Phase I dose escalation study of docetaxel with filgrastim support in patients with advanced solid tumors

Docetaxel has demonstrated activity in a broad range of solid tumors. Phase I trials have shown 100 mg/m² every 21 d to be the recommended dose. This phase I trial was designed to define the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of docetaxel with granulocyte colony-stimulating factor (G-CSF) support in patients with advanced solid tumors. Eligible patients had advanced malignancies and up to two prior chemotherapy regimens, ECOG PS = 0-1, adequate organ function, and gave written, informed consent. Docetaxel was escalated in cohorts of patients starting at 100 mg/m² on a 21-d schedule. Prophylactic G-CSF was administered on d 3-10. The DLT was defined as grade IV neutropenia >4 d, febrile neutropenia, grade IV thrombocytopenia, any grade III non-hematologic toxicity, or the inability to receive cycle 2 because of ongoing toxicity. Twenty-three patients were enrolled at doses up to 145 mg/m². The median age was 59 yr and the median number of prior chemotherapy regimens was 1. No DLT was observed at 100 mg/m², and 2 of 11 patients at 120 mg/m² experienced DLT (neutropenic fever and stomatitis). At 145 mg/m², one of eight patients had DLT (fatigue). Two of eight patients at 145 mg/m² had brief grade IV neutropenia (without fever), and none had grade III-IV thrombocytopenia or anemia. The docetaxel dose can be safely escalated to 145 mg/m² every 21 d with G-CSF support, a 45% increase above the standard recommended phase II dose. Further studies will clarify the role of dose-intensified docetaxel.