Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carboplatin has been incorporated into a new low toxicity combination chemotherapy regimen with methotrexate and vinblastine (CVM) against small cell lung cancer (SCLC). We have compared CVM (carboplatin 300 mg/m2, vinblastine 6 mg/m2, methotrexate 30 mg/m2, all intravenously every 4 weeks) with ACE (doxorubicin 40 mg/m2, cyclophosphamide 600 mg/m2, etoposide 100 mg/m2 all intravenously day 1-3, every 3 weeks) in a randomised trial. 36/54 evaluable patients treated with CVM achieved an objective response (67%) (95% confidence limits [CL] 54-79%) compared with 44/50 treated with ACE (88%) (95% CL 80-97%, P = 0.06). For patients with limited disease treated with CVM, 14/17 (83%) (95% CL 64-100%) had an objective response compared with 14/15 (93%) (95% CL 81-100%) treated with ACE (not significant). Overall median survival was 8 months for CVM and 7 months for ACE. Haematological toxicity was significantly lower for CVM than ACE and consequently dose reduction/delay and infection were less with CVM. Subjective toxicity was low and alopecia was significantly less for CVM than ACE. CVM is an active, well tolerated new chemotherapy regimen for SCLC.
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PMID:Effective new low toxicity chemotherapy with carboplatin, vinblastine and methotrexate for small cell lung cancer: a randomised trial against doxorubicin, cyclophosphamide and etoposide. 165 78

Small cell lung cancer requires aggressive combination chemotherapy. The three active agents, doxorubicin (A) 45 mg/m2 i.v. day 1, cyclophosphamide (C) 1.0 mg/m2 i.v. day 1 and VP16-213 (E) 50 mg/m2/day i.v. days 1-5 were given together. The combination (ACE) was given every 21 days without chest irradiation. One hundred and seventy-four patients have been stratified for extent of disease and randomized on three sequential studies testing ACE vs ACE + MER immunotherapy (38 patients), or ACE vs ACE alternating with CCNU, methotrexate, vincristine and procarbazine (109 patients), or ACE vs ACE II (ACE with continuous VP16-213 - 100 mg/m2/day X 5 days - 27 patients - ongoing). The immunotherapy and the alternating non-cross resistant combination have not proven beneficial with respect to response or survival. The ACE combination, regardless of additional treatments, has produced greater than 90% response overall. In limited disease the complete response (CR) frequency is 65%. The median survival for limited disease overall is 14 months and 18 months for patients achieving CR. In extensive disease the CR frequency is 40% with a median survival of 9 months overall and 13 months for patients achieving CR. Response frequency and survival are identical in the first two studies and 20-30% of patients with limited disease are long-term survivors with one late relapse (greater than 3 years). Patients who achieved CR had a significantly longer survival regardless of other factors such as performance status or extent of disease. Prophylactic cranial irradiation was demonstrated to be useful in prevention or delaying CNS metastases in patients who achieved CR. The third generation study of high-dose VP16-213 infusion seeks to increase the CR frequency. ACE chemotherapy without chest irradiation is a highly effective treatment for all patients with small cell lung cancer and compares favorably with all other studies with or without adjuvant radiotherapy.
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PMID:Doxorubicin, Cyclophosphamide and VP16-213 (ACE) in the treatment of small cell lung cancer. 628 82

This study was conducted to test the feasibility of reducing the interval between cycles of doxorubicin, cyclophosphamide, etoposide (ACE) chemotherapy to 2 weeks, thereby increasing dose intensity, by adding granulocyte colony-stimulating factor (G-CSF) to reduce the duration of neutropenia following a cycle. 20 patients with small cell lung cancer (SCLC) were prescribed six cycles of 2-weekly ACE, with G-CSF on the intermediate days. 3 patients died during the treatment period and a further 5 had ACE terminated, 3 for toxicity and 2 for progressive disease. Of the 71 intervals between cycles, 42 (59%) were of the prescribed 14 days, 9 (13%) of 15-20 days, 15 (21%) of 21 days and five (7%) longer, but during the first four cycles, 36 (77%) of 47 intervals were of 14 days. The main reason for delay was haematological toxicity. All 20 patients experienced WHO grade 3 or 4 neutropenia, but at 2 weeks after a cycle only 3 had grade 4 and 1 grade 3. 17 patients required blood transfusion and 12 platelet transfusion. The only potentially serious adverse reaction to G-CSF was an episode of rash with facial oedema. Adding G-CSF allows ACE chemotherapy to be intensified by reducing the interval between cycles.
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PMID:The feasibility of using glycosylated recombinant human granulocyte colony-stimulating factor (G-CSF) to increase the planned dose intensity of doxorubicin, cyclophosphamide and etoposide (ACE) in the treatment of small cell lung cancer. Medical Research Council Lung Cancer Working Party. 753 33

