Peptide hormones as tumor markers in lung cancer patients.
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Clinical Laboratory Techniques↗
Biomedical subjects
S Krauss
Publications and source records attributed to S Krauss.
Combination chemotherapy in small cell lung carcinoma. A randomized study of two intensive regimens.
From April, 1979 to November, 1981, 293 patients with small cell lung carcinoma (SCLC) were entered on a randomized, controlled study comparing the two induction regimens of high-dose CAV (HD-CAV) (cyclophosphamide [CTX] 1200 mg/m2, doxorubicin [ADR] 70 mg/m2 and vincristine [VCR] 1 mg/m2 intravenously (IV) on days 1 and 21) versus, conventional-dose CAV + VP-16 (etoposide) (CAV-VP) (CTX 1000 mg/m2, ADR 40 mg/m2, VCR 1 mg/m2 IV on days 1 and 21 with VP-16 100 mg/m2 on days 1-3, and 21-23). Responding and stable patients were continued on conventional-dose CAV for 5 consolidation courses. Prophylactic brain irradiation delivered after the first consolidation course in responders was optional. Patients were included in the study if they had extensive disease (i.e., beyond one hemithorax), no prior chemotherapy, or radiotherapy and performance status of 50 or above. After 2 induction courses, 215 cases are evaluable. Of these, 76 of 106 (72%) patients treated with HD-CAV have responded (greater than 50% regression), including 13 complete responders (CRs) versus 80 of 108 (74%) patients on CAV-VP, including 15 CRs. Of the 130 evaluable patients who have completed consolidation (HD-CAV, 65; CAV-VP, 65), an additional 22 patients achieved CR (HD-CAV, 12; CAV-VP, 10) for an overall CR rate of 24%. Median duration of remission was 33.6 weeks for HD-CAV and 35.6 weeks for CAV-VP (P = 0.61). Median duration of complete response for HD-CAV was 33.8 weeks and for CAV-VP 36.7 weeks (P = 0.81). Survival curves were similar for the two regimens, with medians of 42.1 weeks for HD-CAV and 42.3 weeks for CAV-VP (P = 0.35). Survival correlated with performance status and quality of response. As anticipated, the major toxicity for both induction regimens was leukopenia. During induction, granulocyte nadirs of less than 500/mm3 occurred in 81% of patients on HD-CAV and 77% of patients on CAV-VP. Thus, dose intensification appears to produce high response rates and modest complete response rates in extensive SCLC, but it does not appear to improve materially survival compared to prior reports of conventional-dose therapy.
Adult↗
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.
Adenocarcinoma↗
Radioimmunoassay of fragment E-related neoantigen: validation studies and clinical application.
Measurement of fibrinogen-fibrin degradation products (FDP) levels in plasma may provide a direct index of plasmin action, and increased levels of FDP would indicate coagulopathy. We have established an E-neoantigen radioimmunoassay ( Eneo RIA) that can determine normal and pathological plasma levels of E-related FDP. The assay employs rabbit antiserum produced against fragment E derived from a plasmin digest of fibrinogen and subsequently absorbed with fibrinogen. The absorbed antiserum contains antibodies which are equally reactive with fibrinogen derived E (Fg-E) and fibrin derived E (Fb-E) but not with fibrinogen at 1 mg/ml. The Eneo RIA was validated by assay parallelism and by recovery experiments. Plasma Eneo immunoreactivities in 14 normals were 4-22 ng/ml (mean 12.7 ng/ml). Plasma Eneo levels in 23 of 24 patients with neoplastic and haematological diseases were elevated above normal (range 27-2027 ng/ml). Unusually high Eneo values were observed with three patients whose diseases were complicated by either disseminated intravascular coagulation (DIC) or deep vein thrombosis. After heparin therapy, the Eneo level of a patient with chronic DIC declined. A pathological plasma was eluted from a Sephadex G-200 column and Eneo immunoreactivity was determined on the eluates. The gel filtration pattern of Eneo indicates that E-related FDP is a family of plasmic fragments derived from crosslinked fibrin.
Anticoagulants↗
Oxidation and dehalogenation of 4-chlorophenylacetate by a two-component enzyme system from Pseudomonas sp. strain CBS3.
