Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group.

PURPOSE: The trial was undertaken to determine (1) the relative efficacy/toxicity of two commonly used combination chemotherapy regimens in patients with extensive small-cell lung cancer (SCLC) and (2) whether the rapid alternation of these two regimens could provide superior therapeutic results compared with either regimen alone. PATIENTS AND METHODS: In this phase III trial, 437 eligible patients were stratified by performance status (PS) and sex and were randomly assigned to receive either 12 weeks of cisplatin and etoposide (EP); 18 weeks of cyclophosphamide, doxorubicin, and vincristine (CAV); or 18 weeks of alternation of these two regimens (CAV/EP). RESULTS: There were no significant differences in treatment outcome for EP, CAV, or CAV/EP in terms of response rate (61%, 51%, 59%, respectively), complete response rate (10%, 7%, 7%, respectively), or median survival (8.6 months, 8.3 months, 8.1 months, respectively), with a non-statistically significant trend toward a longer median time to progression with alternating therapy (4.3 months, 4.0 months, 5.2 months, respectively). Crossover second-line chemotherapy given at progression produced low response rates and short survival, regardless of the regimen used. Myelosuppression was the dose-limiting toxicity for all patients, although the pattern and severity differed among the treatment arms. CONCLUSIONS: The combination regimens EP and CAV can be considered equivalently effective induction therapies in extensive SCLC, and these two regimens are, to some degree, crossresistant. Alternating therapy provides no therapeutic advantage compared with the use of either of these regimens alone and should not be considered as standard treatment in this clinical setting.

Progressive neuropathologic lesions in vitamin E-deficient rhesus monkeys.

A consistent group of progressive central and peripheral nervous system lesions developed in seven rhesus monkeys maintained on a vitamin E-deficient diet for 30 to 33 months. These lesions were absent from vitamin E-supplemented monkeys. The principal neuropathologic alteration was loss of sensory axons in the posterior columns, sensory roots, and peripheral nerves. Morphologic and morphometric studies indicated that the distal segments of the axons were affected most severely and large-caliber myelinated fibers are selectively involved. Swollen, dystrophic axons (spheroids) occurred infrequently. Degeneration and phagocytosis of small numbers of neuronal perikarya were observed in the dorsal root ganglia and the anterior horns. The number of affected neurons was not proportional to the number of affected axons. Accumulation of lipopigment was evident in neuronal perikarya and CNS endothelial cells. The nervous system lesion were usually accompanied by a chronic necrotizing myopathy. The neuropathologic lesions in vitamin E-deficient monkeys are compared with those in vitamin E-deficient rats and in humans with low serum vitamin E concentrations. A similar type of sensory axonopathy is associated with chronic deficiency of vitamin E in these three species.

Expression of protozoan antigens by hybrids between Leishmania mexicana and myeloma SP2/0.

Hybrid cells were obtained between Leishmania mexicana promastigotes and mouse myeloma SP2/0 cells, and examined for expression of leishmanial antigens. A ratio of 1:10 of myeloma to T. cruzi cells was unsuccessful because of outgrowth of non-fused cells. With a ratio of 2:1 four waves of multiplication of 'chimeric' cells were observed over 45 days. The death of the hybrids after this period is explained by segregation of DNA and loss of chromosome material. Hybrid cells gave a positive reaction with antibodies in the sera from patients infected with Leishmania, as demonstrated by indirect immunofluorescence. Conversely, promastigote forms of Leishmania gave a negative reaction with the same antibodies, which recognize surface antigens of the amastigote stage of Leishmania. It is possible therefore that amastigote stage antigens are expressed on the surface of the 'chimeric' hybrid as a result of transformation of promastigotes following hybridization.

Factors involved in immunization program for swine influenza.

The decision to undertake a nationwide program of vaccination against swine influenza requires assessment of the status of immunity of those in various age groups in our population against this agent. Pools of serum were collected from persons born in the years from 1889 to 1943; they were tested for hemaggultinin inhibiting (HI) antibody against the HSW 1N1 influenza virus strains isolated in 1931 and 1976. The titers secured serve as an indication of the average level of immunity of those of different ages. Persons less than 43 years of age are found to be without antibody protection. The need for vaccination of people in different age groups based on mortality statistics of previous epidemics is evaluated. It is realized that no epidemic may occur and that a reduced virulence of the viral agent and use of antibiotics may reduce the death rate if the infection recurs. The extraordinary high mortality in 1918 in people between 15 and 44 years of age deserves recognition together with the fact that those in the same age group are now without protection. The fact that women of childbearing age fall into this group deserves special consideration in view of increased mortality in puerperal women observed in the pandemics of 1918 and 1957. The degree of protection afforded the newborn by transplacental transmission of maternal antibodies is discussed. The need of increasing the level of immunity in those who have varying titers of HI antibodies is considered in relation to the prevalence of cardiopulmonary complications and other chronic diseases in older subjects.

A phase II trial of vincristine in advanced or recurrent endometrial carcinoma. A Gynecologic Oncology Group Study.

Thirty-three evaluable patients who had not received prior chemotherapy were entered on a study of vincristine therapy for advanced or recurrent endometrial carcinoma. Vincristine 1.4 mg/m2 was given weekly as an i.v. bolus for 4 weeks and then every other week. There was one complete response (CR) lasting 5 months. Five patients had partial responses (PR) lasting 3-18 months. The CR+PR rate was 18% (95% confidence interval for CR+PR was 7-36%). Thirteen patients (38%) had stable disease from 2-28 months, and 14 had progressive disease. The major toxicity was neurological, with 11 patients having grade 2 or 3 peripheral neuropathy. Vincristine at this dose and schedule has modest activity, but troublesome toxicity in advanced or recurrent endometrial carcinoma.