In an attempt to achieve adequate palliation in patients with small cell lung cancer (SCLC) while keeping toxicity to a minimum, we compared CVM (carboplatin/vinblastine/methotrexate) and standard therapy with ACE (doxorubicin/cyclophosphamide/etoposide). None of the 104 SCLC patients with limited or extensive disease who participated had received previous treatment. After stratification according to disease extent, patients were randomized to receive either CVM or ACE. The maximum number of chemotherapy courses was six. When response rates were compared, ACE was found to be somewhat superior to CVM in terms of objective response [CVM 67%, 95% confidence interval (CI) 54-79%; ACE 88%, 95% CI 80-97%; p = 0.06]; however, a significant difference was evident only among extensive-disease patients. Median response durations (CVM 6 months, 95% CI 5-8; ACE 5 months, 95% CI 3-6) and median survival times (CVM 8 months, 95% CI 7-10; ACE 7 months, 95% CI 4-9) were comparable. CVM met the goal of producing significantly less hematologic toxicity than occurred with ACE. Leukopenia affected 92% of ACE-treated patients and 48% of CVM-treated patients (p = 0.005), and was severe in 80% of the ACE group and 20% of the CVM group. Alopecia occurred much more frequently among those treated with ACE (91 vs. 24%; p < 0.001), as did infection (59 vs. 24%; p < 0.001). The selection of a specific chemotherapy regimen must be individualized. CVM may be appropriate for patients in whom intensive chemotherapy is contraindicated due to performance status, age, concomitant medical disease, or patient refusal.
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PMID:CVM versus ACE in the treatment of small cell lung cancer. 823 95

The aim of this Phase II study was to test the feasibility of intensifying standard chemotherapy in the treatment of small cell lung cancer (SCLC) by reducing the interval between cycles from 3 to 2 weeks by adding recombinant human methionyl granulocyte colony-stimulating factor (G-CSF; filgrastim) to shorten the duration of neutropenia following each cycle. Thirty-two patients with SCLC were prescribed six cycles of 2-weekly doxorubicin 50 mg/m2 and cyclophosphamide 1 g/m2 on day 1, and etoposide 120 mg/m2 i.v. on days 1, 2 and 3 (ACE), plus filgrastim in a fixed dose of 300 micrograms s.c. on days 4-14 of each cycle. Three patients died during the treatment period and a further nine had chemotherapy terminated before the sixth cycle, all nine because of toxicity. All 32 patients have been followed up for at least 21 months; 14 (44%) were alive at 12 months and the median survival period was 356 days. Of the 127 intervals between cycles of chemotherapy, 74 (58%) were of the prescribed 14 days, 18 (14%) of 15-20 days, 25 (20%) of 21 days, and 10 (8%) were longer. The results were best during the first four cycles, during which 71% of the 83 intervals were of 14 days and a further 10% were less than 21 days. The main reason for delay was haematological toxicity in 37 of the 53 instances. Symptoms of myelosuppression occurred in 23 patients, but at 14 days after a cycle of chemotherapy, all 127 available neutrophil granulocyte counts were normal. Twenty-one patients received blood transfusion and five platelet transfusion. The only adverse effects attributed to filgastrim were episodes of rash, throat swelling, anorexia and shivering, affecting one patient. We conclude that the policy of adding filgrastim allows the dose intensity of ACE chemotherapy to be increased by reducing the intervals between cycles. The findings reinforce those of a parallel study involving lenograstim.
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PMID:Increasing and planned dose intensity of doxorubicin, cyclophosphamide and etoposide (ACE) by adding recombinant human methionyl granulocyte colony-stimulating factor (G-CSF; filgrastim) in the treatment of small cell lung cancer (SCLC). Medical Research Council Lung Cancer Working Party. 858 54

