Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Resistance to alkylating agents is partly due to the presence of the DNA repair enzyme, termed O6 alkyltransferase (O6AT). Preclinical evidence of the transient restoration of sensitivity of cells resistant to nitrosoureas by pretreatment with a methylating agent, whose role is to deplete cells of O6AT activity and clinical evidence of such a depletion in patients lymphocytes, led us to test the sequential administration of dacarbazine 3 h prior to fotemustine, a chloroethylnitrosourea derivative. 24 patients with measurable advanced melanoma entered the trial and are evaluable. Toxicity was mainly haematological with early neutropenia and/or thrombocytopenia. Clinical activity (33%) was impressive especially on lung metastases with high complete response rate for that site (7/14). Unfortunately, the occurrence of a rapidly fatal pulmonary toxicity precludes further use of the regimen before a plausible explanation for this unexpected toxicity is obtained. Indeed, similar cases have been reported in other trials using the sequential schedule while no lung toxicity was reported in single agent or alternated administrations. Preclinical studies are ongoing to test the hypothesis of a glutathione depletion and the possibility of a rescue treatment.
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PMID:Sequential administration of dacarbazine and fotemustine in patients with disseminated malignant melanoma--an effective combination with unexpected toxicity. 159 Oct 62

From 1985 to 1988, 261 unselected patients entered a nationwide Danish study of surveillance only for testicular seminoma stage I. The median follow-up time after orchidectomy was 48 months, range 6-67 months. 49 patients relapsed (19%). Sites of relapse were paraaortic lymph nodes in 41 patients, pelvic lymph nodes in 5, inguinal lymph nodes in 2 and lung metastases in 1 patient. The median time to relapse was 14 months, range 2-37 months. The 4-year relapse-free survival was 80%. 37 of the relapsing patients (76%) had radiotherapy as relapse treatment. Of these patients, 4 (11%) had a second relapse and received chemotherapy. 1 died of disseminated seminoma. Of the relapsing patients, 12 (24%) had chemotherapy as relapse treatment because of bulky (11 patients) or disseminated disease (1 patient). None of these patients have had a second relapse. However, 2 patients died of infection due to chemotherapy-induced neutropenia. Thus, there have been three seminoma-related deaths (1.1%). The testicular tumour size had an independent prognostic significance. The 4-year relapse-free survivals were 94, 82 and 64% for tumours < 3, 3 to < 6 and > or = 6 cm, respectively. Patients with tumours > or = 6 cm will now be given prophylactic radiation treatment, whereas we will continue to use surveillance only after orchidectomy for patients with tumours < 6 cm.
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PMID:Surveillance following orchidectomy for stage I seminoma of the testis. 828 Apr 82

The aim of this phase II study was to determine the efficacy of high-dose ifosfamide with moderate dose etoposide in childhood osteosarcoma. From January 1992 to January 1995, 27 children (15 male, 12 female) with relapsed or refractory evaluable osteosarcoma were included in a phase II study of two courses of ifosfamide 3g/m2/day and etoposide 75 mg/m2/day for 4 days. Median age was 14 years (7-19 years). All but one had received high-dose methotrexate and doxorubicin as first-line treatment. 22 patients had previously received ifosfamide. This regimen was given as first-line in 1 patient, second-line in 23 and third-line in 3. Evaluable disease was lung metastases in 21 patients, local relapse in 5 and adenopathy in 1. There were six complete responses, seven partial responses, three minor responses, six stable disease and five progressive disease (including one mixed response). Response rate was 48% (95% confidence interval, 29-67%). Duration of response was not available (10 responding patients had other treatments). Response rate was equivalent in the subgroup of 22 patients who had previously received ifosfamide (4 CR, 6 PR). Among 3 patients who received the phase II regimen as third-line chemotherapy, there was 1 PR. All but 4 patients had a well tolerated grade 4 neutropenia. Transient mild confusion or seizures were each observed once. 5 patients are alive 15-31 months after the beginning of chemotherapy. This combination of drugs at this dosage has tolerable toxicity, is efficient and deserves evaluation in phase III studies.
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PMID:Ifosfamide and etoposide in childhood osteosarcoma. A phase II study of the French Society of Paediatric Oncology. 913 94