In cell-free extracts from Pseudomonas sp. strain CBS3 the conversion of 4-chlorophenylacetate to 3,4-dihydroxyphenylacetate was demonstrated. By Sephacryl S-200 chromatography two protein fractions, A and B, were obtained which both were essential for enzyme activity. Fe2+ and NADH were cofactors of the reaction. NADPH also activated the enzyme, but less effectively than NADH. FAD had no influence on enzyme activity. 4-Hydroxyphenylacetate, 4-chloro-3-hydroxyphenylacetate, and 3-chloro-4-hydroxyphenylacetate were poor substrates for the enzyme, suggesting that these substances are not intermediates of the reaction. We therefore suggest that the reaction proceeds via a dioxygenated intermediate.
Cations, Divalent↗
Treatment of hypertension in mild asthmatic patients with atenolol.
Fourteen patients with uncomplicated essential hypertension and mild asthma were treated with Atenolol 50-125 mg/day for up to 8 months. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), rate pressure index (RPI), stress testing time (STT) and peak expiratory flow rate (PEFR) were measured before, during and after stress testing (ST) before and during treatment. Atenolol significantly lowered HR, SBP, DBP and RPI. It prolonged STT and had no effect on PEFR. Furthermore, Atenolol did not worsen the patient's asthma except for one patient. The drug did not interfere with the bronchodilatation effect of salbutamol. Atenolol can be used cautiously to treat hypertension in asthmatic patients under certain conditions.
Adult↗
Randomized trial of radiotherapy to the thorax in limited small-cell carcinoma of the lung treated with multiagent chemotherapy and elective brain irradiation: a preliminary report.
A total of 304 patients with limited small-cell carcinoma of the lung were treated with a combination of cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, Ohio), and vincristine (CAV) and elective brain irradiation (3,600 rad TD in 14 fractions). The patients were randomized to either receive or not receive thoracic irradiation (4,000 rad TD, split course). Of the 304 patients, 291 were eligible for the study. Two hundred eighteen (75%) were completely evaluable. In each group, 81% of the patients had a Karnofsky index of 80% or higher and 14% had supraclavicular or scalene lymph nodes. Patients treated with CAV and no thoracic irradiation had a complete response (CR) of 48%, in contrast to 63% for those receiving chest irradiation (P = .05). In the first group, the complete and partial response rate was 70%; in the second, 80%. The median survival for the eligible patients treated with CAV and brain radiation therapy was 49 weeks; for those treated with the same regimen plus thoracic irradiation, the median survival was 60 weeks. The actuarial two-year tumor-free survival is 19% in the first group and 28% in the second group. The median survival for the responders in the CAV plus brain irradiation group was 57 weeks and for those receiving thoracic irradiation, 78 weeks (P = .12). Thoracic failure was 52% in patients not treated with thoracic radiation therapy v 36% in those receiving it (P = .06). The distant metastases incidence was 23% in patients not treated with thoracic radiation and 35% in patients treated with thoracic radiation. Hematologic toxicity was comparable in both groups; 30% of the patients had moderate to severe granulocytopenia and 6%, low homoglobin. Two toxicity-related deaths occurred (one in each group). Moderate gastrointestinal toxicity was noted in 41% and severe in 16% of the patients receiving CAV and brain irradiation without thoracic radiotherapy v 44% and 20% in those irradiated in the thorax. Disease-free survival is enhanced in the patients receiving thoracic irradiation. More effective chemotherapy is critically needed to significantly improve overall survival. These preliminary results suggest that thoracic irradiation should be a primary component in the therapy of these patients, although this combined therapy is moderately toxic.(ABSTRACT TRUNCATED AT 400 WORDS)
Antineoplastic Combined Chemotherapy Protocols↗
Randomized phase III comparison of three doxorubicin-based chemotherapy regimens in advanced non-small cell lung cancer: a Southeastern Cancer Study Group trial.
From 1978 to 1981, 537 patients with advanced non-small cell lung cancer were randomly assigned to three regimens containing cyclophosphamide and doxorubicin alone or in combination with methotrexate or cisplatin. Eligible patients had measurable disease and had no prior exposure to chemotherapy. Of the patients entered on the study, 505 were evaluable for toxicity and 488 were evaluable for response. The overall response rate (complete and partial responses) was only 9%. Response rates did not vary significantly with respect to treatment regimen, histologic subtypes, extent of disease, or performance status. There was no survival advantage for any regimen. The major toxicities were myelosuppression and nausea-vomiting. These doxorubicin-based chemotherapy regimens produced disappointing results in patients with advanced non-small cell lung cancer. A search for more active antitumor agents in lung cancer is necessary.
Adult↗
Randomized trial of cyclophosphamide, doxorubicin, and 5-fluorouracil alone or alternating with a "cycle active" non-cross-resistant combination in women with visceral metastatic breast cancer: a Southeastern Cancer Study Group project.
