Summary report of the Standards, Options and Recommendations for the management of patients with non-small-cell lung carcinoma (2000).
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
B Milleron
Publications and source records attributed to B Milleron.
Cytokine profiles in idiopathic pulmonary fibrosis suggest an important role for TGF-beta and IL-10.
Modulation of cytokine expression represents a potentially useful approach for the treatment of idiopathic pulmonary fibrosis (IPF). To identify potential targets for such intervention, semi-quantitative reverse transcriptase-polymerase chain reaction was used to compare the expression of messenger ribonucleic acids (mRNAs) coding for 17 cytokines in lung tissue obtained from patients with IPF at the time of diagnosis and control subjects. Some cytokines were also studied at the protein level by immunohistochemical techniques. mRNAs coding for all of the cytokines evaluated were detected in both control and fibrotic lung samples. Only transforming growth factor (TGF)-beta and interleukin (IL)-10 mRNAs were quantitatively increased in lung biopsies from patients with IPF compared with those of controls, results confirmed at the protein level by immunohistochemistry. Although mRNAs for platelet-derived growth factor (PDGF)-BB and keratinocyte growth factor (KGF) were expressed in similar amounts in lungs from patients with IPF and controls, localised accumulation of both factors was also observed in IPF. Hyperplastic alveolar epithelial cells were a prominent source of cytokines, where IL-10, PDGF-BB and KGF were present in increased amounts, although increased accumulation in fibroblasts, smooth-muscle cells and matrix components was also observed (PDGF-BB, TGF-beta). These results offer new insights into the cytokines produced in the lung in idiopathic pulmonary fibrosis and suggest that modulation of the production of transforming growth factor-beta and interleukin-10 may represent a potentially useful therapeutic strategy for this disabling disease.
Female↗
[Treatment of localised forms of non small cell bronchial cancers: perspectives in 20003].
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Antineoplastic Combined Chemotherapy Protocols↗
[Do the new drugs improve prognosis of stage IV NSCLC?].
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Antineoplastic Agents↗
[Paraneoplastic opsoclonus-myoclonus syndrome associated with small-cell lung cancer].
Opsoclonus-myoclonus syndrome was observed in a patient treated for small-cell lung cancer. Opsoclonus presented as anarchic involuntary eye movements associated with myoclonies of the limbs and trunk. Opsoclonus-myoclonus is exceptional and a specific expression among several paraneoplastic manifestations described in small-cell lung cancer. These manifestations develop late after diagnosis of cancer. Presence of anti-neuronal antibodies in the serum (inconstant) is a factor of very poor prognosis.
Aged↗
[Locally advanced non-small-cell bronchial cancer: role of exclusive chemoradiotherapy].
Lung cancer is the most frequent form of malignant tumours. The prognosis is poor with a 5-year cure rate which increased from approximately 6% in the sixties to only 15% in the nineties. Surgery remains the reference treatment but only a small minority of patients (about 25%) present with operable disease. The post-surgical 5-year survival is only 25%, providing the rationale for the current research on adjuvant treatments for control of both local and metastatic disease. In that context, the combination of radiotherapy and chemotherapy, commonly referred to as chemo-radiotherapy, has assumed considerable importance: either exclusively in inoperable patients (inoperable tumour or patients inoperable for medical reasons), or pre-operatively. This article reviews the results of the pivotal definitive chemoradiotherapy studies in non-metastatic non-small-cell lung cancer. With exclusive chemoradiation, the concomitant scheme seems to be the most favourable, results issued from randomised studies are expected to confirm that point. An increased toxicity is observed, and the advent of conformal therapy may allow another survival gain. Optimal treatments integration will be necessary.
Antineoplastic Agents↗
[Preoperative chemotherapy and chemoradiotherapy for non-small-cell bronchial cancers].
The very disappointing results obtained by surgery in resectable non-small-cell lung cancer have led to a high active clinical research concerning pre- or postoperative treatment. Preoperative treatment has several distincts goals: to increase survival for patients suitable for surgery, to limit surgery or transform borderline or non resectable cancer into resectable tumors. Available datas on preoperative treatments for non-small-cell lung cancer provide from three types of therapeutics trials: 1/Some phase II studies of neoadjuvant chemotherapy have demonstrated that the neoadjuvant approach was feasible, and didn't compromise surgery. 2/Phase II trials of neoadjuvant chemoradiotherapy, performed for the majority on more extensive cancers, have demonstrated that this approach was also feasible at the expense of higher but still tolerable toxicity. 3/Phase III randomised published trials exclusively deal with preoperative chemotherapy with different results: two of them concerned a small number of patients presenting with non-small-cell lung stage IIIA cancer: they are positive. The third concerned 373 patients presenting with stage I, II, IIIA cancer: the three-year survival was increased by 11%, but this difference is not yet significant. The benefit essentially appeared for stage I and II. One trial comparing preoperative chemotherapy and radiochemotherapy has been reported, concluding to the superiority of the association. These observations suggest that the clinical research should now be different for stages I and II, and stage IIIA.
