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

Gregory A. Masters, Bruce E. Brockstein, Sridhar Mani, Mark J. Ratain

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)7-12
Number of pages6
JournalMedical Oncology
Volume20
Issue number1
DOIs
StatePublished - Mar 29 2003

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Keywords

  • Chemotherapy
  • Docetaxel
  • Dose escalation
  • Growth factor
  • Phase I

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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