Interferon treatment of uterine cervical carcinoma: 20 years of follow-up.

Twenty-seven randomized patients with biopsy proven carcinoma of the uterine cervix were treated with human natural leucocytic interferon (HNLI) and followed up, while 30 randomized patients were followed up in the control group and were not treated with HNLI. International Federation of Gynecology and Obstetrics (FIGO) classification of HNLI-treated patients was IA: 8, IB: 9, IIA and IIB: 10. FIGO classification of control non-treated patients was IA: 9, IB: 10, IIA and IIB: 12. HNLI was applied locally at 2x10(6) U daily in pessaries for 21 days before surgery. Survival analysis of the HNLI-treated patients after 240 months of observation showed that 20 patients (74.07%) out of 27 survived, and in the control group 14 patients (46.67%) out of 30 survived. Statistical difference between the HNLI-treated group and control group of patients is significant P<0.05.

Local interferon therapy for melanoma patients.

BACKGROUND: Melanoma, once considered a rare form of cancer, is increasing in incidence throughout the world. The prognosis of malignant melanoma is inversely related to the depth of tumor invasion. METHODS: Twenty-seven patients were treated with r.IFN alpha 2c. Four patients were treated with human natural leukocyte interferon (HNLI). Interferon was applied locally. Historical control groups were used for comparison in the statistical analysis. The data were evaluated taking into account the single risk factor Clark levels III and IV. In the control group there were 10 patients with Clark levels III and IV; in the group of r.IFN apha 2c-treated patients there were 20 patients. The data were analyzed by using the Kaplan-Meier and Cox methods. RESULTS: The percentage of survivals was higher in the interferon-treated groups with Clark levels III and IV, than in the control group, that is 60% compared to 25%, and 40% compared to 33%, respectively. The results of the statistical analysis after 60 months of follow-up are significantly better in the interferon group (P = 0.0175). CONCLUSIONS: The control group was not selected at random. Therefore, on the basis of our results, one can say that the treatment of the melanoma patients, Clark levels III and IV, with the r.IFN alpha 2c is promising and that further investigation is justified.

Interferon reduces recurrences of basal cell and squamous cell cancers.

BACKGROUND: Interferon is considered to be an important curative agent for dermatologic diseases. We report the follow-up experience of patients with basal cell or squamous cell carcinomas treated with human natural leukocyte interferon (HNLI). RESULTS: Among 52 patients with basal cell carcinoma (BCC) treated with HNLI more than 10 years ago, and among 58 treated more than 5 years ago, only 2 recurrences were observed. There were no recurrences in 75 patients who had a complete response to HNLI treatment, nor were there any in 20 patients with either a partial or complete response to r.IFM alpha 2c treatment. Of 52 patients with squamous cell carcinoma (SCC), 31 had been treated more than 10 years earlier, two recurrences of the disease at the site of the original lesion were observed. CONCLUSION: Interferon treatment makes it possible to achieve a persistent cure in patients with BCC and SCC in a high proportion of cases. The potential advantage of nonsurgical treatment are an enhancement of cosmetic results through the prevention of destruction of important anatomic structures.

[Interferon in the treatment of solid tumors]. / Interferon u lijecenju solidnih tumora.

Discovered almost four decades ago, interferons were being investigated as potential anticancer agents from early sixties, because of their antiviral antiproliferative and immunomodulating properties and their relatively modest toxicity. Unlike very good effects on some lymphoproliferative disorders where complete durable remissions were observed, results of their application in solid tumors are not so unambiguous. Among large number of tumors investigated so far, the best, reproducible, although modest, activity was found against melanoma, renal cell carcinoma and Kaposi's sarcoma. There are still many doubts concerning their optimal doses, sequencing and schedules, most probably in combination with other biological response modifiers and/or cytotoxic agents, which have to be clarified in further clinical trials, together with investigation of more reliable biological indicators of response to interferons in vivo.

Local interferon therapy for lip carcinoma.

