A phase I-II study of paclitaxel, ifosfamide, and vinorelbine with filgrastim (rhG-CSF) support in advanced non-small-cell lung cancer

PURPOSE: We designed a phase I-II trial of three active agents, paclitaxel, ifosfamide, and vinorelbine, in advanced non-small-cell lung cancer (NSCLC) to: 1) define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of paclitaxel with filgrastim (G-CSF) support; and 2) determine the overall response rate and median survival of patients treated on this regimen. PATIENTS AND METHODS: We treated cohorts of patients with stage IIIB or IV NSCLC with ifosfamide 1.2-1.6 g/m2/day x 3 and vinorelbine 20-25 mg/m2/day x 3 and escalating doses of paclitaxel at 100-175 mg/m2 on day 2 with G-CSF support on a 21-day cycle. One prior experimental single-agent chemotherapy regimen was allowed. RESULTS: Fifty-six patients, were enrolled on this trial: 27 on the phase I portion of the study and an additional 29 at the recommended phase II dose (RPTD). Thirteen patients had received prior chemotherapy. Paclitaxel doses of 175 mg/m2 and 150 mg/m2 produced dose-limiting myelosuppression, and the RPTD was determined to be paclitaxel 135 mg/m2 with ifosfamide 1.2 g/m2/day on days 1-3 and vinorelbine 20 mg/m2/ day on days 1-3 with G-CSF support. The overall response rate was 18%, with a median survival of 6.1 months. Six of 35 patients (17%) treated at the RPTD achieved a partial response to therapy. Grade IV neutropenia was observed in 19 of 35 patients at this dose, with eight patients suffering febrile neutropenia. CONCLUSIONS: This non-cisplatin-containing three-drug regimen has substantial toxicity and low activity in advanced NSCLC, and does not seem to improve on prior regimens. It is unclear whether the lack of efficacy relates to an antagonistic reaction between the specific drugs, administration schedule, or to subtherapeutic doses of the individual agents.     

Prevention and Mitigation Strategies to Address Recent Brittle Fractures in Steel Bridges

Brittle fracture results in unplanned loss of service, very costly repairs, concern regarding the future safety of the structure, and potential loss of life. These types of failures are most critical when there is no evidence of fatigue cracking leading up to the fracture and the fracture origin is concealed from view. Hence, the failure occurs without warning and the details are, essentially, noninspectable. In these cases, it appears desirable to take a proactive approach and introduce preventative retrofits to reduce the potential for future crack development. These efforts will help ensure that the likelihood of unexpected fractures is minimized. This paper examines the behavior of two bridge structures in which brittle fractures have developed in recent times, discusses the causes of the failures, and offers suggested design strategies for prevention and retrofit mitigation techniques. In situations where considerable uncertainty exists in the prediction of accumulated damage or in the ability to reliably inspect critical details, preemptive retrofit strategies appear to be highly desirable.     

Psoralen photochemotherapy

Psoralens and sunlight have been used by the Egyptians and Indians for hundreds of years for treating vitiligo. The combination of oral psoralens and artificial ultraviolet A (PUVA) therapy was approved for managing severe psoriasis by the Food and Drug Administration in 1982. Since then, PUVA therapy has been an effective modality for treating many cutaneous conditions (psoriasis, atopic dermatitis, vitiligo, and mycosis fungoides). However, proper knowledge and administration of PUVA therapy are vital to treatment success and reducing side effects.     

Primary sternal osteomyelitis presenting as a pleural-based mass

Osteomyelitis in uncommon locations can present unusual diagnostic difficulties. A patient with primary sternal osteomyelitis who presented with pain over the right supraclavicular area and a radiologic picture of a pleural-based right upper lung mass is discussed. A triple-phase bone scan was consistent with the diagnosis, and a needle aspiration of the mass revealed a staphylococcal abscess. Percutaneous drainage of the contiguous abscess and a prolonged course of antibiotic therapy cured the infection.     

The partial testing design: a less costly way to test equivalence for sensitivity and specificity

We propose a new, less costly, design to test the equivalence of digital versus analogue mammography in terms of sensitivity and specificity. Because breast cancer is a rare event among asymptomatic women, the sample size for testing equivalence of sensitivity is larger than that for testing equivalence of specificity. Hence calculations of sample size are based on sensitivity. With the proposed design it is possible to achieve the same power as a completely paired design by increasing the number of less costly analogue mammograms and not giving the more expensive digital mammograms to some randomly selected subjects who are negative on the analogue mammogram. The key idea is that subjects who are negative on the analogue mammogram are unlikely to have cancer and hence contribute less information for estimating sensitivity than subjects who are positive on the analogue mammogram. To ascertain disease state among subjects not biopsied, we propose another analogue mammogram at a later time determined by a natural history model. The design differs from a double sampling design because it compares two imperfect tests instead of combining information from a perfect and imperfect test.