Biomedical subjects
Publications and source records attributed to H Strander.
This paper updates the results of the clinical trial to examine the efficacy of exogenous leukocyte interferon therapy as adjuvant treatment for osteosarcoma. So far the incidence of metastases is lower and the survival rate is better for the interferon-treated group than for the concurrent control group. The number of treated patients is too small at present to allow proper statistical calculations to be made.
Daily intramuscular injections of 3 X 10(6) international units of human leukocyte interferon were given to five patients with advanced ovarian carcinoma, all of whom previously received other forms of treatment. Ascitic fluid production ceases in two out of two patients. According to the criteria specified by Young and DeVita a partial response was observed in one patient and in two other patients the disease was stable for more than 1 year. Side effects of the interferon therapy were relatively mild. The introduction of interferon therapy was followed by an increase in the natural killer cell activity of peripheral blood lymphocytes in all three patients examined. Natural killer cell activity decreased after cessation of interferon therapy in the one patient where this was tested.
Patients that have received interferon therapy for tumor diseases to date do not total more than a few hundred. Remissions have been reported in some patients with various types of malignant tumors. This is interesting, as interferon therapy represents a new principle in the treatment of tumor diseases. However, prolonged and complete remissions have been rare, and we are not yet in a position to say whether interferon therapy is superior to other treatment methods in current use for any type of malignant tumor. If this proves to be the case for some such diseases, we would still be faced with the tasks of identifying patients that may benefit from the interferon treatment, and of establishing the best procedure for its application. Research toward these ends would be greatly facilitated by the development of methods for producing interferon.
To evaluate the outcome for osteosarcoma patients treated with different forms of adjuvant therapy in nonrandomized series, it is important to realize the possible influence of different prognostic factors. In two series of patients with primary classic osteosarcoma, survival was analyzed in relation to tumor size and site. In the first series comprising 57 patients, no adjuvant therapy was given and the five-year survival rate for all patients was 19%. A significantly (p less than 0.01) higher survival rate (43%) was noted for patients with tumors distally located and less than 0 cm in size (as measured by their largest diameter on radiograms), as compared to 12% for patients with larger and proximally located tumors. These figures were the same at three-and five-year follow-up. In the second series, comprising 22 patients, all received adjuvant interferon treatment. The three-year survival rate was 68%, and the five-year survival rate for the 12 patients followed was 58%. The survival rate for patients with tumors distally located and less than 10 cm in size was 88%, as compared to 57% for patients with larger and proximally located tumors. In the interferon series, tumor size appeared more important than location.
Seven cases of severe juvenile laryngeal papillomatosis were treated with exogenous leukocyte interferon (IFN-alpha). Tumor progression occurred in all cases before treatment. During treatment, the tumors decreased in size. When treatment was discontinued (five cases), tumor growth recurred, and after restarting therapy, the tumors once more decreased in size. In one case, the tumor completely vanished. In another case with extensive papillomatosis that extended up to the base of the tongue, a tracheostomy could be closed with only a thin mass of papillomatous tissue that remained on the vocal cords. Exogenous leukocyte interferon therapy can affect the clinical course of juvenile laryngeal papillomatosis. The optimal schedule for therapy has yet to be determined.
Twenty patients with osteosarcoma were treated with exogenous human leukocyte interferon for periods ranging from 6 to 18 months. Eleven of them remained free from detectable tumour growth during this treatment. Blood samples from all patients were tested for antibodies against interferon and against impurities in the interferon preparations. No patient developed detectable levels of neutralizing antibodies against interferon. All patients formed antibodies against contaminants in the concentrated crude interferon and the partially purified interferon preparation which had been used for treatment.
Radiation therapy was combined with simultaneous administration of bleomycin, cyclophosphamide and 5-fluorouracil for the treatment of 33 patients with carcinoma of the head and neck. This combination increased the toxicity to the normal tissue. Complete response was obtained in 46 per cent, partial response in 36 per cent and no response in 18 per cent. Patients with a complete response had a significantly longer survival than patients with a partial or no response. An increased cytotoxicity was noted after the combined treatment when compared with irradiation alone. However, no evidence of an increased therapeutic effect was obtained with the addition of simultaneous chemotherapy to irradiation.
