Thalidomide in patients with malignant pleural mesothelioma.
OBJECTIVE
The purpose of this study was to describe the experience with the anti-angiogenic agent thalidomide in the treatment of patients with a malignant pleural mesothelioma (MPM).


METHODS
Patients with a histological confirmed diagnosis of malignant mesothelioma received thalidomide orally at night. Increasing doses of 100, 200 or maximally 400 mg were given till progression or unacceptable toxicity. Patients that did not show signs of progression for > or =6 months were considered responders. Neurological examination included the use a sensory nerve action potential (SNAP) test.


RESULTS
Forty patients were evaluable for toxicity and efficacy. Twenty of them (50%) had received prior treatment. Thirty patients (75%) received a dose of 400 mg, 11 (37%) required dose reduction and 10 patients were confined to a dose of 200 mg or less. The major toxicity elicited by thalidomide concerned constipation (18/40 grade I and II) and two patients developed grade II neurotoxicity. A decline in SNAP test (>50%) did not seem to be related to the extent of neurological complaints. Eleven patients (27.5%) showed disease stabilization for >6 months and the median survival was 230 days (CI 130-330).


CONCLUSIONS
The advised dose for future studies in these patients is 200 mg/day. At this dose level, the toxicity is mild and routine monitoring of neurological toxicity (SNAP test) can be omitted. The percentage of patients seen with prolonged disease stabilization upon thalidomide treatment warrants phase III studies in MPM.
Baas
Paul
P
Department of Thoracic Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. p.baas@nki.nl
Boogerd
Willem
W
Dalesio
Otilia
O
Haringhuizen
Annebeth
A
Custers
Frank
F
van Zandwijk
Nico
N
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy*; D008875:Middle Aged; D009460:Neurologic Examination; D010997:Pleural Neoplasms / Q000188:drug therapy*; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D013792:Thalidomide