Patients with visceral patterns of metastatic breast cancer were stratified according to dominant metastatic site and performance status and then randomized to therapy with cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) or CAF alternating with a "cell-cycle active" regimen including cytosine arabinoside, methotrexate with leucovorin rescue, and oncovin ( CAMELEON ). One hundred eighty-seven patients were randomized; response rate for CAF was 44% and for CAF + CAMELEON , 40%. Durations of disease control and survival were not significantly different. Toxicity of CAF was as anticipated with predominant granulocytopenia, vomiting, and alopecia. Toxicity of CAMELEON was less severe than that of CAF, and CAF toxicity was not worsened by preceding courses of CAMELEON ; however, the CAF- CAMELEON regimen was cumbersome and complex leading to both physician and patient noncompliance. Contrary to the preliminary results of a pilot study, and preliminary reports of the present trial suggesting benefit for the CAF- CAMELEON regimen the present randomized trial does not confirm any significant benefit of CAF- CAMELEON over CAF alone in patients with visceral metastatic breast cancer although this conclusion must be viewed in light of the high inevaluability rate due to patient and physician noncompliance.
Agranulocytosis↗
A comparison of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) and cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone (CMFVP) in patients with advanced breast cancer.
The Southeastern Cancer Study Group, in a prospectively randomized study involving patients with advanced breast cancer, has compared a low dose intermittently administered five-drug regimen including cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone (CMFVP) with an aggressively administered three-drug regimen including cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF). CAF induced more responses and more complete responses and a longer duration of disease control. However, only a marginal difference was demonstrated in overall survival between the two regimens (p = less than 0.10). Patients with a good risk pattern of metastases, i.e. those with nodular local chest wall recurrence, nodular pulmonary metastases, or bone-only metastases were more likely to achieve a response and survive longer than those with a poor risk pattern, i.e. lymphangitic pulmonary metastases, pleural effusion with chest wall ulceration, or widespread metastases, including hepatic. All of the differences between the two regimens were noted in the good risk pattern groups. CAF provided no additional benefit to patients presenting with poor risk patterns of metastases. Adriamycin-containing combinations may achieve a greater degree of tumor cell kill in certain subsets of patients with advanced breast cancer, but this provides only a marginal increase in survival.
Antineoplastic Agents↗
2-Haloacid dehalogenase from a 4-chlorobenzoate-degrading Pseudomonas spec. CBS 3.
Pseudomonas spec. CBS 3 contains a 2-haloacid dehalogenase induced by chloroacetate. The enzyme was purified about 25-fold to electrophoretic homogeneity by ammonium sulfate fractionation, hydroxyapatite, DEAE-cellulose and gel filtration. The relative molecular masses, as determined by Sephadex G-75 gel filtration and dodecyl sulfate polyacrylamide gel electrophoresis, were 41 000 and 28 000, respectively. The enzyme dehalogenated all monohaloacetates except fluoroacetate. Low activities were found against dichloroacetate and 2,2-dichloropropionate. The enzyme was inactive against trichloroacetate and 3-chloropropionate, it catalysed the stereospecific dehalogenation of L-2-chloropropionate to D-lactate, the rate of dehalogenation being about 20% of the rate of chloroacetate dechlorination. The enzyme activity was not affected by chelating agents and thiol reagents.
Acetates↗
Staging and prognostic factors in small cell carcinoma of the lung.
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Biopsy, Needle↗
Hairy cell leukemia--cell characteristics and morphology.
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Humans↗
Renal disease after mitomycin C therapy.
Fourteen patients with adenocarcinoma of the gastrointestinal tract and pancreas treated with mitomycin C(MMC) and 5-fluorouracil (5-FU) had renal impairment 6-11 months from the beginning of MMC therapy. Two clinical entities were recognized: an acute fulminating renal failure that was rapidly fatal and a chronic slowly progressive renal impairment. The first entity showed a microangiopathic hemolytic profile with anemia, thrombocytopenia, and erythrocyte fragmentation. Light microscopy and electron microscopy examination of the kidney revealed a primary vascular disease with musculomucoid intimal hyperplasia of arteries and rare fibrin thrombi in arterioles. Interstitial fibrosis, tubular atrophy, and widespread glomerular necrosis were also seen. The disease was ultimately fatal within three to four weeks. The second entity showed a chronic course of renal failure with similar pathologic findings but less pronounced, and a microangiopathic hemolysis was absent. The course in the second group was ultimately fatal between three to eight months.
