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Neo-adjuvant chemotherapy is a promising new concept in the treatment of resemble NSCLC. In 1991, a randomized study was initiated to compare two treatment strategies for patients (pts) with operable stages I (except T1N0), II or IIIa NSCLC. Pts are randomized into two arms. Surgery is performed first in group I. In group 2, pts start with two cycles of chemotherapy; following surgery, two more cycles are administered in responder pts. Chemotherapy is the MIP protocol: mitomycin 6 mg/m 2 day 1, ifosfamide 1.5 g/m 2 days 1 to 3, cisplatin 30 mg/m 2 days 1 to 3. In both groups, if the surgical staging is N2 or T3, a radiotherapy is performed. From June 1991 until Jan. 1995, 256 pts have been randomized; 35% are stage I, 16% are stage II. 205 pts have completed the treatment. In group 1, 105 out of 106 and in group 2, 91 out of 99 pts underwent thoracotomy. Surgery was complete in 85% of group 1, 83% of group 2, incomplete in 10% of group 1, 5% of group 2. The chemotherapy response rate assessed by surgical evaluation was as follow: complete and subcomplete response. 27%, 18%, partial response 31% (overall: 58%). The study is still ongoing as a total number of 350 patients should be included to reach the required power.

A 25%–33% increase in initial doses of cisplatin (CDDP) and cyclophosphamide (CPM), when combined with standard doses of doxorubicin and etoposide, has been found sufficient to significantly improve both disease free and overall survival in patients with limited SCLC (NEJM 1993, 329, 1148–1152). In this following trial, we are testing whether or not an increase in dose-intensity of a quite similar 4drug regimen leads to an improvement in survival. From October 1991 to December 1994, 123 patients with untreated SCLC were enrolled in this study comparing “standard dose” (SD) PEVEP for 6 cycles versus “high dose” (HD) PEVEP + rh-GMCSF (E. Coli derived) for 4 cycles. SD PEVEP consisted of: Epirubicin 40 mg/m2 dl, CDDP 100 mg/m2 d2, Etoposide 75 mg/m2/d dl-3, CPM 400 mg/m2/d dl-3. In the HD PEVEP arm the intended doses for each cycle were increased by 50%, except for CDDP: 25%. This HD PEVEP arm was supported by a systematic use ofrh-GMCSF (5 μg/hg/d s. c.) administered from d4 to dl3. Thus, the cumulative doses in both arms were roughly similar. Responding patients with residual disease confined to the chest were eligible for thoracic radiation. Complete responders were eligible for prophylactic cranial radiation. An interim analysis was performed as planned by the protocol after the inclusion of 50% of 200 patients required to demonstrate a 50% improvement in median survival. Accrual has been closed prematurely on 12/23/94 due to a significant survival difference between the two arms. An updated analysis will be presented.

The results of bronchoalveolar lavage in three patients with a presumptive diagnosis of methotrexate induced lung disease are presented. Lavage fluid was characterised by the presence of large numbers of lymphocytes, which in two patients were predominantly lymphocytes of the T8 phenotype. These findings further support the hypothesis that immune mediated mechanisms may play a part in the pathogenesis of this disorder in some patients, and indicate that bronchoalveolar lavage may be helpful in the evaluation of patients suspected of having methotrexate induced lung disease.

Between January 1981 and December 1983, a prospective therapeutic trial of detorubicin (14-diethoxyacetoxy-daunorubicin [DTR]) was conducted in 40 patients with histologically proven malignant mesothelioma (MM). DTR was given intravenously at 40 mg/m2 on days 1, 2, and 3 for five 21-day cycles, then 40 mg/m2 once every 21 days. Thirty-five patients (32 with pleural MM, 3 with peritoneal MM) were eligible. The overall median survival from onset of chemotherapy was 17 months. Complete relief from chest pain was observed in 8 of 15 cases (53%). Of 21 patients with measurable disease, there were 2 complete responses (10%) and 7 partial responses (33%). Median duration of response was 30 weeks. Congestive cardiac failure developed in two patients after 1100 and 1600 mg/m2 of DTR, respectively. Hematologic toxicity was moderate. This study demonstrates that DTR is effective against MM.

