Phase I trial of a 96 h paclitaxel infusion with filgrastim support in refractory solid tumor patients

Anticancer Drugs. 1998 Aug;9(7):611-9. doi: 10.1097/00001813-199808000-00006.


A phase I study of a 96 h paclitaxel infusion with filgrastim support was performed to determine the toxicity, maximum-tolerated dose (MTD) and pharmacokinetics in patients with refractory solid tumors. In this phase I trial, the initial paclitaxel dose was 140 mg/m2/96 h followed by filgrastim (5 microg/kg/day s.c.) beginning 24 h after the paclitaxel and continued until granulocyte recovery. Cycles were repeated every 21 days. Patients with refractory solid tumors were eligible; however, only one previous chemotherapy regimen was allowed. The dose of paclitaxel was escalated by 20 mg/m2/96 h in subsequent cohorts until dose-limiting toxicity (DLT) occurred. Pharmacokinetic analysis was performed by quantitating paclitaxel concentrations at baseline, 24, 48, 72 and 96 h after the start of the paclitaxel infusion. Twenty-one patients were entered into this trial of which 19 were evaluable. A total of 52 treatment cycles were administered. DLT was seen in two of four patients at 200 mg/m2/96 h, and consisted of diarrhea, mucositis and granulocytopenic infection. The MTD of the 96 h paclitaxel infusion was 180 mg/m2 with filgrastim support. Mucosal and granulocyte toxicity were correlated with steady-state paclitaxel concentrations (Css) greater than 0.100 micromol/l. In the presence of liver function test 1.5 times or lower than normal, metastatic liver disease did not alter paclitaxel Css. Objective responses were observed in non-small cell lung cancer, small cell lung cancer and melanoma. The recommended phase II dose of paclitaxel infused over 96 h with filgrastim support is 180 mg/m2. Paclitaxel Css correlate with mucosal and granulocyte toxicity. In the presence of normal enzymatic function, metastatic liver disease does not affect paclitaxel clearance.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / adverse effects*
  • Antineoplastic Agents, Phytogenic / blood
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Small Cell / drug therapy
  • Chromatography, High Pressure Liquid
  • Clinical Trials, Phase I as Topic
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Filgrastim
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Humans
  • Lung Neoplasms / drug therapy
  • Male
  • Melanoma / drug therapy
  • Middle Aged
  • Neoplasms / drug therapy*
  • Paclitaxel / administration & dosage*
  • Paclitaxel / adverse effects*
  • Paclitaxel / blood
  • Recombinant Proteins
  • Skin Neoplasms / drug therapy
  • Time Factors


  • Antineoplastic Agents, Phytogenic
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Paclitaxel
  • Filgrastim