Early alternating chemotherapy and radiotherapy schedule in limited disease stage small cell lung cancer.

44 patients with limited small cell lung cancer were treated with six cycles of chemotherapy (cisplatinum 60 mg/m2 day 1, doxorubicin 40 mg/m2 day 1, etoposide 100 mg/m2 days 1-3) alternating with three courses of mediastinal irradiation, the first one starting 7 days after the first day of chemotherapy. A total dose of 55 Gy was delivered. Prophylactic cranial irradiation (30 Gy after the third cycle of chemotherapy) was left to the physician's discretion. 4 patients had radical surgery before combined modality treatment. 29 patients finished the scheduled program. The complete response rate (bronchoscopically confirmed) was 25.6% after two cycles of chemotherapy and 41% at the end of treatment. Median survival time was 17.2 months, with an estimated survival of 32% at 2 years. Main toxicity was haematological with one early toxic death and six premature interruptions of treatment. We conclude that this treatment modality is feasible and efficacious. Prospective studies comparing chemotherapy with alternating or concurrent early radiotherapy schedules in limited disease small cell lung cancer are needed to determine the best treatment modality.

Prognostic value of histology in patients with non-small cell lung cancer.

To evaluate the impact of non-small cell lung cancer (NSCLC) histological subtypes on survival, we performed a retrospective multivariate analysis of survival in 361 patients with a NSCLC diagnosed in 1987 and 1988 at the University Hospital in Strasbourg, France. There were 262 (73%) squamous cell carcinomas (SQ), 59 (16%) adenocarcinomas other than bronchioloalveolar carcinoma (ADOBAC), 24 (7%) bronchioloalveolar carcinoma (BAC) and 16 (4%) large cell carcinomas (LC). The proportion of metastatic disease was significantly higher in the ADOBAC group than in the SQ group (30% vs. 15%, P < 0.001). In operated patients, only extent of disease and age were independent prognostic factors. In patients with unresectable NSCLC, extent of disease had also the heaviest impact on survival. However, in these unresected patients, ADOBAC had a pejorative impact on survival, in contrast to BAC which was of better prognosis. If these results are confirmed by prospective studies, this will support stratification according to histological subtypes in clinical trials involving inoperable NSCLC patients.

Weekly systemic combination of cisplatin and interferon alpha 2a in diffuse malignant pleural mesothelioma.

The treatment of diffuse malignant pleural mesothelioma (DMPM) remains grim. Neither surgery, radiotherapy nor chemotherapy can be considered as a standard therapy. Immunotherapy with interferon (IFN) in combination with chemotherapy may be an interesting new approach. In 13 consecutive patients with DMPM, we used a weekly combination of cisplatin (CDDP) (60 mg/m2; day 2) and IFN alpha 2a (6 MU/day; days 1-4) in a protocol of two cycles of 4 weeks on/4 weeks off followed by 3 weeks on/3 weeks off. Total treatment duration was thus 25 weeks. In responders, IFN as maintenance monotherapy was continued for a further 6 months. There were nine males and four females with an average age of 65.3 years (range 51-72 years). Eleven had epithelial, one had mixed and one had a sarcomatoid form of DMPM. Five patients were classified as stage II, six as stage III and two as stage IV, as per the International Mesothelioma Interest Group. Thirty-five cycles were administered with a median of three cycles/patient (range 0.75-4). The median total cumulative dose of CDDP was 596 mg/m2 (range 114-861) and that of IFN alpha 2a was 264 MU (range 72-336). Four patients received IFN maintenance therapy, one for 3 months and three for 6 months. One patient had a complete response, four had a partial response, six had a stable disease and the disease progressed in one. One patient was non evaluable for response. All patients were assessable for toxicity. Hematological toxicity was the most frequently observed but was manageable (grade 3 anemia in five patients, grade 3 thrombocytopenia in three patients, grade 3 neutropenia in five patients). Grade 1 renal toxicity was observed in six patients, grade 2-3 asthenia in six patients and an average 5-kg weight loss was noted in nine patients. In conclusion, systemic combination of CDDP and IFN alpha 2a in large doses is effective at the expense of non-negligible toxicity.

Can we predict very short term survival in small cell lung cancer?