Serum neuron-specific enolase (S-NSE) levels in 43 newly diagnosed untreated patients with small-cell lung cancer (SCLC) were compared with levels in 35 adult controls, 14 patients with non-small cell lung cancer (N-SCLC), and nine patients with noncancerous lung disease (N-CLD). The S-NSE level was raised (≥16 ng/ml) in 28 of 43 patients with SCLC, six of 16 patients with limited stage SCLC, and 22 of 27 of those with extensive stage SCLC. Extensive stage patients with SCLC had a significantly higher mean S-NSE level (50 ng/ml) than did limited stage patients with SCLC (16 ng/ml). Mean S-NSE levels in patients with N-SCLC and in patients with N-CLD were respectively 11 and 7 ng/ml. Serial measurements performed on 19 patients between the three-day-courses of chemotherapy showed an excellent correlation between S-NSE and clinical evolution. In addition, S-NSE was measured during the first three-day course of chemotherapy in 13 other patients; among them, seven had S-NSE levels ≥100 ng/ml (mean: 490 ng/ml); these seven patients were responders; the remaining six had S-NSE levels

A 59-yr-old man was given over a 30-month period a cumulative dose of 36 g of propranolol for treatment of angina pectoris. He then presented with respiratory disease, having all the clinical, radiologic, and functional characteristics of interstitial pneumonitis. No other cause of pneumonitis was found. Bronchoalveolar lavage (BAL) showed a lymphocytic alveolitis with lymphocyte subset inverted ratio. After a 9-wk period of drug withdrawal, clinical and radiologic improvement was observed along with resolution of BAL abnormalities. Propranolol therapy was resumed for 6 wk and induced the recurrence of BAL abnormalities. Propranolol treatment was finally stopped, and 15 wk later, clinical symptoms abated, chest roentgenogram and pulmonary function tests were improved, and BAL data returned to normal. This observation seems to exemplify the possible diagnostic value of coupling provocation test with BAL cell data in some hypersensitivity pneumonitis induced by drugs. In addition, these data support the role of a cell-mediated immunologic mechanism in the pathogenesis of propranolol-induced pneumonitis.

Interstitial pneumonitis developed in a patient who had received a cumulative dose of 985 g of amiodarone in nine years. No other cause for pneumonitis was found. The following findings favor an immunologic mechanism of hypersensitivity due to amiodarone: positive skin and basophil degranulation tests with amiodarone; lymphocytosis and inverted ratio of helper/suppressor T lymphocytes in bronchoalveolar lavage fluid; secretion of leukocyte inhibitory factor, as shown by the inhibition of migration of peripheral blood leukocytes; and positive lymphoblastic transformation in the presence of amiodarone.

To investigate the extrarenal production of 1,25(OH)2D3 in tuberculosis, we extensively evaluated a patient with tuberculosis, hypercalcemia, and an elevated plasma concentration of 1,25(OH)2D3. Fresh total cells and cultured alveolar macrophages obtained by bronchoalveolar lavage were demonstrated to synthesize 1,25(OH)2D3 prior to and after nine months of successful antituberculous therapy. The continued capacity to produce 1,25(OH)2D3 was associated with a persistent lymphocytic alveolitis in this patient. This extrarenal production of 1,25(OH)2D3 probably contributed to the increased levels of plasma 1,25(OH)2D observed in our patient. Nevertheless, a close correlation between plasma 1,25(OH)2D and serum calcium was not observed. These findings suggest that although extrarenal production of 1,25(OH)2D3 occurs in tuberculosis, it need not be a predominant factor producing the abnormalities in calcium homeostasis observed in such patients.

A 25-year-old man developed thyroid tuberculosis associated with mediastinal lymph node enlargement. He was treated by antituberculosis chemotherapy and hemithyroidectomy.

Amiodarone-associated pneumonitis is now a well-known clinical entity, but the mechanism for the induction of the pulmonary disease is ill defined. In four patients with this disorder, evidence was obtained for elaboration of a lymphokine, leukocyte inhibitory factor (LIF), by peripheral blood lymphocytes after incubation with amiodarone in the direct leukocyte migration inhibition test. Control lymphocytes from normal subjects, as well as from patients receiving amiodarone but without pneumonitis, failed to elaborate LIF in the presence of the drug in this test. This production of LIF suggests that pneumonitis associated with amiodarone therapy is also associated with a specific cellular immune response to the drug.

A patient with a 12-year history of occipital ependymoma was found to have late pleuropulmonary metastases without recurrence of the primary tumor. The pleural metastases were diagnosed by histologic, ultrastructural features and finally by glial fibrillary acidic protein (GFAP) labeling positive reaction. This case is unique because of the long interval between occurrence of the initial tumor and the metastases, and because of the apparent quiescence of the cerebral lesion when the pleuropulmonary metastases were discovered.

Two male patients presented with lung disorders with all the characteristics of amiodarone-related pneumonitis. Bilateral exudative pleural effusions were associated with pneumonitis. High lymphocytosis was present in the pleural fluid with a ratio of T-lymphocyte subsets close to that found in peripheral blood; in the blood T-lymphocyte subset ratio was nearly normal. By contrast, and as is usual in similar cases, lymphocytic alveolitis with T-lymphocyte subset imbalance was found in bronchoalveolar lavage fluid. These findings, never published so far to our knowledge, would favor a compartmentalization of the immune response inside the lung.