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Biomedical subjects

S G Spiro

Publications and source records attributed to S G Spiro.

At least 19 recordsLinked to original sources
PubMed2003

Surgery for nonsmall cell lung cancer: can improvements be made?

Low-dose spiral computed tomography (CT) for the earlier detection of lung cancer is at the stage of producing hypothesis-generating studies. These studies have shown that more cancers are found at a favourable stage (IA) in prevalence screening but that the fewer numbers found in incidence screening tend to have a slightly worse stage. Randomised controlled trials will be necessary to resolve the place of spiral CT screening. The role of neo-adjuvant chemotherapy before surgery in nonsmall cell lung cancer looks less promising than suggested by earlier studies and the place of adjuvant chemotherapy following surgery appears to be unhelpful, although results of some large, randomised international studies are still awaited. Radical radiotherapy is a poor alternative to surgery in resectable patients who refuse or are unfit for surgery and postoperative radiotherapy is detrimental. Positron emission tomography scanning offers a genuine opportunity to identify occult disease and improve staging prior to surgery and therefore save futile thoracotomies in approximately 20% of patients otherwise apparently suitable for resection.

Carcinoma, Non-Small-Cell Lung↗
PubMed2002

Mandibular advancement splints and continuous positive airway pressure in patients with obstructive sleep apnoea: a randomized cross-over trial.

This prospective, randomized, cross-over trial was designed to compare the efficacy of a mandibular advancement splint (MAS) with that of nasal continuous positive airway pressure (nCPAP) in patients with obstructive sleep apnoea (OSA). Twenty-four patients (20 males and four females) with mild to moderate OSA (AHI between 10 and 49 events per hour) were enrolled in the study. Each patient used both MAS and nCPAP, with the initial therapy being allocated at random. Treatment periods lasted for two months with a two-week wash-out interval between. Polysomnography was performed prior to the study and after each clinical intervention. Patient and partner questionnaires were used to assess changes in general health and daytime somnolence. The AHI decreased from 22.2 to 3.1 using nCPAP, and to 8.0 using the MAS (P < 0.001 for both devices) and there was no statistically significant difference between the two treatments. The Epworth Sleepiness Score (ESS) fell from 13.4 to 8.1 with nCPAP, and to 9.2 with MAS (P < 0.001), again with no differences between the use of MAS or nCPAP. The questionnaire data showed an improvement in general health scores (P < 0.001) after both treatments, but daytime sleepiness only improved significantly using nCPAP (P < 0.001). Despite this, 17 out of the 21 subjects who completed both arms of the study preferred the MAS. The splints were well tolerated and their efficacy suggests that the MAS may be a suitable alternative to nCPAP in the management of patients with mild or moderate OSA.

Adult↗
PubMed2002

Some factors affecting cerebral tissue saturation during obstructive sleep apnoea.

Measurement of cerebral tissue saturation during obstructive sleep apnoea (OSA) may provide additional information to conventional peripheral oxygen saturation. Thirteen subjects with OSA (mean apnoea/hypopnoea index 65.7+/-27.9) were monitored using full polysomnography and monitoring of near-infrared cerebral tissue oxygenation index (TOI). One-thousand and thirty-six apnoeas and hypopnoeas were analysed, in terms of duration, sleep stage, arterial oxygen saturation (Sa,O2) dip, minimum Sa,O2, TOI dip and minimum TOI. Cerebral TOI is a measure of cerebral tissue saturation of haemoglobin with oxygen, calculated using near-infrared spatially resolved spectroscopy, which has been shown to have a high specificity for intracranial changes. Decreases in cerebral oxygenation were observed during apnoeas and hypopnoeas. Baseline TOI ranged from 50.1-73.0% and mean apnoea/hypopnoea related TOI dips ranged from 1.43-6.85%. Mean Sa,O2 dips varied from 3.8-21.7%. In regression analysis, factors significantly predicting the magnitude of the TOI dip were Sa,O2 dip, minimum Sa,O2, apnoea duration and rapid eye movement sleep stage. The effect of apnoea duration and sleep stage remained significant after Sa,O2 was included in the regression equation. Near-infrared spectroscopy provides a noninvasive technique for monitoring cerebral tissue saturation during obstructive sleep apnoea.

