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.
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-PACEa 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
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.