Acute Kidney Injury↗
Thoracic and elective brain irradiation with concomitant or delayed multiagent chemotherapy in the treatment of localized small cell carcinoma of the lung: a randomized prospective study by the Southeastern Cancer Study Group.
A prospective randomized study was carried out to compare the effectiveness of concomitant or delayed multiagent chemotherapy combined with irradiation to the primary tumor and regional lymph nodes and to the brain in a group of 70 patients with histologically proven small cell undifferentiated carcinoma of the lung. Complete and partial response in both groups was comparable, and the overall survival was comparable. However, relapse-free survival was significantly higher in patients receiving concomitant chemotherapy and irradiation in comparison with the radiotherapy alone group. Disease-free survival was higher in the concomitant chemotherapy-radiotherapy patients, although survival was not significantly modified, probably because of suboptimal chemotherapy. The initial intrathoracic failure rate was 40.7% inthe concomitant chemotherapy-irradiation group, compared with 53.8% in the radiotherapy-alone patients. None of the patients receiving delayed chemotherapy following the radiotherapy recurrence showed significant tumor response to the drugs. The incidence of distant metastasis was slightly lower in the chemotherapy groups. Brain metastases were noted in 7% of the patients in both groups. Increased intrathoracic recurrences were noted in patients with lower doses of irradiation. Nine of 13 patients treated with inadequate portals developed intrathoracic recurrences in comparison to 13 of 40 treated with adequate irradiation fields. The study emphasizes the need for intensive chemotherapy and adequate radiation therapy to improve survival of patients with small cell undifferentiated carcinoma of the lung. Additional trials are necessary to assess the role of each modality in the management of these patients.
Aged↗
A study of immunoreactive calcitonin (CT), adrenocorticotropic hormone (ACTH) and carcinoembryonic antigen (CEA) in lung cancer and other malignancies.
Levels of immunoreactive ACTH and calcitonin (CT), as well as CEA, were determined serially in 144 patients with lung cancer and in 62 patients with metastatic carcinoma to the lungs. Patients with neoplasms not involving the lungs, with nonmalignant blood dyscrasias, and with chronic obstructive pulmonary disease were studied, as were normal control subjects. In 55-91% of lung cancer patients, elevated values of CT were detected; the frequency of elevation varied with cell type and stage. The highest values (mean 1346 +/- 2534 pg/ml) were found in patients with extensive small cell lung carcinoma (SCLC) and were significantly greater than the values for patients with SCLC confined to one hemithorax (196 +/- 287.7 pg/ml, P less than 0.005). ACTH levels were elevated less frequently (24-46%) and were highest (192 +/- 200.9 pg/ml) in patients with extensive small cell carcinoma, although Cushing's syndrome was observed only once. Agreement between all three tumor markers was seen in 25-50% of lung cancer patients; the percentage depended on cell type. Calcitonin levels paralleled changes in the clinical status and tumor burden in 89% of SCLC patients, while ACTH levels reflected the clinical course in 67%. In six patients with small cell carcinoma in remission, rising levels of CT, ACTH, and CEA preceded clinical evidence of relapse, in oe patient, by as long as five months. Among 129 patients with conditions other than primary lung cancer, CT levels were highest (232 +/- 328 pg/ml) in those with cancer metastatic to the lungs and/or pleura; there was no; association between CT levels and the presence of bone metastases.
Adrenocorticotropic Hormone↗
Inhibition of leukocyte adherence by a 3 M potassium chloride extracts of human malignant melanoma.
The tube leukocyte adherence inhibition (LAI) assay was performed using 3 M KCl extracts of malignant melanoma materials and leukocytes taken from 24 malignant melanoma patients. Of these patients, 21 participated in sequential studies which employed a minimum of 3 time points. An increasing non-adherence index (NAI) was found in 5 of 6 patients who exhibited a favorable disease course. In 5 of 6 patients with an unfavorable disease course, NAI values decreased. In 8 of 9 patients with stable disease, the NAI also was stable. These results indicate that the trend of sequential LAI studies reflects the clinical course of malignant melanoma patients.
Female↗
Tumor detection with 1-aminocyclopentane and 1-aminocyclobutane C-11-carboxylic acid using positron emission computerized tomography.
Eight patients with proven or suspected neoplastic lesions were examined with 1-aminocyclobutane C-11-carboxylic acid and 1-aminocyclopentane C-11-carboxylic acid using positron emission computed tomography. The results of this comparative study have shown that both of these unnatural amino acids have a high affinity for malignant tumors. The potential of nonmetabolizable C-11-labeled amino acids as noninvasive indicators of metabolic tumor activity is demonstrated and discussed.
Amino Acids↗