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Temozolomide Followed By Combined Immunotherapy Aids Metastatic Melanoma
A DGReview of :"Temozolomide followed by combined immunotherapy with GM-CSF, low-dose IL2 and IFNalpha in patients with metastatic melanoma"
British Journal of Cancer
03/12/2003
By Anne MacLennan
Oral temozolomide (TMZ) followed by subcutaneous combined immunotherapy is effective in patients with metastatic melanoma, researchers in the Netherlands have found.
Toxicity linked with this treatment is manageable on an outpatient basis, report Dr G C de Gast and colleagues from the Division of Medical Oncology, Netherlands Cancer Institute, Amsterdam.
They sought to determine both the toxicity and efficacy of oral TMZ followed by subcutaneous (sc) low-dose interleukin-2 (IL2), granulocyte-monocyte colony stimulating factor (GM-CSF) and interferon-alpha 2b (IFN alpha) in these patients. The 74 study participants received, in four separate cohorts, escalating doses of TMZ (150-250 mg m-²) for 5 days followed by sc IL2 (4 MIU m-²), GM-CSF (2.5 microg kg-1) and IFN alpha (5 MIU flat) for 12 days.
A second identical treatment was scheduled on day 22, and the cycles were repeated in stable or responding patients following evaluation.
The investigators analysed the data after a median follow-up of 20 months (range: 12 to 30 months).
Overall, the objective response rate was 31% (23 of 74), with responses occurring in all disease sites, including the central nervous system (CNS).
Of the 36 patients with responding or stable disease, none developed CNS metastasis as the first or concurrent site of progressive disease.
Median survival was 252 days (8.3 months), with one year survival of 41%.
Primary toxicity of TMZ was thrombocytopenia and was dose- and patient-dependent. Lymphocytopenia occurred in 48.5% (34 of 70) of fully monitored patients following TMZ and remained after immunotherapy in two.
The main toxicity of combined immunotherapy was flu-like syndrome and transient liver function disturbances.
Br J Cancer 2003 Jan 27;88:2:175-80.
"Temozolomide followed by combined immunotherapy with GM-CSF, low-dose IL2 and IFNalpha in patients with metastatic melanoma"
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