Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred eighty-nine patients received a four-drug combination consisting of cyclophosphamide, Oncovin (vincristine), methyl CCNU, and bleomycin (COMB), according to three different drug regimens, performed sequentially. Of the 189, 62 had a partial response (33%) including 11/33 with squamous lung cancer, 11/32 with squamous carcinoma of the head and neck, 13/15 with oat cell carcinoma of the lung, and 7/41 with malignant melanoma. The response rate for patients with squamous lung or head and neck cancer appeared to be higher at weekly bleomycin doses of 30 and 60 mg (15/33 = 45%), compared to a weekly bleomycin dose of 15 mg (7/32 = 25%). A median survival from treatment of 30 weeks was observed in oat cell carcinoma, which represents considerable prolongation over that expected from supportive care alone or single-agent chemotherapy. Toxicity included: 1) myelosuppression, resulting in hospitalization for antibiotics in 20% of patients; 2) probable bleomycin lung damage in 4% of patients; and 3) dose-limiting vincristine neuropathy in 11%. The combination of twice-weekly vincristine and bleomycin for more than 6 weeks produced a disturbing "debilitation syndrome," characterized by weakness, anorexia, weight loss, and apathy. The encouraging response rate suggests a future role for these drugs in combination, especially for vincristine and bleomycin, with other agents showing activity in squamous and oat cell carcinoma. Toxicity precludes recommendation of this combination, in the regimens tested, for broader Phase III studies.
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PMID:COMB (cyclophosphamide, oncovin, methyl-CCNU, and bleomycin): a four-drug combination in solid tumors. 5 Aug 70

A phase II clinical study of 254-S, a new anticancer platinum complex, for primary lung cancer was conducted by the 254-S Lung Cancer Study Group consisting of 15 institutions nation-wide. Considering the results of the phase I clinical study, 254-S was administered at 100 mg/m2 by intravenous drip infusion and this administration was repeated at least 2 times at 4-week intervals. Of 75 patients registered, 61 patients consisting of 22 with small cell lung cancer (SCLC) and 39 with non-small cell lung cancer (NSCLC) were evaluable for complete tumor response. Partial response (PR) was obtained in 17 patients, for a 27.9% response rate. The response rate for SCLC was 40.9% (9 PR in 22 patients) and that for NSCLC was 20.5% (8 PR in 39 patients). In SCLC patients with no prior chemotherapy, a 50.0% (5 PR in 10 patients) response rate was obtained. In those with prior chemotherapy, the response rate was 33.3% (4 PR in 12 patients). In NSCLC patients with no prior chemotherapy, a 22.6% (7 PR in 31 patients) response rate was obtained. In hose with prior chemotherapy, the response rate was 12.5% (1 PR in 8 patients). Major toxic effects observed were hematotoxicity such as thrombocytopenia and leukopenia, and gastrointestinal toxicity such as nausea, vomiting and anorexia. Nephrotoxicity observed was mild and infrequent in spite of the low-volume hydration performed. Based on these results, it was concluded that 254-S is a useful anticancer agent for the treatment of primary lung cancer.
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PMID:[A phase II clinical study of cis-diammine glycolato platinum, 254-S, for primary lung cancer]. 131 98

In a multicentre study patients with liver metastases stratified to the histology of the primary tumour were investigated. A total of 102 patients with colorectal adenocarcinoma, non-small-cell lung cancer, pancreatic cancer, primary liver carcinoma and malignant melanoma were treated with the thioether lipid ilmofosine. The drug was administered orally as a tablet at a dosage of 150-300 mg/day (75 mg/tablet). The tolerability of ilmofosine was poor. There was a dose-limiting gastrointestinal toxicity with nausea, vomiting and loss of appetite (WHO grade II-IV) in 67% of patients. During the period of therapy (1-29 weeks, 8.5 weeks mean) no complete remission and no partial response were observed. We thus conclude that treatment with oral ilmofosine is not effective in patients with liver metastases due to various malignancies.
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PMID:Treatment results of the thioether lipid ilmofosine in patients with malignant tumours. 132 33

The role of combination chemotherapy in the treatment of advanced non-small-cell lung cancer is controversial. At best, a small survival benefit can be achieved. Therefore, other treatment modalities are needed. On the basis of the promising treatment results with interleukin-2 (IL-2) -containing immunotherapy in renal cell cancer and melanoma, we performed a phase I-II study with IL-2 and interferon alpha (IFN-alpha). Eligible patients were treated with IL-2 18 x 10(6) IU/m2/day by continuous intravenous infusion (c.i.v.) for 3 days. On the same days, 5 x 10(6) U/m2/day IFN-alpha was given intramuscularly. After a rest period of 4 days, patients at the first dose level received IL-2 2.4 x 10(6) IU/m2/day c.i.v. for a period of 28 days, followed by 14 days' rest, 14 days' treatment, 7 days' rest, and a final treatment for 14 days. Patients at the second dose level were treated according to the same schedule, in which the dose of IL-2 was increased to 3.6 x 10(6) IU/m2/day. During low-dose IL-2 treatment, patients received IFN-alpha 5 x 10(6) U/m2/day on days 1 and 4 of each week. Eleven patients were admitted to the study, six at the first and five at the second dose level. Median age was 54 years; all patients had a performance status of 0 or 1. The most important adverse effects included anorexia, fatigue, nausea, and headache, which were not dose limiting. In the 11 patients treated, no responses were seen. Nine patients developed progressive disease during the first 5 weeks of treatment. We concluded that this regimen of IL-2 and IFN-alpha is ineffective.
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PMID:Interleukin-2 and interferon-alpha in the treatment of patients with advanced non-small-cell lung cancer. 132 67

