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Background: The activation of the clotting-fibrinolytic system in cancer patients is common and represents an unfavorable clinical sign. D-dimer (DD) is a sensitive marker of fibrinolysis., Methods: The current study comprised 826 new lung carcinoma patients seen consecutively in a single institution over a 10-year period (1992-2001). For each patient, 31 variables, including DD and survival duration, were available for analysis., Results: Only weak relationships between DD and the other variables were found. The DD variable correlated best with the level of lactate dehydrogenase, performance status, tissue polypeptide antigen, stage of disease, and the number of metastases (rho = 0.33, -0.25, 0.18, 0.18, and 0.15, respectively). The D-dimer distinguished patients with different prognoses. The median survival periods were 154 days (95% confidence interval [CI], 122-189 days) and 308 days (95% CI, 227-409 days; log rank statistic, 26.56; P < 0.01), respectively, for abnormally elevated and normal values. The difference was greater in patients with adenocarcinoma and in patients presenting with a less advanced disease, especially in patients with pathologic Stage Ia disease. The best multivariate survival model selected 10 significant covariates, including DD., Conclusions: The authors recommend measuring the plasma level of DD in all new lung carcinoma patients. This measurement may help to formulate individual prognoses and can be used to indicate adjuvant treatment for surgical patients., (Copyright 2003 American Cancer Society.)

Background: 99mTC-tetrofosmin recently has emerged as a new radiopharmaceutical for cancer visualization. In this study, the authors have investigated, for the first time in a comprehensive way, its ability to assess lung carcinoma dissemination and progression., Methods: A 99mTC-tetrofosmin scan was incorporated into the pretreatment and posttreatment diagnostic workup of all lung carcinoma patients seen in a second referral institution for a province of 500,000 inhabitants during the years 1998 and 1999. Sixty-one patients, strongly suspected of lung carcinoma were photon-scanned; 21 of them were rescanned after completion of their front-line treatment. Eleven patients eventually underwent surgery, and 3 others underwent mediastinoscopy. Both planar and single photoemission computed tomography thoracic views were obtained. Images for the whole body also were acquired., Results: All 57 patients whose lung carcinoma was pathologically confirmed showed accumulation of the radiotracer (100% sensitivity). However, three of the four nonmalignant lesions were also 99mTC-tetrofosmin positive. 99mTC-tetrofosmin scan was highly sensitive for the detection of the T0-T2 disease (97% sensitivity) and highly specific for the N0-N1 disease (83% specificity). In the 16 pathologically staged mediastina, sensitivity, specificity, and accuracy rates were 73%, 100%, and 81%, respectively. 99mTC-tetrofosmin scan correctly detected most skeleton (9 of 10) and brain (5 of 7) metastases. The treatment response evaluation made with 99mTC-tetrofosmin corresponded to the clinical estimate in almost half of the sample., Conclusions: This study shows that 99mTC-tetrofosmin scan is a relatively accurate method for lung carcinoma evaluation. The authors' preliminary data exclude, however, that noninvasive diagnostic efficiency might be substantially increased by a scintigraphy with 99mTC-tetrofosmin. More studies are needed for a better understanding of the real value of this technique., (Copyright 2002 American Cancer Society.)

Background: Cancer in the elderly is becoming a complex and frequent issue. At least 30% of lung carcinomas are expected to arise each year in elderly patients, who often have significant comorbidity. The most appropriate treatment for this large portion of cancer patients remains unknown. The purpose of this Phase II trial was to make a comprehensive evaluation of the activity, toxicity, and tolerability of single-agent vinorelbine in elderly and relatively poorly performing patients with inoperable nonsmall cell lung carcinoma (NSCLC)., Methods: Patients age 70 years or older were eligible to participate in this trial if they had a pathologic diagnosis, a performance status lower than 4 (Eastern Cooperative Oncology Group [ECOG] scale), and gave informed consent. Vinorelbine was given intravenously (i.v.) at a dose of 25 mg/m(2) every week until progression, persistent toxicity, or refusal., Results: Forty-six patients entered the study; their median age was 75 years (range, 70-83 years). Five patients never started on vinorelbine; 27 others had early treatment suspensions. The median number of weekly infusions was 5 (range, 0-28); the median dose intensity was 70% of projected. Toxicity was generally mild, mainly hematologic, and never life-threatening. ECOG performance status, body weight, and almost all the scores from the quality-of-life questionnaires remained constant during the first 6 weeks of treatment. Two patients obtained partial response, 10 patients had some tumor regression, and 26 had tumor stabilization. The estimated median time to progression was 19 weeks (quartile range, 11-23 weeks), and the median survival 34 weeks (quartile range, 16-63 weeks)., Conclusions: In our group of patients who had poor prognoses, vinorelbine was well tolerated, moderately active, and capable of ensuring relatively long survival. It may represent a valuable therapeutic option for the treatment of nonresectable NSCLC in elderly patients., (Copyright 2000 American Cancer Society.)

