Thalidomide best for recently dx patients that only have anemia

[Birgitta-A]

Hi all,
Here is a reveiw of 527 MDS patients treated with Thalidomide:
"EHA 2009 THALIDOMIDE FOR THE TREATMENT OF MYELODYSPLASTIC SYNDROMES: A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE PUBLISHED STUDIES
Musto, P, D'Auria, F, Sparano, A et al. Centro di Riferimento Oncologico della Basilicata, Rionero In Vulture, Italy

Background
Thalidomide has been used to improve the cytopenia of MDS. However, due to the heterogeneity of patient populations treated and of doses/schedules adopted in the different studies so far performed, the efficacy of this drug in MDS remains controversial. Furthermore, some concerns also exist about its tolerability. Indeed, no individual clinical trial has been sufficiently extensive to provide a basis for a decision model to use thalidomide in MDS.

Methods
In order to define better the role of thalidomide in MDS, we performed a systematic review of all published articles on this topic by using a Pub-Med web-site methodology. Ten phase I-II studies, including a total of 527 MDS patients who had received thalidomide as single agent, were identified and examined. Neither phase III trials, nor previous meta-analyses were found.

Results
Thalidomide doses widely varied in the different studies, ranging from 50 to 1000 mg/d. The response criteria also were not uniform.

Overall, average response rate was 32% (range 9-56%) and 43% (range 16-88%) on intention-to-treat analysis or considering only patients able to receive the drug for 12-16 weeks, respectively.

The large majority of responses were erythroid in nature (mostly resulting in transfusion-independence) and were achieved within 2-3 months, without a clear evidence of a dose-response effect.

Responses were more frequently observed in patients with lower IPSS risk score and with a recent diagnosis at treatment (< 1 year). There was no evidence of a correlation between response to thalidomide and baseline levels of endogenous erythropoietin, transfusion support or prior treatment with epoetins. Cytogenetic response or changes in marrow morphology were only occasionally reported.

The duration of response was highly variable, ranging from three months to more than six years. Side effects, mainly peripheral neuropathy, sedation, constipation, and skin rash, were frequent, determining a very high and often early drop-out (mean 44%, range 15-67%), even in responders and especially in elderly patients where thalidomide doses > 200 mg/d were employed.

Despite the fact that no thrombotic prophylaxis was generally adopted, thrombotic events were very rare and exclusively associated with higher doses of the drug. Two studies suggested a possible survival benefit for MDS patients treated with thalidomide.

Conclusions
Based on available evidences, thalidomide remains a possible therapeutic option for selected MDS patients, if appropriately employed and managed. An early use of individualized doses, starting with 100 mg/d and increasing the dose up to no more than 200 mg/d, if well tolerated, is recommended for at least 12 weeks. Lower doses may be enough in elderly subjects or for maintaining response.

Preferable targets appear to be lower risk patients with transfusion-dependent anemia as single cytopenia, who are not candidates for alternative approaches, such as epoetins (high levels of endogenous erythropoietin or prior resistance), lenalidomide (no evidence of the 5q- cytogenetic abnormality) and high dose chemotherapy or hypomethylating agents (no blast excess). "
Kind regards
Birgitta-A