In patients affected with different tumours, disorders concerning clotting are frequently observed. The biological processes leading to coagulation are probably involved in the mechanisms of metastasis. We studied plasma levels of thrombin-antithrombin III complexes (TAT) in 90 patients affected with lung tumours subgrouped in small cell and non-small cell (NSC) lung cancer: 17 patients had no evidence of disease after surgery (NE); the remaining 73 patients were divided according to the absence (LOC) or the presence (META) of metastases. All the patients were followed up for several months. In all the lung cancer patient groups, at the beginning of the study we detected TAT levels that were higher than in controls. During the follow-up period, the NSC-NE patients with no recurrence of the disease as well as the NSC-LOC patients responding to the treatment had a decrease in TAT levels (p < 0.01 and p < 0.05, respectively). The NSC-META patients with progression of their disease had, in contrast, an increase in TAT levels (p < 0.01). Our data reveal the presence of 'latent coagulation disorders' as assessed by the presence of high TAT levels in the majority of lung cancer patients. The follow-up study indicates that in the NSC group, a relation exists between coagulation activation and rate of tumour progression and/or response to treatment. In cancer patients the early detection of coagulation disorders could also allow, therefore, the prevention of thromboembolism and/or haemorrhage by administration of appropriate treatment.

Antithrombin III↗

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Lonidamine plus cyclophosphamide in the treatment of adanced non-small cell lung cancer in the elderly: a phase II study.

AIM AND BACKGROUND: The aim of this Phase II trial was to verify the therapeutic activity and tolerability of chemotherapy with lonidamine (LND) plus cyclophosphamide (CTX) in advanced non-small cell lung cancer (NSCLC) in the elderly. The rationale of the combination is reported. CTX showed mild toxicity, with a 12% objective response (OR) in monochemotherapy; LND potentiated the in vitro antiproliferative activity of alkylating agents, mainly CTX, without increasing myelotoxicity, particularly important in the elderly. METHODS: The schedule consisted of CTX, 600 mg/m2/i.v. on day 1 every 21 days for 6 cycles; LND, 450 mg/die/p.o. from day 1 to progression. RESULTS: Between November 1990 and April 1991, 41 patients with stage III-IV NSCLC were enrolled; 35 were assessable for response. Median age was 73 years (range, 71-79 years); 13 patients (32%) presented stage III A, 20 (49%) stage III b, and 8 (19%) stage IV disease. Cardiovascular conditions and/or chronic respiratory failure contraindicated surgical treatment in stage III A patients. Of enrolled patients, 14.6% experienced PR, 48.8% SD and 14.6% dropped out of the study. Median time to progression was 4 months (range, 2-9 months) and median survival 9 months (range 3-45 months). No patient showed WHO grade IV LND-related toxicity. In 1 patient (2.5%), LND was discontinued after 5 therapy cycles due to WHO grade III myalgia; in 80% of patients, LND oral dosage was reduced to 300 mg/day due to WHO grade II myalgia, and 20% of patients completed treatment with the full dose. CONCLUSIONS: CTX plus LND can be considered a well tolerated therapeutic approach in the elderly with NSCLC with good PS and good liver, renal and cardiac conditions, but 14.6% PR is a slightly better result as compared with 12% PR obtainable with CTX alone as reported in the literature, even though most patients presented with advanced disease and no specific toxic effect was observed. Therefore, a confirmatory randomized trial (CTX vs CTS plus LND) would hardly be useful.

Aged↗

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The role of vindesine and lonidamine in the treatment of elderly patients with advanced non-small cell lung cancer: a phase III randomized FONICAP trial. Italian Lung Cancer Task Force.

