Food produced a slight reduction (9%) in absorption of temozolomide. Temozolomide demonstrated linear and reproducible pharmacokinetics and was rapidly absorbed (mean T max ~1 h) and eliminated (mean t 1/2 = 1.8 h). Clinical activity was observed against several advanced cancers, including malignant glioma and metastatic melanoma. The most common non-haematological toxicities were mild to moderate nausea and vomiting. When given orally once daily for 5 days, temozolomide was well tolerated and produced a non-cumulative, transient myelosuppression. Subsequently, patients received the MTD to study how food affects the oral bioavailability of temozolomide. The DLT was thrombocytopenia, and the MTD was 200 mg m –2 day –1. To determine dose-limiting toxicities (DLT) and the maximum tolerated dose (MTD), temozolomide 100–250 mg m –2 was administered once daily for 5 days every 28 days. Thirty patients with minimal prior chemotherapy were enrolled in this phase I trial to characterize the drug’s safety, pharmacokinetics and anti-tumour activity, as well as to assess how food affects oral bioavailability.
Temozolomide, an oral cytotoxic agent with approximately 100% bioavailability after one administration, has demonstrated schedule-dependent clinical activity against highly resistant cancers.
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