Background: Combination chemotherapy with conventional antiproliferative drugs is becoming the treatment of choice for patients with advanced non-small cell lung cancer (NSCLC), a good performance status, and no major clinical contraindications. Lonidamine (LND), a new drug with an innovative mechanism of action, might potentiate anticancer activity, without increasing toxicity., Methods: In a Phase II study, 46 patients with advanced NSCLC were assigned to receive chemotherapy with the methotrexate, doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH), cyclophosphamide, and lomustine (MACC) regimen, as originally described, plus LND, 150 mg orally, three times per day. Treatment was continued until progression of disease, occurrence of unacceptable toxic effects, or refusal by the patient (the median duration of MACC treatment was 6 weeks; 7 weeks for LND)., Results: For the whole group of patients, actual dose intensities (DI) of MACC and LND were 95% and 67% of those projected (median values), respectively. There was a negative correlation between duration of chemotherapy and the DI of MACC reached in each patient. On the contrary, there was no correlation between the duration of treatment with LND and its DI. The DI of LND and MACC were not correlated with each other. In all, seven objective responses (only partial responses) were observed. The overall median survival time was 42 weeks (confidence limits [CL], 20-52). The median survival length of patients receiving the full dose of LND (450 mg daily for at least 1 week) was 46 weeks (CL, 28-67), as compared with the median survival of 19 weeks (lower CL, 9 weeks) for the remaining patients; this difference was statistically significant (P < 0.05, Breslow test). Toxic effects were as expected with the use of MACC. They were mainly gastrointestinal (any grade of toxicity occurring in 64% of the patients), hematologic (anemia, 44%; leukopenia, 36%; thrombocytopenia, 8%), oral (25%), renal (14%), and cardiac (11%). There was only one treatment-related death, from myocardial infarction and neutropenic sepsis. Uncommon side effects, which were attributed to LND, were mild to moderate and reversible; they included myalgia (26%), asthenia (15%), testicle pain (11%), visual problems (7%), and gastric intolerance (7%)., Conclusions: MACC plus LND is a moderately active regimen in advanced NSCLC, with foreseeable and reversible toxic effects of low-medium grade. Potential enhancements of antitumor activity and possible host survival benefits may be expected by the addition of LND to MACC, but a Phase III study must be performed to identify them.

Background: Anticarcinoembryonic (CEA) monoclonal antibodies are able to react specifically with the antigen and have the potential for the detection of CEA-bearing tumors., Methods: The authors photoscanned with indium 111 (111In)-labeled F(ab')2 fragments of the murine CEA monoclonal antibody FO23C5 63 patients with a newly diagnosed and pathologically documented bronchogenic carcinoma. Planar dual views of the thorax, abdomen, and brain were acquired between the 24th and 144th hour after the radiotracer injection. Patients had a complete pretreatment workup, which included a routine multiorgan computed tomography (CT) scan, and the determination of the serum and tissue CEA concentration. All patients were followed up clinically and radiologically. Nineteen needle aspirations and biopsies, 23 surgical explorations, and 4 mediastinoscopic studies yielded 121 pathologically documented sites of reference., Results: Fifty-seven of 63 scans were positive for the primary tumor (sensitivity, 0.90). The uptake of the radiotracer correlated significantly with the intensity of tissue CEA expression (Spearman R [Rs], 0.25; P less than 0.05), but not with the serum CEA level or with the histotype. Overall, the sensitivity of the anti-CEA immunoscintigraphy (IS) for the N1, N2, N3, T3, T4, and M1 disease (1987 International Union Against Cancer [UICC] staging classification) was 0.67, 0.64, 0.62, 0.31, 0.29, and 0.86, respectively. Corresponding values of specificity were 0.67, 0.81, 0.90, 1, 1, and 0.93; accuracy values were 0.67, 0.71, 0.85, 0.71, 0.76, and 0.92. The authors limited the analysis to all of the pathologically documented sites and obtained slightly superior values but no meaningful differences. The stage derived from IS readings was correct in 33 patients. The same figure was obtained after an initial clinical workup, which included physical examination, laboratory routine tests, chest radiographs, bronchoscopy, and any diagnostic procedure indicated by those tests., Conclusions: Anti-CEA FO23C5-F(ab')2 fragments are not yet "magic bullets" for perfect diagnoses; however, their staging potential seems to be remarkable. Technical improvements, single-photo emission CT, and the use of such fragments in combination with other imaging techniques might enable researchers to further improve the current results.

