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| 1: Cancer. 2006 Oct
15;107(8):1883-90. |
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Phase II study of temozolomide and thalidomide in
patients with metastatic melanoma in the brain: high rate of
thromboembolic events (CALGB 500102).
Krown
SE, Niedzwiecki
D, Hwu
WJ, Hodgson
L, Houghton
AN, Haluska
FG; Cancer
and Leukemia Group B.
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New
York, New York, USA.
BACKGROUND: Preliminary studies suggesting that extended-dose
temozolomide with thalidomide is safe and active in patients with
metastatic melanoma have led to frequent use of this oral regimen. To
confirm these observations the combination was tested in a multicenter
Phase II trial in patients with melanoma brain metastases. METHODS:
Eligible patients had melanoma brain metastases, with or without
systemic metastases. The primary endpoint was response rate in brain
metastases. Patients received temozolomide at a dose of 75 mg/m2/day
for 6 weeks with a 2-week rest between cycles, and thalidomide
(escalated to 400 mg/day for patients age < 70 years or to 200
mg/day for patients age > or = 70 years). A 2-stage design required
> or = 3 responses in the first 21 patients before enrolling 29
additional patients in the second stage. RESULTS: Sixteen eligible
patients were enrolled. No objective responses were observed. The
median survival was 23.9 weeks. Seven patients withdrew because of
tumor progression; 7 were removed during Cycle 1 because of adverse
events, including allergic reaction (1 patient), severe fatigue (1
patient), sudden death (1 patient), and thromboembolic events
(pulmonary embolism in 3 patients and deep vein thrombosis in 1
patient); 2 patients withdrew when the study was suspended and
subsequently closed. No associations could be established between
baseline characteristics and toxicity. CONCLUSIONS: The proportion of
patients with lethal or potentially life-threatening adverse events
was high (0.31, 95% confidence interval, 0.11-0.59), and the absence
of objective responses made it unlikely that further accrual would
demonstrate the efficacy of the regimen. These observations provide
little support for the use of this combination for melanoma brain
metastases unless safe and effective methods to prevent thrombosis are
developed. 2006 American Cancer Society
Publication Types:
- Clinical Trial, Phase II
- Multicenter Study
- Research Support, N.I.H., Extramural
PMID: 16986123 [PubMed - indexed for MEDLINE]
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| 2: Cancer. 2006 Oct
15;107(8):1866-72. |
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Clinical factors affecting acquired resistance to
gefitinib in previously treated Japanese patients with advanced
nonsmall cell lung cancer.
Segawa
Y, Hotta
K, Umemura
S, Fujiwara
Y, Shinkai
T, Ueoka
H, Takigawa
N, Tabata
M, Kiura
K, Tanimoto
M.
Department of Medicine and Thoracic Oncology, National Hospital
Organization Shikoku Cancer Center, Matsuyama, Japan. ysegawa@shikoku-cc.go.jp
BACKGROUND: The risk factors for the development of acquired
resistance in nonsmall cell lung cancer (NSCLC) patients responding to
gefitinib are unclear. The current study assessed clinicopathologic
factors affecting acquired resistance to gefitinib in previously
treated patients with advanced NSCLC. METHODS: Between 2000 and 2004,
197 consecutive Japanese patients with advanced NSCLC underwent
treatment with gefitinib. Of these patients, 56 who had continued
gefitinib treatment without disease progression for at least 6 months
were included in the study. RESULTS: At a median follow-up time of
21.6 months (range, 7.7-59.7 months), the median time to disease
progression was 19.5 months, with progression-free survival rates of
68.5% at 1 year, 33.6% at 2 years, and 21.2% at 3 years. In a
multivariate analysis using a Cox regression model, baseline brain
metastasis was the strongest prognostic factor affecting acquired
resistance to gefitinib (hazards ratio, 2.14; 95% confidence interval,
1.10- 4.17 [P = .025]). In addition, a decreased baseline hemoglobin
level (P = .074) and the administration of >1 chemotherapy regimen
before gefitinib treatment (P = .069) tended to be significant
negative prognostic factors. CONCLUSIONS: In patients undergoing
treatment with gefitinib, the presence of brain metastasis was
strongly associated with the emergence of acquired resistance in the
current series of NSCLC patients. The finding requires confirmation in
a large cohort of patients with advanced NSCLC, including a
non-Japanese/Asian population. 2006 American Cancer Society
Publication Types:
- Research Support, Non-U.S. Gov't
PMID: 16967452 [PubMed - indexed for MEDLINE]
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| 3: J Neurooncol.
2006 Dec 14; [Epub ahead of print] |
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Interstitial chemotherapy for malignant gliomas:
the Johns Hopkins experience.
Lawson
HC, Sampath
P, Bohan
E, Park
MC, Hussain
N, Olivi
A, Weingart
J, Kleinberg
L, Brem
H.
Department of Neurological Surgery, Johns Hopkins Medical
Institutions, Baltimore, MD, USA.
Malignant gliomas are very difficult neoplasms for clinicians to
treat. The reason for this is multifaceted. Many treatments that are
effective for systemic cancer are unable to cross the blood-brain
barrier and/or have unacceptable systemic toxicities. Consequently, in
recent years an effort has been placed on trying to develop innovative
local treatments that bypass the blood-brain barrier and allow for
direct treatment in the central nervous system (CNS)-interstitial
treatment. In this paper, we present our extensive experience in using
interstitial chemotherapy as a strategy to treat malignant brain
tumors at a single institution (The Johns Hopkins Hospital). We
provide a comprehensive summary of our preclinical work on
interstitial chemotherapy at the Hunterian Neurosurgery Laboratory,
reviewing data on rat, rabbit, and monkey studies. Additionally, we
present our clinical experience with randomized placebo-controlled
studies for the treatment of malignant gliomas. We compare survival
statistics for those patients who received placebo versus Gliadel((R))
as initial therapy (11.6 months vs. 13.9 months, respectively) and at
the time of tumor recurrence (23 weeks vs. and 31 weeks,
respectively). We also discuss the positive impact of local therapy in
avoiding the toxicities associated with systemic treatments.
Furthermore, we provide an overview of newer chemotherapeutic agents
and other strategies used in interstitial treatment. Finally, we offer
insight into some of the lessons we have learned from our unique
perspective.
PMID: 17171441 [PubMed - as supplied by publisher]
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