We retrospectively reviewed the charts of 151 consecutive patients diagnosed as small cell lung cancer in our department and who had at least one course of chemotherapy. Nineteen patients died during the first 2 months, of the probability were reported to construct a receiver operating characteristic curve i.e. 13% of the population. The probability of dying within 2 months was investigated through a stepwise logistic regression. A performance status < or = 70 (Karnofsky index), an age > 60, a platelet count < or = 150,000/mm3, elevated alkaline phosphatase and a sodium < or = 135 mmol/l were independent predictors of a very short term survival and contributed to the equation for the probability of dying within a 2-month period. Sensitivity and specificity for various cutoff points characteristic curve allowing one to determine for a given patient his risk of being a very short term survivor. Such an approach could prevent inclusion of patients with high risk of early death in clinical trials and help to choose appropriate treatments for such poor risk patients.

[Is chemotherapy with cisplatin useful in non small cell bronchial cancer at staging IV? Results of a randomized study]. / La chimiothérapie comportant du cisplatine est-elle utile dans le cancer bronchique non microcellulaire au stade IV? Résultats d'une étude randomisée.

The benefit of chemotherapy for patients with disseminated non small cell lung cancer (NSCLC) is controversial. The introduction of cisplatinum in the combination chemotherapy for NSCLC gave rise to higher response rates. To study the question of the usefulness of cisplatinum-based chemotherapy in disseminated NSCLC we conducted a prospective randomized trial comparing best supportive care to vindesine + cisplatin. Between December 1985 and March 1988, 49 patients with stage IV NSCLC were enrolled. Of the 46 eligible patients 24 were in the chemotherapy group and 22 in the best supportive care group. The treatment groups were not significantly different in terms of age, performance status, histology. Toxicity on the chemotherapy arm grade 3 or more was observed in 17.5% for neutropenia, in 8.75% for vomiting. There was one death related to treatment. The overall response rate in the chemotherapy group was 41.7%. Patients of the chemotherapy group had a median survival time of 199 days and the patients of the best supportive care group had a median survival time of 73 days. The difference in survival is highly significant (p less than 0.001).

[Contribution of an induction treatment in the surgical treatment of locally advanced non-small-cell cancers]. / Apport d'un traitement d'induction dans le traitement chirurgical des cancers non microcellulaires localement avancés.

From October 1988 to July 1990, 18 patients with marginally resectable non-small cell cancer (10 stage IIIa and 8 stage IIIb) were entered in a phase-II trial combining induction therapy with a subsequent thoracotomy. Induction therapy included 2 courses of chemotherapy (5-FU and cisplatinum) and radiotherapy (30 Gray in split course). Partial response was observed in 10 patients, and minimal response in 3. Thoracotomy disclosed unresectability in 3 patients. Fifteen complete resections consisted in 1 lobectomy and 14 pneumonectomies. There were no operative deaths (30 days). Postoperative recovery was uneventful in 3 patients with exploratory thoracotomy and in 1 patient with lobectomy. Following pneumonectomy, we observed 2 bronchopleural fistulae and 1 empyema. On pathology, 10 patients were stage IIIa, and 3 were stage I, whereas no residual tumor was found in 2 patients. During follow-up, local recurrence occurred in 2, and metastases in 8. On December 31st, 1993, 3 patients were alive at 44, 52, and 62 months respectively. Nine patients had died from cancer, and 3 from unrelated causes. Estimated survival was 66.7% at 1 year, 33.3% at 3 years, and 20% at 5 years. We conclude that induction therapy allowed satisfactory resection for marginally resectable tumors. Operative morbidity was increased in this group. However, the 5-year survival was similar to resectable stage IIIa cancer.

[Acute pleuro-pneumonitis resulting from leptospirosis]. / Une pleuro-pneumopathie sévère révélant une leptospirose.

We report a case of acute pneumonitis with pleural effusion and respiratory distress syndrome that was the inaugural sign of leptospirosis in a 37-year-old patient exposed to rat dejections at home. The patient was given penicillin and oxygen therapy with evacuation of the pleural effusion. Lung manifestations in leptospirosis usually occur as non-specific cough and hemoptysis. Pleural effusion is uncommon. Adult respiratory distress syndrome and profuse hemoptysis can also occur, requiring special care.

[Difficult intubation in patients with endotracheal prosthesis]. / Difficulté d'intubation imprévue mais prévisible.

We report a case of two consecutive episodes of difficult intubation in a patient with an endotracheal Dumon's prosthesis inserted two years before. Despite several preanaesthetic visits and ENT examination, the absence of recollection by the patient and the lack of information in her previous medical records led to the impossibility to introduce a normal tube into her trachea during two consecutive anaesthetic procedures. This case points out the limits of preanaesthetic visits. It allows to remind special measures that must be taken in patients having tracheal prosthesis and scheduled for anaesthesia and surgery.

