Safety and efficacy of sequential chemotherapy with carboplatin plus gemcitabine followed by weekly paclitaxel in advanced non-small cell lung cancer.

BACKGROUND: Improving survival in non-small cell lung cancer (NSCLC) will require new strategies or new drugs. Sequential administration of conventional non-cross-resistant cytotoxic drugs offers an opportunity to increase drug diversity while maintaining dose intensity. This Phase II trial was designed to assess the efficacy and feasibility of such a regimen in advanced NSCLC. METHODS: Patients with NSCLC stage IIIB or IV received as first-line treatment four cycles of carboplatin (AUC 5) (day 1) plus gemcitabine 1000 mg/m(2) (days 1 and 8) every 3 weeks. Thereafter, treatment continued with 12 weekly cycles of paclitaxel 80 mg/m(2). RESULTS: In total, 46 patients were included. Median age was 59.6 years (range 41.3-74.3 years) and 93.5 % (n = 43) had Eastern Cooperative Oncology Group performance score of 0 or 1. All but 6 had stage IV disease, and 13 (28.3 %) had squamous cell carcinomas. Thirty-six (78 %) patients completed 4 cycles of carboplatin-gemcitabine and 35 patients received at least 1 cycle of paclitaxel, of whom 16 (46 % of total) patients completed 12 cycles of paclitaxel. The overall objective response rate was 49 %. Sixteen (37 %) patients had a response to carboplatin-gemcitabine, increasing to 21 (49 %) patients after administration of paclitaxel. Of the 13 assessable patients who showed a partial response (PR) on carboplatin-gemcitabine, 12 (92 %) patients showed also a PR on paclitaxel. Of 19 assessable patients with stable disease (SD) on carboplatin-gemcitabine, 4 (21 %) had a PR and 13 (68 %) SD on paclitaxel. Toxicity was moderate: 24 % stopped because of toxicity. CONCLUSION: Sequential chemotherapy with carboplatin-gemcitabine and weekly paclitaxel is active and feasible in advanced NSCLC patients.

A 37-Year-Old Woman With Recurrent Hemoptysis.

CASE PRESENTATION: A 37-year-old woman presented with a 2-month history of recurrent hemoptysis and coughing. Her symptoms started 2 months after the delivery of her third child. In total, she endured four episodes of hemoptysis. All pregnancies were induced by intracytoplasmic sperm injections. She lacked a pulmonary or smoking history and had no history of foreign body aspiration or intubation. There was no dyspnea, dysphagia, fever, or chest pain, and the patient did not complain of purulent sputum. She currently did not use medication and was generally in good health.

Reproducibility of hypercapnic ventilatory response measurements with steady-state and rebreathing methods.

In this study, the hypercapnic ventilatory response (HCVR) was measured, defined as the ventilation response to carbon dioxide tension (PCO2 ). We investigated which method, rebreathing or steady-state, is most suitable for measurement of the HCVR in healthy subjects, primarily based on reproducibility. Secondary outcome parameters were subject experience and duration. 20 healthy adults performed a rebreathing and steady-state HCVR measurement on two separate days. Subject experience was assessed using numeric rating scales (NRS). The intraclass correlation coefficient (ICCs) of the sensitivity to carbon dioxide above the ventilatory recruitment threshold and the projected apnoea threshold were calculated to determine the reproducibility of both methods. The ICCs of sensitivity were 0.89 (rebreathing) and 0.56 (steady-state). The ICCs of the projected apnoea threshold were 0.84 (rebreathing) and 0.25 (steady-state). The steady-state measurement was preferred by 16 out of 20 subjects; the differences in NRS scores were small. The hypercapnic ventilatory response measured using the rebreathing setup provided reproducible results, while the steady-state method did not. This may be explained by high variability in end-tidal PCO2 . Differences in subject experience between the methods are small.

Comparison of acetazolamide and medroxyprogesterone as respiratory stimulants in hypercapnic patients with COPD.

BACKGROUND: Acetazolamide and medroxyprogesterone acetate (MPA) are two respiratory stimulants that can be used in patients with stable hypercapnic COPD. DESIGN AND METHODS: The effects of acetazolamide, 250 mg bid, and MPA, 30 mg bid, on daytime and nighttime blood gas values and the influences on the hypercapnic and hypoxic ventilatory and mouth occlusion pressure (P(0.1)) at 100 ms response were studied in a crossover design in 12 hypercapnic patients with stable COPD (FEV(1), 33 +/- 4% predicted [mean +/- SEM]). RESULTS: Daytime PaCO(2) decreased from 47.3 +/- 0.8 mm Hg (placebo) to 42.0 +/- 1.5 mm Hg during acetazolamide treatment (p < 0.05) and to 42.8 +/- 1.5 mm Hg during MPA treatment (p < 0.05). Daytime PaO(2) improved with acetazolamide from 65.2 +/- 2.3 to 75.0 +/- 3.0 mm Hg (p < 0.05), whereas no significant changes were seen with MPA. Mean nocturnal end-tidal carbon dioxide tension decreased with both treatments, from 42.0 +/- 2.3 to 35.3 +/- 2.3 mm Hg with acetazolamide (p < 0.05) and to 34.5 +/- 0.8 mm Hg with MPA (p < 0.05). The percentage of time that the nocturnal arterial oxygen saturation was < 90% was reduced significantly with acetazolamide, from 34.9 +/- 10.7% to 16.3 +/- 7.5% (p < 0.05). Mean nocturnal saturation did not change with MPA. Resting minute ventilation increased significantly only with MPA from 9.6 +/- 0.7 to 10.8 +/- 0.8 L/min (p < 0.05). The slope of the hypercapnic ventilatory response did not change during acetazolamide and MPA therapy. The hypoxic ventilatory response increased from - 0.2 +/- 0.05 to - 0.4 +/- 0.1 L/min/% during acetazolamide (p < 0.05) and to - 0.3 +/- 0.1 L/min/% during MPA (p < 0.05). The hypoxic P(0.1) response improved with acetazolamide treatment from - 0.05 +/- 0.008 to - 0.15 +/- 0.02 mm Hg/% (p < 0.05). CONCLUSIONS: This study shows that acetazolamide and MPA both have favorable effects on daytime and nighttime blood gas parameters in ventilatory-limited patients with stable COPD. However, the use of acetazolamide is preferred because of its extra effect on nocturnal saturation.

Etanercept-related extensive pulmonary nodulosis in a patient with rheumatoid arthritis.

OBJECTIVE: Although nodulosis is a common extraarticular manifestation of rheumatoid arthritis, accelerated pulmonary nodulosis is a rare event. The etiology of rheumatoid nodules is still unknown. Nodulosis is not necessarily associated with active joint inflammation, suggesting different pathogenic mechanisms for nodule formation and synovial tissue inflammation. We describe a patient with extensive pulmonary nodulosis, probably related to etanercept treatment. Our case emphasizes the need for careful monitoring for adverse events during treatment with biologicals, especially since the differential diagnosis often includes a broad spectrum of diseases.

Pulmonary sclerosing hemangioma detected by fluorodeoxyglucose positron emission tomography in familial adenomatous polyposis: report of a case.

We present a 53-year-old female suffering from familial adenomatous polyposis, who was found to have a positive nodus, lateral to the hilus of the left lung, on routine FDG-PET scan. This lesion was found to be a sclerosing hemangioma. We found an aberrant beta-catenin expression on immunohistochemical staining, suggesting that sclerosing hemangioma and familial adenomatous polyposis share the same pathophysiology. It is important to be aware of the association of familial adenomatous polyposis and sclerosing hemangioma.