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Since 1971, Interferon has been used by the authors in the treatment of 46 consecutive cases of osteosarcoma. Two thirds of the cases were treated by amputation, the remainder being treated by resection followed by grafting or a prosthesis. No case was treated by radiotherapy or chemotherapy. Before 1971, the survival rate was 15 p. 100; in contemporary cases treated without Interferon, the rate of survival was 30 p. 100. In the present series the rate of survival was 50 p. 100 after 5 years. It is concluded that Interferon seems to have a positive action. The selection of cases which can be treated by local resection is difficult.
Eleven biopsies from 9 patients with Burkitt's lymphoma were tested for their sensitivity to the cell multiplication inhibitory activity of interferon. Three were resistant to interferon while 8 were sensitive to various degrees. Different biopsies from the same patient did not differ in interferon sensitivity. These results indicate that Burkitt's lymphoma cells might be resistant to interferon already in vivo as previously shown for some derived cell lines tested in vitro. The results imply an inverse relationship between patient survival and interferon sensitivity of the tumor cells.
Human leukocyte interferon was given as adjuvant treatment for osteosarcoma in 26 patients. Blood from these patients was studied at regular intervals for antibodies to various micro-organisms. A continuous record of clinically manifest infections during the course of interferon therapy was made in 23 of the 26 patients. Distant metastases arose in 14 patients - the metastasis group. The report presents comparisons between these patients and the non-metastasis group. Seroconversion in tests with any of the studied micro-organisms was not common. Most of the seroconversions were not associated with clinical symptoms. Seroconversion during interferon therapy was confined to patients in the metastasis group. In some cases there was a chronologic link with early evidence of metastasis. The results of the serologic investigations are discussed and are correlated to the course of interferon therapy and of the neoplastic disease.
The effect of daily injections of 3 x 10(6) units of human leukocyte IF on the spontaneous cytotoxicity of peripheral lymphocytes was studied in 43 patients with a variety of diseases. An increase in spontaneous cytotoxicity was observed 12 to 24 h after the first IF injection with the peak of activity occurring, in most cases, at 24 h. In some patients a decrease in spontaneous cytotoxicity, observed 6 h after the injection, preceded this increase. The increment in spontaneous cytotoxicity was not significantly correlated to preinjection level of cytotoxicity, disease, age, sex, previous therapy, leukocyte counts or proportions of lymphocytes and monocytes. A second injection of IF maintained the spontaneous cytotoxicity at an increased level and during prolonged IF therapy, up to 9 months, the cytotoxicity remained elevated. IF treatment in vitro caused an enhancement of spontaneous cytotoxicity in lymphocytes drawn prior to IF injection. This IF-induced increase in cytotoxicity in vitro was correlated to the increase in cytotoxicity induced by IF in vivo. Six hours after the first IF injection the ability of IF in vitro to enhance spontaneous cytotoxicity was decreased and during prolonged therapy the ability of IF in vitro to enhance spontaneous cytotoxicity remained decreased.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Leukocyte interferon was given by i.m. injection as adjuvant therapy to 9 patients with osteosarcoma. The dose was 3 X 10(6) standard units daily for one month, and then 3 times a week for the next 17 months. Blood samples were drawn at intervals for a number of routine tests during the 18-month course of interferon administration and during the subsequent 18 months. On withdrawal of the interferon treatment, the mean Hb concentration rose significantly and the mean ESR fell significantly. There was no significant change in the leukocyte and platelet counts or in the alkaline phosphatase, alanine and aspartate aminotransferase or plasma protein levels.
Prognostic factors and the blood chemistry were analyzed prior to treatment in 33 consecutive patients with primary osteosarcoma. The only variables of blood chemistry with values outside the normal range were alkaline phosphatase and ESR, which were increased. There was a correlation between certain prognostic factors and between some of these and a number of the blood variables. The degree of malignancy tended to be lower in the female than in the male patients. Distally located tumors tended to be smaller and were assessed with a less marked effect on the blood variables than those located proximally.
Following an intramuscular injection of human leukocyte interferon blood leukocyte counts decreased in most patients as tested 24 h after the injection. This decrease comprised lymphocytes, monocytes and granulocytes, 24 h after interferon injection, the proportion of lymphocytes forming E rosettes was incresed in most patients, whereas the proportion of lymphocytes forming EA and EAC rosettes was not significantly changed.