Thalidomide in Hematologic and Oncologic Disease
The use of thalidomide (Thalomid) in the treatment of hematologic diseases and in solid tumors as monotherapy or in combination with other agents is an exciting development in cancer therapy. Researchers actively involved in studying the role of thalidomide in cancer treatment were convened at a special investigators’ meeting held this past May in New Orleans. The articles in this supplement are based on the presentations made at this investigators’ meeting.
Introduction
The use of thalidomide (Thalomid) in the treatment ofhematologic diseases and in solid tumors as monotherapy or in combination withother agents is an exciting development in cancer therapy. Researchers activelyinvolved in studying the role of thalidomide in cancer treatment were convenedat a special investigators’ meeting held this past May in New Orleans. Thearticles in this supplement are based on the presentations made at thisinvestigators’ meeting.
The clinical utility of thalidomide has grown significantly overthe past 2 to 3 years, and at the present time, there are over 100 differentstudies underway using thalidomide in about 40 different illnesses. The clinicaluses of thalidomide can be loosely associated with a number of biological orcellular activities. In particular, modulation of tumor necrosis factor-alpha(TNF-alpha) inhibition, antiangiogenic properties, and stimulation of the immunesystem have been reported to be responsible for these positive clinicalactivities.
Thalidomide was developed as a sedative back in the 1950s andbecame popular when sold as an over-the-counter product in Europe and Canada.Shortly thereafter, however, negative effects of the drug started to appear withchronic use. In particular, these included peripheral neuropathy, now a familiarside effect of thalidomide, and teratogenicity, which ultimately was responsiblefor the drug being taken off the market.
It was not until the early 1990s that researchers at RockefellerUniversity identified thalidomide as an inhibitor of TNF-alpha, and soonthereafter, reports of thalidomide’s antiangiogenic properties were also made.It has only been within the past 2 years that encouraging results have emergedwith the use of thalidomide in cancer, and in particular, multiple myeloma.
Clinical Trials of Thalidomide
The articles in this supplement will discuss the status ofseveral ongoing clinical trials of thalidomide. Studies at the University ofArkansas, the Mayo Clinic, and several other institutions worldwide areevaluating the role of single-agent thalidomide in the treatment of multiplemyeloma. Although its mechanism of action in myeloma is still not clear,thalidomide appears to be active in some patients with refractory myeloma. Thisis discussed further in my article entitled "Thalidomide in MultipleMyeloma." Investigators at the Royal Marsden Hospital and UniversityCollege in London have studied thalidomide both as low-dose (100 mg orally,every night) and high-dose (600 mg, given as 300 mg, twice daily) therapy forpatients with a variety of solid tumors. Dr. Timothy Eisen presents a report onthese studies in his article "Thalidomide in Solid Tumors."
Clinical experience with thalidomide has also includedobservation of improvement in patients with prostate cancer and apparentresponses in patients with metastatic disease refractory to chemotherapy. Dr.Danai Daliani and colleagues have initiated a study of neoadjuvant thalidomidetreatment in patients with locally advanced prostate cancer. They have alsoinitiated a phase I/II trial of thalidomide, paclitaxel (Taxol), andestramustine (Emcyt) treatment in patients with metastatic androgen-independentprostate cancer who may have failed on up to two courses of chemotherapy. Theseare discussed further in Dr. Daliani’s article "Development ofAngiogenesis Inhibition as Therapy for Prostate Cancer."
A combination of thalidomide and temozolomide is currently beinginvestigated in a phase I/II study in metastatic melanoma. This is discussedfurther in Dr. Wen-Jen Hwu’s article "New Approaches in the Treatment ofMetastatic Melanoma: Thalidomide and Temozolomide." In Dr. RangaswamyGovindarajan’s article "Irinotecan and Thalidomide in MetastaticColorectal Cancer," the author discusses an ongoing phase II protocol usingthis regimen and has noted a remarkable absence of grade 3/4 gastrointestinaltoxicities. The author concludes that further testing of this regimen iswarranted.
Finally, in a pilot study performed at The University of TexasM. D. Anderson Cancer Center, investigators looked to determine the feasibilityof using thalidomide in a population of renal-cell carcinoma patients withprogressive disease, despite chemotherapy and immunotherapy. Dr. Robert Amatopresents a case report of one patient in this pilot trial in his article"Thalidomide for Recurrent Renal-Cell Cancer in a 40-Year-Old Man."