Adult↗
PubMed2001

Long-term use of mandibular advancement splints for snoring and obstructive sleep apnoea: a questionnaire survey.

A mandibular advancement splint (MAS) may be an alternative treatment for snoring and obstructive sleep apnoea (OSA). However, there is little subjective or objective information concerning long-term effectiveness, compliance and side effects. A retrospective questionnaire was used to survey these issues plus patient satisfaction and maintenance requirements in 166 patients who could have worn a mandibular advancement splint for over a year. One-hundred and twenty-six (76%) subjects returned the questionnaire, (84 with OSA, 42 snorers), of whom 69 (55%) reported still using the splint regularly, 47 (37%) every night. The most common reported reasons for stopping use were discomfort (29/ 57; 52%) of nonusers), and poor perceived efficacy (12 subjects). Users reported more daytime symptoms, and they and their partners were more likely to observe improvements with splint use. Side effects were reported by 49 subjects, more commonly in nonusers. Sixty-five of 67 current users and 23 of 41 nonusers reported less snoring with splint use (p = < 0.001). Long-term mandibular advancement splint usage appeared less satisfactory than previously reported, however, splints were considered effective by 97% of current users and even by over half of those who had stopped use. Reasons for stopping use included side effects, social circumstances, dental treatment, as well as lack of perceived efficacy.

Female↗
PubMed2000

Inhaled steroid therapy in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) remains difficult to manage. Patients with COPD present with progressive dyspnea; difficulty in stopping smoking; recurrent exacerbations; and, ultimately, respiratory failure. Because of the lack of proven treatments for COPD and because inhaled corticosteroids can prevent airway inflammation and permanent lung damage in patients with asthma, it has become common practice to prescribe inhaled corticosteroids for patients with COPD despite a lack of data suggesting that these agents have any long-term benefit in these patients. In the past 12 months, three randomized, double-blind, placebo-controlled clinical trials (the European Respiratory Society Study on Chronic Obstructive Pulmonary Disease, the Copenhagen City Lung Study, and the Inhaled Steroids in Obstructive Lung Disease study) designed to assess the long-term effect of inhaled corticosteroids in patients with varying severity of airway obstruction have been presented. The results of these studies have been disappointing; they show little to suggest that any long-term benefit is gained from using inhaled corticosteroids in most patients with COPD, whether they continue to smoke or not.

Administration, Inhalation↗
PubMed2000

Recruitment of patients with lung cancer into a randomised clinical trial: experience at two centres. On behalf of the Big Lung Trial Steering Committee.

BACKGROUND: The entry of patients into randomised clinical trials (RCTs) in lung cancer is low. A study was undertaken to assess the reasons why patients with non-small cell lung cancer did not enter a trial involving randomisation to receive or not receive three courses of cisplatin based chemotherapy in addition to primary treatment by surgery, radiotherapy, or best supportive care. METHODS: The study was carried out in two large London institutions with a special interest in recruiting patients to lung cancer trials. Patients recently diagnosed as having non-small cell lung cancer were prospectively identified and followed to see whether they entered the RCT and, if not, to identify the main reasons why. RESULTS: Six hundred and eighty eight patients newly diagnosed with non-small cell lung cancer were identified between November 1995 and July 1998; 274 (39.8%) were deemed ineligible for the RCT for clinical reasons, most frequently their general condition rendering them unfit for chemotherapy. Another 161 (23.4%) were ineligible for logistical reasons-for example, they were discharged to centres not participating in the RCT or they were not considered for the trial at an appropriate time in their management. Of 253 potentially eligible patients, only 63 (24.9% of those eligible) agreed to enter the RCT and four entered another study. Of those who did not enter, 77 (41.4%) declined without stating a reason, 61 (32.8%) did not want chemotherapy, and only eight (4.3%) expressed a wish to have chemotherapy. CONCLUSIONS: Despite considerable time and effort, the proportion of patients recruited was small (9.2%). Many seen were ineligible but, of 253 potentially eligible patients, 186 (73.5%) refused to enter the RCT.

Adult↗
PubMed2000

Pulmonary embolism: clinical features and management.

