Results of the clinical study of the antineoplastic antibiotic bleomycetin

Bleomycetin was applied to the treatment of 68 patients with common forms of malignant tumors. The objective therapeutic effect was observed in 21 patients (31 per cent). The frequency of the favourable therapeutic effects was the most significant in the group of patients with generalized forms of lymphogranulomatosis: objective remissions for 1 to 4 months and stabilization of the tumor process were attained in 12 (41 per cent) and 8 out of 29 patients, respectively, in 9 patients (31 per cent) treated with bleomycetin progression of the underlying disease was recorded. A less pronounced therapeutic effect (33 per cent of the remissions) was recorded in the patients with nonlymphogranulomatous lymphomas. The use of bleomycetin in 48 out of 68 patients was complicated by certain adverse reactions. Intravenous infusions of bleomycetin in a dose of 10-15 mg twice a week (the total dose up to 125 mg) may be recommended as the initial therapeutic regimen in the oncological practice. The trials have showed that bleomycetin made in the USSR has a sufficiently pronounced activity against lymphogranulomatosis and nonlymphogranulomatous lymphomas. In this respect it is not inferior to the bleomycin analog made in Japan.     

Belomycetin in the combined chemotherapy of testicular tumors

The results of the treatment of 21 patients with testicle tumors of various histological structure, stages III and IV, are presented. The combination of bleomycetin (bleomycin A5), an antitumor antibiotic made in the USSR, with vinblastine and platinum derivatives was used. The antitumor effect was observed in 63 per cent of patients, including 21 per cent of patients with complete regression of tumors. The periods of complete and partial remission were 3--13 and 1--9 months, respectively. The combination is sufficiently effective and may be recommended for the treatment of patients with disseminated malignant tumors of the testicle.     

Serum enzymatic activity in oncological patients treated with carminomycin]

Karminomycin effect on the activity of some serum enzymes, such as hexokinase (HK), lactate dehydrogenase (LDG), its isoenzymes and glucose-6-phosphatase (G-6-P-ase) was studied. Biochemical assays were applied to 52 patients with neglected malignant tumors. The course dose of the drug was on the average 72mg. The objective antitumor effect was registered in 15 patients. A reliable increase in the values of LDG-5 and G-6-P-ase was observed after the treatment course in the combined group consisting of all the patients subjected to the biochemical assay. Normalization of the serum enzyme spectrum was observed in 15 patients effectively treated with karminomycin: activity of HK and the cathode fractions of LDG decreased. When treatment with karminomycin was ineffective (37 cases), the changes in the enzymatic activity recorded before the treatment further aggraviated. It was found that the level of G-6-P-ase in the patients' treated with karminomycin increased independent of the treatment effect which was probably associated with its toxic effect on the liver. The increase was reversible.     

Clinical study of the therapeutic effectiveness of an ointment consisting of swine leukocytic interferon

The ointment containing pig leukocytic interferon had a pronounced therapeutic effect in herpetic affections of the face skin and genitalia. It prevented eruption, shortened the period of its healing and eliminated subjective sensations. The therapeutic effect was observed in 265 (87.7 per cent) out of 302 patients with recurring Herpes simplex treated with ointment.     

Antitumor activity of carminomycin antibiotic used orally]

Antitumor activity of karminomycin used perorally was studied with respect to 3 strains of mouse transplantable tumors, i. e. one ascitic strain of lymphadenosis NK/LI and two solid strains of lymphosarcoma L10-1 and sarcoma 180. Karminomycin was shown to have a high antitumor activity against the above tumors on its oral administration. In the experiments with lymphadenosis NK/LI the efficiency of karminomycin was higher when it was used perorally as compared to its intravenous administration. It was found that karminomycin had practically the same inhibitory effect on growth of lymphosarcoma L10-1 and sarcoma 180 on its peroral and intravenous administration in doses equivalent by their toxicity.     

Rifampicin in the therapy of gonorrheal urethritis in men]

The therapeutic efficiency of benemycin (rifampicin of Polish production), a semisynthetic antibiotic was studied in 96 male cases with gonorrhea urethritis. The antibiotic was used in a dose of 300 mg every 6 hours (2.1--3gm for the treatment course depending on the desease severity). Observation of the patients for 1--2 months showed etiological recovery in 91 (94.8 per cent) out of 96 patients. Postgonorrhea inflammatory processes were observed in 8.7 per cent of the cases. For studying late results of the treatmant 62 patients were observed for 3 to 12 months. Gonococci were isolated from none of the patients. No side reactions were found in the patients treated with rifampicin.     

