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)

An early phase II clinical study of S-1 in patients with advanced or recurrent breast cancer was undertaken by a cooperative study group (Breast Cancer Working Group) of 14 institutes in Japan. S-1 was administered twice daily at 75 or 50 mg (dose FT)/body for 28 consecutive days with 14 days rest (one course). Twenty-eight patients were enrolled, 27 were eligible for the study, and 25 were evaluable for efficacy. Four complete responses and seven partial responses were obtained, and the response rate was 40.7% (11/27) [ninety percent confidence interval for this response was 26.7-56.4%]. The major adverse reactions observed were myelosuppression represented by leukopenia 44.4% (12/27), neutropenia 40.7% (11/27), RBC decreased 37.0% (10/27), hemoglobin decreased 29.6% (8/27), anorexia 55.6% (15/27), nausea/vomiting 48.1% (13/27), and fatigue 33.3% (13/27). The results suggested that the efficacy and safety of S-1 were effective against advanced or recurrent breast cancer. The objective of study judged should be investigated in a late phase II clinical study.
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PMID:[An early phase II clinical study of S-1 in patients with breast cancer. S-1 Cooperative Study Group (Breast Cancer Working Group)]. 964 19

In developing new anticancer agents, the most important thing is the balancing of antitumor activity and toxicity. To achieve high activity and low toxicity, S-1 was designed, in which tegafur, prodrug of 5-FU, was combined with two classes of modulators. CDHP, inhibitor of 5-FU degradation in liver and Oxo, inhibitor of 5-FU phosphoribosylation in digestive tract, respectively. This cooperative study with 15 nation-wide institutes was conducted to evaluate the antitumor activity and toxicity of S-1 in patients with advanced head and neck cancer from Jan. 1994 to March 1996 in Japan. Out of 26 patients, CR was achieved in 1 and PR in 11 with a response rate of 46.2%, while adverse events of grade 3 were as follows: hemoglobinemia (7.7%), leukocytopenia, neutropenia, stomatitis and anorexia (3.8%), each. Neither grade 4 adverse event nor treatment-related deaths were observed. Based on these findings, it was concluded that S-1 is a useful anticancer agent with the low grade toxicities for treatment of the patients with advanced head and neck cancer, and the effects of CDHP and Oxo found in preclinical studies might be also reflected in these results.
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PMID:[Early phase II study of S-1 in patients with advanced head and neck cancer. S-1 Cooperative Study Group (Head and Neck Working Group)]. 967 77

A 10-center cooperative clinical study with a new formulation of epirubicin hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with breast cancer. One course of treatment consisted of one intravenous administration of Epirubicin-RTU at the dose of 60 mg/m2 followed by a 3-week drug-free interval and concomitant daily administration of oral cyclophosphamide at 100 mg/day during the period between Days 1 through 14. At least, two courses of treatment were given. Among 20 registered cases, all 20 cases were eligible and 16 cases completed the whole course of the study. In 16 completers, PR was observed in 5 cases, indicating the efficacy rate of 31.3% (5/16).. No local irritation was observed at the injection sites. Adverse reactions frequently observed were leukopenia, neutropenia, anorexia, alopecia, and nausea/vomiting, which were all reversible and tolerable. From the above results, Adverse reactions both locally and systemically were tolerable. Intravenous administration of Epirubicin-RTU was considered to be useful for the treatment of breast cancer.
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PMID:[Results of clinical study with epirubicin hydrochloride injectable solution and cyclophosphamide in breast cancer]. 975 98

An effective local-regional therapy is needed for adenocarcinomas of the pancreas. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton NJ) may enhance the effect of radiation therapy. Paclitaxel synchronizes cells at G2/M, a relatively radiosensitive phase of the cell cycle. We have shown that response to paclitaxel and concurrent radiation (paclitaxel/RT) was not affected by p53 mutations in non-small cell lung cancer (NSCLC). This suggested that paclitaxel/RT was a rationale treatment approach for other malignancies which frequently harbor p53 mutations such as upper gastrointestinal malignancies. We have completed a phase I study of paclitaxel/RT for locally advanced pancreatic and gastric cancers. The maximum tolerated dose (MTD) of paclitaxel was 50 mg/m2/week for 6 weeks with abdominal radiation. The dose limiting toxicities were abdominal pain within the radiation field, nausea and anorexia. Twenty-five patients with locally advanced pancreatic cancer have now completed treatment at the phase II dose level of paclitaxel 50 mg/m2/week with 50 Gy concurrent RT. Thus far, the only grade 3/4 toxicities have been hypersensitivity reactions in 2 patients, asymptomatic grade 4 neutropenia in 3 patients, and non-neutropenic biliary sepsis in 1 patient. Of the first 22 assessable patients treated at the phase II study, 8 obtained a partial response (PR) for a preliminary response rate of 36%. These findings demonstrate that paclitaxel/RT is well tolerated with substantial activity for locally advanced pancreatic cancer.
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PMID:Paclitaxel and concurrent radiation for locally advanced pancreatic carcinoma. 979 3

