Thalidomide And Dexamethasone

Thalidomide has activity against relapsed and refractory myeloma as a single agent59-65 and in combination with pulse dexamethasone,66, 67 with responses noted in 25-55% of patients in various trials. In two large Phase II studies of TD in previously untreated patients, response rates of 64% and 72% were reported.68, 69 Investigators from the Mayo Clinic treated 50 patients with 200 mg of thalidomide daily with dexamethasone 40 mg/day on days 1-4, 9-12, and 17-20.68 In the other study, 40 patients at M.D. Anderson Cancer Center (MDACC) were started on thalidomide 100-200 mg daily with dose increase to 400 mg/day allowed (median maximum dose achieved was 200 mg/day), and dexamethasone 20 mg/m2 on the same schedule as in the Mayo trial.69 As would be predicted from trials involving patients with relapsed/ refractory MM,65' 66 thalidomide therapy caused neuropathy, sedation, and constipation. Thrombotic complications occurred in 12% and 15% of patients treated in these two induction trials. In the MDACC study, a 25% thrombosis rate was observed in the first 24 patients treated, despite prophylaxis with 1 mg of coumadin daily. The next 16 patients received therapeutic doses of coumadin or low-molecular-weight heparin and no thrombotic events occurred.69 Based on the results of these Phase II trials, a randomized study comparing TD to dexamethasone alone was undertaken by ECOG. In this study, after four cycles of randomized therapy, patients with at least stable disease were given the option of proceeding to HDC/ ASCS. Although a statistically higher response rate was observed in the patients treated with TD (63% vs 41%), they also experienced more toxicity (including throm-botic complications), without any difference in sur-vival.70 TD induction has no negative effect on stem cell collection and quality of subsequent engraftment in patients treated with going on to HDC/ASCS.68, 70 71 Conclusions regarding the long-term outcome for patients treated with TD without subsequent HDC/ ASCS on this ECOG study are limited because almost all patients went on to high-dose therapy. The overall duration of response and survival for the 21 patients continuing TD beyond four cycles were 18 and 21 months, respectively,72 similar to the rates noted in the initial report of a large randomized trial of dexametha-sone ± thalidomide without HDC/ASCS (TTP: 17 months, OS: 25 months).73 These results are very similar to what one can expect from traditional cytotoxic regimens such as VAD. This, plus the fact that this convenient oral regimen can be used safely prior to HDC/ASCS or in the setting of renal insufficiency,74 has made TD the most widely used induction regimen in the United States.

Constipation Prescription

Constipation Prescription

Did you ever think feeling angry and irritable could be a symptom of constipation? A horrible fullness and pressing sharp pains against the bladders can’t help but affect your mood. Sometimes you just want everyone to leave you alone and sleep to escape the pain. It is virtually impossible to be constipated and keep a sunny disposition. Follow the steps in this guide to alleviate constipation and lead a happier healthy life.

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