Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : Celgene-CELG -- Ignore unavailable to you. Want to Upgrade?

To: LLCF who wrote (466)	9/27/2000 1:13:12 PM
From: Ben Wa	Read Replies (1) \| Respond to of 804

do you realize how stupid the title of that research piece is?

To: LLCF who wrote (466)	9/27/2000 11:00:40 PM
From: Miljenko Zuanic	Read Replies (1) \| Respond to of 804

I do not see this as big issue. T and D combination toxicity seams as sort of anti-inflammatory and pro-immunostimulatory combination. Somehow D itensify T skin toxicity (and, my guess, maybe T efficiency as anti-cancer agent in MM). Major problem (and reason that I eliminate my small CELG position for second time) is no real plan (no real marketing plan) at CELG when issue is T+chemo. Company present MC at ~3.5 BB is more than many SHs did hope for. Miljenko

To: LLCF who wrote (466)	9/28/2000 2:37:26 PM
From: sim1	Read Replies (1) \| Respond to of 804

Here's the referenced NEJM letter on thalidomide toxicity. The New England Journal of Medicine -- September 28, 2000 -- Vol. 343, No. 13 Life-Threatening Toxic Epidermal Necrolysis with Thalidomide Therapy for Myeloma To the Editor: Thalidomide has recently been shown to be effective for the treatment of refractory myeloma. (1,2) We report a case of life-threatening toxic epidermal necrolysis with the combined use of thalidomide and dexamethasone in a patient with previously untreated myeloma. A 64-year-old man with newly diagnosed myeloma presented with multiple lytic bone lesions, anemia, and hypercalcemia, with a serum IgA-lambda monoclonal protein level of 41 g per liter and 90 percent plasma cells in the bone marrow. After obtaining informed consent, we initiated treatment with thalidomide and dexamethasone as part of an ongoing phase 2 trial. The patient received 200 mg of thalidomide per day for 14 days and had no adverse effects. The dose was then increased to 400 mg per day. Ten days after the dose was increased, the patient noticed a rash, and the thalidomide was discontinued. Within three days, he had diffuse erythema of the trunk, extremities, and face, with blistering skin lesions and large areas with a scalded-skin appearance due to biopsy-proven, full-thickness epidermal necrosis -- findings that are characteristic of toxic epidermal necrolysis (Figure 1). There was also ulceration of the mouth and oropharynx. The patient was hospitalized and recovered after two weeks of intensive therapy. Two additional patients in the group of eight patients who have thus far received thalidomide and dexamethasone for newly diagnosed myeloma have had unexpectedly severe dermatologic toxic effects, including one patient who required urgent hospitalization for generalized erythroderma. Both patients recovered fully after the thalidomide had been discontinued. Toxic epidermal necrolysis is the result of drug-induced interactions between Fas and Fas ligand in keratinocytes, resulting in the separation of large areas of the epidermis from the dermis. (3) Interestingly, thalidomide was recently studied as a treatment for toxic epidermal necrolysis in a randomized, placebo-controlled trial. (4) However, the study was terminated because of an excess number of deaths in the thalidomide group. Although rashes and a minor degree of exfoliation are seen in 20 to 25 percent of patients receiving thalidomide, (1) toxic epidermal necrolysis has been reported only rarely. (5) We have treated 55 other patients with thalidomide alone, and none of them have had toxic epidermal necrolysis. We are therefore concerned about the possibility of an adverse interaction between dexamethasone and thalidomide. Thalidomide undergoes spontaneous nonenzymatic cleavage to a variety of metabolites, the levels of which may be affected by dexamethasone. Dexamethasone is often used alone or in combination with other agents in patients with myeloma, and there is interest in combining it with thalidomide for the treatment of this disease. Although the combination appears to be very effective and merits study, we recommend that until a safe dose schedule has been determined, dexamethasone (or other corticosteroids) not be used in combination with thalidomide for the treatment of newly diagnosed myeloma, except in closely monitored trials. Caution should be exercised when combining thalidomide with other drugs known to cause serious skin reactions, such as sulfonamides and allopurinol. S. Vincent Rajkumar, M.D. Morie A. Gertz, M.D. Thomas E. Witzig, M.D. Mayo Clinic Rochester, MN 55905 References 1. Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999;341:1565-71. [Erratum, N Engl J Med 2000;342:364.] 2. Rajkumar SV, Fonseca R, Dispenzieri A, et al. Thalidomide in the treatment of relapsed and refractory myeloma. Blood 1999;94:Suppl 1:316a. abstract. 3. Viard I, Wehrli P, Bullani R, et al. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. Science 1998;282:490-3. 4. Wolkenstein P, Latarjet J, Roujeau JC, et al. Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis. Lancet 1998;352:1586-9. 5. Horowitz SB, Stirling AL. Thalidomide-induced toxic epidermal necrolysis. Pharmacotherapy 1999;19:1177-80. nejm.org