Carminomycin study in breast cancer]

Karminomycin was used for the treatment of cases with disseminated cancer of the mammary gland in doses of 5 mg/m2 of the body surface intravenously every day for 5 days (15 patients) or 6 mg/m2 twice a week for 2-3 weeks (30 patients). Partial remission or diminution of the tumor size at least by 50 per cent was observed in 26 and 17 per cent of the patients respectively. The remission duration was from 2 to 6 months. With the use of the shortperiod scheme the frequency of the direct side reactions increased. Leucopenia as a side effect was registered in 100 and 40 per cent of the patients and thrombocytopenia was registered in 18 and 3 per cent of the cases respectively.     

Use of carminomycin on children and adolescents with osteogenic sarcoma]

The therapeutic effect of carminomycin was studied in clinic at different treatment schemes with respect to 14 children and juvenile patients with osteogenic sarcoma. Pronounced local effect evident from disappearance of the pain and in some cases decrease of the metastatic tumor were noted in the patients with metastases of the osteogenic sarcoma to the bones or relapses of the primary tumor. Subjective improvement and objective effect were observed respectively in 90 and 53 per cent of the patients with metastases into the lungs and pronounced lung symptomatology.     

The so-called partial synchronization in the treatment of malignant lymphomas. A clinical study

In a randomized study the effectiveness of a modified MOPP scheme (CVPP scheme) and a so-called partial synchronisation treatment (vincristine or vinblastine respectively and cyclophosphamide) was compared in 72 patients predominantly pretreated with Hodgkin lymphomas and non-Hodgkin lymphomas. From 49 patients affected with lymphogranulomatosis of stage IIIB and IV, 24 were treated according to CVPP scheme; in 10 of them a complete remission was achieved and in 4 of them a partial remission. 25 patients were treated in the control group with synchronization therapy. In 13 of them a complete remission and in 12 of them a partial remission was achieved. With CVPP therapy the mean remission time amounted to 14.4 months and with synchronization therapy 9.2 months. There was no significant statistical difference. From 23 patients with advanced non-Hodgkin lymphomas of a high malignancy 11 received a therapy with CVPP scheme; 2 of them came into a complete remission and 3 of them into a partial one. 12 patients received a synchronization therapy; 7 of them came into a partial remission. With CVPP therapy the mean remission time amounted to 14.4 months, with partial synchronization therapy--10.8 months. Even in non-Hodgkin lymphomas there was no significant difference between the forms of therapy used. Even a comparison of the two survival times of both forms of treatment does not reveal any significance. Thus, both procedures of treatment seem to be comparable in their therapeutic efficaciousness, even if the number of complete remissions during the treatment with CVPP scheme was greater in our investigations. The assumed lower toxicity of synchronization therapy could not be confirmed by our study. In addition to the controversial synchronization effect, the good efficaciousness of treatment according to the so-called synchronization therapy may be due to sensibilizing phenomena and recruitment phenomena.     

Use of carminomycin on adult patients with acute leukemias]

The data on the clinical trials of karminomycin, a new antitumor antibiotic are presented. The drug was used in the treatment of 46 adult patients with leukemia. Karminomycin was used in primary inducing therapy and treatment of relapses. The results of the trials showed that karminomycin had a definite therapeutic activity in treatment of acute myeloblast leukemia at various stages of the process. A rapid effect of the antibiotic provided its use in emergency cases with rapidly progressing variants of the disease.     

PERFORATED PEPTIC ULCER—Selective Gastric Resection in Emergency Treatment

In a series of 240 cases of perforated peptic ulcer prior to 1952 there was a total mortality of 17 per cent. This included cases treated conservatively as a planned procedure or because of other morbid conditions and undiagnosed cases, all ending in death.In cases treated by simple suture, mortality was 2.6 per cent for patients under 50 years of age and 17 per cent for those over 50, the rate rising very steeply with each decade over 50.From 1953 through 1959 selective gastric resection was carried out, the operation being done in all cases of perforated gastric ulcers, of chronic duodenal ulcers and of perforations associated with hemorrhage.During this period 303 perforated ulcers were treated, with a mortality of 15.5 per cent. Patients with associated morbid conditions and those admitted moribund and died, or died undiagnosed were again included.In this series also the mortality increased steeply from age 50 onward.Gastric resection was carried out in 148 cases of perforated peptic ulcer with a mortality of 6 per cent. In 105 cases under 60 years of age there were no deaths but in those over 60 the mortality rate was 21.8 per cent. Results in the patients who had resection, as determined after three years of observation, compared favorably with the results in patients who were treated by suture.The mortality of perforated ulcers in females was higher than in males.Emergency gastric resection has a definite place in the treatment of perforated peptic ulcer.     