Antineoplastic Combined Chemotherapy Protocols↗
[When should surgical lung biopsy be proposed for patients with diffuse infiltrating lung disease?].
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Biopsy↗
[Screening for bronchial carcinoma].
Bronchial carcinoma is the principal cause of cancer death. Unlike cancers of the breast and colon that are already the subject of screening programmes, proof has not yet been provided that screening for bronchial carcinoma is of value in terms of reduction in mortality. Technological improvements and the advent of low dose spiral CT scanning has lead to a recent renewal of interest in this subject. The first preliminary studies seem to indicate that 2/3 of bronchial carcinomas discovered by CT scanning are detected at an early stage. Other data suggest a possible improvement in survival of tumours discovered by screening. Nevertheless it is necessary to demonstrate that screening improves the survival of patients with bronchial carcinoma. The present consensus does not advocate mass screening by CT scanning but that high risk subjects should voluntarily participate in randomised controlled trials which alone will confirm or refute the validity of this approach.
Bias↗
[DEPISCAN--a pilot study to evaluate low dose spiral CT scanning as a screening method for bronchial carcinoma].
The outcome of collaboration between INSERM (National Institute for Health and Medical Research), SFR (French Radiological Society) and SPLF (French Language Society of Pneumology), DEPISCAN is a pilot study for a large randomised trial which aims to evaluate screening for broncho-pulmonary cancer by the low dose spiral CT scanner. The principal objective of this preliminary study is to test the feasibility of a randomised study comparing the CT scanner and the chest x-ray in 1,000 smokers and ex-smokers aged over 50 and followed up for 2 years. Recruitment of subjects will be undertaken by 130 general practitioners based on 14 hospital centres distributed throughout France. We will evaluate the safety of the patients and the effect of screening on their quality of life and their tobacco consumption as well as the economic and methodological aspects of the study.
Aged↗
[Screening for bronchial carcinoma].
Bronchial carcinoma is the principal cause of cancer death. Unlike cancers of the breast and colon that are already the subject of screening programmes, proof has not yet been provided that screening for bronchial carcinoma is of value in terms of reduction in mortality. Technological improvements and the advent of low dose spiral CT scanning has lead to a recent renewal of interest in this subject. The first preliminary studies seem to indicate that 2/3 of bronchial carcinomas discovered by CT scanning are detected at an early stage. Other data suggest a possible improvement in survival of tumours discovered by screening. Nevertheless it is necessary to demonstrate that screening improves the survival of patients with bronchial carcinoma. The present consensus does not advocate mass screening by CT scanning but that high risk subjects should voluntarily participate in randomised controlled trials which alone will confirm or refute the validity of this approach.
Aged↗
[Screening for bronchial-pulmonary cancer].
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Bronchial Neoplasms↗
Etoposide plus cisplatin with or without the combination of 4'-epidoxorubicin plus cyclophosphamide in treatment of extensive small-cell lung cancer: a French Federation of Cancer Institutes multicenter phase III randomized study.
BACKGROUND: The combination of etoposide plus cisplatin (EP) is considered to be standard therapy for small-cell lung cancer (SCLC). To determine whether drug intensification improves survival of patients with extensive SCLC, we compared this treatment with a four-drug regimen containing EP plus cyclophosphamide and 4'-epidoxorubicin (PCDE). METHODS: In a phase III clinical trial organized by the French Federation of Cancer Institutes, patients were randomly assigned to receive either EP (n = 109; etoposide at a dose of 100 mg/m(2) on days 1-3 plus cisplatin at 100 mg/m(2) on day 2) or PCDE (n = 117; etoposide and cisplatin given as in EP plus cyclophosphamide at 400 mg/m(2) on days 1-3 and 4'-epidoxorubicin at 40 mg/m(2) on day 1) every 4 weeks. Both groups received a total of six cycles. Survival differences were analyzed by Wilcoxon and log-rank tests. Associations of treatment group and putative prognostic variables with survival were tested in the Cox proportional hazards model. Quality of life was assessed from the responses to the European Organization for Research and Treatment of Cancer quality-of-life questionnaire (C30, health status and lung cancer module 13). All statistical tests were two-sided. RESULTS: Patients in the PCDE arm had a statistically significant higher frequency of combined complete plus partial responses compared with those in the EP arm (21% plus 55% versus 13% plus 48%, respectively; P =.02 for difference in combined objective responses). Patients in the PCDE arm survived longer than those in the EP arm (1-year survival rate: 40% and 29%, respectively; median survival: 10.5 and 9.3 months, respectively; log-rank P =.0067). In the Cox model, the relative risk of death for patients in the PCDE arm compared with those in the EP arm was 0.70 (95% confidence interval = 0.51 to 0.95); the disease also progressed more slowly in patients in the PCDE arm. Hematologic toxicity was higher in the PCDE arm (22% with documented infections compared with 8% in the EP arm; P =.0038), and the toxicity-related death rate was 9% in the PCDE arm versus 5.5% in the EP arm (P =.22). The global health status showed similar improvement in both arms during treatment. CONCLUSION: Compared with the EP regimen, the PCDE regimen yielded higher response rates and better survival rates in patients with extensive SCLC without affecting the quality of life of the patients during chemotherapy.
