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V Ninane

Publications and source records attributed to V Ninane.

At least 37 records · Page 2Linked to original sources
PubMed2003

Epidermal growth factor receptor expression in pre-invasive and early invasive bronchial lesions.

The 1999 World Health Organization/International Association for the Study of Lung Cancer histological classification of preneoplastic bronchial lesions has been shown to be reproducible but little is known about its biological significance. The current study evaluated the correspondence between the morphological changes of the bronchial epithelium and epidermal growth factor receptor (EGF-R) expression. Thirteen normal bronchial epithelia, 19 hyperplasia, 16 metaplasia, 10 mild dysplasia, one moderate dysplasia, 10 severe dysplasia (SD), 14 carcinoma in situ (CIS) and 11 microinvasive tumours were assessed. A global EGF-R score obtained by the sum of the positivity score plus the EGF-R staining intensity score was calculated for each lesion. A global EGF-R score of >5 was reached only in one metaplasia, in six SD, in six CIS and in six microinvasive tumours. There was no difference in EGF-R expression between normal, hyperplastic and metaplastic epithelia versus mild dysplasia or between severe dysplasia versus CIS and microinvasive tumours but there was a statistically significant difference between mild versus severe dysplasia. This study demonstrates that epidermal growth factor receptor expression rate changes with the stage of the bronchial lesion, increasing from normal epithelium to carcinoma in situ and microinvasive tumours with a statistically significant difference between mild versus severe dysplasia.

Adult↗
PubMed2003

Fragile histidine triad protein expression in nonsmall cell lung cancer and correlation with Ki-67 and with p53.

Fragile histidine triad (FHIT) is a tumour suppressor gene, which is altered in a variety of epithelial tumours, including lung cancer. Biochemical and functional pathways of its tumourigenicity are not yet understood. Its role in tumour proliferation is particularly controversial. The purpose of this study was to correlate the expression of FHIT protein in nonsmall cell lung cancer (NSCLC) with tumour proliferation as estimated by Ki-67 antigen and with p53, a suppressor gene. FHIT, Ki-67 and p53 expression were evaluated by immunohistochemistry in 119 resected NSCLC. Altogether, 58 tumours were negative (expression <10%) for FHIT. The median expression in tumours was 15% positive cells, in comparison with 100% in normal matched lung tissue. The expression was as strong as in normal tissue in only 19 cases. FHIT expression was significantly lower in squamous cell carcinoma (SCC) (5%) than in adenocarcinoma (ADC) (64%). The median expression of Ki-67 was 20% and 69% of tumours were positives (expression >10%). Ki-67 expression was significantly higher in SCC (33.3%) than in ADC (10%). The loss of FHIT protein was not correlated with the expression of p53 (median: 7.5%, 58% of positive tumours for a cut-off of 10% of positive cells) or Ki-67. But percentage of labelled cells for p53 and Ki-67 were significantly correlated. The results suggest that for fragile histidine triad, the pathway of tumourigenesis is independent of p53 and of tumoural proliferation, as reported previously in vitro.

Acid Anhydride Hydrolases↗
PubMed2003

[EGF-R expression correlation between biopsy and surgical specimens of lung carcinoma].

INTRODUCTION: Most of the time, biological parameters are evaluated on tissues obtained on surgical samples of the primary tumour. New approaches in non small cell lung cancer (NSCLC) treatment consist to administer neoadjuvant chemotherapy or anti-EGF-R (epidermal growth factor receptor) drug. METHODS: We assessed the expression of EGF-R by immunohistochemistry on biopsy samples and on the paired resected tumours in 27 patients. RESULTS: The mean percentage of EGF-R positive neoplastic cells was 11% in surgical specimens compared to 28% in biopsy specimens (p=0.02) although a good correlation (R=0.67; p=0.0001) between biopsies and surgical specimens was observed. Furthermore, the positivity (cut-off > 1% cells) rate was not statistically different between biopsies (55%) and tumours (48%) (p=0.63). In term of positivity rate, we found 85% concordant results between biopsies and resected tumours, 4% false negative and 11% false positive on biopsies in comparison with the resected tumours. The positive and negative predictive value of the biopsies were respectively 80% and 92%. CONCLUSIONS: The evaluation of EGF-R by immunohistochemistry on biopsies may provide reliable information about non small cell lung cancer EGF-R status.