Two policies of palliative thoracic radiotherapy for non-small-cell lung cancer have been compared in a randomised multicentre controlled trial. A total of 369 patients with inoperable, histologically or cytologically confirmed disease, too advanced for radical 'curative' radiotherapy, and with their main symptoms related to the primary intrathoracic tumour even if metastases were present, were studied. They were allocated at random either to a regimen of 17 Gy given in two fractions of 8.5 Gy 1 week apart (F2 regimen), or to a conventional multifractionated regimen of either 30 Gy in ten fractions or 27 Gy in six fractions (a biologically equivalent dose), given daily except at weekends (FM regimen). On admission, 93% of the patients had cough, 47% haemoptysis, 57% chest pain, 58% anorexia, and 11% dysphagia. As assessed by the clinicians, palliation of the main symptoms was achieved in high proportions of patients ranging in the F2 group from 65% for cough to 81% for haemoptysis and in the FM group from 56% for cough to 86% for haemoptysis. Haemoptysis, chest pain, and anorexia disappeared for a time in well over half the patients with these symptoms, and cough in 37%. For all the main symptoms, the median duration of palliation was 50% or more of survival. Performance status improved in approximately half of the patients with a poor status on admission. All these results were similar in the two treatment groups. As assessed daily by the patients using a diary card, the quality of life deteriorated slightly during treatment but then improved steadily during the next 5 weeks. The proportion of patients with dysphagia increased considerably during treatment, but fell to the pretreatment level during the next 2 weeks. The results were similar in the two groups. Radiation myelopathy was suspected in one (F2) patient. There was no difference in survival between the two groups (log-rank test), the median survival time from the date of allocation being 179 days in the F2 and 177 days in the FM group. In the light of all the findings, the regimen of two fractions of 8.5 Gy given 1 week apart is recommended.
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PMID:Inoperable non-small-cell lung cancer (NSCLC): a Medical Research Council randomised trial of palliative radiotherapy with two fractions or ten fractions. Report to the Medical Research Council by its Lung Cancer Working Party. 170 40

We conducted a phase I study of CI-898 (trimetrexate), a new diaminoquinazoline antifolate in 22 patients with solid cancer in a multicenter collaborative study. The dosage schedule was single-dose intravenous administration (single treatment), followed by one or two courses of 5-day intravenous administration (5-day treatment) at 3-week intervals. Starting at 2 mg/m2 (1 n), the dose was increased up to 15 mg/m2 (7.5 n) for single treatment and 12 mg/m2 (6 n) for 5-day treatment. Evaluable cases numbered 18 for single treatment and 17 for 5-day treatment. In single treatment, the highest dose of 15 mg/m2 caused no serious side effect and did not reach the maximum tolerated dose (MTD). In 5-day treatment, leukocytopenia and thrombocytopenia were found dose dependently, the dose-limiting factor was bone marrow depression, and MTD was 10 mg/m2/day. The leukocyte and platelet counts reached the nadir in 1-3 weeks after initiation of 5-day treatment. The recovery from the nadir required about one week. Subjective side effects included mucitis (mouth, anus), malaise and gastro-intestinal symptoms (nausea, anorexia, diarrhea). None of alopecia, cardiotoxicity and nephrotoxicity were found. In the present phase I study, a tendency of tumor reduction was found in one case each of breast cancer (adenoma) and lung cancer (squamous cell carcinoma). The plasma concentration of the unchanged compound after single treatment showed a biphasic elimination pattern (t1/2 alpha 0.8-1.4 hr, t1/2 beta 9.4-13.0hr). The urinary excretion of the unchanged compound was 14.7-23.5% of the administered dose. In 5-day treatment, no accumulation was found. From the results of the present study, the recommended dosage of CI-898 in the early phase II study was considered to be 8 mg/m2/day intravenously for 5 days (every 3-4 weeks).
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PMID:[Phase I study of CI-898. CI-898 Study Group]. 183 40

