Interferon treatment of human neoplasia.
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Animals↗
Biomedical subjects
H Strander
Publications and source records attributed to H Strander.
Interferon therapy in disseminated renal cell carcinoma.
Twenty patients with pulmonary metastases of renal cell carcinomas have been treated in a randomized study with either leucocyte interferon in daily doses of 3 x 10(6) I.U.i.m or irradiation of both lungs in a calculated mean central dose of 10 Gy in 4 weeks in combination with bleomycin and vincristine. Most patients had a short time to progression of their disease. Three patients in the interferon group had complete response (CR) and partial response (PR) and one patient in the other group had PR. The numbers of patients in both arms of the study are too small to allow any conclusions whether beneficial effects are more frequent in one group than in the other, but there is a more favourable tendency in the interferon group.
Adult↗
Adjuvant chemotherapy of malignant melanoma. A pilot study.
In a pilot study, 26 patients with stage I malignant melanoma, tumor thickness greater than 2.25 mm, and/or Clark level IV, and Stage II tumors were randomized to adjuvant chemotherapy with either DTIC, DTIC/CCNU/vincristine, or to a control group with no further treatment after surgery. The chemotherapy group contained 17 patients and the control group nine patients. The follow-up time is 37-54 months. The recurrence-free and overall survival is significantly longer in the patient group treated with adjuvant chemotherapy as compared to controls (p less than 0.025, according to the log-rank test).
Adult↗
Influence of human alpha-interferon on four human osteosarcoma xenografts in nude mice.
Growth-inhibiting effects of human alpha-interferon (HuIFN-alpha) were investigated in four human osteosarcoma xenografts in nude mice. In addition to effects on growth, the HuIFN-alpha treatment was evaluated by histological examination and DNA flow cytometric analysis. Daily doses of 2 X 10(5) IU HuIFN-alpha completely arrested the growth of two osteosarcoma xenografts and partially inhibited one, whereas 1 X 10(6) IU/day were necessary to arrest the growth of the fourth. Growth inhibition was reversible and tumor size independent. The histological appearance, including mitotic indices, and S-phase proportions were unchanged in three xenografts. The mechanism of the HuIFN-alpha-induced growth inhibition of these three xenografts was therefore not considered to be a direct antiproliferative effect, but rather due to increased cell loss and/or increased cell cycle time. The modal DNA value of one xenograft was changed from aneuploid to diploid during HuIFN-alpha treatment. Histologically, these xenografts were partly replaced by normal appearing bone and bone marrow. The S-phase proportion was also reduced in these xenografts, implying that HuIFN-alpha can also have a direct antiproliferative effect.
Animals↗
Treatment of patients with disseminated colorectal cancer with recombinant human alpha 2-interferon. Studies on the immune system.
The influence of recombinant human alpha 2-interferon (alpha 2-IFN) therapy on various aspects of the immune system was studied in 18 patients with disseminated colorectal cancer. The IFN was given as continuous (20 X 10(6) units/m2 three times weekly) or intermittent (50 X 10(6) units/m2 daily for 5 consecutive days every 4 weeks) treatment. Natural killer (NK) cell activity increased during continuous treatment and in the patients receiving repeated cycles of IFN, all cycles seemed to be associated with an elevation of NK activity. Prior to treatment, addition of IFN to the assay in vitro induced an enhancement of NK activity, whereas during treatment, IFN in vitro did not cause any further enhancement of NK activity. The proportions of total T cells, suppressor T cells and helper T cells, as measured by Leu 1, Leu 2a and Leu 3a monoclonal antibodies, were not altered to any major extent during treatment. This was found to be the case also for the number of cells detected by monoclonal antibodies against NK cells (Leu 7). The phagocytic activity of granulocytes was not altered during IFN therapy, whereas the capacity of these cells to reduce nitroblue tetrazolium (NBT) increased after the first injection of IFN. The in vivo influence of high doses of highly purified recombinant alpha 2-IFN on NK cells and granulocytes seems to be similar to that of partially purified natural IFN-alpha.
Adenocarcinoma↗
Studies with interferon-alpha in human tumors.
Clinical trials with IFN-alpha, produced from buffy coats of leukocytes, have been going on at Radiumhemmet, Karolinska Hospital since 1969. In some of the benign and malignant tumor diseases studied, IFN has been shown to induce regressions. In the case of the benign tumor juvenile laryngeal papillomatosis, IFN has been shown to be superior to other treatment modalities. So far IFN has not been shown to be superior to conventional treatment in any of the malignant tumors studied.
Clinical Trials as Topic↗
Effect of interferon on heterotopic new bone formation in mice.
To study the effect of interferon (IFN) on bone induction and new bone formation, heterotopic bone was induced by implanting pieces of demineralized bone matrix in soft tissue of mice. Mouse IFN was given as daily subcutaneous injections of 2 X 10(5) IU/mouse. Treatment was started one week before bone matrix implantation and continued until sacrifice. As a measure of chondrogenesis in the implants short-term incorporation of 35sulphur administered 11 days after implantation was measured. The amount of mineralized tissue formed in connection with the implant was estimated by 45calcium incorporation 20 days after implantation. There was no indication of a negative effect of IFN on bone induction, new bone formation, or metabolism of orthotopic bone. This is in agreement with our findings in the clinical use of IFN after reconstructive surgery in osteosarcoma.
