Thalidomide versus dexamethasone for the treatment of relapsed and/or refractory multiple myeloma: results from OPTIMUM, a randomized trial.

BACKGROUND: Thalidomide has potent antimyeloma activity, but no prospective, randomized controlled trial has evaluated thalidomide monotherapy in patients with relapsed/refractory multiple myeloma. DESIGN AND METHODS: We conducted an international, randomized, open-label, four-arm, phase III trial to compare three different doses of thalidomide (100, 200, or 400 mg/day) with standard dexamethasone in patients who had received one to three prior therapies. The primary end-point was time to progression. RESULTS: In the intent-to-treat population (N=499), the median time to progression was 6.1, 7.0, 7.6, and 9.1 months in patients treated with dexamethasone, and thalidomide 100, 200, and 400 mg/day, respectively; the difference between treatment groups was not statistically significant. In the per-protocol population (n=465), the median time to progression was 6.0, 7.0, 8.0, and 9.1 months, respectively. In patients who had received two or three prior therapies, thalidomide significantly prolonged the time to progression at all dose levels compared to the result achieved with dexamethasone. Response rates and median survival were similar in all treatment groups, but the median duration of response was significantly longer in all thalidomide groups than in the dexamethasone group. Adverse events reported in the thalidomide groups, such as fatigue, constipation and neuropathy, confirmed the known safety profile of thalidomide. CONCLUSIONS: Although thalidomide was not superior to dexamethasone in this randomized trial, thalidomide monotherapy may be considered an effective salvage therapy option for patients with relapsed/refractory multiple myeloma, particularly those with a good prognosis and those who have received two or three prior therapies. The recommended starting dose of thalidomide monotherapy is 400 mg/day, which can be rapidly reduced for patients who do not tolerate this treatment. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00452569).

Estimated global distribution and regional spread of HIV-1 genetic subtypes in the year 2000.

The objective of this study was to estimate the global distribution and regional spread of different HIV-1 genetic subtypes and circulating recombinant forms (CRFs) in the year 2000. These estimates were made based on data derived from global HIV/AIDS surveillance and molecular virology studies. HIV-1 incidence during the year 2000 was estimated in defined geographic regions, using a country-specific model developed by WHO-UNAIDS. The proportion of new infections caused by different HIV-1 subtypes in the same geographic regions was estimated by experts from the WHO-UNAIDS Network for HIV Isolation and Characterization, based on results generated by HIV molecular epidemiology studies in 1998 to 2000. The absolute numbers and relative proportions of new infections due to different genetic subtypes of HIV-1 by different geographic regions were calculated using these two sets of estimated data. The results of the study demonstrated that the epidemiology of HIV-1 subtypes and CRFs is characterized by their differential distribution and varying significance as a driving cause of the pandemic on regional and global basis. The largest proportion of HIV-1 infections in the year 2000 was due to subtype C strains (47.2%). Subtype A/+CRF02_AG was estimated to be the second leading cause of the pandemic (27%), followed by subtype B strains (12.3%). The same analysis confirmed an increasing role of HIV-1 CRFs in the pandemic. The authors conclude that combined analysis of data based on the global HIV/AIDS surveillance and molecular virology studies provides for a useful model to monitor the dynamics of the global spread of HIV-1 subtypes and CRFs on regional and country levels-the information of potential importance for diagnosis and treatment of HIV/AIDS, as well as for the development globally effective HIV vaccines.

Standard operating procedures for clinical investigators

It provides instructions for planning, performing, documenting and reporting clinical studies supported by TDR, and also provides a useful glossary of terms. Document in pdf format; Acrobat Reader needed.