Adult↗
Tumor-derived granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor prolong the survival of neutrophils infiltrating bronchoalveolar subtype pulmonary adenocarcinoma.
We evaluated the role of the tumor environment in the regulation of apoptosis of tumor-infiltrating neutrophils, the number of which correlates negatively with outcome, in patients with adenocarcinoma of the bronchioloalveolar (BAC) subtype. We examined three different parameters of apoptosis, namely morphological aspect, annexin-V expression, and DNA fragmentation. Bronchoalveolar lavage fluid (BALF) supernatants from patients with BAC significantly inhibited the 24-hour spontaneous apoptosis of normal peripheral blood neutrophils in vitro compared to BALF supernatants from control patients (64 +/- 4% versus 90 +/- 2% measured by annexin-V flow cytometry, P = 0.04). The alveolar neutrophil count correlated positively with the granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations in the patient's BALF. Furthermore, neutralizing antibodies (Abs) against GM-CSF and G-CSF significantly inhibited BALF anti-apoptotic activity (15 to 40% and 34 to 63% inhibition, respectively), whereas neutralizing Abs against interleukin (IL)-8, IL-6, IL-1beta and tumor necrosis factor-alpha had no significant effect. In an attempt to identify the cell origin of anti-apoptotic cytokines, we tested in vitro the effect of BAC cells (A549 cell line and primary culture derived from a patient's BAC tumor) on the apoptosis of peripheral blood neutrophils. Cell-free supernatants from tumor cells did not inhibit neutrophil apoptosis. In contrast, cell-free supernatants from tumor cells previously exposed to conditioned media from peripheral blood mononuclear cells and alveolar macrophages significantly inhibited spontaneous neutrophil apoptosis. This inhibition was partially lifted when conditioned media from mononuclear cells were previously treated with Abs against IL-1beta and tumor necrosis factor-alpha. As in vivo, neutralizing Abs against GM-CSF significantly inhibited the anti-apoptotic activity of cell culture supernatants, and combination with Abs against G-CSF had an additive effect. In vivo, GM-CSF and G-CSF were strongly expressed by tumor cells and moderately or not expressed by the normal epithelium, as assessed by immunohistochemical studies. These findings demonstrate that the tumor environment generates local conditions that prolong alveolar neutrophil survival through the production of soluble factors, thereby contributing to the persistence of the neutrophil alveolitis observed in BAC.
Adenocarcinoma, Bronchiolo-Alveolar↗
The relationship between introduction of American society of clinical oncology guidelines and the use of colony-stimulating factors in clinical practice in a Paris university hospital.
BACKGROUND: Clinical practice guidelines are issued periodically by professional medical societies or committees to assist practitioners in clinical decision making. However, it is unclear whether such guidelines have any lasting impact on clinical practice. OBJECTIVE: The purpose of this study was to assess the impact of the American Society of Clinical Oncology (ASCO) guidelines regarding use of hematopoietic colony-stimulating factors (CSF) on cancer care in a university hospital in Paris. METHODS: The study was performed at Hĵpital Tenon, an 830-bed university hospital in Paris, in 1996 and 1997, both before and after the ASCO guidelines were implemented. The guidelines were first disseminated as a continuing medical education program and then actively implemented using a CSF prescription order form summarizing the guidelines. This form had to be used during the patient consultation and was sent to the Hĵpital Tenon pharmacy for CSF dispensation. Even if CSF use did not comply with the ASCO guidelines, the pharmacy filled the prescription. Seven other university hospitals in Paris, where the ASCO guidelines were not actively implemented, comprised the control group. The main outcome measure was the proportion of prescriptions in compliance with the 1996 update of the ASCO guidelines. Secondary outcome measures were the proportions of prescriptions in compliance with ASCO guidelines regarding primary prophylactic, secondary prophylactic, and therapeutic CSF administration. RESULTS: Before implementation of the ASCO guidelines, CSF use in compliance with the guidelines was 39% (41/105) at the study site and 31% (16/51) at the control sites (P > 0.05). Six months after dissemination and implementation of the guidelines, the proportion of CSF prescriptions complying with ASCO guidelines increased significantly versus baseline (P = 0.003) in the study group, to 61% (50/82). However, even after the guidelines were implemented, compliance with guidelines on primary prophylactic CSF administration did not change significantly versus before implementation in the study group (12% [5/41] before implementation vs 6% [2/33] after implementation; P > 0.05). CONCLUSIONS: The results suggest an association between the active implementation strategy (continuing medical education and CSF prescription reminder form) and physician compliance with the ASCO guidelines. Implementation of the ASCO guidelines appears to have had some impact on medical practice.
