Decreased metastasis and improved survival with early thoracic radiotherapy and prophylactic cranial irradiation in combined-modality treatment of limited-stage small cell lung cancer.

In an attempt to verify the relative efficacy of early concurrent vs. sequential timing of thoracic radiotherapy (TRT) and platinum/etoposide chemotherapy, 48 patients with limited-stage small cell lung cancer treated with either early-concurrent (29 patients) or sequential (19 patients) TRT and platinum/etoposide chemotherapy were evaluated. Disease-specific prognostic variables and the role of prophylactic cranial irradiation (PCI) were also analyzed. Thirty-four patients (71%) received TRT to a dose of 45 Gy in 25 fractions (range, 30-55 Gy). Most patients (75%) received 4-6 cycles of chemotherapy. Twenty-one of 27 patients achieving a complete response after completion of TRT and chemotherapy received PCI. Median follow-up was 29.3 months (range, 12-98 months). Variables of potential prognostic significance were evaluated by both univariate and multivariate analysis. The absolute and relapse-free survival rates for all patients were 42% and 35% at 2 years and 32% and 31% at 5 years, respectively. Thirty-six sites of failure were observed in 27 patients. Thoracic recurrence occurred in nine patients, and the central nervous system (CNS) was the most common site of distant failure (15 patients). Multivariate analysis demonstrated that (a) early concurrent TRT and chemotherapy vs. chemotherapy followed by sequential TRT and (b) disease volume [less than or greater than one-third of the thoracic width] were significantly predictive for survival (P=0.036 and P=0.05, respectively). Rates of control of thoracic disease were 79% for patients with a disease volume less than one-third of the thoracic width vs. 36% for disease volumes greater than one-third of the thoracic width (P=0.0009). Early concurrent TRT and chemotherapy resulted in a significantly lower incidence of distant metastasis (26% for concurrent vs. 63% for sequential; P=0.008). In patients who received PCI, the CNS control rate was 86% vs. 56% in patients not treated with PCI. Our findings suggest that (a) treatment with early concurrent TRT and platinum/etoposide chemotherapy may improve survival when compared with sequential treatment and (b) PCI for patients with complete systemic responses is effective in preventing CNS recurrence. We also conclude that thoracic disease volume is a significant prognostic factor for both local control and overall survival.

A phase III trial of high-dose cytosine arabinoside with or without etoposide in relapsed and refractory acute myelogenous leukemia. A Southeastern Cancer Study Group trial.

A phase III clinical trial was developed to test whether the addition of etoposide to a high-dose cytosine arabinoside regimen would improve the remission rate, duration of remission, and survival in relapsed and refractory patients with acute myelogenous leukemia. One hundred and thirty-one patients stratified by age, performance status, percentage of marrow blasts, platelet count, bilirubin and presence or absence of clinical infection, refractory or relapsed (+/- 9 months) were randomized to receive high-dose cytosine arabinoside, 3 g/m2 every 12 h for 6 days with or without three doses of etoposide, 100 mg/m2 days 7-9. Of 67 patients randomized to cytosine arabinoside alone, 31% obtained a complete remission with a median remission duration of 11.9 months. Of 66 patients randomized to the combination regimen, 38% obtained a complete remission with a median duration of 25 months. None of these differences were statistically significant. Significantly (p = 0.036) longer survival was seen in patients on the combination regimen under the age of 50. There was no difference in overall survival. Six and 8%, respectively, of patients were free of disease at 5 years. The addition of etoposide to a high-dose cytosine arabinoside regimen had at best a marginal effect at the expense of some increase in toxicity.

New uses for old vitamins. The treatment of myelodysplastic disorders.

The treatment of myelodysplastic disorders with vitamins A and D or derivatives and nutrients has been less than satisfactory. Combinations of vitamin D3 and 13-CRA with or without cytosine arabinoside appear to offer no advantage over any of the single agents alone. Until other vitamin D derivatives are developed that are effective but do not cause hypercalcemia, vitamin D3 cannot be recommended for the treatment of MDS. 13-CRA has been shown to be effective in some patients with MDS; however, it cannot be recommended as standard therapy because of the conflicting data cited above. Further clinical trials with 13-CRA perhaps in combination with vitamin E or colony-stimulating factors are clearly indicated for this disease for which we have no effective therapy.

High-grade B-cell lymphoma presenting as polyserosal disease. Diagnosis by flow cytometry.

Two patients presenting with anasarca were found to have aggressive B-cell lymphoma. No bulky disease was detected. The diagnosis was rapidly established by the flow cytometric analysis of cell surface immunophenotype and cell cycle fractions of pleural or peritoneal cells. Such presentation of lymphoma is unusual and previously undescribed, and it may have a significant negative prognostic impact. The authors' observations indicate that lymphoma be included in the differential diagnosis of anasarca and that flow cytometry can be useful for a fast confirmation of the diagnosis.

Diagnostic and therapeutic utility of monoclonal antibodies in urologic oncology.