Pulmonary embolism (PE) often presents diagnostic difficulties, as its presentation is varied and non-specific. This article attempts a logical approach to the management of a patient with suspected PE, starting with how it may occur, the assessment of clinical probability of PE and subsequent investigations and treatment.

Acute Disease↗
PubMed1999

Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life.

PURPOSE: Chemotherapy for non-small-cell lung cancer (NSCLC) remains controversial. We describe the two largest reported, randomized, parallel trials designed to determine whether the addition of chemotherapy influences duration and quality of life in localized, unresectable (mitomycin, ifosfamide, cisplatin [MIC]1 trial) and extensive (MIC2 trial) disease. PATIENTS AND METHODS: Ambulatory patients with NSCLC, aged 75 years or younger, with localized disease, were randomized in MIC1 to receive up to four cycles of chemotherapy (CT: mitomycin 6 mg/m(2), ifosfamide 3 g/m(2), and cisplatin 50 mg/m(2)) every 21 days, followed by radical radiotherapy (CT + RT) or radiotherapy (RT) alone. Extensive-stage patients were randomized in MIC2 to identical chemotherapy plus palliative care (CT + PC) or palliative care (PC) alone. Short-term change in quality of life (QOL) was assessed in a subgroup of patients. Data from the two trials were combined to allow multivariate and stratified survival analyses. RESULTS: Seven hundred ninety-seven eligible patients were randomized, 446 in MIC1 and 351 in MIC2. MIC CT improved survival in both trials (significantly in MIC2). The median survival time in MIC1 was 11.7 months (CT + RT) versus 9.7 months (RT alone) (P =.14); whereas in MIC2, median survival time was 6.7 months (CT + PC) compared with 4. 8 months (PC alone) (P =.03). QOL, assessed in 134 patients from start of trial to week 6, showed improvement with chemotherapy and deterioration with standard treatment. In the combined analysis of 797 randomized patients, the positive effect of MIC on survival was significant overall (P =.01) and after adjusting for prognostic factors (P =.01). CONCLUSION: MIC chemotherapy prolongs survival in unresectable NSCLC without compromising QOL.

Adult↗
PubMed1997

Five-day oral etoposide treatment for advanced small-cell lung cancer: randomized comparison with intravenous chemotherapy.

BACKGROUND: Oral etoposide is an active single agent in small-cell lung cancer (SCLC) and is widely prescribed as first-line treatment as an alternative to intravenous combination chemotherapy in patients with extensive disease. PURPOSE: The intention of this study was to determine if the effects of oral etoposide therapy on survival and quality of life are equivalent to those of intravenous chemotherapy. METHODS: In a randomized trial of palliative treatment in advanced SCLC, oral etoposide (100 mg given twice daily for 5 days) was compared with intravenous chemotherapy consisting of alternating cycles of cisplatin and etoposide (PE) and cyclophosphamide, doxorubicin, and vincristine (CAV). Six cycles of chemotherapy were administered every 21 days in both regimens. Symptom control and quality of life were measured with the Rotterdam Symptom Checklist and a daily diary card. In January 1996, after 155 patients had been randomly assigned from a projected intake of 365 patients, an independent Data Monitoring Committee examined the interim results. Survival was determined by the Kaplan-Meier method, and the logrank test was used to compare treatments. For quality-of-life comparisons, average scores were calculated for each time point. The Mann-Whitney U test was used to determine any significant overall differences between treatments. For the Rotterdam Symptom Checklist, separate analyses were done for each subset (psychological well-being, physical symptoms, lung cancer symptoms, treatment symptoms, activity, and quality of life). Response rates and toxicity scores were compared by using chi2. All statistical tests were two-sided. RESULTS: Survival was inferior at 1 year in the oral etoposide group compared with intravenous therapy (9.8% for oral versus 19.3% for intravenous; difference = 9.5%; 95% confidence interval of difference = 0.3%-18.7%; P<.05), and there was a trend toward inferior overall survival. Median survival was 4.8 months for oral treatment and 5.9 months for intravenous therapy. Progression-free survival was worse in the oral etoposide arm (median = 3.6 months versus 5.6 months; P<.001), as well as overall response rate (32.9% versus 46.3%; P<.01). With the exception of acute nausea and vomiting associated with intravenous chemotherapy, all aspects of symptom control and quality of life were either the same or worse in the oral etoposide group. Study closure was recommended. CONCLUSIONS: These interim results show that this schedule of oral etoposide is inferior to intravenous chemotherapy in the treatment of advanced SCLC and should not be used as first-line treatment of this disease.