Mortality rates in patients with burns; a report of experience at San Francisco City and County Hospital, 1943-1956

A review was made of the cases of 93 patients with burns covering more than 20 per cent of the body surface who were treated at the San Francisco City and County Hospital, University of California Service, between 1943 and 1956. The mortality rate increased from 40 per cent during 1943-1947 to 69 per cent during 1952-1956. A significant change in survival time was noted: During 1943-1947, 69 per cent of the deaths occurred within 48 hours of admission; during 1952-1956, only 19 per cent of the deaths occurred within the first 48 hours. In the period 1943-1947 the majority of deaths resulted from shock in the immediate post-burn period; in the later years of the study the major cause of death was infection. No patient more than 50 years of age who had burns of more than 25 per cent of the body surface survived. Only one patient with burns involving more than 45 per cent survived. No patient who had a blood culture positive for bacteria survived. The use of antibiotics had no effect on the incidence of infection. Elderly patients, children and alcoholics were less able to resist the effects of infection. The lowest mortality rate was in the age group of 15 through 35 years.     

Therapeutic use of carminomycin in Ewing's sarcoma in children]

The therapeutic effect of carminomycin in various combinations with other antitumor drugs, i. e. vincristin, cyclophosphan, dactinomycin and metatrexate was studied in clinics on 18 children with wide-spread Juing sarcoma. Satisfactory direct effect was observed with the use of the above combinations in 47.0 per cent of the patients, which was evident from a decrease in the secondary tumor, disappearance of the pains and improvement of the general state of the patients.     

A THERAPEUTIC REGIMEN FOR TUBERCULOUS MENINGITIS

The results of treatment of tuberculous meningitis in Highland Alameda County Hospital, since the advent of streptomycin, in 34 cases were: dead, 21 patients, or 61 per cent; alive, 10 patients, or 29 per cent. Three cases were excluded from the ultimate report due to inadequate follow-up. The mean survival time of the ten survivors at the time of report was 35 months, the longest being 74 months.The composite results of treatment elsewhere, as reported in the literature, have been: dead, 892, or 59 per cent; alive, 629, or 41 per cent.The pathogenesis of the disease and the effects of chemotherapy are discussed.A therapeutic regimen for tuberculous meningitis is presented, which has been used at Highland Hospital since INH became established as the most effective component in the combined chemotherapeutic attack on the disease.     

Preparation of dihydrocarminomycin and a comparison of its antitumor activity with the activity of carminomycin]

A dihydro derivative of karminomycin was prepared using chemical reduction with potassium boron hydride. When dihydrokarminomycin was administered intravenously to healthy albino mice in a single dose it practically showed the same toxicity as karminomycin. However, unlike the latter dihydrokarminomycin induced the death of the animals at later periods of time. Studies on mice with transplantable tumours showed high antitumor activity of dihydrokarminomycin against lymphosarcoma L10-1, sarcoma 180, Garding-Passy melanoma, lymphoid leukosis L-1210 and lymphocytal leukosis P-388. In treatment of the mice with leukosis L-1210 and Garding-Passy melanoma dihydrokapminomycin was much inferior by its efficiency than karminomycin.     

Experience with using aclarubicin in the treatment of acute leukemia and blast crisis of chronic myeloid leukemia]

The clinical efficacy of aclarubicin, an anthracycline antibiotic, was studied in 48 patients with leukemia. The antibiotic was used in the following combinations with cytarabine: "7 + 7", "5 + 5" and "7 & 3". A complete remission was stated in 14 (42.4 per cent) out of 33 patients with acute nonlymphoid leukemia, 6 (43 per cent) out of the 14 patients having relapses. The combined therapy was effective in 4 out of 5 pre-resistant patients. The "7 + 3" scheme was the most beneficial. The most common adverse reactions were nausea and vomiting.     

