We evaluated and previously reported the efficacy of alpha-interferon (alpha-IFN) in 84 cancer patients (19). IFN was administered in a pulse fashion given for 3 consecutive days every 4 weeks. We also evaluated the immunomodulatory effect of IFN which constitutes the basis for the current report. Before, during and after courses of IFN treatment, the immune status of the patients was assessed by: (i) circulating immune complexes, (ii) change in lymphocyte type including (a) natural killer (NK) cells, (b) T-cell subsets (suppressor, helper) and (c) HLA-Dr antigen positivity, (iii) myelopoietic differentiation, (iv) macrophage-dependent tumor cytotoxicity with measurements of macrophage-derived growth factor (MDGF), (v) granulocyte functions, (vi) antibody formation against IFN, and (vii) antiproliferative activity of IFN. In addition, LDH, beta-2 microglobulin, and CEA as tumor markers were obtained. High serum or plasma IFN levels were associated with increased activity of T suppressor cells, increased HLA-Dr antigen, and increased NK activity. The increase of these three parameters was directly related to tumor response. In vitro inhibition of tumor cells in tissue culture by IFN culture was predictive of objective tumor response in those patients whose tumor cells were tested. In addition, IFN induced release of MDGF by monocytes. It is apparent that in addition to direct antitumor effect, IFN has multiple modulatory effects on the immune system in man that may aid in tumor control when given in a pulse schedule.

Thirty-two patients with squamous cell carcinoma of head and neck not amenable to surgery or radiotherapy were treated with a combination of methotrexate 0.6 mg/kg IV weekly, bleomycin 15 mg IV weekly, and hydroxyurea 1,000 mg/m2 three oral doses weekly. Eleven complete responses and ten partial responses of more than 50% were observed. The mean duration was 43 weeks for complete responses and 35 weeks for partial responses. Toxicity consisted in leukopenia, thrombocytopenia, nausea, vomiting, stomatitis, and cutaneous alterations. Only one patient suffered reversible lung toxicity. These results suggest that a combination of three drugs in squamous cell head and neck cancer may be more effective than a combination of bleomycin and methotrexate only.

No abstract

No abstract

No abstract