Treatment of inoperable non-small cell carcinoma of the lung with radiation therapy, with or without levamisole. A randomized trial of the Southeastern Cancer Study group.

In a randomized trial, 251 patients with inoperable non-small cell lung cancer received radiation therapy (RT) with or without levamisole (2.5 mg/kg twice weekly for 1 year, or until progression). Radiation therapy was delivered to 6000-6500 rad for Stages I and II, and 4000-4500 rad by continuous or split course for Stage III disease. Responses were observed in 40% of patients receiving placebo, and in 29% of patients taking levamisole. Relapse occurred at local sites only in 53% of the placebo- and 75% of the levamisole-treated patients. The frequency of relapse in distant sites was lower (25%) in the levamisole group as compared with the placebo group (47%). No significant difference in survival was observed between the placebo and levamisole-treated groups (median survival, 48.2 and 45 weeks, respectively). Responders to radiotherapy survived significantly longer than nonresponders (median survival, 73 vs. 33.3 weeks, p = 0.001). Among responders, the median survival of patients treated with levamisole was shorter (63.9 weeks) than that of patients receiving placebo (92.7 weeks). Toxicity attributable to levamisole included severe granulocytopenia in five patients and severe nausea and vomiting in nine. It is concluded that levamisole is without significant benefit in this setting.

Immunoenzymatic determination of antibody-bound soluble antigens ofTrypanosoma cruzi.

Anti-Major Cathodic Antigen (MCA) monospecific immunoglobulins ofT. cruzi have been used for the preparation of polyamide-linked immunoadsorbents. A high proportion of serologically positive patients with Chagas disease show the presence of a soluble antigen complexed with human immunoglobulins, which complex binds to those immunoadsorbents as determined by a double sandwich reaction and a peroxidase final determination.

[Electroreceptor characteristics of elasmobranchs with pint sources of the electric field]. / Analiz kharakteristik élektroretseptorov plastinozhabernykh rib s pomoshch'iu tochechnykh istochnikov élektricheskogo polia.

Using mathematical modelling methods and experimental data possible space mechanisms of information conversion processes with Lorenzinian ampullary apparatus during detection of the dipole electric field were studied. The space selectivity of the ampullary groups was shown and its biological significance is discussed.

[Effective stimulation of Turkestan catfish electroreceptors]. / Effektivnyi stimul élektroretseptorov turkestanskogo somika.

In Turkestan catfish (Clyptosternum reticulatum) passive electrical properties of the skin, the structure of electrical field near and within the fish as well as single nerve fibre impulse activity of electroreceptors, were studied. The resistance and capacity of the skin were 18-25 kOhm.cm2 and 1 micro F/cm2, resp. The effective stimulus for the electroreceptors involved the voltage drop across the skin. The significance of the skin electrical properties for functional characteristics of electroreceptors is discussed.

[Effect of focused ultrasound on the electroreceptor system of skates and certain fish and amphibian tissues]. / Deistvie fokusirovannogo ul'trazvuka na élektroretseptornuiu sistemu skatov i na nekotorye tkani ryb i amfibii.

The effects of focused ultrasound have been investigated on the structures of electroreceptor system of the Black Sea skates (Raja clavata, Dasyatis pastinaca), as well as on the tissues of some other poikilotherms (fishes Belone belone and Solea lascaris, toad Bufo viridis, frog Rana temporaria). It was shown that focused ultrasound evokes excitation (onset of impulse activity) when applied to the pore of electroreceptors and inhibition of the activity when applied to the ampulla itself. The data obtained indicate that thermal conductivity of tissues in poikilotherms is lower than that in homoiotherms.

[The clinico-hematological indices of the participants in the cleanup of the aftermath of the Chernobyl accident]. / Kliniko-gematologicheskie pokazateli uchastnikov likvidatsii posledstvii Chernobyl'skoi avarii.

Clinicohematological investigations and cytogenetic analysis of blood lymphocytes were made 5-7 years after the Chernobyl accident in 201 liquidators who had worked in the radionuclide-contaminated zone. Among the somatic diseases found in the examinees statistically more prevalent were cardiovascular and gastrointestinal affections, asthenic syndrome, thyroid disorders. Hemograms presented a rise in hemoglobin, red cell and eosinophil content, a drop in the number of neutrophils. A tendency to erythrocytosis was observed in 20.3% of the wreckers. Dicenters and rings were abundant in the lymphocytes of 69% of the cytogenetically examined examinees 5-7 years after the exposure to radiation.

[Multi-profile analysis of survival rate and cause of death in patients with non-Hodgkin's lymphoma]. / Mnogoprofil'nyi analiz vyzhivaemosti i prichin smerti bol'nykh nekhodzhkinskimi limfomami.

A relationship has been established between the survival rate of 378 patients who had died of non-Hodgkin's lymphoma (NHL) and their sex, age, ABO- and Rh-factors of the blood, primary focus of the tumor lesion, morphological variant, diagnostic period duration, and the treatment intensity. A higher incidence rate and a higher mean survival were recorded in 222 males, as compared to 156 females. Favourable and unfavourable for survival age interval has been distinguished for NHL disease. Patients with Rh+ showed a higher survival rate, although the incidence rate among Rh+ and Rh- subjects was similar. Prognostically favourable and unfavourable sites of the primary tumor and morphological variants of NHL were specified. The time spent for detailed verification of the diagnosis has been justified, and the presence of a direct proportional relationship between the intensity of the treatment and the mean survival of patients with varying forms of NHL has been proved.