Thalidomide Clinical Trials
What are the latest clinical trials involving thalidomide? Find out in
this easy-to-navigate collection of recent MEDLINE Abstracts compiled by
the editors at Medscape Pharmacotherapy. [Medscape Pharmacotherapy, 2000]
Phase II Evaluation of Thalidomide in Patients with
Metastatic Breast CancerBaidas SM, Winer EP, Fleming GF, et
J Clin Oncol. 2000;18(14):2710-2717
Purpose: To determine the efficacy, safety,
pharmacokinetics, and effect on serum angiogenic growth factors of two
dose levels of thalidomide in patients with metastatic breast cancer.
Patients and Methods: Twenty-eight patients with
progressive metastatic breast cancer were randomized to receive either
daily 200 mg of thalidomide or 800 mg to be escalated to 1,200 mg.
Fourteen heavily pretreated patients were assigned to each dose level.
Each cycle consisted of 8 weeks of treatment. Pharmacokinetics and growth
factor serum levels were evaluated.
patient had a true partial or complete response. On the 800-mg arm, 13
patients had progressive disease at or before 8 weeks of treatment and one
refused to continue treatment. The dose was reduced because of somnolence
to 600 mg for five patients and to 400 mg for two and was increased for
one to 1,000 mg and for four to 1,200 mg. On the 200-mg arm, 12 patients
had progressive disease at or before 8 weeks and two had stable disease at
8 weeks, of whom one was removed from study at week 11 because of grade 3
neuropathy and the other had progressive disease at week 16. Dose-limiting
toxicities included somnolence and neuropathy. Adverse events that did not
require dose or schedule modifications included constipation, fatigue, dry
mouth, dizziness, nausea, anorexia, arrhythmia, headaches, skin rash,
hypotension, and neutropenia. Evaluation of circulating angiogenic factors
and pharmacokinetic studies failed to provide insight into the reason for
the lack of efficacy.
thalidomide has little or no activity in patients with heavily pretreated
breast cancer. Further studies that include different patient populations
and/or combinations with other agents might be performed at the lower dose
Activity of Thalidomide in AIDS-Related Kaposi's
SarcomaLittle RF, Wyvill KM, Pluda JM, et al
Purpose: To assess the toxicity and activity of oral
thalidomide in Kaposi's sarcoma (KS) in a phase II dose-escalation study.
Patients and Methods: Human immunodeficiency virus
(HIV)-seropositive patients with biopsy-confirmed KS that progressed over
the 2 months before enrollment received an initial dose of 200 mg/d of
oral thalidomide in a phase II study. The dose was increased to a maximum
of 1,000 mg/d for up to 1 year. Anti-HIV therapy was maintained during the
study period. Toxicity, tumor response, immunologic and angiogenic
factors, and virologic parameters were assessed.
Results: Twenty patients aged 29 to 49 years with a
median CD4 count of 246 cells/mm(3) (range, 14 to 646 cells/mm(3)) were
enrolled. All patients were assessable for toxicity, and 17 for response.
Drowsiness in nine and depression in seven patients were the most frequent
toxicities observed. Eight (47%; 95% confidence interval [CI], 23% to 72%)
of the 17 assessable patients achieved a partial response, and an
additional two patients had stable disease. Based on all 20 patients
treated, the response rate was 40% (95% CI, 19% to 64%). The median
thalidomide dose at the time of response was 500 mg/d (range, 400 to 1,000
mg/d). The median duration of drug treatment was 6.3 months, and the
median time to progression was 7.3 months.
Conclusion: Oral thalidomide was tolerated in this
population at doses up to 1,000 mg/d for as long as 12 months and was
found to induce clinically meaningful anti-KS responses in a sizable
subset of the patients. Additional studies of this agent in KS are
warranted. Sucessful treatment of multiple myeloma relapsing after
high-dose therapy and autologous transplantation with thalidomide as a
Thalidomide in the Treatment of Cutaneous Lupus Refractory
to Conventional TherapyOrdi-Ros J, Cortes F, Cucurull E, et
J Rheumatol. 2000;27(6):1429-1433
Objective: We describe a prospective treatment study
of thalidomide in a series of 22 patients with cutaneous lupus refractory
to other treatments.
