Early recognition, prompt intervention, and a conservative approach are important in managing the risk associated with noninfectious pneumonitis in association with everolimus. Clinical trial registered with www.clinicaltrials.gov (NCT 00410124).

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Purpose: To evaluate the toxicity profile of inhalational doxorubicin in patients with malignant disease in the lung. Experimental Design:The OncoMyst Model CDD-2a inhalation device aerosolizes compounds to particles of 2 to 3 Am and prevents exhaled aerosol from escaping into the environment. Deposition efficiency of inhaled Technetium 99m was used to predict deposition of doxorubicin and calculate dose. Treatment was repeated every 3 weeks. No more than moderate pulmonary dysfunction was permitted (forced expiratory volume in 1 s, forced vital capacity, and diffusing capacity for carbon monoxide, all >50% predicted; resting SaO 2 >90%).Results: Fifty-three patients were enrolled at 13 dose levels ranging from 0.4 to 9.4 mg/m 2 . The most common histologic diagnoses were sarcoma (n = 19) and non^small cell lung cancer (n = 16). Dose-limiting toxicity (DLT) was observed at the 9.4 mg/m 2 dose level when two of four patients experienced pulmonary DLT. Of 11 patients treated at the 7.5 mg/m 2 dose level, only one showed DLT consisting of a decline in forced vital capacity of >20% from baseline. No significant systemic drug-related toxicity was observed. Several patients experienced declines in pulmonary function test variables, which were attributed to progressive disease. Observed activity included a partial response in a patient with metastatic soft tissue sarcoma previously treated with i.v. doxorubicin and ifosfamide. Conclusions: Inhaled doxorubicin is safe up to a dose of 7.5 mg/m 2 every 3 weeks in patients with cancer who had normal to moderately impaired pulmonary function.Pulmonary metastases commonly occur in solid tumors and are often the predominant or sole site of metastatic involvement. A problem in treating these lesions is the inability to achieve adequate therapeutic concentrations of drugs at the tumor site without suffering substantial systemic toxicity. One approach to improving therapeutic efficacy is targeted dose intensification. This approach has been effectively used in a variety of tumors, including liver, ovarian, and bladder cancer (1 -6), but there is little experience delivering chemotherapeutics directly to the lungs via inhalation (7).Inhalational chemotherapy was first described by Shevchenko and Resnik in 1968. (8). The concept was tested in dogs and subsequently in 58 patients. Antitumor efficacy was observed in 24 patients, but the data are difficult to interpret because of the concurrent use of radiotherapy and less precise methods for response assessment. Tatsumura et al. (9) tested the administration of 5-fluorouracil by inhalation in dogs and found high levels of the drug in the trachea, bronchi, and regional nodes. Subsequently, the same authors treated 10 patients with inoperable lung tumors with 5-fluorouracil via supersonic nebulizer at a dose of 250 mg twice daily for 2 to 3 days per week. There was notable antitumor efficacy, and the therapy was well tolerated. Similar proof-of-principle studies using inhaled doxorubicin or paclitaxel in dogs with macroscopic...

Ganciclovir, when combined with high-dose intravenous immune globulin, appears to have significantly altered the outcome of patients with cytomegalovirus pneumonia after allogeneic bone marrow transplantation.

The yield and impact of open lung biopsies in patients with hematologic malignancies and unexplained pulmonary processes were assessed and analyzed to determine factors that affected the yield. Records of 63 patients with hematologic malignancy, who underwent 67 open lung biopsies for diagnosis of an unknown pulmonary process from 1996 to 1998 at Memorial Sloan-Kettering Cancer Center, were retrospectively reviewed. A specific diagnosis was found in 41 (62%) of the biopsies. Changes in therapy were made in 37 (57%) of patients after biopsy results, but in 69% of those with a specific diagnosis. Survival at 30 and 90 d was increased in those with specific rather than a nonspecific pulmonary diagnosis. The factor most predictive of finding a specific diagnosis was the presence of a focal rather than a diffuse radiographic abnormality (79% versus 36%, p = 0.003). Neutropenic patients or those on mechanical ventilation had a low chance of finding a specific diagnosis. Having received pulmonary toxic chemotherapy in the 6 mo before the biopsy was associated with finding a nonspecific lung injury. Specific pulmonary diagnoses found were inflammatory diseases in 23% of cases, infections in 21%, and malignancy in 18%. Bronchiolitis obliterans with organizing pneumonia (BOOP) was the most common inflammatory disorder and fungi and bacteria were the most frequent infectious pathogens. Complications occurred in 13% of the biopsies, including five patients who required mechanical ventilation post-procedure; one death was associated with the biopsy. The risk was increased in those with less than 50,000 platelets. Complications were similar with video-assisted thoracoscopy (VATS) compared with thoracotomy. We conclude that open lung biopsy in patients with hematologic malignancy has a significant yield and impact on management of patients with hematologic malignancy.

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Symptoms of drug-associated interstitial lung disease (ILD) are nonspecific and can be difficult to distinguish from a number of illnesses that commonly occur in patients with non-small-cell lung cancer (NSCLC) on therapy. Identification of drug involvement and differentiation from other illnesses is problematic, although radiological manifestations and clinical tests enable many of the alternative causes of symptoms in advanced NSCLC to be excluded. In lung cancer patients, high-resolution computed tomography (HRCT) is more sensitive than a chest radiograph in evaluating the severity and progression of parenchymal lung disease. Indeed, the use of HRCT imaging has led to the recognition of many distinct patterns of lung involvement and, along with clinical signs and symptoms, helps to predict both outcome and response to treatment. This manuscript outlines the radiology of drug-associated ILD and its differential diagnosis in NSCLC. An algorithm that uses clinical tests to exclude alternative diagnoses is also described.

The level of serum lactate dehydrogenase (LDH) has been reported to be useful as a marker of Pneumocystis carinii pneumonia (PCP) in patients infected with the human immunodeficiency virus (HIV). In this study, we evaluated the clinical role of measurements of LDH in determining diagnosis and prognosis in 84 patients infected with HIV who presented with pulmonary problems. The mean serum LDH level of the 54 patients with PCP was 361 IU, which was significantly higher than the mean of 224 IU found in the 30 patients with other causes of pulmonary disease (p less than 0.001). Overlap of individual values occurred between the 2 groups. Levels greater than 450 IU consistently predicted PCP in our population, however, and normal values were found in only 7% of the patients with PCP. LDH levels in a group of 8 patients who developed PCP from conventional causes of immunosuppression were similar to those seen in PCP associated with HIV. LDH determinations prior to the episode of PCP were available in 45 patients and 39 (87%) showed an increase of greater than 50 IU at the time of diagnosis. The mean LDH in those who survived PCP was 340 IU, which was significantly less than the mean of 447 IU found in those who died (p less than 0.05). Significant overlap between the groups precluded use of the LDH as a predictor of mortality in an individual patient. Serial determinations of LDH during treatment for PCP showed that 27 of 36 (75%) of the survivors had gradual decreases of LDH, whereas 9 of 12 (75%) nonsurvivors had rising values during treatment.(ABSTRACT TRUNCATED AT 250 WORDS)