A late phase II clinical study of RP56976 (docetaxel) was conducted in patients with advanced/recurrent gastric cancer as a multicenter cooperative trial. Docetaxel was administered intravenously at a dose of 60 mg/m2 every 3-4 weeks. Of the 76 patients enrolled, 66 patients were eligible and 59 patients were evaluable for response. One patient showed complete response (CR), 13 patients partial response (PR), 1 patient minor response (MR), 19 patients no change (NC) and 25 patients had progressive disease (PD). The overall response rate in 59 evaluable patients was 23.7% (95% CI = 13.6-36.6%). The primary tumor showed a 4.3% (1/23) response, while the metastatic lesions in the abdomen, pelvic mass, lung, liver, and lymph nodes showed response rates of 62.5% (5/8), 33.3% (1/3), 33.3% (1/3), 14.8% (4/27), and 13.9% (5/26), respectively. About hematological toxicity, severe (Grade 3 or more) leukopenia was observed in 36 patients (56.3%) and neutropenia in 52 patients (81.3%). Other major toxicity (Grade 3 or more) included nausea/vomiting in 11 patients (17.2%), anorexia in 9 patients (14.1%), fatigue in 5 patients (7.8%), and alopecia in 7 patients (10.9%), all which were tolerable. The results show that docetaxel is an effective anticancer agent for advanced/recurrent gastric cancer.
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PMID:[Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent gastric cancer: a Japanese Cooperative Study Group trial (group A)]. 979 14

We conducted multi-site early phase II trial or oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer in cooperation with 19 institutes. Fifty mg/body of oral etoposide was administered daily for 21 consecutive days. Cycles were repeated every 28 days. In cervical cancer, 24 patients were enrolled and 17 of them were evaluated. The overall response rate including CR and PR was 23.5% (4/17). In ovarian cancer, 18 patients out of 21 enrolled were evaluated. The overall response rate was 16.7% (3/18). The primary toxicity observed was myelosuppression such as leukopenia, neutropenia, hemoglobin decrease and thrombocytopenia. Other adverse effects were anorexia, nausea, vomitting, fatigue, alopecia and stomatitis. From these results we concluded that oral etoposide administered for 21 consecutive days was effective against cervical cancer.
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PMID:[Early phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer. ETP 21 Study Group--Cervical-Ovarian Cancer Group]. 983 8

The North Central Cancer Treatment Group designed a phase II trial to assess the efficacy and toxicity of topotecan in patients with unresectable malignant pleural mesothelioma. Twenty-two previously untreated patients with unresectable pleural mesothelioma and good performance status (Eastern Cooperative Oncology Group performance status 0, 1, or 2) were enrolled on this trial from October 1993 through July 1994. Nineteen men and three women, median age 66 years (range, 44-78 years), were treated with topotecan 1.5 mg/m2 intravenously over 30 minutes daily for 5 days at 3-week intervals until toxicity, progression of disease, or a patient decided to discontinue treatment. There were seven patients with measurable disease and 15 with evaluable disease; all were assessable for response and toxicity. A total of 113 cycles of treatment were given, for a median of three cycles (range, 1-26 cycles). Myelosuppression was the most frequent toxicity. Eighteen of 21 patients (86%) experienced grade 3 or 4 neutropenia during the initial treatment cycle. The median neutrophil nadir was 0.5 x 10(3)/microl (range, 0.1-1.6 x 10(3)/microl), and the median platelet nadir was 127 x 10(3)/microl (range, 18-460 x 10(3)/microl). Other toxicities more than grade 2 included malaise (two patients), and anorexia, infection, fever, pulmonary, and cardiac in one patient each. There were no objective responses, and 18 patients had stable disease for a median of 74 days. The median survival for all patients was 230 days, with 23% alive at 1 year. Topotecan as administered in this trial is reasonably well tolerated; however, the response rate was insufficient to warrant additional study in pleural mesothelioma.
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PMID:Phase II trial of topotecan for the treatment of mesothelioma. 985 66