Adenocarcinoma↗
PubMed2002

A phase II study testing paclitaxel as second-line single agent treatment for patients with advanced non-small cell lung cancer failing after a first-line chemotherapy.

The purpose of this study was to determine the activity of paclitaxel as a second-line chemotherapy for non-small cell lung cancer (NSCLC). This multicentric trial included patients who had failed to a first-line chemotherapy with platinum derivatives and/or ifosfamide. After registration, patients were treated by paclitaxel i.v. at a dose of 225 mg/m(2) given over 3 h administered every 3 weeks. Response was assessed after three courses of therapy. Sixty-seven patients were registered, one was ineligible and 64 were assessable for response. Two partial responses were observed (3% of the eligible patients; 95% confidence interval: 0-7%). No change was documented in 16 cases (24%). Tolerance was acceptable, the main toxicity being cumulative polyneuropathy. Median survival duration was 4.5 months with a 1-year rate at 19%. We concluded that paclitaxel is not active in terms of response as second-line chemotherapy for NSCLC.

Adult↗
PubMed2002

A three-arm phase III randomised trial comparing combinations of platinum derivatives, ifosfamide and/or gemcitabine in stage IV non-small-cell lung cancer.

OBJECTIVE: To determine, in stage IV non-small-cell lung cancer (NSCLC), if the combination of gemcitabine-a new active drug-with ifosfamide (IG) or with the cisplatin-carboplatin association (CCG) will improve survival (primary end point) in comparison with a first-generation regimen, cisplatin-carboplatin-ifosfamide (CCI). PATIENTS AND METHODS: A total of 284 chemotherapy-naïve patients with metastatic NSCLC were randomised. Four were ineligible and 16 were not assessable for responses. Cisplatin was given at 60 mg/m2 on day 1, carboplatin AUC 3 mg.min/ml on day 1, ifosfamide 4.5 g/m2 on day 1 and gemcitabine 1 g/m2 on days 1, 8 and 15. Courses were repeated every 4 weeks. Response was assessed after three courses and chemotherapy was continued in responding patients until best response. There were 94 eligible patients in the CCI arm, 92 in CCG and 94 in the IG arm. RESULTS: The objective response rates for CCI, CCG and IG were 23% [95% confidence interval (CI) 15% to 32%], 29% (95% CI 20% to 39%) and 25% (95% CI 16% to 33%), respectively ( P = 0.61). Median survival time was 24, 34 and 30 weeks, respectively (P = 0.20). One-year survival was 23, 33 and 35%, and 2-year survival was 11, 14 and 17%, respectively. In some subgroups (older patients, women), there was a significant survival advantage for CCG and IG compared with CCI. Toxicity was tolerable: severe alopecia was less frequent in the CCG arm, and IG was associated with significantly more thrombopenia while CCG was associated with more leucopenia. CONCLUSION: In stage IV NSCLC, treatment with regimens including the new drug gemcitabine were associated with a better but not statistically significant observed survival compared with a classical first-generation cisplatin-containing regimen. The non-platinum combination of gemcitabine was as effective as its combination with platinum.

Adult↗
PubMed2002

A phase II randomised trial comparing the cisplatin-etoposide combination chemotherapy with or without carboplatin as second-line therapy for small-cell lung cancer.

BACKGROUND: A phase II randomised trial was performed with patients with SCLC to determine if the addition of carboplatin to cisplatin-etoposide might improve the response rate in second-line therapy. PATIENTS AND METHODS: Sixty-five eligible patients were randomised: 31 for CE (cisplatin 20 mg/m(2) and etoposide 100 mg/m(2) on days 1-3) and 34 for CCE (carboplatin 200 mg/m(2) on day 1, cisplatin 30 mg/m(2) on days 2-3, etoposide 100 mg/m(2) on days 1-3). RESULTS: Eighty-two per cent of these patients had an objective response to first-line therapy and, among responders, 63% had a treatment-free interval of >3 months after previous therapy. The best response rates were 29% [95% confidence interval (CI) 13-45] and 47% (95% CI 30-64) for CE and CCE, respectively, with median survival times of 4.3 and 7.6 months. Dose-intensity analysis revealed a significant improvement in the relative dose-intensity and etoposide absolute dose-intensity for CE. Toxicity was tolerable and comparable between the two study arms. CONCLUSION: CCE appears to be associated with a high objective response rate. The phase II randomised study design suggests that a comparison between the two regimens in a phase III trial would be interesting, but will probably be difficult to perform for reasons of accrual.