A Phase II study of CPT-11, a new camptothecin, was performed in patients with primary lung cancer. Patients with previously untreated non-small cell carcinomas (group A), or previously treated non-small cell carcinomas (group B), and with small cell carcinomas (group C), were enrolled in this study. CPT-11 was given at a dose of 100 mg/m2 i.v. infusion once a week for three weeks or more. Out of 153 patients enrolled, 128 (A: 67; B: 26; C: 35) were assessed to be evaluable for response by an extramural review committee. Response rates were 34.3% (23/67) for A, 0% (0/26) for B and 37.1% (13/35) for C. The response rate was 50% for previously untreated patients (4/8), and 33.3% for previously treated patients (9/27) including 2 complete responses in the group C. Major toxicities were leukopenia, nausea/vomiting, diarrhea, anorexia and alopecia. Leukopenia and diarrhea were considered to be dose limiting toxicities, but they were reversible. It was, however, suggested that some patients should be monitored carefully for severe reactions and delay in recovery. The results showed that CPT-11 was highly effective against non-small cell and small cell carcinomas of the lung.
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PMID:[A phase II study of CPT-11, a camptothecin derivative, in patients with primary lung cancer. CPT-11 Cooperative Study Group]. 185 8

Carboplatin, a new analogue of cisplatin, was administered into the serous cavity in nine primary lung cancer patients with malignant effusion, consisting of six malignant pleural effusions, two malignant pericardial effusions and one malignant ascites. Clinical effects, toxicities and pharmacokinetics were studied. The doses of carboplatin were 300 mg/m2 in seven patients, 200 mg/m2 in one patient and 1,100 mg/body in one patient. In seven evaluable patients, consisting of four non-small cell lung cancers and three small cell lung cancers, the response rate was 85.7% with 3 CR cases, 3 PR cases and 1 NR case. As toxicities, thrombocytopenia was observed in 57.1%, leukopenia in 57.1%, anemia in 71.4%, anorexia in 42.9%, nausea or vomiting in 28.6%, and low grade fever in 14.3%. However local pain, renal or liver dysfunction were not observed. The pharmacokinetics of free platinum concentration was analyzed with a two-compartment model (t1/2 beta = 18.60 hours) and 14.8% of total platinum remained free in effusion 24 hours after intracavitary administration. A high level of free platinum in effusion was maintained over a long period after carboplatin administration. This method was considered to be effective for the treatment of malignant effusion from the viewpoint of pharmacokinetics and less toxicity.
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PMID:[Evaluation of carboplatin administration into the serous cavity in the treatment of malignant effusion]. 187 19

The efficacy and safety of intrapleural LC9018 (Yakult Co. Ltd., Tokyo, Japan) with or without doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) were evaluated in a randomized, controlled trial performed in 95 patients with malignant pleural effusions secondary to lung cancer. Seventy-six patients were eligible for the assessment of efficacy. The response rate for treatment with intrapleural doxorubicin plus LC9018 (38 patients) was 73.7%, which was significantly higher than the response rate of 39.5% for the control group treated with doxorubicin alone (38 patients) (P less than 0.01). The LC9018 group also showed a significantly greater improvement in performance status (PS) and symptoms (chest pain, chest discomfort, and anorexia) than the control group (P less than 0.05). A significant prolongation of survival was noticed in the LC9018 group (P less than 0.05). The main side effects of LC9018 were fever and transient hepatic dysfunction, but there were no serious adverse reactions. These results suggest that the intrapleural instillation of LC9018 can be recommended for the treatment of malignant pleural effusions.
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PMID:A comparative trial of LC9018 plus doxorubicin and doxorubicin alone for the treatment of malignant pleural effusion secondary to lung cancer. 189 48

Fifteen patients aged over 65 years of age with advanced non-small-cl lung cancer (mean age = 70.7, stage IIIb: IV = 4:11) were treated with combination chemotherapy consisting of Cisplatin (50 or 80 mg/m2) and a vinca-alkaloid (Vindesine 3 mg/m2 or Etoposide 80 mg/m2). The effectiveness and side effects of this cisplatin therapy in different combinations of vinca-alkaloid regimens (Vindesine vs Etoposide) were examined. The mean dose of Cisplatin in the Etoposide combination group (75.2 mg/m2) was significantly higher than that in the Vindesine combination group (54.3 mg/m2) (p less than 0.01). A notable reduction the tumor size was observed in 25% of the Etoposide group, only. The 6-month survival rate and one-year survival rate were respectively 85.7%, 57.1% in the Vindesine + Cisplatin group, and 87.5%, 50% in the Etoposide + Cisplatin group. The common side effects were nausea, vomiting, anorexia, and alopecia. These symptoms were either alleviated by antiemetic drugs or followed by spontaneous recovery. Leucopenia, anemia and thrombocytopenia were found in both groups, and there was no difference in the time course of myelosuppression between the two groups. The extent of nephrotoxicity was assessed by creatinine clearance rate. Its decrease in the Vindesine group (60.1----38.9 ml/min) was higher than that in the Etoposide group (64.9----48.9 ml/min), while there was no significant change in BUN, serum creatinine and urine NAG between the two groups. There were no cases in which chemotherapy schedules had to be interrupted due to myelosuppression and nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Cisplatin and vinca alkaloid combination chemotherapy of advanced non-small-cell lung cancer in the aged]. 196 86


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