Remarkable advances in the treatment of urologic malignancies have recently been made. Monoclonal antibodies selective for a variety of normal and malignant urologic tissues have been useful in defining normal antigens and tumor-associated antigens and have potential as diagnostic and immunotherapeutic agents. In renal cancer, monoclonal antibodies can define serum markers, radiolabel tumor xenografts, and assist in specific tissue diagnosis. Additionally, there is potential for these antibodies either alone or as conjugates to localize and kill tumors. Monoclonal antibodies to bladder cancer associated antigens are able to demonstrate differential antigen expression on superficial versus invasive tumors, to refine urinary cytologic diagnosis of bladder cancer, and to predict invasive recurrence of superficial cancer. Monoclonal antibodies have localized bladder tumor xenografts and can inhibit tumor growth when conjugated to radioisotopes or toxins. In prostate cancer monoclonal antibodies to prostate antigens are not usually tumor specific. Monoclonal antibodies to prostate antigen (PA) and prostatic acid phosphatase (PAP) are able to localize prostate cancer metastases. Chemotherapy-conjugated anti-PAP monoclonal antibodies have demonstrable inhibition on human prostate cancer xenografted tumor growth. Monoclonal antibodies have defined normal and tumor-associated antigens in urologic cancers and are expected to be useful in immunodiagnosis and cancer therapy in the near future.

Comparative evaluation of enalapril and hydrochlorothiazide in elderly patients with mild to moderate hypertension.

Initial treatment of elderly hypertensive patients with an angiotensin-converting enzyme inhibitor is currently discouraged due to such patients' typical low-renin profile. To validate this principle, we studied 38 elderly males (aged greater than or equal to 65 years) with mild to moderate hypertension, comparing hemodynamic responses to and subjective impressions of enalapril or hydrochlorothiazide (HCTZ). After gradual withdrawal of existing antihypertensive therapy and a four-week, single-blind placebo period, each patient was randomized in a double-blind fashion to receive either enalapril 10-20 mg/d or HCTZ 12.5-25 mg/d for two to four weeks. Combination therapy with both agents was employed if either alone failed to reduce seated diastolic BP to less than or equal to 90 mm Hg. Equivalent proportions of patients receiving enalapril or HCTZ (8 of 19 and 10 of 19, respectively; p = ns) responded with significant reductions in systolic and diastolic BP in seated and standing positions. Combination therapy was most effective in patients receiving HCTZ prior to enalapril. In patients receiving enalapril before HCTZ, BP changes were minimal. No adverse effects were observed in the enalapril group but occurred in an equivalent fraction of patients in the other groups (4 of 10 HCTZ alone, 6 of 20 enalapril + HCTZ; p = ns). We conclude that enalapril may be considered a reasonable monotherapeutic antihypertensive agent in some elderly patients. Combination with HCTZ is beneficial in patients who fail to respond adequately to HCTZ alone.

Arteriovenous malformation of the mandible: report of case.

Arteriovenous malformations are rare, but, considering the life-threatening consequences of these lesions, they must constantly be considered in a differential diagnosis. The management of this patient from the initial symptoms emphasizes the need for a methodical approach to oral diagnosis using the fundamental techniques of inspection, auscultation, and palpation, as well as the more recent techniques of laboratory and radiographic evaluation.

Antibody-dependent cell-mediated cytotoxicity of cryopreserved human monocytes.

Human peripheral blood monocytes (PBM) modulate and participate in a variety of host defences. Cryopreservation of PBM has facilitated studies of their function. Peripheral blood samples cleared of red cells and granulocytes by centrifugation over Ficoll-Hypaque were cryopreserved at 1 degree C/min in 10% Me2SO and stored at -150 degrees C. Cryopreserved cells were thawed rapidly, diluted at a constant rate over 10 min with 9 vol of media, and washed twice prior to study. Antibody-dependent cell-mediated cytotoxicity (ADCC) activity against anti-D-coated Rh-positive erythrocytes of both fresh and cryopreserved PBM was tested and found to be equal (52.5 vs 51%). The myeloperoxidase positive, EA-rosette-positive population in cryopreserved cells was 39% compared with 17% for fresh cells (P less than 0.0001). This difference is due to preferential recovery of cryopreserved monocytes among mononuclear cells. The proportion of cells expressing Fc receptors among the myeloperoxidase-positive mononuclear cell population increased after freezing, suggesting an alteration in membrane structure induced by cryopreservation. It is concluded that PBM can be cryopreserved in Me2SO and that ADCC function is fully retained in the cryopreserved cells. This study along with a previous study (R.S. Weiner and S.J. Norman, J. Natl. Cancer Inst. 66, 255-260, 1981) demonstrate the feasibility of using cryopreserved human PBM for functional studies.

Purified human monocyte subsets as effector cells in antibody-dependent cellular cytotoxicity (ADCC).

Human peripheral blood monocytes are heterogeneous with respect to their size and function. Two monocyte subsets were isolated by countercurrent centrifugal elutriation and were studied with respect to their ability to effect antibody-dependent cellular cytotoxicity (ADCC) and for the presence of Fc receptors on their surface. Both monocyte subsets display Fc surface receptors and are effectors of ADCC against sensitized human erythrocyte target cells. The demonstration of ADCC by monocyte effectors is dependent on their concentration in the incubation mixture. Dilution of monocytes below 10% by unlabeled and unsensitized erythrocytes or lymphocytes significantly suppresses ADCC, presumably by steric inhibition of effector and target contact.