Administration, Oral↗
PubMed1996

A randomised trial of low-dose/high-frequency chemotherapy as palliative treatment of poor-prognosis small-cell lung cancer: a Cancer research Campaign trial.

We report the results of a randomised trial in extensive small-cell lung cancer (SCLC) of a novel approach to palliative chemotherapy. A widely used 3 weekly regimen was compared with the same drugs given at half the dose but twice the frequency with the same intended overall dose intensity (DI). A total of 167 patients defined as having extensive SCLC with adverse prognostic features were randomised to receive either a 3 weekly regimen of cisplatin 60 mg m-2 i.v. on day 1 and etoposide 120 mg m-2 i.v. on day 1 and 100 mg b.d. orally on days 2 and 3 alternating with cyclophosphamide 600 mg m-2 i.v., doxorubicin 50 mg m-2 i.v. and vincristine 2 mg i.v. all on day 1 for a maximum of six courses (3 weekly); or treatment with the same drugs but with each course consisting of half the 3 weekly dose given every 10 or 11 days for a maximum of 12 courses. In the 10/11 day regimen overall response rate was 58.9% (95% CI, 47.9-69.2%) with 12.8% complete responses (CR). For the 3 weekly treatment the overall response rate was 44.9% (95% CI, 35.0-55.5%) with 10.1% CR. Median survival was similar in the two arms at 6.4 months (95% CI, 4.9-7.3 months) and 5.8 months (95% CI, 4.0-6.6 months) respectively. Survival at 1 year was 9.9% (95% CI, 5.0-18.5%) and 8.9% (95% CI, 4.6-16.6%). The 95% CI for the difference in survival at 1 year is -7.09% to +9.09%. Haematological toxicity and treatment delays owing to infection were more frequent with the 10/11 day regimen but other toxicities were equal in both arms. Other aspects of quality of life were measured in a small representative cohort of patients using a daily diary card (DDC). There was a trend of improved quality of life on the 10/11 day arm, but there was little difference between the two treatments. The trial shows that a low-dose/high-frequency regimen with the same DI as conventionally scheduled chemotherapy gives similar response rates and survival. This and other modifications of the schedule may offer new approaches to palliative treatment of advanced cancer. However, in this trial there was no significant benefit in toxicity or other aspects of quality of life.

Adult↗
PubMed1995

Assessment of 'quality of life' using a daily diary card in a randomised trial of chemotherapy in small-cell lung cancer.

BACKGROUND: Quality of life (QOL) was assessed using a daily diary-card within a multicentre randomised trial of treatment of small-cell lung cancer. The trial compared a weekly dose-intensive regimen with a 3-weekly conventional treatment in good prognosis patients, that is patients with limited disease or extensive disease with a good performance status (ECOG 0or 1) and alkaline phosphatase of less than one and a half times the upper limit of normal. The trial which has been previously reported detected no difference in response or survival. PATIENTS AND METHODS: Daily diary cards (DDCs) were collected for up to eight months from the first day of chemotherapy in a cohort of 75 patients at one centre. Percentages of scores over a specified level were calculated for each of the eight diary card questions and comparisons were made between treatment arms. RESULTS: During the period of chemotherapy compliance in completing DDCs was 72.5% in the weekly arm and 77.2% in the 3 weekly. Significantly worse scores were reported with weekly chemotherapy during this period for six of the eight parameters, namely: ;nausea, vomiting, happiness, appetite, general well-being and sleep. Recognised problems of QOL data collection, in particular, compliance, attrition and generalisability are highlighted by this study and are discussed in the paper. CONCLUSIONS: The QOL measurements indicate that 3 weekly chemotherapy is the preferred treatment. This study demonstrates that QOL measurements may be helpful in choosing between treatment alternatives where no difference in outcome is observed.

Adult↗
PubMed1994

Phase II study of fotemustine in untreated inoperable non-small-cell lung cancer.

