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Antitumor Activity of Thalidomide in Refractory Multiple Myeloma

Antitumor Activity of Thalidomide in Refractory Multiple Myeloma. By Ezra Kassin. Background. Refractory Multiple Myeloma A malignant tumor in the bone marrow. Usually affecting flat bones (skull, pelvis, shoulder blade).

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Antitumor Activity of Thalidomide in Refractory Multiple Myeloma

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  1. Antitumor Activity of Thalidomide in Refractory Multiple Myeloma By Ezra Kassin

  2. Background Refractory Multiple Myeloma • A malignant tumor in the bone marrow. Usually affecting flat bones (skull, pelvis, shoulder blade). • The disease occurs when B lymphocytes multiply into clones of plasma cells. • Healthy B lymphocytes are active in the formation of antibodies. • Plasma cells have no infection fighting ability. • They begin to invade and crowd out the functional cells in the bone marrow.

  3. Multiple Myeloma accounts for 10% of all hematologic cancers. • Conventional chemotherapy is ineffective . • Melphalan-based high dose chemotherapy and stem cell support is the protocol. • Many patients still relapse with this treatment and other therapies are limited. • Death within three years of diagnosis is common.

  4. Thalidomide • Developed in the 1950s as a sedative that appeared to be very nontoxic during testing. • Women began taking it as a treatment for morning sickness and as a sedative. • Sharp increase in babies born with stunted limbs. • 1960s it was discovered that Thalidomide was a potent teratogen and antiangiogenetic drug. • Banned worldwide after causing 12,000 babies to be born with no limbs or flipper like arms and legs, facial deformities and defective organs.

  5. In 1998 Thalidomide was approved again to treat leprosy. • New research is showing that Thalidomide can be an effective treatment for AIDS, different types of cancers and many other diseases. • In Theory Cancer cells, like all cells needs a constant blood supply for tumor progression.Thalidomide Stops blood vessel growth to developing cells and they die from lack of nutrients.

  6. Thalidomide as Treatment for Multiple Myeloma Patients and Treatment • Patients with Multiple Myeloma show an increase in vascularization of bone marrow. • Leading to the spread of the cancer throughout the body. • This lead researchers to use antiangiogenic drugs in treatment.

  7. There were 84 patients with advanced myeloma who were previously treated with high dose chemotherapy • Orally administered thalidomide was the sole treatment. • 200 mg. A day was administered. • The dose was increased every two weeks by 200 mg. • The final dose was 800 mg.

  8. Evaluation • Evaluations includedcomplete blood counts • test of renal liver function • paraprotein levels • % of plasma cells and vascularity in bone marrow through biopsies. • These tests were performed on a weekly basis for the first two months followed by monthly exams.

  9. Results Paraprotein levels • In 27 patients (32%) the paraprotein levels decreased by at least 25%. • Any paraprotein level less than 25% was considered non responsive to the Thalidomide. • Two patients had a complete remission meaning greater than 90% reduction in paraprotein levels.

  10. Bone Marrow Response • A bone marrow response was defined as the presence of less than 5% of plasma cells in bone marrow. • A paraprotein response was associated with a bone marrow response in 81% of the patients.

  11. Microvascular Density of BoneMarrow • The microvascular density and the percentage of plasma cells in bone marrow correlated throughout the treatment.

  12. Adverse Effects of Thalidomide • Most adverse effects were mild to moderate. • Constipation, fatigue, weakness, and tiredness occurred in one third or more of the patients. • Less than 10% of the patients suffered serious side effects. • Nine patients could not tolerate the drug.

  13. Activity on cancer cells • Thalidomide suppresses the production of tumor necrosis factor. • Increases the production of interleukin 10. • Enhances cell mediated immunity by stimulating cytotoxic T cells. • Interaction between thalidomide and T cells increase levels of cytokines such as interferon. • Thalidomide increases lymphocytes, CD8 and CD4 T cells counts.

  14. Conclusion • This study shows us that Thalidomide has substantial antitumor activity in myeloma patients. • 10% of the patients had complete or nearly complete remission. • 32% had a marked reduction in paraprotein levels which was accompanied by a reduction in plasma cells in bone marrow and an increase in hemoglobin.

  15. Thalidomide is now being used in combination with chemotherapy as a treatment for many different types of cancers. • The results in this experiment are very promising but researchers must be careful when using this powerful drug. • They must remember the tragedy that occurred when the drug was first introduced 50 years ago.

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