Animals↗
Interferon-alpha treatment of a patient with acute lymphoblastic leukaemia and Down's syndrome. Effects on natural killer cell activity and mitogen responsiveness.
A 32-year-old female with Down's syndrome and common ALL was treated with human leucocyte interferon-alpha (IFN-alpha) at a dose of 3 X 10(6) units i.m. daily. Side-effects consisted of slight tenderness and localized haematomas at the sites of injection. During treatment the number of leukaemic cells decreased in the peripheral blood. The proportion of blast cells in the bone marrow decreased only slightly, but a large fraction of them became vacuolized. After the initial response the disease progressed and IFN was withdrawn after treatment for 67 d. Prior to initiation of IFN treatment the natural killer activity of the patient's lymphocytes, as well as the response of these cells to mitogenic stimuli, was low. During IFN therapy these functions increased. Following the withdrawal of IFN therapy the patient received vincristine/prednisone treatment and a complete remission was achieved after 5 weeks. She is still in remission and on maintenance therapy 24 months after initiation of treatment.
Adult↗
Interferon therapy in juvenile laryngeal papillomatosis.
Seventeen patients with severe juvenile laryngeal papillomatosis (12 in Stockholm and five in Umeå) were treated with exogenous leukocyte interferon (IFN-alpha) prepared in Helsinki and Umeå, respectively. Tumor progression occurred in all cases before treatment. During treatment tumor growth diminished in all cases, up to complete tumor disappearance. Of 17 patients, nine were cured and no longer are being treated, four exhibit no tumor growth but are still being treated, one has visible tumor but only slight growth, two still have active but diminished growth, and one, who has refused further treatment, is experiencing active tumor growth as before the start of interferon therapy. It is concluded that IFN-alpha therapy in a dosage of 3 X 10(6) units three times a week intramuscularly can arrest papilloma growth. Further trials are needed to optimize treatment.
Adolescent↗
Epstein-Barr virus-specific serodiagnostic tests in carcinomas of the head and neck.
Sera from 256 patients with cancers of the head and neck were examined for their profiles of IgG and IgA antibodies to Epstein-Barr virus (EBV)-specific, viral capsid antigen (VCA), the diffuse (D) and the restricted (R) components of the early antigen (EA) complex, and the EBV-associated nuclear antigen (EBNA), in order to assess the value of these procedures in the routine diagnosis of poorly or undifferentiated nasopharyngeal carcinoma (NPC). In 13 NPC patients, the carcinoma had invaded cervical lymph nodes, and their sera revealed, in addition to high IgG anti-VCA titers, elevated levels of IgA antibodies to VCA, of IgG antibodies to D, and most also had IgA anti-D. Such profiles were seen in very few of the patients with carcinomas at other sites of the head and neck. They had not developed in four NPC patients whose tumors were limited to the postnasal space, and in three patients with other tumors at that site. Among 15 patients with cervical node metastases from occult primary tumors, 2 had EBV-specific antibody profiles compatible with NPC, 1 was judged to have NPC on clinical grounds, and the other died of a pulmonary carcinoma, or possibly pulmonary metastases. In 4 of the remaining 13 patients with occult tumors, the primary site was found outside the nasopharynx, whereas it escaped detection in the other 9. These results lend further support to the usefulness of the EBV-specific serology to clinicians in the diagnosis of NPC, especially in cases of lymph node invasion by undetected primary tumors. The data also emphasize the need of complementing the serology with the examination of biopsies for the presence of EBV deoxyribonucleic acid (DNA) or, more readily performed, EBNA-positive carcinoma cells.
Aged↗
Sequential methotrexate-5-fluorouracil treatment of squamous cell carcinoma of the head and neck.
Thirty-six patients with squamous cell carcinoma of the head and neck were treated with sequential methotrexate-5-fluorouracil followed by leucovorin rescue. The frequency of objective tumor regression obtained was 64% (complete response + partial response) with 19% complete regression. In 20 not previously treated patients, the objective response rate was 70%. Approximately the same result was obtained for tumors of different anatomical sites of the head and neck. The degree of differentiation of the squamous cell carcinoma did not seem to be of prognostic importance for the initial tumor response. Toxicity was very mild and usually disappeared when the interval between the chemotherapy courses was prolonged from 1 to 2 weeks. Radiotherapy could be added sequentially to the treatment without measurable escalated toxicity.
Carcinoma, Squamous Cell↗
Influence of human interferon-alpha therapy on cytotoxic functions of blood lymphocytes. Studies on lectin-dependent cellular cytotoxicity, antibody-dependent cellular cytotoxicity, and natural killer cell activity.