AIMS: To evaluate the efficacy and treatment compliance in elderly patients with advanced non-small cell lung cancer (NSCLC) of two chemotherapeutic agents with mild toxicity, 153 previously untreated patients aged over 70 years were randomized to receive lonidamine (450 mg daily p.o. until progression), vindesine (3 mg/m2/daily i.v. weekly for 4 weeks and then every 2 weeks until progression), the combination of the two drugs at the same dose and schedule, or supportive therapy only in a four-arm factorial randomized trial. METHODS: 126 patients were included in the final analysis. Their median age was 75 years. Forty percent had stage IV disease and 60% stage III. Most patients were males (85%) and the majority had squamous histology (68%). RESULTS: Among 104 patients evaluable for response there were only 3 PRs (1/30 in the lonidamine arm and 2/33 in the lonidamine + vindesine arm). Overall, 8.7% and 9.5% of the patients, respectively, progressed or died early, before response evaluation; another 9.4% refused treatment continuation because of poor compliance with the study protocol. Eighty-five patients were fully evaluable for toxicity, which was generally mild. Leukopenia grade 1-3 was found in less than 30% of patients treated with vindesine or vindesine + lonidamine. The most common complaints associated with lonidamine treatment were myalgia (70% of patients), fatigue (55% and 83% of patients treated with lonidamine or lonidamine + vindesine, respectively) and testicular pain in nearly 40% of cases. The overall median survival was 170 days, with no significant impact on survival of either lonidamine or vindesine. CONCLUSIONS: The low response rate and survival together with the poor treatment compliance, even in the presence of mild toxicity, do not support the usefulness of these "gentle" chemotherapies in elderly NSCLC patients. The standard management of advanced NSCLC in elderly patients remains to be defined. Specifically designed studies to address this issue are warranted.

Aged↗

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Treatment of inoperable non-small cell lung carcinoma stage IIIb and IV with cisplatin, epidoxorubicin, vindesine and lonidamine: a phase II study.

AIMS AND BACKGROUND: The polychemotherapeutic regimen PEV (cisplatin, epidoxorubicin and vindesine) + lonidamine proved to be valid in terms of activity and efficacy in the treatment of patients with advanced, previously untreated non-small cell lung carcinoma. The goal of the study was to verify whether a different dose of lonidamine, together with an increase in cisplatin and epidoxorubicin compared to the standard regimen, is able to improve the activity and efficacy of PEV without increasing toxicity. PATIENTS AND METHODS: Thirty-one patients were treated with cisplatin (80 mg/m2/i.v.), epidoxorubicin (70 mg/m2/i.v.) and vindesine (3 mg/m2/i.v.) every 28 days for 6 courses in combination with lonidamine (600 mg/day on days 1 and 2 of each course followed by 450 mg/day until progression of disease or intolerance). All the patients were monitored for clinical response, median duration of response and survival and for toxicity. RESULTS: The clinical response in the 29 assessable patients was: 41.4% partial remission, 48.3% stable disease, and 10.3% progression of disease. The median duration of response was 8.5 months (range, 4-26+) and median survival was 12 months (range, 4-26+). Survival was above the median in 15 stage IIIb patients, and 2 patients were long survivors at 26+ months. The toxicity of PEV + lonidamine was mild; there were no toxic deaths nor acute toxicity of grade 4 according to the WHO scoring system. CONCLUSIONS: Our polychemotherapeutic regimen proved to be valid in terms of activity and efficacy, and a further dose increase in single chemotherapeutic agents as well as lonidamine could therefore be justified.

Aged↗

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Comparative analysis of CEA and SCC serum markers with IAP in human lung cancer.

Serum levels of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and immunosuppressive acidic protein (IAP) were measured in 37 patients with lung cancers, in 24 with non-cancer pulmonary diseases and in 24 normal controls We evaluated the sensitivity, specificity and accuracy of these three markers alone and combined. The highest specificity was observed for SCC (83.3%) and the highest sensitivity for IAP (94.6%). The best accuracy was obtained with the combined determination of CEA and SCC. In cancer and non-cancer pulmonary diseases the best correlation was observed between CEA and SCC (r = 0.30 in cancer and r = 0.45 in non-cancer pulmonary diseases). Although the IAP test is not specific in the detection of lung cancer, its use may be helpful in monitoring the acute phase reactions that occur very frequently in this malignancy.

Adenocarcinoma↗

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