Glioblastoma multiforme remains virtually incurable, with reported median
survivals of less than 2 years with standard treatment. In recent years,
thalidomide (Thalomid) has shown activity in high-grade gliomas as a single
agent and in combination with nitrosoureas and carboplatin (Paraplatin).[2-4] I
will describe three cases in which patients with recurrent, multicentric
glioblastoma responded to thalidomide plus chemotherapy after failing initial
treatment with conventional radiation and chemotherapy for a single malignant
A 43-year-old man diagnosed with anaplastic astrocytoma underwent a right
frontal craniotomy and gross total resection in July 1998. The surgery was
followed by external-beam radiation therapy and four cycles of cisplatin,
etoposide, and vincristine. In December 1999, disease progression was found, and
treatment was switched to single-agent temozolomide (Temodar). Disease continued
to progress, and multiple enhancing lesions were documented in February 2000
The patient then received six cycles of procarbazine (Matulane), lomustine
(CCNU [CeeNu]), and vincristine in combination with daily thalidomide at a dose
of 400 mg. Initial dose escalation of thalidomide to 600 mg/d was not well
tolerated, and thereafter, the dose was maintained at 400 mg/d. Complete
resolution of all lesions was observed after four cycles of therapy (see Figure
2, p 278).
Mild thrombocytopenia and leukopenia resolved upon completion of therapy with
procarbazine, lomustine, and vincristine. Minor sensory peripheral neuropathy
was noted but did not prevent the patient from working full time while receiving
treatment. At 1½ years after disease recurrence, the patient continues to
receive single-agent thalidomide.
Cases 2 and 3
Two other cases involving combination chemotherapy and thalidomide after
failure of first-line therapy resulted in partial responses at our institution.
In both cases, the patients were women with a history of breast cancer. Single
brain lesions were initially suspected to be metastatic disease, but surgical
resection identified them as primary anaplastic astrocytoma. These neoplasms did
not respond to treatment with radiation therapy and temozolomide, and the
disease progressed to multiple enhancing lesions in each patient, with a brain
biopsy-confirmed diagnosis of glioblastoma multiforme.
1. Louis DN, Cavenee WK: Neoplasms of the central nervous system, in: DeVita
VT Jr, Hellman S, Rosenberg SA (eds): Cancer: Principles & Practice of
Oncology, 6th ed, pp 2091-2160. Philadelphia, Lippincott Williams & Wilkins,
2. Fine HA, Figg WD, Jaeckle K, et al: Phase II trial of the
antiangiogenic agent thalidomide in patients with recurrent high-grade gliomas.
J Clin Oncol 18:708-715, 2000.
3. Fine HA, Maher EA, Wen PY, et al: Phase II trial of thalidomide and
BCNU in recurrent high-grade gliomas (abstract 218). Proc Am Soc Clin Oncol
4. Glass J, Gruber ML, Nirenberg A: Phase I/II study of carboplatin and
thalidomide in recurrent glioblastoma multiforme (abstract 551). Proc Am Soc
Clin Oncol 18:144a, 1999.