A PHASE-II STUDY OF TEMOZOLOMIDE IN ADVANCED UNTREATED PANCREATIC-CANCER

Temozolomide (SCH 52365) is an imidazotetrazine derivative which exhib its broad spectrum activity against murine tumors and is structurally related to dacarbazine (DTIC). Temozolomide cytotoxicity is schedule d ependent in vivo with a daily x 5 schedule showing the highest activit y. Oral temozolomide is rapidly and completely absorbed with minimal i nterpatient and intrapatient variability in pharmacokinetics. Clinical studies have demonstrated activity against melanoma and glioma. The p resent study examined the activity of oral temozolomide against patien ts with pancreatic cancer. Patients with advanced pancreatic adenocarc inoma previously untreated with chemotherapy received temozolomide 200 mg/m(2)/day once daily orally for 5 days with cycles repeated every 2 8 days. There were 16 patients entered on study with 15 evaluable for response and toxicity. There were no responses seen in 15 evaluable pa tients with 14 manifesting progressive disease within 2 months of star ting therapy. Toxicity was primarily hematological with 3 patients exp eriencing greater than or equal to grade 3 neutropenia and thrombocyto penia respectively. Other toxicities were relatively modest. In conclu sion, temozolomide in the once daily x 5 schedule is inactive against adenocarcinoma of the pancreas.