The FDA Experience on the Use of Thalidomide in Advanced Malignancies

In 1997 and 1998, the Division of Oncology Drug Products at the U.S. Food and Drug Administration approved 575 single-patient investigational new drug applications for the use of thalidomide (Thalomid) for advanced malignancies. We subsequently surveyed 544 practitioners with a questionnaire, and received responses from 359 (response rate: 66%) with data on 480 patients.

The male-to-female ratio was almost even, with ages ranging from 11 to 90 years (median age: 52 years). The most common diagnoses were glioblastoma multiforme, melanoma, and breast, prostate, colon, pancreas, and renal-cell cancers. There were more than 30 other diagnoses that had fewer than 20 patients.

In general, thalidomide was well tolerated, with patients receiving up to 2,400 mg/d orally. One-third of the patients received 400 mg/d, 26% received 200 mg/d, 18% received 800 mg/d, 15% received 1,200 mg/d, and the remaining 8% received doses ranging from 50 to 2,400 mg/d. The most common reported side effects were somnolence, constipation, rash, fatigue, and mental status changes. Less common side effects were shortness of breath, dry mouth, and peripheral neuropathy. Fifty-eight patients (31%) were documented as having received other anticancer agents in combination with thalidomide. There was no evidence of enhanced toxicity in those patients on combination therapy.

Responses were reported in 36 patients (7.5%). Of the responders, 10 (28%) were documented to have received other anticancer agents. Response criteria were not defined. The majority of patients (53%) were withdrawn due to progressive disease, 10% were withdrawn due to toxicity, and 23% did not have a documented reason for withdrawal. There were no data collected on quality of life. Thirteen percent of the patients have continued thalidomide for 1 year or longer.

CONCLUSION: Thalidomide was generally well tolerated over a wide dose range in a population of patients with advanced malignancies. Withdrawals were primarily due to progressive disease. The overall response rate was modest, and in this heterogeneous population, there did not seem to be any added benefit from using thalidomide in combination with other agents. What role, if any, there may be for thalidomide in advanced malignancies warrants further study.

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