEV1 between 0730 and 1300 h were significantly higher on U, S, and C compared with P (p < 0.006). Morning peak flow and FEV1 (0730 h) were significantly higher on U and C compared with S and P (p < 0.01). Evening peak flow was higher on U than P (p < 0.001), and C was higher than S and P (p < 0.01). Rescue salbutamol inhaler use was significantly higher on P than on U, C, or S (p = 0.0001). Patient rating of asthma symptoms during C was significantly better than on S or P (p < 0.05). Patient rating of asthma control and study phase preference was significantly higher on combination and Uniphyl alone than on placebo, the combination also being superior to salbutamol alone. Addition of Uniphyl or a combination of Uniphyl and salbutamol significantly improves pulmonary function and asthma symptoms in patients treated with high doses of inhaled corticosteroids and as-needed beta agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

[Monoclonal antibodies and bronchial cancer]. / Anticorps monoclonaux et cancer bronchique.

Techniques of production of monoclonal antibodies (MoAb) have provided powerful tools to study biological lung cancer behavior. Immunochemistry is more sensitive than conventional light microscopy examination to detect tumour cells in sputum or pleural effusion, or small cell lung cancer metastases in bone marrow. Immunochemistry is also helpful for the differential diagnosis of carcinoma versus lymphoma or sarcoma, using antibodies directed against antigens such as cytokeratins, vimentin, EMA, LCA, SP100, CEA. In lung cancer, immunochemistry may detect neuroendocrine differentiation, or help to distinguish metastatic carcinoma from primary lung cancer. A positive immunostaining with CEA, Leu-M1, SP1, B72-3 supports the diagnosis of pleural metastatic adenocarcinoma versus mesothelioma. Immunoscintigraphy is a non invasive imaging technique which allows local and distant disease evaluation and could replace in the future the present staging work up. To evaluate the potential therapeutic efficacy of MoAbs in Lung cancer, phase I studies have been performed. Therapeutic effect is based on: 1) indirect cytotoxicity (cells are killed by ADCC or K cells) or direct cytotoxicity (MoAb are carriers of toxins, radioisotopes or drugs). 2) Immune response modulation by anti-idiotypic Ab. 3) Interferences with growth factors. Results of most of phase I trials are disappointing. Improvement of MoAb selectivity, improvement of conjugates stability, reduction of humoral response to MoAb, enhanced tumour localisation, and reduction of nonspecific captation should lead to a better efficacy.