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

Background and purpose: 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. Patients and methods: 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. Results: 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 ≥grade 3 non-hematologic toxicity and ≥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. Conclusions: 9NC, 1 mg/m²/day, can be given concurrently with radiation with acceptable toxicity.