A phase I study of concurrent 9-nitro-20(s)-camptothecin (9NC/Orathecin) and radiation therapy in the treatment of locally advanced adenocarcinoma of the pancreas.

Abstract

In vitro studies have suggested that 9-nitro-20(s)-Camptothecin (9NC/Orathecin/Rubitecan) can enhance the effects of radiation. We conducted a phase I study to assess the toxicity and determine the maximum tolerated dose of 9NC when combined with radiation in patients with locally advanced adenocarcinoma of the pancreas. Eleven patients with locally advanced adenocarcinoma of the pancreas received 9NC, orally during radiation. Radiation therapy consisted of 45 Gy in 25 fractions given over 5 weeks. The starting dose of 9NC was 1 mg/m2/day. Eight patients received 9NC at a dose of 1 mg/m2/day and three patients received a dose of 1.25 mg/m2/day. Dose-limiting toxicity (DLT) was defined as >or=grade 3 non-hematologic toxicity and >or=grade 4 hematologic toxicity. Dose-limiting toxicity of grade 3 nausea/vomiting developed in one patient at the first dose level. At dose level 2, two of three patients developed DLT. Both developed grade 3 nausea, fatigue, and anorexia. Additionally, one of these patients had grade 3 dehydration and the other had grade 4 leukopenia, grade 3 vomiting, and grade 3 weakness. 9NC, 1 mg/m2/day, can be given concurrently with radiation with acceptable toxicity.