Replacement of bortezomib with carfilzomib for multiple myeloma patients progressing from bortezomib combination therapy.

In this open-label, intra-patient phase I/II trial, bortezomib was replaced with carfilzomib (escalated from 20 to 45 mg/m(2) on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle) for multiple myeloma (MM) patients who progressed while on or within 12 weeks of receiving a bortezomib-containing combination regimen. Study objectives included determination of the maximum tolerated dose (MTD), overall response rate (ORR), clinical benefit rate (CBR), time to progression, time to response, duration of response, progression-free survival and overall survival (OS). Of 38 registered patients, 37 were treated and evaluable for efficacy and safety. Thirty-one carfilzomib-based regimens using 14 different drug combinations were tested. One regimen (carfilzomib (45 mg/m(2)), ascorbic acid (1000 mg) and cyclophosphamide (2.2 mg/kg)) reached MTD. ORR and CBR were 43.2 and 62.2%, respectively. Median progression-free survival, time to progression and OS were 8.3, 9.9 and 15.8 months, respectively. Hematologic adverse events (AEs; ⩾grade 3) included lymphopenia (35.1%), thrombocytopenia (24.3%), anemia (10.8%) and neutropenia (10.8%). Nonhematologic AEs (⩾grade 3) included fever (5.4%) and hypokalemia (5.4%). These results demonstrate that replacing bortezomib with carfilzomib is safe and can be effective for MM patients failing bortezomib-containing combination regimens. This trial was registered at http://www.clinicaltrials.gov (#NCT01365559).

Preoperative and adjuvant chemotherapy in locally advanced non-small cell lung cancer.

The continued favorable results with surgery in early stage lung cancer have led many investigators to use radiation and chemotherapy to reduce the size of unresectable tumors either before or after definitive surgery. Although earlier results with both radiation and chemotherapy have been poor, the newer cisplatin-containing combination chemotherapy regimens have yielded decreased local recurrence rates when used postoperatively following a complete resection and have produced increased complete resection rates when given preoperatively to patients with locally advanced and unresectable non-small cell lung cancer at diagnosis.

Waterborne Legionella bozemanii and nosocomial pneumonia in immunosuppressed patients.

From October 1983 to February 1984, five episodes of nosocomial pneumonia caused by Legionella bozemanii occurred in immunosuppressed patients at a 300-bed community hospital. Pulmonary infiltrates were predominantly patchy and present in multiple lobes and bilaterally; cavitation occurred in one patient. Patients responded promptly and completely to treatment with erythromycin and rifampin. Epidemiologic studies showed that all patients had been continuously or recently hospitalized at the same institution. Legionella bozemanii was cultured from four of the five infected patients, from tapwater in patient care areas, from the hospital's hotwater holding tank, and from soil in an area of excavation and new construction on hospital property. Chlorination and heat sterilization of the tank eliminated L. bozemanii from the water and no further cases were seen. This outbreak reaffirms that excavation and construction are risk factors for the outbreak of nosocomial legionella pneumonia and is the first description of nosocomial infection due to L. bozemanii.