Role of substance P in hypersensitivity reactions induced by paclitaxel, an anticancer agent

Peptides. 2004 Jul;25(7):1205-8. doi: 10.1016/j.peptides.2004.04.004.

Abstract

The role of substance P in adverse pulmonary reactions induced by an anticancer agent paclitaxel was investigated in rats and humans who undertook post-operative chemotherapy for ovarian cancer. In rats, paclitaxel caused a marked plasma extravasation and edema in lungs with a concomitant decrease in arterial partial oxygen pressure, which were reversed by an NK1 antagonist LY303870. Substance P level in rat plasma and bronchoalveolar lavage fluid increased after paclitaxel injection. In 13 patients, plasma level of substance P but not histamine significantly (P < 0.05) increased during paclitaxel infusion. Therefore, substance P rather than histamine may be involved in paclitaxel hypersensitivity.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Bronchoalveolar Lavage Fluid / chemistry
  • Female
  • Histamine / blood
  • Humans
  • Hypersensitivity / blood
  • Hypersensitivity / complications
  • Hypersensitivity / physiopathology*
  • Indoles / pharmacology
  • Male
  • Neurokinin-1 Receptor Antagonists
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / complications
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / pathology
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects*
  • Paclitaxel / therapeutic use
  • Piperidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Distress Syndrome / blood
  • Respiratory Distress Syndrome / chemically induced
  • Retrospective Studies
  • Substance P / analysis
  • Substance P / blood
  • Substance P / metabolism*

Substances

  • 1-(N-(2-methoxybenzyl)acetylamino)-3-(1H-indol-3-yl)-2-(N-(2-(4-(piperidin-1-yl)piperidin-1-yl)acetyl)amino)propane
  • Antineoplastic Agents
  • Indoles
  • Neurokinin-1 Receptor Antagonists
  • Piperidines
  • Substance P
  • Histamine
  • Paclitaxel