Methods: From 1992 to 1998, 22
patients with cutaneous lupus (9 with discoid lupus erythematosus, 7 with
subacute cutaneous lupus, 4 with profundus lupus, 2 with nonspecific rash)
were treated with thalidomide. Initial treatment was started at 100 mg
daily. If the cutaneous lesions vanished, the dose was lowered to 50-25 mg
daily as a maintenance therapy and it was considered a complete remission.
If the lesions improved but remained, this was considered a partial
response and treatment was continued until the lesions were not further
modified. Periodically, adverse effects were evaluated.
Results: Three patients discontinued treatment
because of side effects such as vertigo, persistent drowsiness, or
paresthesia. Rash improved in 16/19 patients (84%). Complete remission
occurred in 12/16 (75%). In 9 (65%) the rash resolved, but recurred 4-16
weeks after withdrawal of thalidomide; when it was used again, they
improved. Partial response was achieved in 4/16 (25%) patients. No
response occurred in 3/19 (16%). Many patients noted improvement within 2
weeks after starting thalidomide and maximum benefit was achieved within 3
months. Five of the 14 women had amenorrhea during the treatment with
Conclusion: Thalidomide is effective in
the treatment of cutaneous lupus refractory to other treatments. However,
only some patients had a remission; the remainder relapsed when treatment
was withdrawn, or required low doses of thalidomide to preserve inactive
lesions. Amenorrhea was observed as a new secondary effect of thalidomide.
Phase II Trial of the Antiangiogenic Agent Thalidomide in
Patients with Recurrent High-Grade GliomasFine HA, Figg WD,
Jaeckle K, et al
J Clin Oncol. 2000;18(4):708-15
Purpose: Little progress has been made in the
treatment of adult high-grade gliomas over the last two decades, thus
necessitating a search for novel therapeutic strategies. Malignant gliomas
are vascular or angiogenic tumors, which leads to the supposition that
angiogenesis inhibition may represent a potentially promising strategy in
the treatment of these tumors. We present the results of a phase II trial
of thalidomide, a putative inhibitor of angiogenesis, in the treatment of
adults with previously irradiated, recurrent high-grade gliomas.
Patients and Methods: Patients with a histologic
diagnosis of anaplastic mixed glioma, anaplastic astrocytoma, or
glioblastoma multiforme who had radiographic demonstration of tumor
progression after standard external-beam radiotherapy with or without
chemotherapy were eligible. Patients were initially treated with
thalidomide 800 mg/d with increases in dose by 200 mg/d every 2 weeks
until a final daily dose of 1,200 mg was achieved. Patients were evaluated
every 8 weeks for response by both clinical and radiographic criteria.
Results: A total of 39 patients were accrued, with 36
patients being assessable for both toxicity and response. Thalidomide was
well tolerated, with constipation and sedation being the major toxicities.
One patient developed a grade 2 peripheral neuropathy after treatment with
thalidomide for nearly a year. There were two objective radiographic
partial responses (6%), two minor responses (6%), and 12 patients with
stable disease (33%). Eight patients were alive more than 1 year after
starting thalidomide, although almost all with tumor progression. Changes
in serum levels of basic fibroblastic growth factor (bFGF) were correlated
with time to tumor progression and overall survival.
Conclusion: Thalidomide is a generally well-tolerated
drug that may have antitumor activity in a minority of patients with
recurrent high-grade gliomas. Future studies will better define the
usefulness of thalidomide in newly diagnosed patients with malignant
gliomas and in combination with radiotherapy and chemotherapy.
Additionally, studies will be needed to confirm the potential utility of
changes in serum bFGF as a marker of antiangiogenic activity and/or glioma
An Open-Label Pilot Study of Low-Dose Thalidomide in
Chronically Active, Steroid-Dependent Crohn's
DiseaseVasiliauskas EA, Kam LY, Abreu-Martin MT, et
Background & Aims: Thalidomide decreases
production of tumor necrosis factor alpha, a proinflammatory cytokine
associated with Crohn's disease (CD). In this study the safety, tolerance,
and efficacy of low-dose thalidomide were evaluated for treatment of
moderate-to-severe, steroid-dependent CD.
Twelve adult male patients with Crohn's Disease Activity Index (CDAI)
scores of > or = 250 and < or = 500 despite > or = 20 mg
prednisone/day were enrolled. The first 6 patients received 50 mg
thalidomide every night, the next 6 received 100 mg every night. Steroid
doses were stable during the first 4 weeks of treatment, then tapered
during weeks 5-12. CDAI was used to assess response.
