Prognostic factors of small cell lung cancer.
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Biomarkers↗
Biomedical subjects
Domenico Ferrigno
Publications and source records attributed to Domenico Ferrigno.
Second-line weekly paclitaxel in patients with inoperable non-small cell lung cancer who fail combination chemotherapy with cisplatin.
UNLABELLED: This phase II study was designed to assess single-agent paclitaxel (Taxol), as second-line chemotherapy. ELIGIBILITY CRITERIA: pathological diagnosis of inoperable non-small cell lung cancer (NSCLC) relapsing or refractory to standard front-line platinum (P)-based chemotherapy, performance status < or = 3, normal lab tests, informed consent. Ineligibility criteria: history of second or third cancer (unless surgically cured), mental instability or impairment, pre-existing moderate/severe peripheral neuropathy, previous chemotherapy non-including cisplatin, and previous second-line chemotherapy. Paclitaxel was given by intravenous infusion at a dose of 100 mg/m2 every week, until completion of the treatment plan of 21 weeks, disease progression, persistent toxicity, or patient refusal. Thirty-eight patients (32 males) entered the study; median age was 63 years (range 44-74); cell types were: adenocarcinoma (20), squamous (14), large cell (4). Previous chemotherapies: P and vinorelbine (31 patients) and P, mitomycin C and vinblastine (7 subjects), followed by 21 objective responses. Two patients had one course of paclitaxel; six other patients had early treatment suspensions. The median number of weekly infusions was 12 (range 1-21); median dose-intensity was 75% of projected. Toxicity was generally mild, mainly neurological and never life threatening (only 2 grade 4 toxicity out of 468 pre-chemotherapy evaluations). Six patients obtained a partial response; 7 others showed some tumor regression, 3 had tumor stabilization, and 13 disease progression. From the start of paclitaxel, the estimated median time to progression was 20 weeks, the median survival 58 weeks. Second-line treatment with single-agent paclitaxel is well-tolerated, active, and associated to long survivals.
Adult↗
Front-line weekly chemotherapy with gemcitabine for unfit patients with non-small cell lung cancer (NSCLC).
Chemotherapy (CT) for elderly patients is becoming a standard, since the first demonstration by Gridelli and co-workers that chemotherapy (in their case Vinorelbine (VNB), single agent) is capable to produce significant survival benefits. Much less is known concerning the use of CT for unfit patients. The purpose of this phase II trial was to perform a comprehensive evaluation of activity, toxicity, and tolerability of single-agent Gemcitabine (GEM) (Gemzar) as a first-line chemotherapy for unfit patients with inoperable or recurrent non-small cell lung cancer. Patients were eligible if they had a pathological diagnosis and no previous chemotherapy; they should be younger than 76, with a performance status (ECOG-PS) equal to three; informed consent was also required. Gemcitabine was given by intravenous infusion at a weekly dose of 1250 mg/m2, 3 weeks per month, every 28 days. Treatment was given until progression, persistent toxicity, or refusal. Forty-five patients (39 males) entered the study; median age was 73 years (range 45-75); cell types were: adenocarcinoma (21), squamous (18), large cell (6). Previous surgical treatments included three lobectomies and one pneumectomy. Because of rapid clinical deterioration or consent withdrawal, six patients, registered for study, never started their treatment; other six had early chemotherapy suspension. These patients were included in the analysis, on an "intent-to-treatment" basis. The median number of chemotherapy cycles was nine (range 0-15); median dose-intensity was 75% of projected. Toxicity was mild, mainly hematological and never life threatening (only 1 grade 4 toxicity out of 325 pre-chemotherapy evaluations). Four patients obtained a partial response (9%, C.I. 1-17%) and other six patients had some tumor regression (13%, C.I. 3-23%). The estimated median time to progression was 17 weeks (quartile range: 9-24), with a median survival of 35 weeks (quartile rage: 20-51). We have found that single-agent gemcitabine represent a sufficiently safe therapeutic option in unfit patients with inoperable non-small cell carcinoma (NSCLC).
Aged↗
Prognostic factors.
The best predictive models of today can predict no more than 50% of the natural variability of the disease, despite the sophisticated mathematic analyses and the dozens of variables assessed. Clearly, a universe of still unknown prognostic factors remains to be discovered. Analogous to infinity being immeasurable, the fate of the individual patient will never be calculated mathematically. As the discovery of new prognostic factors continues, however, the prediction of the outcome of patients becomes more reliable. Although some prognostic factors (eg, tumor neoangiogenesis and quality of life) are already supported by a large body of evidence, recent research has introduced new groups of prognostic factors (eg, molecular genetic markers and the subclinical activation of coagulation fibrinolysis). Other intriguing factors (eg, a state of mental depression) might also be recognized as important in the near future. A new small portion of the universe has been explored.
Biomarkers, Tumor↗
Familial and personal history of cancer in bronchogenic carcinoma--frequency and clinical implications.