Adult↗
PubMed2002

Expiratory flow limitation during exercise in COPD: detection by manual compression of the abdominal wall.

Manual compression of the abdomen (MCA) during spontaneous expiration is a simple method for the detection of flow limitation in the chronic obstructive pulmonary disease (COPD) patients during resting breathing, based on comparison of flow/volume curves obtained during MCA with that of the preceding control breath. It was assessed whether this nonstandardized technique is also feasible during exercise. MCA was performed during resting breathing and constant-exercise work at one- and two-thirds maximal mechanical power output (W'max) in six normal subjects and 12 COPD patients. Changes in end-expiratory lung volume (EELV) were also studied. With the aid of inspection, abdominal palpation and lung auscultation, MCA could always be applied during expiration. Flow limitation was never detected in the six normal subjects, whereas four of the COPD patients were flow limited at rest, seven during exercise at one-third W'max and nine during exercise at two-thirds W'max. Expiratory flow limitation detected by MCA was always associated with an increase in EELV during exercise, indicating dynamic hyperinflation occurrence or increase. It is concluded that manual compression of the abdomen is a very simple and reliable method for the detection of flow limitation during exercise.

Abdominal Wall↗
PubMed2001

A three-arm phase III randomised trial assessing, in patients with extensive-disease small-cell lung cancer, accelerated chemotherapy with support of haematological growth factor or oral antibiotics.

The European Lung Cancer Working Party (ELCWP) designed a 3-arm phase III randomised trial to determine the role of accelerated chemotherapy in extensive-disease (ED) small-cell lung cancer (SCLC). Eligible patients were randomised between the 3 following arms: (A) Standard chemotherapy with 6 courses of EVI (epirubicin 60 mg m(-2), vindesine 3 mg m(-2), ifosfamide 5 g m(-2); all drugs given on day 1 repeated every three weeks. (B) Accelerated chemotherapy with EVI administered every 2 weeks and GM-CSF support. (C) Accelerated chemotherapy with EVI and oral antibiotics (cotrimoxazole). Primary endpoint was survival. 233 eligible patients were randomised. Chemotherapy could be significantly accelerated in arm B with increased absolute dose-intensity. Best response rates, in the population of evaluable patients, were, respectively for arm A, B and C, 59%, 76% and 70%. The response rate was significantly higher in arm B in comparison to arm A (P = 0.04). There was, however, no survival difference with respective median duration and 2-year rate of 286 days and 5% for arm A, 264 days and 6% for arm B and 264 days and 6% for arm C. Severe thrombopenia occurred more frequently in arm B but without an increased rate of bleeding. Non-severe infections were more frequent in arm B and severe infections were less frequent in arm C. Our trial failed to demonstrate, in ED-SCLC, a survival benefit of chemotherapy acceleration by using GM-CSF support.

Administration, Oral↗
PubMed2001

Bronchoscopic invasive diagnostic techniques in the cancer patient.

The cancer patient often presents with fever and pulmonary infiltrates, in particular during the course of chemotherapy or after bone marrow transplantation. In these conditions, specific diagnoses are mainly related to an infective cause, but noninfectious processes, malignant or not, are also found alone or in combination with infection. Identification of the pulmonary process can be achieved by bronchoscopic techniques, including bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB). BAL may help identify opportunistic organisms but also bacterial pneumonia, provided quantitative cultures are performed, and TBB has been shown to increase the diagnostic yield of BAL. These two procedures should then be combined, provided there is no contraindication.

Biopsy↗
PubMed2001

Detection of expiratory flow limitation by manual compression of the abdominal wall.

