Phase II trial and pharmacokinetic study of thalidomide in patients with metastatic colorectal cancer.
BACKGROUND
This study was designed to estimate the percentage of objective tumor responses, toxicity profile, and obtain additional information about the plasma pharmacokinetics of thalidomide in patients with refractory and progressing metastatic colorectal cancer.


METHODS
This phase II clinical trial was conducted according to the two-stage Simon method with the inclusion of consecutive patients. The study protocol was approved by the Institutional Review Board (IRB) of the Academic Hospital (HCPA) of the Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.


METHODS
Seventeen patients with previously treated, refractory progressive metastatic colorectal cancer were eligible. Six patients had prior radiotherapy. The patients had a median of one previous chemotherapy regimen. Patients were initially treated with 200 mg/day of thalidomide with an increase in dose by 200 mg/day every 2 weeks until a final daily dose of 800 mg/day was achieved. Patients were evaluated every 8 weeks for response by radiographic criteria. Plasma pharmacokinetics studies were performed in four patients at 200 mg level and in one patient at 600 mg during the first 24 h.


RESULTS
A total of 17 patients were accrued, all of them being evaluable for toxicity and 14 for response. Thalidomide was well tolerated, with constipation, somnolence, dizziness, and dry mouth being the major toxicities. There were no objective response or stable disease. The median survival was 3.6 months. Single-agent thalidomide is a generally well-tolerated drug that showed no antitumor activity in patients with advanced pretreated metastatic colorectal cancer. Although thalidomide did not show antitumor activity in this patient population, future studies of this agent in patients at initial stages of the disease (when its antiangiogenic properties may be more relevant to disease progression) could be considered.
Department of Medical Oncology, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Lissandra
L
Dal Lago
Marc F
MF
Richter
Anna I
AI
Cancela
Sabrina A
SA
Fernandes
Keylla T
KT
Jung
Ana C
AC
Rodrigues
Teresa Dalla
TD
Costa
Luciane P
LP
Di Leone
Gilberto
G
Schwartsmann
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013792:Thalidomide / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D013792:Thalidomide