[Pre-therapeutic prognostic factors of survival in small cell bronchial cancer. Retrospective study in a series of 112 patients]. / Facteurs pronostiques préthérapeutiques de la survie dans le cancer bronchique à petites cellules. Etude rétrospective d'une série de 112 patients.

Pretherapeutic prognostic factors were studied retrospectively in 112 consecutive patients diagnosed as small cell lung cancer between January 1st 1986 and December 30th 1990 in our department. Mean age of the population was 59.3, 89.3% were males. Median survival time of the whole population is 11.66 months. It is 15.3 months for the 48 patients with limited disease stage and 9.74 months for 64 patients with extensive disease stage. Among the patients with limited disease stage, those with supraclavicular lymph nodes had a significantly shorter survival (p < 0.001). Univariate analysis of survival identified age, performances status, weight loss, T, N, bone and liver involvement, serum sodium, albumin and sedimentation rate as prognostic factors. The final model in multivariate analysis of survival includes for the patients with performance status < or = 70, extent of disease as an independent prognostic factor and for the patients with performance status < 70, extent of disease, serum sodium and albumin.

[Survey of the attitude of specialists faced with bronchial small cell carcinoma]. / Enquête sur l'attitude de spécialistes confrontés à un carcinome bronchique à petites cellules.

The practice of therapeutic trials is indispensable in the management of bronchial carcinoma if one hopes to improve the results. We have questioned 134 doctors in the Alsace region who are involved in the diagnosis and treatment of bronchial cancer. We asked how they would wish to be treated if they had a small cell cancer, and if they would agree to participate in a therapeutic trial should the occasion arise. Four different clinical situations of small cell carcinoma localised to the hemithorax were presented, illustrating current controversy on the best treatment or treatments to apply. The 4 proposed protocols were refused by 50% to 84% of the doctors questioned in different cases. The greater the level of consensus on a therapeutic treatment in a given clinical situation the greater the level of refusal to participate in a randomised protocol was. The fact that at least half of the specialist doctors questioned would refuse to be included in a current therapeutic protocol which is underway for patients in Europe leads to the suggestion that before the application for new protocols experts surrogates should give their opinion in association with ethical committee.

[Occupational asthma: an experimental asthma. Apropos of isocyanate-induced asthma]. / L'asthme professionnel: un asthme expérimental. A propos de l'asthme aux isocyanates.

Isocyanate-induced occupational asthma is a model of experimental asthma related to the environment. Many of its features are identical with those of allergic asthma by sensitization to air-borne allergens. Exposure to isocyanate before the first symptoms of asthma varies from a few weeks to several years. The prevalence of isocyanate-induced asthma has been estimated at 5 to 25%. Atopy is found in less than 30% of the cases. A significant increase of HRBNS can be demonstrated in most patients, but it may be absent. It may also fluctuate with the working periods or after a bronchial provocation test with isocyanate. Elimination of this compound reduces the HRBNS level in only one quarter of the cases. Delayed or biphasic reactions are frequent: 30 to 60% depending of the authors. An early diagnosis followed by total elimination may result in complete cure, but more than 50% of the patients remain symptomatic and with HRBNS. An IgE-dependent mechanism can be demonstrated in about 20% of the cases. The course of isocyanate-induced asthma is interesting in that the same phenomena are probably observed in chronic asthma resulting from repeated exposures to environmental allergens.

[Bronchiolitis obliterans with organizing pneumonia. Retrospective study of 19 cases]. / La bronchiolite oblitérante avec pneumopathie d'organisation. Etude rétrospective de 19 cas.

