Paclitaxel plus gallium nitrate and filgrastim in patients with refractory malignancies - A phase I trial

To determine the maximally tolerated dose of paclitaxel with and without filgrastim (G-CSF) when administered as a 24-hour intravenous infusion after a 120-hour infusion of gallium nitrate at a fixed dose of 300 mg/m(2)/24 hours, 40 patients were entered onto a trial lasting from September 1994 to September 1996. Eligibility included a diagnosis of an advanced malignancy not amenable to curative therapy and up to one previous chemotherapy regimen fur metastatic disease. Gallium was administered at a fixed dose of 300 mg/m(2)/day as a continuous intravenous infusion for 120 hours. Paclitaxel starting at 90 mg/m(2) was given concurrently with the last 24 hours of the gallium as a 24-hour intravenous infusion. Cycles were repeated every 21 days. Once the maximum tolerated dose (MTD) of paclitaxel was reached, G-CSF (5 mu g/kg/day days 7-16) was added and paclitaxel dose escalation continued. The MTD for paclitaxel without G-CSF was 110 mg/m(2) and 225 mg/m(2) with G-CSF, with neutropenia being the dose-limiting toxicity. A partial response was noted in a patient who had thymoma and a complete response was achieved in a patient who had colon cancer. The recommended phase TT dosage is gallium nitrate at 300 mg/m(2)/day over 120 hours, with paclitaxel at 110 mg/m(2) over 24 hours without G-CSF or 225 mg/m(2) over 24 hours with G-CSF and 0.5 mg calcitriol on days 1 through 7. Further trials of this modified regimen for outpatient administration are in progress.