A familial and personal history of cancer might be associated with a more aggressive cancerous disease. This study was carried out on 1277 consecutive lung cancer (LC) patients, seen from January 1989 to October 2002 in a single institution. A set of 31 clinical laboratory, radiological and pathological variables was recorded prospectively for all patients. In addition, both the number of first-degree blood-relatives with cancer (lung and non-lung cancers) and the personal history of previously cured cancers were noted. There were 368 patients (28.8% of the sample) who had one first-degree relative with cancer (112, 8.7% of the sample with LC), 100 (7.8%) had two first-degree relatives (six with LC) and 31 (2.4%) had three or more relatives affected (four with LC). In total, 1142 patients (89.4% of the sample) have never been treated for another cancer; the remaining 135 patients (10.6%) had already been diagnosed with a variety of tumours, including head and neck cancer (36 patients, 2.8%), bladder cancer (33 patients, 2.6%), colorectal cancer (24 patients, 1.9%), breast cancer (seven patients, 0.6%), melanoma (five patients, 0.4%), skin (five patients, 0.4%) and prostate cancer (five patients, 0.4%). Among the variables studied, none was found to be significantly associated with a personal and/or family history of cancer. Survival expectancy was similar among patients with or without a familial or personal history of cancer. A familial and a personal history of cancer are common features in LC, but are not of clinical significance.
Adult↗
Plasma levels of D-dimer in lung carcinoma: clinical and prognostic significance.
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.
Adult↗
Identifying patients at risk of early postoperative recurrence of lung cancer: a new use of the old CEA test.
BACKGROUND: In the current study, we report the carcinoembryonic antigen (CEA) capability to predict early tumor relapses after a pulmonary resection for nonsmall cell lung cancer (NSCLC). METHODS: We studied 118 consecutive NSCLC patients who were clinically judged operable and were eventually operated upon. Anthropometric, clinical, and CEA data along with the results of both preoperative and postoperative stage classifications were recorded. All patients were followed up for at least 1 year after surgery and the time to the first clinical recurrence recorded. Receiver-operating characteristic (ROC) curves and diagnostic formulas were used for data analysis. RESULTS: In this series the CEA test was among the most accurate methods to predict an early postoperative recurrence (ROC area: 0.72, 95% confidence interval [CI]: 0.60 to 0.85, p = 0.001; accuracy rate for CEA at the threshold of 10 ng/mL: 83%, CI: 76% to 90%). Also predictive was the postoperative pathologic stage of disease (ROC area: 0.68, CI: 0.56 to 0.80, p = 0.007). In tumors pathologically classified in stage Ia to IIb, a preoperative CEA level higher than 10 ng/mL was associated with a 67% probability of tumor relapse. In the same stages of disease, a CEA level less than 10 ng/mL increased the baseline probability of no recurrence from 80% to 88%. CONCLUSIONS: In operable patients with NSCLC the frequency of abnormal serum concentrations of CEA is low (17% in our series). However, it is important to identify such a small group of high-risk patients as many of them (in our study, 55% and 70% of those with a CEA value in excess of, respectively, 5 and 10 ng/mL) will develop an early postoperative recurrence. Such patients should be investigated preoperatively by mediastinoscopy or positron emission tomography in even in the absence of suspicious symptoms and signs. Then after an apparently successful operation, they should be carefully followed up. These patients could represent a suitable target for neoadjuvant clinical trials of selected high-risk groups.
Adult↗
Neuron-specific enolase is an effective tumour marker in non-small cell lung cancer (NSCLC).
BACKGROUND: Neuron-specific enolase (NSE) is a well known marker of small cell lung cancer. The present study was designed to assess the clinical value of NSE in non-small cell lung cancer (NSCLC), as compared to that of carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA). METHODS: The study comprised 448 new consecutive NSCLC patients seen from 1996 to 2001. A set of 30 anthropometric, clinical, physical, laboratory, radiological, and pathological variables was prospectively recorded for all patients. Patients were carefully followed-up, and their subsequent clinical course recorded. RESULTS: Increased values of NSE were present in 32% of the patients. Bivariate analyses showed that NSE, TPA and CEA were significantly correlated with each other, lactate dehydrogenase, tumour diameter, and disease extent. Univariate analyses showed that patients with elevated concentration of both NSE and TPA had significantly shorter survivals than patients with low values (30 [95% CI: 25-35] vs. 61 weeks [46-76], and 30 [CI: 24-36] vs. 59 weeks [40-79], respectively, P=0.0000). The Cox proportional hazards model including all the 22 variables significant in univariate analysis selected, in decreasing order of significance, the following variables: (1) N factor; (2) main treatment; (3) ECOG PS; (4) CNS metastasis; (5) age; (6) tumour cavitation; (7) NSE; (8) T factor; and (9) adrenal gland metastasis. CONCLUSIONS: This data indicates that serum assay of NSE is a useful marker also in NSCLC and a significant predictor of survival, independently of the other prognostic factors.