Results: (1) Disease activity improved consistently
in all patients during weeks 1-4: 58% response, 17% remission. (2)
Clinical improvement was generally maintained despite steroid taper during
weeks 5-12. All patients were able to reduce steroids by >/=50%.
Forty-four percent discontinued steroids entirely. In weeks 5-12, 70% of
patients responded and 20% achieved remission. (3) Side effects were mild
and mostly transient, with the most common being drowsiness, peripheral
neuropathy, edema, and dermatitis.
Low-dose thalidomide appears to be well tolerated and effective over a
12-week period. Results of this pilot study support the need for
controlled multicenter trials of thalidomide for treatment of CD.
Thalidomide Therapy for Patients with Refractory Crohn's
Disease: An Open-Label TrialEhrenpreis ED, Kane SV, Cohen LB,
Cohen RD, Hanauer SB
Background & Aims: Inhibition of tumor necrosis
factor is a proposed mechanism for the anti-inflammatory properties of
thalidomide. We performed an open-label trial of thalidomide in refractory
Methods: Twenty-two patients with
refractory Crohn's disease (Crohn's Disease Activity Index [CDAI] > 200
and/or draining perianal disease) initiated therapy with thalidomide, 200
mg at bedtime (18 patients), or 300 mg at bedtime (4 patients). CDAI and
goal interval scores (GIS) were assessed at weeks 0, 4, and 12. Clinical
response for patients with luminal disease was defined as reduction in
CDAI score of >150 points and for fistula patients was 2 scores of
>/=1+ in 3 parameters of the GIS. Clinical remission was defined as a
total CDAI < 150 (luminal patients) or >/=2+ for all parameters of
the GIS (fistula patients).
Results: Nine patients
with luminal disease and 13 with fistulas (16 male, 6 female) were
enrolled. The median CDAI score at entry was 371 (95-468). Sixteen
patients completed 4 weeks of treatment (12 clinical responses, 4 clinical
remissions). All 14 patients completing 12 weeks met criteria for clinical
response. Nine achieved clinical remission (3 luminal, 6 fistula
patients). The median CDAI score was 175 (30-468; P < 0.001 vs.
Conclusions: Thalidomide is efficacious in
some patients with refractory Crohn's disease.
Antitumor Activity of Thalidomide in Refractory Multiple
MyelomaSinghal S, Mehta J, Desikan R, et al
N Engl J
Background: Patients with myeloma who relapse after
high-dose chemotherapy have few therapeutic options. Since increased bone
marrow vascularity imparts a poor prognosis in myeloma, we evaluated the
efficacy of thalidomide, which has antiangiogenic properties, in patients
with refractory disease.
previously treated patients with refractory myeloma (76 with a relapse
after high-dose chemotherapy) received oral thalidomide as a single agent
for a median of 80 days (range, 2 to 465). The starting dose was 200 mg
daily, and the dose was increased by 200 mg every two weeks until it
reached 800 mg per day. Response was assessed on the basis of a reduction
of the myeloma protein in serum or Bence Jones protein in urine that
lasted for at least six weeks.
Results: The serum or
urine levels of paraprotein were reduced by at least 90 percent in eight
patients (two had a complete remission), at least 75 percent in six
patients, at least 50 percent in seven patients, and at least 25 percent
in six patients, for a total rate of response of 32 percent. Reductions in
the paraprotein levels were apparent within two months in 78 percent of
the patients with a response and were associated with decreased numbers of
plasma cells in bone marrow and increased hemoglobin levels. The
microvascular density of bone marrow did not change significantly in
patients with a response. At least one third of the patients had mild or
moderate constipation, weakness or fatigue, or somnolence. More severe
adverse effects were infrequent (occurring in less than 10 percent of
patients), and hematologic effects were rare. As of the most recent
follow-up, 36 patients had died (30 with no response and 6 with a
response). After 12 months of follow-up, Kaplan-Meier estimates of the
mean (+/-SE) rates of event-free survival and overall survival for all
patients were 22+/-5 percent and 58+/-5 percent, respectively.
Conclusions: Thalidomide is active against advanced
myeloma. It can induce marked and durable responses in some patients with
multiple myeloma, including those who relapse after high-dose