Expanded Data on Thalidomide in Advanced Myeloma

New clinical data presented at the 41st meeting of the American Society of Hematology (ASH) expand on previously published results on the use of thalidomide (Thalomid) in treating advanced and refractory multiple myeloma. The studies include the use of thalidomide as a single agent and in combination with other chemotherapeutic agents.

Researchers from the Myeloma and Transplantation Research Center of the Arkansas Cancer Research Center presented results of a phase II trial of 180 patients who were treated with thalidomide between December 1997 and May 1999. Initial results from a smaller number of patients in this study were first reported at the 1998 ASH meeting in Miami, Florida, and were later published in The New England Journal of Medicine (November 1998).

Favorable Paraprotein Responses

Of the 180 patients, 36% achieved a ³ 25% reduction in tumor burden. The paraprotein responses included 18 patients who achieved a ³ 90% reduction; 14, a ³ 75% reduction; 16, a ³ 50% reduction. An additional four patients achieved a complete response. To be considered a response, these paraprotein reductions must have been observed on two occasions at least 6 weeks apart. The reported side effects included constipation, weakness/fatigue, and somnolence.

“These results are very encouraging,” said Sol J. Barer, phd, president and chief operating officer of Celgene. “As these and other studies are completed, Celgene is moving forward in developing this indication for submission to the FDA.”

Patients received an initial thalidomide dose of 200 mg/d, which was escalated every 2 weeks to a maximum dose of 800 mg/d. In all, 77% of the patients had undergone prior high-dose therapy and 53% had undergone two or more cycles of such therapy.

Thalidomide is contraindicated in pregnant women and women capable of becoming pregnant. Even a single capsule taken by a pregnant woman can cause severe birth defects or death to an unborn baby.

DT-PACE Study

In a separate presentation, researchers from the Arkansas Cancer Research Center reported on a study of 33 previously treated multiple myeloma patients who were evaluated following completion of two cycles of DT-PACE—a combination of dexamethasone (40 mg qid), thalidomide (400 mg/d), and a 4-day regimen of daily infusions of Platinol (cisplatin), Adriamycin (doxorubicin), cyclophosphamide, and etoposide.

After two cycles of DT-PACE, 40% of these patients achieved a ³ 75% in tumor mass, including 19% who achieved a 90% tumor reduction and 5% who had a complete remission. Side effects associated with this regimen included neutropenic fever, DVT, and constipation; the investigators believe that the last two were probably associated with thalidomide.