In a prospective non-randomized study 21 patients with lower lip squamous cell carcinoma were treated with human natural leukocyte interferon (HNLI). The response rate was measured by a size reduction of more than 25% and was 81%. A complete response rate was considered to be a cure according to histopathological and clinical findings and was 48%. The response rate of six lower lip squamous cell carcinoma cases treated with recombinant interferon alpha 2c was 67% and the complete response rate was 17%. Three patients with basal cell carcinoma of the upper lip were also treated with HNLI. All three patients were cured, as determined by histopathological and clinical findings. These findings indicate that interferon can be a useful alternative therapy for lip carcinoma either with or without surgery.

Basal cell carcinoma treated with interferon.

Human natural leukocytic interferon (HNLI) and recombinant interferon (rIFN) alpha 2c can be used in the therapy of basal cell carcinoma. Seventy-two patients were treated for 3 to 6 weeks with a single dose of 400,000 to 1,200,000 units (HNLI) and 2,000,000 to 5,000,000 units (rIFN alpha 2c). According to histopathologic and clinical findings, 52 patients were cured, and cancer cells were not found in the biopsy material taken after HNLI treatment for the second biopsy. In nine of 72 patients the cancer lesion was reduced 25% to 90%. In 11 patients it was not reduced or was reduced less than 25%. With rIFN alpha 2c therapy given five times per week for 4 weeks, histopathologic and clinical findings showed that five patients out of 12 were cured, and cancer cells were not found in the biopsy material taken after treatment. In seven patients out of 12 the cancer lesion was reduced 25% to 90%. Both types of interferons are effective in the treatment of basal cell carcinoma. Side effects were mild.

Interferon therapy for basal cell carcinoma and squamous cell carcinoma.

Totally 161 basal cell and squamous cell carcinoma (BCC, SCC) patients were treated with human natural leucocytic interferon (HNLI) and recombinant IFN alpha 2c. After HNLI treatment, 61 out of 86 BCC patients and 29 out of 45 SCC patients were cured according to histopathologic and clinical findings. In 13 BCC and 13 SCC patients, the cancer lesion was reduced 25%-90%. After recombinant IFN alpha 2c treatment, 14 of 20 BCC patients and 4 of 10 SCC patients were cured according to histopathologic and clinical findings. In 6 BCC patients and 5 SCC patients the cancer lesion was reduced 25% to 90%. Both types of interferons are effective in the treatment of BCC and SCC patients. Local application of interferon stimulates immune reaction at the site of the tumor. There is a marked difference between the spontaneous macrophage activity and that induced by interferon. The interferon activated macrophages are significantly larger, the number of lysosomes and the density of macrophages is increased. In difficult locations intralesional therapy can be considered to avoid disfigurement of the patients with or without surgery.

Treatment of squamous cell carcinoma with interferon.

Human natural leukocytic interferon and recombinant HulFN alpha 2c can be used in the therapy of squamous cell carcinoma. The duration of treatment was 3-6 weeks. A single dose was 400,000-5,000,000 units given weekly for 3-6 weeks. Clinically and histologically 19 of 32 patients were cured and tumor cells were not found in the material taken after interferon treatment for the second biopsy. In ten patients tumor size was reduced 25-90%, and in three patients tumor size was not reduced according to clinical findings. With recombinant HulFN alpha 2c therapy given 5 times per week for 4 weeks. Four of ten patients with similar tumors were cured clinically and histologically clinical findings. In five patients tumor size was reduced 25-90%, while in one patient there was no reduction in tumor size. Both types of interferons are effective in the treatment of squamous cell carcinoma. Side reactions were mild.

Influence of interferon on C19-steroids in urine of malignant skin melanoma and malignant breast neoplasm patients.