Eleven recurrent postmenopausal breast cancer patients with osseous or lung metastases were received fadrozole hydrochloride at a dose of 1 mg twice a day for more than 8 weeks. The median disease-free interval of these 11 patients with metastasis was 74 months. Out of 11 evaluable cases, 2 PR, 6 long-NC and 3 PD were observed. The overall response rate was 18.2% and the long-NC rate was 54.5%. The average overall duration of responses and long-NC were 567 days and 573 days, respectively. There was no adverse drug reaction. A combination therapy with fadrozole hydrochloride 2 mg daily and cyclophosphamide 100 mg orally on days 1-14 was given to 14 postmenopausal patients with recurrent breast cancer. The median disease-free interval of these 14 patients with metastasis was 33 months. There were 2 CR, 3 PR, 4 long-NC, 2 NC and 3 PD. The overall response rate and long-NC rate were 35.8% and 28.6%, respectively. The average overall duration of responses and long-NC were 700 days and 443 days, respectively. The adverse drug reactions were anorexia (Grade 2) and neutropenia (Grade 1 and 2). These results suggested that a combination therapy with fadrozole hydrochloride and cyclophosphamide can be effective and contribute to survival time in the treatment of postmenopausal breast cancer.
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PMID:[Clinical trial of fadrozole hydrochloride for postmenopausal patients with recurrent breast cancer]. 1039 24

A 53-year-old female underwent mastectomy for left breast cancer in April, 1993. She was given oral tamoxifen but this had to be discontinued due to its side effects. In March, 1998, she developed bone and lung metastases, in spite of treatment with combination chemotherapy (CEF). We thus treated here with docetaxel 90 mg three times and 40 mg six times. After the chemotherapy, she achieved complete remissions of the lung metastases and a decrease in serum CEA, CA 15-3, NCC-ST439, and BCA225. Adverse reactions to docetaxel were grade 2 alopecia, grade 4 neutropenia, dysgeusia, and fluid retention. All were tolerable. This new agent may play an important future role in chemotherapy for recurrent breast cancer.
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PMID:[A case of recurrent breast cancer successfully treated with docetaxel]. 1050 May 38

Raltitrexed (Tomudex), a novel folate-based inhibitor of thymidylate synthase, has demonstrated anti-tumour efficacy comparable with 5-fluorouracil and leucovorin in patients with advanced colorectal cancer (CRC). This phase II study was conducted to evaluate the anti-timor efficacy and tolerability of raltitrexed in patients with advanced CRC who had received one previous chemotherapy regimen. Raltitrexed was administered at a dose of 3.0 mg/m2 i.v. over 15 min once every 3 weeks. Of 43 eligible patients, 53% had colon cancer and 47% rectal cancer. Objective responses were observed in 16% of patients [95% confidence interval (CI): 7-31%; seven partial responses). The median duration of response was 101 days (range: 45-239 days), the median overall duration of response was 145 days (range: 104-302 days) and the median survival was 11.6 months (95% CI: 9.4-14.7 months). Liver metastases showed a 17% (three of 18) response rate and lung metastases a 12% (three of 25) response rate. Adverse events of grade 3 or 4 reported for more than 5% of patients were neutropenia (23%), leukopenia (9%), reversible SGPT increase (7%) nausea/vomiting (19%), anorexia (14%), asthenia (9%) and hypotension (7%). Grade 3 or 4 diarrhea, stomatitis and alopecia were not observed. In summary, raltitrexed had an acceptable toxicity profile and promising anti-tumor activity against advanced CRC in patients who had received prior chemotherapy. Further clinical trials of combination chemotherapy using raltitrexed are warranted.
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PMID:Phase II study of raltitrexed (Tomudex) in chemotherapy-pretreated patients with advanced colorectal cancer. Tomudex Cooperative Study Group. 1057 7

