title: Granulocyte macrophage-colony stimulating factor plus interleukin-2 plus alpha-interferon plus 5-fluorouracil in the treatment of metastatic renal cell cancer: induction of CD80/86+ T cells indicates adverse outcome.
abstract: Even in the era of multitargeted therapies, cytokines remain at least one of different treatment options in renal cell cancer (RCC), particularly for patients belonging to the good prognostic risk category according to Memorial Sloan Kettering Cancer Center criteria. Granulocyte macrophage-colony stimulating factor plays a central role in the differentiation and activation of antigen presenting cells. This clinical phase 1/2 chemoimmunotherapy trial in metastatic RCC used sequential application of alpha-interferon /5-fluorouracil followed by granulocyte macrophage-colony stimulating factor/interleukin-2. The study was performed before multikinase inhibitors were available for routine use. Twenty patients with metastatic RCC were enrolled into this phase 1/2 protocol. Sequential chemoimmunotherapy was feasible and safe on an outpatient basis. The regimen had only modest antitumor activity with 4 mixed responses and 4 stable diseases being documented after 4 treatment cycles. Enhanced proliferative and stimulatory capacity of peripheral blood mononuclear cells was only observed in patients with mixed responses/stable diseases whereas patients with progressive disease did not show any change. Most interestingly, there was a significant increase of T cells expressing the costimulatory molecules CD80/86 in patients with progressive disease. This finding is reported here for the first time under chemoimmunotherapy of RCC. In conclusion, clinical response rates of this cytokine-based regimen do not justify further clinical evaluation. However, the study suggests that CD80/86+ T cells might have negative regulatory function under cytokine treatment and are possibly useful as a negative predictive marker for clinical response.
authors.affiliation: Department of Hematology and Oncology, Charité, University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany. joerg.westermann@charite.de
authors.forename: Jörg
authors.initials: J
authors.lastname: Westermann
authors.forename: Ann-Christine
authors.initials: AC
authors.lastname: Hecker
authors.forename: Anne
authors.initials: A
authors.lastname: Flörcken
authors.forename: Bernd
authors.initials: B
authors.lastname: Dörken
authors.forename: Antonio
authors.initials: A
authors.lastname: Pezzutto
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D019496:Cancer Vaccines; D016898:Interferon-alpha; D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005472:Fluorouracil