Adult↗
Clinical equivalence of two cytokeratin markers in mon-small cell lung cancer: a study of tissue polypeptide antigen and cytokeratin 19 fragments.
STUDY OBJECTIVES: We have longstanding experience with tissue polypeptide antigen (TPA), a tumor marker of the cytokeratin (CK) family. In the mid-1990s, a new CK marker, CK 19 fragments (CYFRA 21-1), became popular and widely accepted. This is the first study specifically designed to compare the two markers. DESIGN: Analysis of a single institution database over a 3-year period (ie, 1998 to 2000). SETTING: Community-based hospital and second referral level institution for a province of 500,000 people. PATIENTS: The study included 180 new consecutive patients (143 men) with pathologically documented non-small cell lung cancer (NSCLC), who were observed during and after treatment, and eventually were assessed for status. INTERVENTIONS: Anthropometric, clinical, and laboratory data, including TPA and CYFRA 21-1 serum levels, were recorded prospectively. Standard nonparametric tests, Kaplan-Meyer survival analyses, Cox proportional hazards models, receiver-operating characteristic (ROC) curves, and estimates were used for statistical analysis. MEASUREMENTS AND RESULTS: A total of 1,299 twin TPA and CYFRA 21-1 serum assays (180 performed at diagnosis and 1,119 performed during or after treatment) were obtained. Intermarker correlation tests revealed incredibly high Spearman rho indexes, ranging from 0.935 at diagnosis to 0.813 to 0.921 at the different follow-up times. The substantial equivalence of the two tests explained all the other results, as follows: their similar profile of correlation with the other variables (objective treatment response: TPA rho, 0.456; CYFRA 21-1 rho, 0.463; follow-up performance status: rho range, 0.424 to 0.435); their superimposable capability to predict important clinical situations (eg, recognizing a metastatic disease at diagnosis with areas under the ROC curve of 0.742 and 0.706, respectively); their nearly identical prognostic significance (the D statistic of the goodness-of-fit of a multivariate survival model: TPA, 851.0; CYFRA 21-1, 851.6). CONCLUSIONS: In most of their traditional clinical applications the two serum tests are equivalent because of their virtual identity. We strongly recommend using a CK test in the evaluation of each NSCLC patient. The choice between TPA and CYFRA 21-1 can be based on nonclinical factors, such as the laboratory experience or preference, and the cost of the two kits.
Adult↗
99mTC-tetrofosmin scintigraphy in lung carcinoma staging and follow-up evaluations.
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.
Adult↗
Cisplatin and vinorelbine remains a valid option for the front-line chemotherapy treatment of NSCLC.
BACKGROUND: This study was designed to confirm the activity of the cisplatin/vinorelbine (C/V) combination in non-small cell lung carcinoma (NSCLC). PATIENTS AND METHODS: Treatment consisted of vinorelbine, i.v. slow infusion of 30 mg/m2 every week, and cisplatin, 120 mg/m2 on days 1 and 29 and then every 6 weeks. Treatment was continued until completion of the 22-week treatment plan, disease progression, persistent toxicity, or patient refusal. RESULTS: Seventy-five patients entered the study. The median age was 62 years; major cell types were adeno- (38), squamous (26) and large cell carcinomas (7). Nineteen patients received a suboptimal treatment with less than 6 courses of vinorelbine. The median courses of C/V were 3 (range 0-4) and 15 (range 0-22), respectively. For both drugs, the median dose-intensity was 75% of projected. Toxicity was generally acceptable, mainly hematological and never life-threatening. Thirty-five patients responded, with 8 complete responses, for an overall response rate of 46.7%. The estimated median time to progression was 28 weeks (quartile range: 13-46); the median survival 60 weeks (quartile rage: 17-108). CONCLUSION: The C/V combination is fairly well tolerated, decidedly active and associated with prolonged survivals.
Adult↗
Weekly chemotherapy with cisplatin and paclitaxel in inoperable non-small cell lung cancer: an extended phase II study.
BACKGROUND: A phase II study of a cisplatin/paclitaxel combination given on a weekly schedule in the front-line treatment of non-small cell lung cancer (NSCLC) is reported. PATIENTS AND METHODS: Treatment consisted of an intravenous infusion of cisplatin, 25 mg/m2, and paclitaxel, 80 mg/m2, every week. Chemotherapy was continued until completion of a 22-week treatment plan, disease progression, persistent toxicity, or patient refusal. RESULTS: Seventy-nine patients entered the study. The median number of infusions per patient was 14 (range 0-22). The median dose-intensity was 75% of that projected. Toxicity was generally acceptable, and never life-threatening. Seven complete responses (pathologically documented in 4 patients) and 27partial responses were observed for an overall response rate of 43%. The estimated median survival and median time to progression was 55 (95% CI: 38-71) and 37 weeks (95% CI: 31-44), respectively. CONCLUSION: In our experience, the weekly combination of cisplatin and paclitaxel is well tolerated, active and associated with remarkably long survivals.
Adult↗