The paper evaluates the effect of human leukocyte interferon (HLI) in patients with malignant skin melanoma and malignant neoplasm of the breast. HLI was administered intramuscularly in a daily dose of 2 X 10(5) IU 7 days at 8-week intervals over a period of 12 months. The chosen patients were in the surgical stage of the disease, i.e. they had undergone surgical operation on the primary tumor or on the regional lymph nodes T1-3, N0-1, M0. During the HLI treatment the values of C19-steroid metabolites and particularly of Dehydroepiandrosterone (DHA) were established and the following conclusions have been drawn: the application of HLI in a dose of 2 X 10(5) by the described method has an impact on the change of C19 steroid metabolism in terms of normalization.

Edmonston-Zagreb strain of measles vaccine: epidemiologic evaluation in Yugoslavia.

According to epidemiologic data in Yugoslavia, a high level of immunity (95%) must be attained in the susceptible population between eight months and 30 years of age for the eventual eradication of measles (to cut off the seasonal peak and to prevent the epidemiologic wave). Where the vaccination rate produced a lower level of immunity (e.g., 85% and 67%), the cyclic wave did not disappear completely but was greatly reduced. Live measles vaccine prepared from a further-attenuated Edmonston-Zagreb strain was used for vaccination in Yugoslavia.

Antiviral and anti-invasive titers of human interferons.

The titers of preparations of human leukocyte and human fibroblast interferon were examined to determine their antiviral and anti-invasive activity. The examinations showed a very high correlation of these activities in human fibroblast interferon (r = 0.99), whereas the correlation for human leukocyte interferon was lower. These two interferons have also been found to differ in the relation between antiviral and anti-invasive titers. This difference is highly significant (p less than 0.001).

Histopathologic and histoenzymatic observations in carcinomas treated with human leukocyte interferon.

In this study histologic and histochemical examinations were performed on the bioptic material of 30 cases of head and neck tumors and 34 cases of uterocervical carcinomas after treatment with human leukocyte interferon (HLI). Particular attention was paid to the interaction between stromal and neoplastic cells as a possible host response to the treatment with interferon. In addition to tumor biopsies, regional lymph nodes were also examined microscopically. Stromal cells (macrophages, T and B lymphocytes, and granulocytes) were detected by enzyme-histochemical methods. Histologic and histochemical criteria for classification of tumor biopsies into five groups included the frequency, the cellular composition of peritumoral stroma, the grade of macrophage infiltration into the tumor (expressed quantitatively), and cytologic changes, followed by the regression of tumor. The overall appraisal of patients with cervical carcinoma based on histopathologic and chemical criteria showed the positive effect of HLI therapy in 70% of the cases; observations of head and neck carcinoma treated with HLI showed positive effects in 82% of the cases.

The clinical use of human leukocyte interferon in viral infections.

This review presents the results of the clinical use of human leukocyte interferon (HLI) in certain diseases with viral etiology. Viral infections with manifestations in the eye, skin, and/or mucous membranes and in the respiratory system were treated with HLI by local application. HLI was incorporated into ointment, oil suspension, powder, dilution for inhalation, and dilution for subcutaneous and subconjunctival injections. The treatment in some of the diseases yielded statistical results that were highly significant in favor of interferon.

Topical application of human leukocyte interferon in stasis ulcers and deep burns.

Human leukocyte interferon (HLI) incorporated in ointment (4,000 units/g) applied topically for 4 weeks induced the process of "scavenging" granulation and epithelialization of stasis ulcers. This therapy had a better effect than that of the other combined local and general therapy also given in the study. A comparison of the effects of both therapies was made on nine pairs of stasis ulcers. A favorable effect of HLI on granulation and epithelialization was observed in a patient with deep burns, who had been given HLI topically in the form of powder and solution. This type of HLI activity calls for further clinical trials, especially as regards deep burns.

Application of human leucocyte interferon in patients with tumours of the head and neck.

