Corticosteroids significantly delay the onset of docetaxel-induced fluid retention: final results of a randomized study of the European Organization for Research and Treatment of Cancer Investigational Drug Branch for Breast Cancer

J Clin Oncol. 1997 Sep;15(9):3149-55. doi: 10.1200/JCO.1997.15.9.3149.

Abstract

Purpose: To confirm the efficacy of docetaxel in patients with breast cancer previously treated with one chemotherapy regimen for advanced or metastatic disease and to compare the incidence of fluid retention (FR) and skin toxicity when docetaxel is administered with and without prophylactic corticosteroids.

Patients and methods: Eighty-three patients, pretreated with one chemotherapy regimen for metastatic breast cancer (MBC) with bidimensionally measurable and progressive disease, were eligible for this randomized trial. Docetaxel with prophylactic oral antihistamine was administered at a dose of 50 mg/m2 as a 1-hour infusion on days 1 and 8 every 21 days and patients were randomized to receive methylprednisolone (40 mg days -1, 0, 1, 7, 8, and 9 of each cycle) (arm A) or no methylprednisolone (arm B).

Results: Twenty-eight patients (34%, 95% confidence interval [CI], 23% to 45%) achieved on objective response. The median time to disease progression and median overall survival time were 5 and 13.5 months, respectively. In total, 415 cycles of docetaxel were administered (arm A: N = 219, median = six; arm B: N = 196, median = five). The most common toxicity observed was grade 3 or 4 neutropenia, which occurred in 79% of patients. Clinically significant nonhematologic side effects included skin reactions and asthenia. In an intent-to-treat analysis, patients who received methylprednisolone premedication had a delayed onset of FR (median time to onset of FR: arm A, 84 days; arm B, 62 days; P = .01) and received a higher median cumulative dose of docetaxel before the onset of FR (arm A, 333 mg/m2; arm B, 215 mg/m2; P = .001). There was no statistically significant difference in the incidence of skin toxicity between the two arms.

Conclusion: Docetaxel, at this dose and schedule, has definite antitumor activity in pretreated MBC patients. Moreover, this is the first randomized trial to show that corticosteroids have a favorable impact on docetaxel-induced FR.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Phytogenic / adverse effects*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Body Fluids / drug effects*
  • Breast Neoplasms / drug therapy*
  • Cetirizine / therapeutic use*
  • Docetaxel
  • Drug Administration Schedule
  • Drug Eruptions / prevention & control
  • Edema / prevention & control
  • Europa
  • Female
  • Histamine H1 Antagonists / therapeutic use*
  • Humans
  • Methylprednisolone / therapeutic use*
  • Middle Aged
  • Paclitaxel / adverse effects
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / therapeutic use
  • Pleural Effusion / prevention & control
  • Severity of Illness Index
  • Skin / drug effects*
  • Taxoids*
  • Treatment Outcome
  • Water-Electrolyte Imbalance / chemically induced
  • Water-Electrolyte Imbalance / prevention & control*

Substances

  • Antineoplastic Agents, Phytogenic
  • Histamine H1 Antagonists
  • Taxoids
  • Docetaxel
  • Paclitaxel
  • Methylprednisolone
  • Cetirizine