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Granulocyte-macrophage colony-stimulating factor improves immunological parameters in patients with refractory solid tumours receiving second-line chemotherapy: correlation with clinical responses.

Abstract
In this report, we studied the immunorestorative properties of subcutaneously administered granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with refractory solid tumours receiving second-line chemotherapy. Such patients exhibit abnormal immune responses in vivo and in vitro and, therefore, it was of interest to examine the effect of GM-CSF-induced immunomodulation on clinical response. We examined patients with primary malignant carcinomas (head and neck, n = 10; urogenital tract, n = 17; penis n = 6; colorectal, n = 8) who were treated with carboplatin (JM8), 300 ng/m2 on days 1 and 22, leucovorin (LV), 200 mg/m2 plus 5-fluoracil (5-FU), 500 mg/m2 on days 8, 15 and 29 and four cycles of daily injections with placebo or GM-CSF, 300 micrograms/day on days 3-6, 10-13, 17-20 and 24-27. Peripheral blood was collected from the patients one day after the end of each of the four-cycle injections with placebo or GM-CSF, namely on days 7, 14, 21 and 28. Peripheral blood mononuclear cells (PBMC) were tested in the autologous mixed lymphocyte reaction (AMLR) and for natural killer (NK) or lymphokine-activated killer (LAK) cell activity. Cytokine levels in serum were measured by immunoenzymatic (ELISA) assay. A total of 21 patients received a four-cycle regimen with GM-CSF (Group 1) and 20 were similarly treated with placebo (Group 2). All received standard chemotherapy as outlined above. Before GM-CSF treatment, all patients exhibited increased serum levels of interleukin-1 (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), IL-6 and prostaglandin E2 (PGE2) and decreased serum levels of IL-2. Cellular immune responses (AMLR, NK- and LAK-cytotoxicity) were also low in all patients. Five patients from Group 1 had a PR (partial response), 2 patients had CR (complete response), and 14 patients had stable disease. Seven patients from Group 2 showed progressive disease, 3 had a PR and 10 had stable disease. All immune parameters were significantly improved during treatment in Group 1 but remained unchanged or even deteriorated in Group 2. Administration of GM-CSF during treatment of cancer patients with conventional chemotherapeutic drugs results in a marked potentiation of deficient cellular immune responses in vitro and a change towards normalisation of cytokine serum levels. The results reported herein support the use of GM-CSF as immunopotentiator during chemotherapy, but more patients must be studied before definite conclusions can be drawn.
AuthorsC N Baxevanis, N B Tsavaris, S I Papadhimitriou, I K Zarkadis, N G Papadopoulos, E A Bastounis, M Papamichail
JournalEuropean journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 33 Issue 8 Pg. 1202-8 (Jul 1997) ISSN: 0959-8049 [Print] ENGLAND
PMID9301443 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article)
Chemical References
  • Cytokines
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Carboplatin
  • Fluorouracil
Topics
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Carboplatin (administration & dosage)
  • Cytokines (blood)
  • Cytotoxicity, Immunologic
  • Female
  • Fluorouracil (administration & dosage)
  • Granulocyte-Macrophage Colony-Stimulating Factor (therapeutic use)
  • Humans
  • Killer Cells, Lymphokine-Activated (immunology)
  • Killer Cells, Natural (immunology)
  • Lymphocyte Culture Test, Mixed
  • Male
  • Middle Aged
  • Neoplasms (drug therapy, immunology, therapy)

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