Natural cytotoxicity in breast cancer patients receiving neoadjuvant chemotherapy: effects of L-arginine supplementation

Eur J Surg Oncol. 1994 Aug;20(4):467-72.


Certain cytotoxic drugs have been shown to suppress host anti-cancer defence mechanisms. The amino acid L-arginine can significantly enhance natural killer (NK) and lymphokine-activated killer (LAK) cell cytotoxicity in patients with locally advanced breast cancer. In this study, the effect of L-arginine supplementation on natural cytotoxicity was determined in patients with breast cancer receiving CHOP chemotherapy. This cytotoxic regimen caused a transient immunosuppression, maximal on day 14 of each cycle (P < 0.001); this was not cumulative during the four cycles of treatment. Those patients receiving L-arginine supplementation (30 g/day for 3 days prior to each course of chemotherapy) had a smaller and delayed onset of immunosuppression (day 14), compared with those patients who had CHOP only (day 9). L-Arginine was able to repeatedly stimulate NK and LAK cell cytotoxicity in patients who were receiving CHOP chemotherapy (P < 0.003). In conclusion, further studies are required to determine the optimal use of chemotherapeutic agents, alone or in combination with immunostimulators, to avoid inhibition of host anti-cancer defence mechanisms.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Arginine / administration & dosage
  • Arginine / pharmacology
  • Arginine / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / surgery
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Female
  • Humans
  • Killer Cells, Lymphokine-Activated / drug effects
  • Killer Cells, Natural / drug effects*
  • Middle Aged
  • Prednisone / administration & dosage
  • Vincristine / administration & dosage


  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Arginine
  • Prednisone

Supplementary concepts

  • CHOP protocol