Recommendations concerning the continuation of chemotherapy in nonresponding patients with non-small cell lung cancer (NSCLC) and stable disease after the first chemotherapy test are empirical and often conflicting. Between 1984 and 1987, 116 inoperable NSCLC patients were treated with methotrexate, doxorubicin, cyclophosphamide, and lomustine (MACC regimen). After two or three cycles of therapy, 74 patients were judged to have stable disease and assigned at random either to chemotherapy maintenance with the same regimen (38 subjects) or to chemotherapy discontinuation (36 subjects). The two study groups were comparable for all the major prognostic factors. Median time to progression was 26 weeks for the chemotherapy group compared to 24 weeks for the nonchemotherapy group (P = NS). Median survival was prolonged in the treatment arm (47 weeks) compared to nontreatment arm (30 weeks), which was statistically nonsignificant. A patient self-assessment of the quality of life revealed a significantly worse tolerance to therapy and a better physical condition in the chemotherapy group. Objective MACC toxicity was significant with two treatment-related deaths. This study failed to demonstrate sufficient therapeutic benefits to justify the increased cost and toxicity of continuing treatment in nonresponding NSCLC patients.

In 98 newly diagnosed patients with histologically proven bronchogenic carcinoma seen at Cuneo Hospital of Chest Diseases from July 1983 to December 1984, multiple biomarker assays were performed. Fiftynine cases had more than one carcinoembryonic antigen (CEA) and/or tissue polypeptide antigen (TPA) assay during the course of the disease, at 3- to 12-week intervals. A total of 209 CEA (91 pretreatment), 170 TPA (80 pretreatment), 62 human chorionic gonadotropin (HCG)-beta subunits and 60 lactate dehydrogenase (LDH) was assayed. In addition, serum samples were taken from 141 blood donors and their TPA values were used as a control. The percentages of elevated values were, respectively, 37%, 52%, 18%, and 25%. In 85% of the patients at least one biomarker was found to be higher than normal. Neither significant differences between mean biomarker levels in tumors of various histologic types nor positive intermarker correlations were found. The number of patients with elevated CEA, TPA, and LDH serum levels and their mean values increased significantly according to the disease extent. Among evaluated markers TPA showed the highest accordance to tumor burden. The raising of two markers was never associated with Stage I-II disease, except in one patient. Both CEA and TPA concentrations changed significantly during the course of the illness in relation to the clinical status assessment. Abnormal pretreatment levels of CEA, LDH, and particularly, TPA were independently and significantly associated with a poor outcome. Patients with abnormal levels of TPA and LDH and, to a lesser degree, TPA and beta-HCG had shorter survival as compared with patients with high TPA values, irrespective of the LDH and beta-HCG levels, although not significantly so.

One hundred six patients with histologically proven bronchogenic carcinoma were tested for carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), and carbohydrate antigenic determinant 19-9 (CA19-9). A total of 349 CEAs, 350 TPAs, and 317 CA19-9s were measured. In addition, sera were assayed from 57 patients with pulmonary benign diseases and their CEA, TPA, and CA19-9 levels were used as negative controls for specificity and accuracy. One hundred twenty healthy subjects provided our normal CA19-9 reference value. Sensitivity, specificity, and accuracy were obtained for CEA, TPA, and CA19-9, respectively. Significant intermarker correlations were found both at diagnosis and during follow-up, CEA and CA19-9 being the most closely related substances. The percentage of patients with elevated levels of TPA increased significantly according to tumor load. Individual values of TPA related significantly to the stage of disease. Concentrations of CEA, TPA, and CA19-9 varied significantly during the course of the illness in relation to treatment response; however, TPA showed the closest relationship to the clinical status assessments of the follow-up period. Abnormal pretreatment levels of TPA were significantly associated with a poor outcome. Biomarker combinations were clinically evaluated by calculating the mean of the percentage of the reference value for each combined marker. Using this method, any association of TPA with CEA and/or CA19-9 revealed neither a greater diagnostic accuracy nor a more reliable predictive capacity for the above clinical variables than TPA evaluated on its own. The authors believe that a single TPA assay should be added to the initial and subsequent clinical assessments of patients with bronchogenic carcinoma.