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
The clinical utility of thalidomide has grown significantly over
the past 2 to 3 years, and at the present time, there are over 100 different
studies underway using thalidomide in about 40 different illnesses. The clinical
uses of thalidomide can be loosely associated with a number of biological or
cellular activities. In particular, modulation of tumor necrosis factor-alpha
(TNF-alpha) inhibition, antiangiogenic properties, and stimulation of the immune
system have been reported to be responsible for these positive clinical
Thalidomide was developed as a sedative back in the 1950s and
became popular when sold as an over-the-counter product in Europe and Canada.
Shortly thereafter, however, negative effects of the drug started to appear with
chronic use. In particular, these included peripheral neuropathy, now a familiar
side effect of thalidomide, and teratogenicity, which ultimately was responsible
for the drug being taken off the market.
It was not until the early 1990s that researchers at Rockefeller
University identified thalidomide as an inhibitor of TNF-alpha, and soon
thereafter, reports of thalidomide’s antiangiogenic properties were also made.
It has only been within the past 2 years that encouraging results have emerged
with the use of thalidomide in cancer, and in particular, multiple myeloma.
Clinical Trials of Thalidomide
The articles in this supplement will discuss the status of
several ongoing clinical trials of thalidomide. Studies at the University of
Arkansas, the Mayo Clinic, and several other institutions worldwide are
evaluating the role of single-agent thalidomide in the treatment of multiple
myeloma. Although its mechanism of action in myeloma is still not clear,
thalidomide appears to be active in some patients with refractory myeloma. This
is discussed further in my article entitled "Thalidomide in Multiple
Myeloma." Investigators at the Royal Marsden Hospital and University
College 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 for
patients with a variety of solid tumors. Dr. Timothy Eisen presents a report on
these studies in his article "Thalidomide in Solid Tumors."
Clinical experience with thalidomide has also included
observation of improvement in patients with prostate cancer and apparent
responses in patients with metastatic disease refractory to chemotherapy. Dr.
Danai Daliani and colleagues have initiated a study of neoadjuvant thalidomide
treatment in patients with locally advanced prostate cancer. They have also
initiated a phase I/II trial of thalidomide, paclitaxel (Taxol), and
estramustine (Emcyt) treatment in patients with metastatic androgen-independent
prostate cancer who may have failed on up to two courses of chemotherapy. These
are discussed further in Dr. Daliani’s article "Development of
Angiogenesis Inhibition as Therapy for Prostate Cancer."
A combination of thalidomide and temozolomide is currently being
investigated in a phase I/II study in metastatic melanoma. This is discussed
further in Dr. Wen-Jen Hwu’s article "New Approaches in the Treatment of
Metastatic Melanoma: Thalidomide and Temozolomide." In Dr. Rangaswamy
Govindarajan’s article "Irinotecan and Thalidomide in Metastatic
Colorectal Cancer," the author discusses an ongoing phase II protocol using
this regimen and has noted a remarkable absence of grade 3/4 gastrointestinal
toxicities. The author concludes that further testing of this regimen is
Finally, in a pilot study performed at The University of Texas
M. D. Anderson Cancer Center, investigators looked to determine the feasibility
of using thalidomide in a population of renal-cell carcinoma patients with
progressive disease, despite chemotherapy and immunotherapy. Dr. Robert Amato
presents 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."