A Phase I II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma

Temozolomide is an alkylating agent with activity in the treatment of melanoma metastatic to the brain. Lomustine is a nitrosurea that crosses the blood brain barrier and there is evidence to suggest that temozolomide may reverse resistance to lomustine. A multicentre phase I/II study was conducted...

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Bibliographic Details
Published in:	British journal of cancer Vol. 96; no. 1; pp. 44 - 48
Main Authors:	LARKIN, J. M. G, HUGHES, S. A, BEIRNE, D. A, PATEL, P. M, GIBBENS, I. M, BATE, S. C, THOMAS, K, EISEN, T. G, GORE, M. E
Format:	Journal Article
Language:	English
Published:	Basingstoke Nature Publishing Group 15-01-2007
Subjects:	Administration, Oral Adult Antineoplastic Combined Chemotherapy Protocols - adverse effects Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Brain Neoplasms - drug therapy Brain Neoplasms - secondary Clinical Study Dacarbazine - administration & dosage Dacarbazine - adverse effects Dacarbazine - analogs & derivatives Dermatology Dose-Response Relationship, Drug Drug Administration Schedule Female Follow-Up Studies Humans Lomustine - administration & dosage Lomustine - adverse effects Male Maximum Tolerated Dose Medical sciences Melanoma - drug therapy Melanoma - secondary Middle Aged Neutropenia - chemically induced Thrombocytopenia - chemically induced Treatment Failure Tumors Tumors of the skin and soft tissue. Premalignant lesions Antineoplastic agent Human Nitrosoureas Central nervous system melanoma Malignant tumor Metastasis Encephalon Alkylating agent Chemotherapy Cancerology Treatment Nitrogen mustard Phase II trial Malignant melanoma Phase I trial Lomustine Temozolomide cerebral metastases
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Summary:	Temozolomide is an alkylating agent with activity in the treatment of melanoma metastatic to the brain. Lomustine is a nitrosurea that crosses the blood brain barrier and there is evidence to suggest that temozolomide may reverse resistance to lomustine. A multicentre phase I/II study was conducted to assess the maximum-tolerated dose (MTD), safety and efficacy of the combination of temozolomide and lomustine in melanoma metastatic to the brain. Increasing doses of temozolomide and lomustine were administered in phase I of the study to determine the MTD. Patients were treated at the MTD in phase II of the study to six cycles, disease progression or unacceptable toxicity. Twenty-six patients were enrolled in the study. In phase I of the study, the MTD was defined as temozolomide 150 mg m(-2) days 1-5 every 28 days and lomustine 60 mg m(-2) on day 5 every 56 days. Dose-limiting neutropaenia and thrombocytopaenia were observed at higher doses. Twenty patients were treated at this dose in phase II of the study. No responses to therapy were observed. Median survival from starting chemotherapy was 2 months. The combination of temozolomide and lomustine in patients with brain metastases from melanoma does not demonstrate activity. The further evaluation of this combination therefore is not warranted.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0007-0920 1532-1827
DOI:	10.1038/sj.bjc.6603503