Volume 5
Archive

1: Cancer. 2006 Oct 15;107(8):1883-90.

 
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]

 

2: Cancer. 2006 Oct 15;107(8):1866-72.

 
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]

 

3: J Neurooncol. 2006 Dec 14; [Epub ahead of print]

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]