The effect of Edrecolomab (Mo17-1A) or fluorouracil-based chemotherapy on specific immune parameters in patients with colorectal cancer. A comparative study.
OBJECTIVE
We investigated the immune profile of patients with resected Dukes' stage C colorectal cancer (CRC), receiving adjuvant therapy with edrecolomab (Mo17-1A) or first-line 5-fluorouracil (5-FU)-based chemotherapy.


METHODS
Patients received either 5 doses of Mo17-1A over 13 weeks, or 5-FU/leucovorin, or 5-FU/levamisole over 6 and 12 months, respectively. Peripheral blood was collected postoperatively and 4 months after therapy initiation. Peripheral blood mononuclear cells were tested in the autologous mixed lymphocyte reaction (AMLR), for natural killer (NK) and lymphokine-activated killer (LAK) cell activity. Serum cytokines were quantified by ELISA.


RESULTS
Fifty-two patients entered the study. Postoperatively, they exhibited decreased levels of interleukin (IL)-2, interferon-gamma, IL-12, granulocyte-macrophage colony-stimulating factor and IL-15, low cellular immune responses (AMLR, NK- and LAK-cytotoxicity) and increased levels of IL-1beta, tumor necrosis factor-alpha, IL-6, IL-10 and prostaglandin E(2). After four months of therapy, patients receiving edrecolomab demonstrated enhanced AMLR, NK, LAK activity, increased serum levels of cytokines regulating such responses and reduced levels of acute-phase cytokines and immune suppressors, compared to patients treated with conventional chemotherapy.


CONCLUSIONS
Postoperative adjuvant therapy with edrecolomab restores the in vivo deficient immune responses of patients with resected Dukes' C CRC despite its clinical ineffectiveness in recent randomized adjuvant trials. These results suggest that further immunological studies with the combination of edrecolomab and chemotherapy are required.
Tsavaris
Nick B
NB
Department of Pathophysiology, Oncology Unit, Laikon General Hospital, Athens, Greece.
Katsoulas
Haralabos L
HL
Kosmas
Christos
C
Papalambros
Efstathios
E
Gouveris
Panayiotis
P
Papantoniou
Nikitas
N
Rokana
Sophia
S
Kosmas
Nicolaos
N
Skopeliti
Margarita
M
Tsitsilonis
Ourania E
OE
D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D017024:Chemotherapy, Adjuvant; D003082:Colectomy; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D016207:Cytokines / Q000097:blood*; D015232:Dinoprostone / Q000097:blood; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007378:Interleukins / Q000097:blood; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D016207:Cytokines; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; C400149:Edrecolomab; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015232:Dinoprostone; D005472:Fluorouracil