Local administration of crude human leucocyte interferon (HLI) produced substantial or total remission in patients with cancers of the head and neck. At the end of HLI therapy 10 of 30 patients were considered completely cured. In 10 patients unepithelialised skin lesions were hardly visible, in 5 the tumours were significantly reduced in size and had clear-cut borders, in 2 the tumours showed a tendency towards regression, and in 3 there was no effect. Application of HLI close to the tumour site appears to prevent dispersal of tumour cells during surgical removal of the tumour. It also inhibits metastatic spread, thereby reducing the likelihood of recurrence.

Application of human leucocyte interferon in patients with urinary bladder papillomatosis, breast cancer, and melanoma.

Eight patients with malignant papillomaosis of the bladder, four with breast cancer, and two with malignant melanoma, all of whom had a poor prognosis, were treated with injection of crude human leucocyte interferon (HLI) into the tumour or the adjacent tissue and in some cases with intramuscular HLI injection also. All tumours showed complete or partial regression after treatment for up to 6 months. One patient with breast cancer died from distant metastases; all other patients in the trial were recurrence-free after 3--30 months of follow-up.

Application of human leucocyte interferon in patients with carcinoma of the uterine cervix.

15 patients with invasive squamous-cell carcinoma of the uterine cervix were treated with crude human leucocyte interferon (HLI) for 3 weeks before surgical removal of the tumour. 9 patients were given HLI topically and intramuscularly and 6 topically only. In 3 patients the surgical material was free from tumour cells, in 3 it showed a lower grade of carcinoma, and in 9 the findings remained unchanged. In only 1 patient the tumour metastasised to the lymph nodes. Typically a tumour regressed to about a third of its original size. There was a sharp distinction between the tumour mass and the healthy tissue manifested in the formation of a fibrous wall. On the basis of the scores--i.e., stromal response, relation between tumour-cell and macrophage activity and reactivity, and reactivity of the original lymph nodes--the overall appraisal of the response caused by HLI therapy was as follows: in 6 patients excellent, in 5 very good, in 1 moderate, in 2 poor, and in 1 no response. It is suggested that HLI is suitable for administration both before and after surgery in patients with cervical cancer of grade I or II. If stroma cannot be induced to respond within 21 days of treatment, HLI application should be discontinued.

Interferon treatment of uterine cervical precancerosis.

Human leukocyte interferon (HLI) was used in a randomized study of patients with precancerous states on the uterine cervix. The daily dose of HLI was 10(6) units and its was applied by the contraceptive pessary technique. In patients how had had only viral alterations on the cervix the treatment lasted 14 days (Singer et al. 1979) and in those with changed cytologic findings 21 days. The cytologic findings of the interferon treated patients showed no progression of the pathologic process during the ensuing 2 years. In the control group, however, they showed the aggravation of the process and the patients were directed to surgical therapy. The control of cytologic findings has been continued and in now performed at 3 month intervals.

Influence of human leukocyte interferon on squamous cell carcinoma of uterine cervix: clinical, histological, and histochemical observations. III. Communication.

Fifteen patients with invasive squamous cell carcinoma of the uterine cervix were treated with human leukocyte interferon (HLI). HLI was applied topically and i.m. to nine patients, and only topically to six. After therapy, surgical material was free from tumor cells in three patients, tumor cells were identified as invasive carcinoma in one patient and as CA in situ in two patients. Findings remained unchanged in nine patients. Tumor metastases in the lymph nodes were found in only one patient. The patients' overall response to therapy was assessed on the basis of stromal response, relation of tumor cells and macrophage activity, and the reactivity of lymph nodes.

Human leukocyte interferon in therapy of patients with urinary bladder papillomatosis, breast cancer, and melanoma.

The authors report the result of local and parenteral applications of human leukocyte crude interferon in the therapy of eight patients with urinary bladder papillomatosis, four patients with breast cancer, and two patients with melanoma. The doses and effects of treatment are presented in tables. Clinical application of human leukocyte interferon (HLI) to these three types of malignant tumors has yielded encouraging results. The authors believe that investigations on HLI applications to some malignant tumors should continue because the results obtained indicate that interferon possesses not only an antiviral but also an antitumor activity.