A total of 43 patients with advanced, previously untreated non-small-cell lung cancer (NSCLC) were treated with a novel nitrosourea, fotemustine, given at 100 mg/m2 on days 1 and 8. Maintenance treatment consisted of a single injection of 100 mg/m2 given every 21 days. 37 patients were evaluable for response. Of these, 5 patients had a partial response (13.5%; 95% confidence interval, 6%-28%). Toxicity comprised mainly anaemia and thrombocytopenia. Other toxicities were mild. This phase II study confirms that fotemustine is a moderately active and well-tolerated drug in NSCLC.

Aged↗
PubMed1994

The selection of antibodies for targeted therapy of small-cell lung cancer (SCLC) using a human tumour spheroid model to compare the uptake of cluster 1 and cluster w4 antibodies.

Spheroids of a small-cell lung cancer (SCLC) cell line POC were used to evaluate the uptake and penetration of two antibodies recognising different SCLC antigens. Spheroids approximately 300-400 microns in diameter were incubated with 1 microgram ml-1 125I-labelled NY.3D11, an antibody which reacts with the cluster 1 group antigen (neural cell adhesion molecule; NCAM) and [125I]SWA11, which binds to the cluster w4 antigen. The rate of uptake of both antibodies was similar; an initially rapid phase was seen during the first 8 h and maximum uptake occurred by 24 h. The mean uptake per spheroid at 24 h was 0.97 ng for [125I]NY.3D11 and 0.45 ng for [125I]SWA11. An objective measurement of antibody penetration into spheroids was developed using a computerised image analysis of immunostained sections of spheroids. The concentration of antibody and incubation times were varied. Both antibodies penetrated the spheroids to a depth of 50 microns after 30 min. This increased to about 100 microns after 4 h incubation with 1 or 100 micrograms ml-1 SWA11. The results with 1 microgram ml-1 NY.3D11 were similar, but in the presence of 100 micrograms ml-1 NY.3D11 penetration into the spheroid was deep and diffuse. These results demonstrate a major concentration-dependent difference in the uptake and penetration of cluster 1 and cluster w4 antibodies in this spheroid model and they have implications for the selection of antibodies for targeted therapy of SCLC.

Antibodies, Monoclonal↗
PubMed1994

Received dose-intensity: a randomized trial of weekly chemotherapy with and without granulocyte colony-stimulating factor in small-cell lung cancer.

PURPOSE: A prospective randomized trial to determine if granulocyte colony-stimulating factor (G-CSF) could increase the received dose-intensity (RDI) of weekly chemotherapy in patients with small-cell lung cancer (SCLC). PATIENTS AND METHODS: Forty patients with SCLC with good prognostic features (all patients with limited disease [LD], and extensive-disease [ED] patients with Eastern Cooperative Oncology Group [ECOG] 0 or 1 and plasma alkaline phosphatase levels < 1.5 times the upper limit of normal) were randomized to receive weekly chemotherapy with or without G-CSF. G-CSF (5 micrograms/kg) was self-administered subcutaneously on days when chemotherapy was not given. Chemotherapy consisted of cisplatin 50 mg/m2 intravenously (IV) on day 1 and etoposide 75 mg/m2 IV on days 1 and 2 alternating weekly with ifosfamide 2 g/m2 IV (with mesna) and doxorubicin 25 mg/m2 on day 1, for a total of 12 courses. Dose modifications (dose reductions and treatment delays) were made according to defined hematologic criteria. RESULTS: Dose reductions were made at some point during treatment in 12 of 17 patients in the control arm and in 11 of 23 patients in the G-CSF arm (P = .20). The proportion of patients experiencing dose reductions due to leukopenia was significantly higher in the control arm (nine of 17) compared with the G-CSF arm (four of 23, P < .04). Cycle delays due to leukopenia were similar in both arms of the study. The RDI was 82% of projected in the control arm (95% confidence interval [CI], 79% to 84%) and 84% in patients receiving G-CSF (95% CI, 82% to 87%) (P value not significant). CONCLUSION: In this randomized trial, G-CSF significantly decreased dose reductions due to neutropenia. However, administration of G-CSF did not decrease dose reductions or treatment delays to a level that would allow an increase in received dose-intensity. Nonhematologic toxicities such as increased creatinine concentration also prevented an increase in the RDI in the G-CSF arm.

Adult↗