We have assessed a new method, manual compression of the abdominal wall (MCA) during expiration, in the detection of expiratory flow limitation. Twelve stable patients with chronic obstructive pulmonary disease (COPD) and five normal subjects were studied during spontaneous breathing in the supine and seated posture. MCA was performed during expiration with one hand at the umbilical level and we measured flow, volume, pleural (Ppl) and gastric (Pga) pressures and abdominal anteroposterior (AP) diameter at the umbilical level with magnetometers. No increase in expiratory flow during MCA relative to the preceding breath despite associated increases in pressures was considered as indicating expiratory flow limitation. In seven additional patients with increased upper airway collapsibility (obstructive sleep apnea syndrome [OSAS]), MCA was compared with negative expiratory pressure (NEP). In normal seated subjects, MCA was associated with a decrease in abdominal AP dimension (mean +/- SD: -27 +/- 6%), an increase in Pga (14.7 +/- 7.4 cm H(2)O) and Ppl (6.2 +/- 2.2 cm H(2)O), and an increase in expiratory flow. MCA caused similar changes in abdominal AP dimension and pressures in seated patients with COPD but six of them (50%), including four patients with FEV(1) less than 1 L, had no increase in expiratory flow. In the supine posture, MCA always increased expiratory flow in normal subjects but four additional patients with COPD showed evidence of flow limitation. MCA invariably increased expiratory flow in patients with OSAS whereas the NEP method suggested flow limitation in some cases. We conclude that MCA is a very simple method that allows detection of flow limitation in different positions.

Abdominal Muscles↗
PubMed2000

Prognostic factors for patients with small cell lung carcinoma: analysis of a series of 763 patients included in 4 consecutive prospective trials with a minimum follow-up of 5 years.

BACKGROUND: The purposes of this study were to identify prognostic factors for response to chemotherapy, overall survival, and long term survival of patients with small cell lung carcinoma and to construct a classification of patients on the basis of their expected overall survival. METHODS: In the 763 patients registered in 4 consecutive clinical trials conducted by the European Lung Cancer Working Party from 1982 to 1993, the impact of 21 pretreatment variables assessable in a routine practice was analyzed for the various outcomes with a minimum follow-up of 5 years. RESULTS: The key prognostic role of disease extent was confirmed for all the outcomes. Additional independent prognostic factors for response to chemotherapy were gender, neutrophil count, and hemoglobin level; for overall survival, these factors were Karnofsky performance status, gender, and neutrophil count. Recursive partitioning and amalgamation algorithms (RECPAM) analysis classified patients into 4 groups, taking into consideration disease extent, Karnofsky performance status, age, gender, and neutrophil count. Median survival times for the 4 groups were 60, 47, 36, and 28 weeks, respectively. For long term survival, defined as a minimum survival of 2 years (9% of the patients), Karnofsky performance status was the only independent predictive factor, along with the achievement of a complete response (if this was taken into consideration). Small cell lung carcinoma remained the main cause of death among these patients. Cure was infrequent, with only 14 patients alive and disease free at 5 years (1.8%). CONCLUSIONS: In this study the long term prognosis associated with small cell lung carcinoma was poor. The well-known prognostic values of disease extent and Karnofsky performance status were confirmed, but the authors also identified age and gender (which are more controversial) as independent characteristics, in addition to citing the role of complete response in the attainment of long term survival. The independent role of neutrophils observed by the authors. must be validated by further studies.

Adult↗
PubMed2000

A phase II trial testing gemcitabine as second-line chemotherapy for non small cell lung cancer. The European Lung Cancer Working Party. 101473.1044@compuserve.com.

The purpose of the present trial was to determine the activity of gemcitabine as a second-line chemotherapy for non small cell lung cancer (NSCLC). To be eligible, patients had to have pathologically proven NSCLC that has failed to respond to a first-line chemotherapy with a cisplatin-containing regimen, a Karnofsky performance status greater than 50 and adequate renal, haematological and hepatic functions. After registration, patients were treated by gemcitabine given i.v. at a dose of 1 g/m(2) on days 1, 8, 15 every 4 weeks. Response was assessed after two courses of therapy. Eighty-two patients have been registered, five are ineligible and 65 are assessable for response. Four partial responses were observed (6%). No change was documented in 18 cases (28%). Tolerance was good. A few grade III leucopenia and grade III-IV thrombopenia were observed. We conclude that gemcitabine has a modest activity as second-line chemotherapy for NSCLC. It has the advantage to be well tolerated and may thus be one drug to be proposed to the patients who have disease progression after a first-line chemotherapy and who ask for further treatment.

Adult↗