Serum angiotensin converting enzyme activity (ACE), plasma renin activity (PRA), blood pressure (BP), blood pH, blood gases and lung function parameters were measured in patients with emphysema, extrinsic and intrinsic asthma, malignant pulmonary neoplasms, active sarcoidosis and healthy adults. Serum ACE activity was significantly higher in sarcoidosis (250.22+/-34.18 U/L); in small cell carcinoma of lung (155.10+/-38.25 U/L); emphysema (149.82+/-18.31 U/L); extrinsic asthma (141.22+/-25.30 U/L) and lower in intrinsic asthma (98.12+/-15.11 U/L) and squamous cell carcinoma of lung (97.294+/-18.85 U/L) when compared with that of control subjects (108.20+/-13.15 U/L). PRA and BP values of the patients with sarcoidosis, emphysema and small cell carcinoma were markedly elevated and sACE activity was found to be correlated with PRA and mean BP in the same diagnostic groups. sACE activity, PRA and BP of smokers were higher than those of non-smokers in control subjects and in patients with emphysema, extrinsic asthma and small cell carcinoma of lung. Oxygen tensions of the patients with emphysema , extrinsic asthma and small cell carcinoma of lung were found to be significantly decreased. Negative correlations between the sACE activity and oxygen tension (r= -0.68) and between the sACE activity and lung function parameters (r= -0.69 ) were found in these diagnostic groups suggesting that increased sACE level might appeared as a response to chronic hypoxia in the patients with emphysema, extrinsic asthma and small cell carcinoma of lung.
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PMID:Serum angiotensin converting enzyme activity in pulmonary diseases: correlation with lung function parameters. 930 53

Many chemotherapy regimens are used for treating SCLC in the United Kingdom, but it is not known, in any detail, which regimens are used, by which specialists, for which types of patient. We conducted a survey among all medical and clinical oncologists, respiratory physicians and general physicians with respiratory interest in the United Kingdom to find out. The questionnaire asked for the number of SCLC patients treated annually; how many were given chemotherapy; the drugs, doses and schedules chosen according to prognostic group (as defined by the clinician); and the reasons for choice of regimen. 1214 questionnaires were sent out, and responses were received from 1070 (88%) clinicians; 266 (25%) of these treated SCLC with chemotherapy. Of 4674 patients given chemotherapy annually, 36% were given it by clinical oncologists, 30% by medical oncologists, 27% by respiratory physicians, and 7% by general physicians. In all, 34 regimens were reported with 151 different combinations of dose and schedule. In 2311 good prognosis patients, 23 regimens were used, the commonest being ACE (doxorubicin, cyclophosphamide, etoposide), ICbE (ifosfamide, carboplatin, etoposide), CAV (cyclophosphamide, doxorubicin, vincristine), CbE (carboplatin, etoposide), and PE (cisplatin, etoposide). In 1517 poor prognosis patients, 21 regimens were used, the commonest being CAV, EV (etoposide, vincristine), CbE, CAV alternating with PE, and oral etoposide. 452 patients were treated regardless of prognosis and for 219 no prognostic criteria were specified. The remaining 175 were given second-line chemotherapy or were given regimens chosen to avoid toxicity or because of intercurrent disease or other reasons. The main reasons affecting choice of regimen were routine local practice, patients' convenience, quality of life considerations, trial results and cost. The results show wide variation in routine practice and will be useful in reporting and planning clinical trials and in deciding on local treatment policies.
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PMID:A national survey of the chemotherapy regimens used to treat small cell lung cancer (SCLC) in the United Kingdom. 1138 91

A 69-year-old woman was diagnosed with sarcoidosis, which was not treated with corticosteroid therapy. Her levels of angiotensin converting enzyme decreased significantly over 4 years and a mass lesion was detected near the lower part of her left main bronchus, and diagnosed as small cell lung cancer (SCLC). Treatment of the SCLC with a series of chemotherapeutic agents produced excellent results. The pulmonary sarcoidosis did not show any deterioration despite the frequent use of amrubicin, which is known to be a cause of interstitial pneumonia. This is a case report of SCLC complicated with sarcoidosis in a stage of spontaneous remission, possibly suggesting an association between sarcoidosis and tumor immunity, since recent reports have suggested that immune checkpoint inhibitors might be involved in the development of sarcoidosis.
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PMID:Small Cell Lung Cancer with Sarcoidosis in Spontaneous Remission: A Case Report. 3046 48