Because of the low number of active cytotoxic drugs and their limited activity, the evaluation of new anti-cancer agents for their activity in soft tissue sarcomas is a continuing need. The objectives of this prospective phase II trial of gemcitabine were to estimate the response rate and to define the toxicities of prolonged infusions of low-dose gemcitabine in patients with pretreated advanced soft tissue sarcomas. Patients were eligible if they had a histologic diagnosis of unresectable, recurrent or metastatic, progressive soft tissue sarcoma, and if they had been treated with at least one prior chemotherapy consisting of an anthracycline- and/or ifosfamide-containing regimen. Gemcitabine was administered as a 360 min infusion on days 1, 8 and 15 of a 28 day cycle. The initial dose of gemcitabine was 200 mg/m2 in all patients. Dose escalation to 250 mg/m2 was allowed in the case of stable disease and good tolerability of the drug. All 18 patients (median age 58 years) who enrolled were treated with gemcitabine, and all were assessable for toxicity, response and survival. Only two of these 18 patients had an objective response to a previous palliative chemotherapy. A median of 3 cycles (range 1-7) of gemcitabicin were administered. Two (11%) of the patients had a partial response lasting 5 and 6 months, respectively. Both of these patients had only lung metastases. Whereas one of these patients had a transient partial response to the foregoing chemotherapy (consisting of ifosfamide and doxorubicin), the other patient has been progressive on these drugs. One additional patient, progressive on ifosfamide and doxorubicin, had an objective response of greater than 50% confined to the lungs and stable local recurrence for 6 months. Six patients had stable disease for 3-6 months and nine patients had disease progression. The median survival was 8 months. Treatment generally was well tolerated with six patients having transient grade 3 non-hematologic toxicity, four having grade 3 neutropenia, and one having grade 4 neutropenia and thrombocytopenia. Gemcitabine, given as a prolonged infusion at a low dose level, has a favorable toxicity profile and displays antitumor activity in patients with intensively pretreated, advanced soft tissue sarcomas.
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PMID:Phase II trial of gemcitabine in patients with pretreated advanced soft tissue sarcomas. 1091 48

A 67-year-old woman presented to our hospital with a chief complaint of bloody sputum. A plain chest X-ray a CT scan revealed a tumor shadow 3 cm in size in the middle lobe of the right lung, multiple nodular shadows in the bilateral lung fields and enlarged hilar and mediastinal lymph nodes. A tumor biopsy done under bronchoscopy revealed poorly differentiated adenocarcinoma of the lungs (cT2N3M1). She was given two courses of combination therapy consisting of cisplatin (80 mg/m2) and vinorelbine (20 mg/m2). The primary tumor in the middle lobe of the right lung and the lung metastases were markedly reduced in size, and a complete response was obtained. The only adverse events were grade 4 neutropenia and grade 2 nausea and vomiting.
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PMID:[A case of non-small-cell lung cancer successfully treated using combination chemotherapy with CDDP and vinorelbine]. 1101 2

A 56-year-old male patient underwent a right upper lobectomy and lymph node dissection for non-small cell lung cancer in March 1994. Multiple lung metastases in the right lung were found 45 months after the operation, and chemotherapy with docetaxel was administered. A liver metastasis was detected 11 months later, and it was refractory to docetaxel. Therefore, the patient was treated with cisplatin, mitomycin C and vinorelbine, which resulted in no change to the liver metastasis. He was next treated with gemcitabine, which resulted in a partial response of the liver metastasis. The adverse effects of gemcitabine were Grade 3 thrombocytopenia and Grade 2 neutropenia. The response duration for gemcitabine therapy was three months.
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PMID:[Non-small cell lung cancer with liver metastasis responsive to gemcitabine--a case report]. 1138 23

The purpose of this study was to determine the maximum tolerated dose (MTD) of infusional gemcitabine given in conjunction with intravenous (i.v.) cyclophosphamide, and to determine whether the regimen produced a response rate of at least 40% in patients with metastatic breast cancer who have been previously treated with taxanes. Patients received cyclophosphamide (600 mg/m2) i.v. followed immediately by gemcitabine (100, 150, or 200 mg/m2) given as a 24-hour infusion (every 3 weeks) using an accelerated dose-escalation schema. Dose-limiting toxicity was defined as a neutrophil nadir < 500/microL, platelet nadir < 50,000/microL, or > or = grade 2 nonhematologic toxicity (> or = grade 3 toxicity during the standard dose-escalation portion of the study). Twelve patients received a total of 32 cycles of therapy. The MTD of gemcitabine was 150 mg/m2. Dose-limiting toxicities at 200 mg/m2 included neutropenia and mucositis. One patient with lymphangitic lung metastases had a partial response (8%; 95% confidence intervals: 0%, 23%). This patient developed grade 4 transaminase and total bilirubin elevation that occurred after the sixth cycle of therapy. The study was terminated due to an insufficient number of responses. The MTD of gemcitabine given as a 24-hour infusion is 150 mg/m2 when used in conjunction with cyclophosphamide (600 mg/m2) every 3 weeks. This regimen is not likely to produce more than a 40% response rate in patients with metastatic breast cancer previously treated with taxanes.
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PMID:Phase I/II trial of gemcitabine plus cyclophosphamide in patients with metastatic breast carcinoma previously treated with taxanes. 1189 62


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