Colony-Stimulating Factors↗
Etoposide phosphate with carboplatin in the treatment of elderly patients with small-cell lung cancer: a phase II study.
BACKGROUND: Although the average age of lung cancer patients is increasing, many elderly patients remain undertreated, mainly because of the fear of higher treatment toxicity in this category of patients. We conducted a study to evaluate the efficacy and tolerability of a combination therapy with carboplatin (C) and etoposide phosphate (EP) in elderly patients with Small-Cell Lung Cancer (SCLC). PATIENTS AND METHODS: Previously untreated patients older than 70 years with stage IIIB/IV SCLC received a combination of EP (100 mg/m2 D1, D2, D3) and C (D1, dose calculated according to the Calvert formula). Response rate, survival and toxicity were assessed. RESULTS: Thirty-eight patients (mean age 76 years, range 70-88 years) received a total of 162 cycles. Eighteen patients (47%) received the six scheduled cycles. Thirty patients were evaluable for efficacy (2 CR and 20 PR). The median survival was 237 days and the one-year probability of survival was 26%. The most common adverse effect was transient grade 3 or 4 neutropenia, observed during 57% of evaluable cycles, while five episodes of febrile neutropenia also occurred, with one fatal (bacteremia). It is noteworthy that no renal or liver toxicity was observed, and no mucitis was noted. Unfortunately, a relatively high proportion of patients died shortly after the start of the study. Although most deaths seemed unrelated to the treatment, the possibility of its exacerbatory effect on comorbidities, especially cardiovascular, cannot be excluded. CONCLUSION: The two-drug regimen of carboplatin and etoposide phosphate is feasible in most elderly patients with an acceptable toxicity, and the overall results suggest that patients even older than 70 years may benefit from full treatment. Therefore, consideration should be given to offering active treatment to most patients with SCLC, regardless of age but with special attention paid to comorbidities.
Age Factors↗
[Standards, options and recommendations for the management of locally advanced non small cell lung carcinoma].
CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the management of locally advanced non small cell lung carcinoma. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations are: 1) The management of the locally advanced non small cell lung carcinoma has two main goals: firstly to obtain local control of the disease (or to at least delay local progression in order to improve the survival or relapse free survival), and secondly to prevent the development of metastases. 2) There is a consensus that locally advanced non small cell lung carcinoma should be irradiated. External beam radiotherapy should be of optimal quality and delivered at a minimal dose of 60 Gy by standard fractionation. For patients with a poor life expectancy, this can be delivered as a split-course or hypofractionated scheme. 3) Treatment for patients with a performance status of 0-1 should consist of short duration induction chemotherapy (with a least two drugs one of which must be cisplatin), combined sequentially with conventional radiotherapy. 4) Surgery is contraindicated in extensive N3 disease. Combined radio-chemotherapy (adjuvant or neoadjuvant) is not indicated outside clinical trials. Surgery is justified in stage N2 disease as good local control can be achieved. T4-N0 disease should be treated surgically with curative intent.
Adult↗
[Standards, Options and Recommendations for the management of stage I or II primary bronchial cancers treated exclusively with radiotherapy].
CONTEXT: The 'Standards, Options and Recommendations' (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French cancer centres and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the management of stage I and II non small cell lung carcinoma treated by radiotherapy alone. METHODS: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French cancer centres. RESULTS: The main recommendations for the management of stage I and II non small cell lung carcinoma treated by radiotherapy alone are: 1) The curative external irradiation with a continual course is an alternative to surgery only in the case of medically inoperable tumors or because the patient refuses surgery; 2) The external irradiation of the primary tumor only without the mediastinum could be proposed in peripheral stage IA. In proximal stage IA and IB, external irradiation should be carried out only as part of prospective randomised controlled trials comparing a localised irradiation of the primary tumor with a large irradiation of the mediastinum and the primary tumor. The treated volume must include the macroscopic tumoral volume with or without the microscopic tumoral volume and with a security margin from 1.5 to 2 cm; 3) There is a benefit to delivering a total dose in the primary tumor higher than 60 Gy in so far as the proposed irradiation, taking into account the respiratory function, does not increase the likelihood of severe adverse events due to radiation; and 4) The change in fractionation, the radiochemotherapy combination, the endobronchial brachytherapy with high dose rate alone or with external irradiation could be proposed only as part of prospective controlled trials for tumors classified as stage IB or II.
Aged↗