The results of the use of bleomycin and its analogs in the VAB-6 protocol in treating testicular tumors

Efficacy and toxicity of VAB-6 combinations with bleomycin, bleomycetin or peplomycin were studied in treatment of 77 patients with metastases of germ-cell tumors: testicle tumors in 71 patients and extragonadal tumors in 6 patients. After the chemotherapy complete regression was observed in 37 patients (48.7 per cent). In 44 patients (57.1 per cent) residual metastases after the chemotherapy were resected. The frequency of complete regression after using the VAB-6 combinations with bleomycin, bleomycetin and peplomycin amounted to 58.8, 61.5 and 47.1 per cent respectively. The treatment results depended on the disease extent. When the disease extent was minimal complete regression was observed in 87.5 per cent of the patients. The respective figures for the disease moderate and significant extents were 66.7 and 37.8 per cent. During the average observation period of 22.1 months (7-40 months) 39 patients survived and had no signs of the disease. The combinations markedly differed in their toxicity.     

MORTALITY RATES IN PATIENTS WITH BURNS—A Report of Experience at San Francisco City and County Hospital, 1943-1956

A review was made of the cases of 93 patients with burns covering more than 20 per cent of the body surface who were treated at the San Francisco City and County Hospital, University of California Service, between 1943 and 1956.The mortality rate increased from 40 per cent during 1943-1947 to 69 per cent during 1952-1956. A significant change in survival time was noted: During 1943-1947, 69 per cent of the deaths occurred within 48 hours of admission; during 1952-1956, only 19 per cent of the deaths occurred within the first 48 hours. In the period 1943-1947 the majority of deaths resulted from shock in the immediate post-burn period; in the later years of the study the major cause of death was infection.No patient more than 50 years of age who had burns of more than 25 per cent of the body surface survived. Only one patient with burns involving more than 45 per cent survived.No patient who had a blood culture positive for bacteria survived. The use of antibiotics had no effect on the incidence of infection. Elderly patients, children and alcoholics were less able to resist the effects of infection.The lowest mortality rate was in the age group of 15 through 35 years.     

Clinical use of rubomycin in neuroblastoma in children]

The results of treatment of 23 children at the age of 7 months to 11 years suffering from neuroblastoma are presented; 22 patients with tumors, relapses or metastases were subjected to the treatment and 1 child was treated prophylactically after radical operation. Four patients were subjected to roentgen therapy in addition to the treatment with rubomycin. The antibiotic was administered intravenously in doses of 0.7--1.5 mg/kg in 1--3 days or daily. The caurse dose (3--12 mg/kg) was determined by the treatment efficiency and the side reactions. The objective effect was observed in 68 per cent of the patients, including the pronounced objective effect (marks 3 and 2) in 41 per cent of the cases. Leucopenia (less than 4000 cells in 1 mm3 of the blood). thrombocytopenia, vomiting (or nousea) and changes in the ECG were registered in 20 (87 per cent), 4,9 and 2 patients respectively. When the results of the treatment were positive, repeated courses of the therapy within 1.5--2 years were carried out; 18 patients died within 4 months to 2 years after the first course of the treatment with rubomycin because of the disease development. No signs of the disease were observed in 4 children with in 3--6 years of observation.     

Purulent complications in the surgical treatment of patients with mouth cancer and their prevention]

Local purulent complications after surgical operations for mouth cancer were recorded in 49 (61.3 per cent) out of 80 cases and were mainly due to associations of 2 or more pathogens. The analysis of the factors influencing the development of the complications showed that there was no reliable increase in the number of the complications in the patients subjected at the first stage to the treatment with various antitumor agents: 17 (53.1 per cent) events in the group of the patients subjected to radiotherapy in a total focal dose of 40 Gy, 8 (72.7 per cent) events in the group of the patients subjected to radiotherapy in a dose of more than 60 Gy, 13 (59.1 per cent) events in the group of the patients treated with antitumor drugs and 8 (66.7 per cent) events in the group of the patients operated at the first stage of the treatment. The incidence of osteomyelitis was significantly higher in the group of the patients subjected to radiotherapy before the operation: 13 (30.2 per cent) events vs. 2 (5.4 per cent) in the group of the patients not subjected to radiotherapy. With increasing of the radiation dose, the incidence of osteomyelitis as well increased: 8 (25.0 per cent) osteomyelitis events in the group of the patients subjected to radiotherapy in a dose of 40 Gy and 5 (45.5 per cent) events in the group of the patients subjected to radiotherapy in a dose of more than 60 Gy. The method of osteosynthesis of the lower maxilla with titanium miniplates was also of great importance. The use of various schemes for antibiotic prophylaxis of wound infection in such patients was equally efficient.