Various cytotoxic functions of blood lymphocytes were studied in 101 patients undergoing daily treatment with human interferon-alpha (IFN). Antibody-dependent cellular cytotoxicity and lectin-dependent cellular cytotoxicity were not altered to any major extent after 1 day or 1 week of IFN therapy. After 3 and 6 months of treatment a decrease in these functions was observed in most patients. Natural killer cell activity increased following the first injection of IFN and remained elevated during 1 year of IFN therapy.
Antibody-Dependent Cell Cytotoxicity↗
The effect of systemic human interferon-alpha administration to patients with glioblastoma multiforme.
This report presents the results of a phase I trial of the value of human leucocyte interferon-alpha in the treatment of glioblastoma. Twelve patients entered the trial. In one case we believe that the patient benefitted from the interferon treatment. CT scans of patients on interferon did not reveal the true extent of the tumorous tissue.
Adult↗
Systemic interferon alpha treatment of human condylomata acuminata.
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Adult↗
Methotrexate and 5-fluorouracil in head and neck cancer.
Since experimental data strongly suggest a synergistic cytotoxic effect when methotrexate (MTX) and 5-fluorouracil (5-FU) are administered sequentially, we investigated antitumor effects and toxicity with sequential MTX/5-FU followed by leucovorin rescue in 52 patients with carcinoma of the head and neck. MTX (200 mg/m2) was given as an i.v. infusion over 1 hr. At 2 hr, 5-FU (600 mg/m2) was started as an i.v. infusion for 2 hr. At 24 hr, the leucovorin rescue was started. The chemotherapy course was repeated every week until toxicity (mainly gastrointestinal) occurred, after which the interval between courses was prolonged to 2 wk. Toxicity was mild and usually disappeared when the interval between the chemotherapy courses was prolonged to 2 wk. The regression rate was 15% for complete and 48% for partial regression (response rate, 63%). In 31 of the patients not previously treated, the objective response rate was 74%. About the same results were obtained for tumors of different anatomic sites of the head and neck. Radiotherapy could be added sequentially without measurable escalation of toxicity. We conclude that sequential MTX/5-FU treatment, which produces a very mild toxicity to normal tissue, is effective in inducing antitumor response in patients with carcinoma of the head and neck.
Carcinoma, Squamous Cell↗
In vitro and in vivo effects of interferon on the response of human lymphocytes to mitogens.
Previous studies have shown that addition of IFN to the assay in vitro inhibits the proliferative response of lymphocytes to mitogens, whereas long term treatment by IFN in vivo has no major effect on the mitogen responsiveness of tumour patient's lymphocytes. Possible reasons for the discrepancy between the results obtained following treatment by IFN in vitro and in vivo were investigated. It was observed that the proliferative response of tumour patients lymphocytes to various mitogens was not affected to any major extent 24 hr after a single injection of 3 million units of interferon-alpha (IFN-alpha). Lymphocytes from tumour patients and healthy donors were found not to differ in their susceptibility to IFNs' anti-proliferative effect in vitro. Pure IFN-beta, present in the assay throughout the incubation period, inhibited the response of lymphocytes to polyclonal mitogens and PPD showing IFN and not contaminants in the preparations to be responsible for this effect. Although the presence of IFN in the assay throughout the incubation period inhibited the proliferative response of lymphocytes, pre-treatment of these cells with IFN-alpha in vitro was found to have no major effect on their response to mitogens. We conclude that the lack of effect on the proliferative response of lymphocytes following treatment by IFN in vivo, is probably due to the fact that the lymphocytes were only treated with IFN prior to the assay.
Cells, Cultured↗
Interferon therapy in neoplastic diseases.
Three types of interferon preparation (alpha, beta and gamma) have been used in the treatment of tumours in vivo. At the time of writing no information is available on IFN-gamma treatment of tumour patients. Treatments with IFN-alpha and IFN-beta have been undertaken at many clinical centres. Both types of preparation can exert side effects. Both types have also been able to cause regression of certain tumours in individual patients. At our hospital, IFN-alpha has been given to tumour patients over the last decade. Antitumour effects have been registered on patients with juvenile laryngeal papillomatosis, Hodgkin's disease, myelomatosis, ovarian carcinoma, hypernephroma and glioblastoma. Further study is needed on how therapy with IFN should best be undertaken and also how such treatment compares with other treatments of various tumour diseases. IFN therapy should also be combined with other such treatments.
Antineoplastic Agents↗
Interferon and natural killer activity in multiple myeloma. Lack of correlation between interferon-induced enhancement of natural killer activity and clinical response to human interferon-alpha.
Natural killer (NK) activity of peripheral lymphocytes was measured in 39 patients with multiple myeloma prior to and during interferon (IFN) therapy. NK activity increased in a majority of patients following the first injection of IFN and remained at an increased level during 1 year of therapy. Lower doses of IFN seemed to induce a greater increase in NK activity than higher doses. No correlations could be observed between the response of the tumors to IFN therapy and pretreatment levels of NK activity, IFN-induced enhancement of NK activity in vitro or IFN-induced enhancement of NK activity in vivo.
Adult↗