We report a series of 19 cases of bronchiolitis obliterans with organized pneumonitis (BOOP) observed in two pneumology units at the Strasbourg University Hospital between July 1987 and June 1997. Mean patient age was 60 years. Clinical features included dry cough, exercise-induced dyspnea, and a flu-like syndrome in three-quarters of the cases. Standard chest x-ray showed a diffuse non-systemized alveolar syndrome with a air bronchogram in 18 cases and an interstitial syndrome in one-third of the cases. computed tomography of the thorax visualized bronchial dilatations by traction of the alveolar syndrome in one-third of the cases. Pulmonary function tests showed moderate restriction. Lymphocytes predominated in bronchio-alveolar lavage fluid. Pathology examination of surgical lung specimens (5 cases), transbronchial biopsies (5 cases) and scan-guided transparietal punctures (4 cases) provided the diagnosis. In 5 cases the diagnosis was based on the radiological and clinical presentation and favorable course on corticosteroid therapy. Recurrence was observed at corticosteroid withdrawal or dose reduction in 7 cases. In this series, bronchiolitis obliterans with organized pneumonitis was probably secondary to rheumatoid arthritis (1 case), breast radiotherapy (3 cases), and drugs (amiodarone: 1 case: sotalol: 2 cases: betaxolol: 1 case). An association with betaxolol has not been previously reported in the literature.

Mite allergen content in mattress dust of Dermatophagoides-allergic asthmatics/rhinitics and matched controls.

It has been suggested that the mites Dermatophagoides pteronyssinus and D. farinae are important indoor environmental factors facilitating both the sensitization of atopic subjects and asthmatic attacks of house dust-sensitive patients. Contradictory results have been reported about the current exposure to mites or their allergens among patients and control groups of atopic or non-atopic subjects. In order to determine whether there is a difference in mite exposure levels between D. pteronyssinus-sensitized asthmatics and/or rhinitis and control subjects we considered a case-control study of 70 patients with asthma and/or rhinitis and positive skin test reactions to D. pteronyssinus and twice as many control subjects who were matched as to age and sex. The first control subject for each patient was an immediate neighbour of the patient and the second was patient arbitrarily chosen among hospitalized patients. Mite allergen exposure was measured in mattress dust collected under standardized conditions, by measuring Der p I+Der fI content and by performing a semiquantitative guanine determination (Acarex-test). The content of Der p I and Der fI was very high both in the homes of patients and those of healthy individuals: 69% of the total samples contained more than 10 micrograms Der pI+Der fI/g of dust. There was no significant difference between cases and controls with respect to Der p I, Der fI, Der p I+Der fI content and Acare class distributions. The calculated odds-ratios associated with the Acarex test and the mite allergens did not differ significantly from the level 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)

A double-blind, placebo controlled trial of solidified benzyl benzoate applied in dwellings of asthmatic patients sensitive to mites: clinical efficacy and effect on mite allergens.

BACKGROUND: The aim of this double-blind, randomized study was to investigate the effectiveness of an acaricidal cleaning product in modifying both clinical symptoms and mite allergen levels over a period of at least 1 year. METHODS: Twenty-six asthmatic patients with proven Dermatophagoides pteronyssinus (Dp) asthma were selected; three were withdrawn from the trial. The patients' homes were divided into two groups; 11 homes were treated with solidified benzyl benzoate and tenside agents (A), and 12 were treated with a placebo (P). Two applications were performed at the beginning of the trial and at least 6 months later. Patients were examined 1 month before the trial, at the beginning of the trial, and every 3 months over a period of 1 year. Indoor mite exposure was evaluated by three methods: semiquantitative guanine determinations, quantitative guanine determinations, and the measurement of Der p I + Der f 1 (antigen P, of Dp + antigen F1 of D. farinae) levels. RESULTS: The symptom scores established at the beginning of the trial and 12 months later showed a statistically significant improvement only in the A group (p < 0.01). The visual analog scale also showed a statistically significant difference both in the A (p < 0.05) and P groups (p < 0.01). No statistical differences were found between medication scores in the A or P groups. A statistically significant increase was also observed for forced expiratory volume in 1 second and maximal expiratory flow rate 25/75 in the two groups (p < 0.05 for P group; p < 0.01 for A group). The mean decreases in Der p I + Der f 1 in patient mattresses between the beginning of the trial and after 12 months were 20% for the acaricide group and 17% for the placebo group, respectively (NS). For house dust samples with origins other than the patients' mattresses we found significant decreases in Der p I+Der f 1 in the A group (p < 0.01 for carpets and p < 0.05 for upholstery elements).

Recurrent interlobar pneumothorax in an asthmatic patient.

We report a case of spontaneous interlobar pneumothorax, an uncommon condition. The diagnosis was suspected from the frontal chest X-ray, which showed an incompletely circumscribed air-containing space, with a fluid level. The diagnosis was confirmed by the lateral projections of standard X-ray and tomography, and by thoracic computed tomography (CT). Such air-fluid levels should not be confused with pneumatocele, cystic or cavitary diseases.