We conducted a multi-site late phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical cancer in cooperation with 32 institutes. Fifty mg/body of oral etoposide was administered daily for 21 consecutive days. Treatment cycles were to be repeated at 4- to 5-week intervals. Eighty patients were enrolled and 70 patients were evaluated. The overall response rate (95% CI), including one complete response patient and 18 partial response patients, was 27.1% (19/70). The most commonly observed toxicity was myelosuppression such as leukopenia, neutropenia, hemoglobin decrease and thrombocytopenia. Other adverse effects were gastrointestinal toxicities such as anorexia, nausea, stomatitis and vomiting, as well as fatigue and alopecia. These adverse effects were well tolerated and controlled with medications. From these results we concluded oral etoposide administered for 21 consecutive days was an effective drug against cervical cancer.
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PMID:[Late phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical cancer. ETP 21 Study Group--Cervical Cancer Group]. 988 Oct 82

A late phase II clinical study of RP56976 (docetaxel), a new anticancer agent for advanced/recurrent head and neck cancer, was conducted in 29 institutions all over Japan as a multi-institutional cooperative study. Docetaxel was administered by 1 to 2-hour intravenous infusion at a dose of 60 mg/m2 every 3 to 4 weeks. Of 63 patients eligible in this study, 59 were judged as complete cases. Complete response (CR) was observed in 1 patient, partial response (PR) in 13, no change (NC) in 25, and progressive disease (PD) in 20, for an overall response rate of 22.2% (14/63, 95% CI: 12.7-34.5%) in eligible cases, and 23.7% (14/59, 95% CI: 13.6-36.6%) in complete cases. Previously treated patients showed a 17.9% (10/56) response rate, whereas treatment--naive patients showed a 57.1% (4/7) response rate. Among 46 patients who received prior chemotherapy, one CR and 7 PR were observed with a 17.4% response rate. Major hematological toxicities were leucopenia in 95.1% (> or = grade 3, 59.7%) and neutropenia in 90.3% (> or = grade 3, 79.0%). Other severe toxicities (> or = grade 3) included anorexia in 9.7% (6 cases), diarrhea in 3.2% (2 cases), dyspnea in 3.2% (2 cases), and fatigue in 3.2% (2 cases). One patient had a grade 3 interstitial pneumonia; however, symptoms were resolved by the administration of corticosteroids. During this study, one patient died due to multiple organ failure (MOF) caused by disseminated intravascular coagulation (DIC), and this case was reported as a therapy-related death. Based on these results, docetaxel is an active agent for treatment of head and neck cancer.
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PMID:[Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent head and neck cancer]. 998 6

Carzelesin is a cyclopropylpyrroloindole analogue which acts as a DNA-sequence-specific alkylating agent. In this phase I study, Carzelesin was given as a 4-weekly 10 min i.v. infusion to 51 patients with advanced solid tumours. Patients received a median of two courses (range 1-5) at one of nine dose levels: 24, 48, 96, 130, 150, 170, 210, 250 and 300 microg m(-2). According to NCI-CTC criteria, non-haematological toxicities (grade 1/2) included fever, nausea and vomiting, mucositis and anorexia, none of which was clearly dose related. The dose-limiting toxicity was haematological and consisted mainly of neutropenia and to a lesser extent thrombocytopenia. From the dose level 150 microg m(-2), the haematological toxicity (particularly thrombocytopenia) was delayed in onset, prolonged and cumulative in some patients. In several courses, double WBC nadirs occurred. The maximum tolerated dose for a single course was 300 microg m(-2). From the dose level 170 microg m(-2), the intended dose intensity could not be delivered to most patients receiving > 2 courses owing to cumulative haematological toxicity. The dose level with the best dose intensity for multiple courses was 150 microg m(-2). The pharmacokinetics of Carzelesin and its metabolites (U-76,073; U-76,074) have been established in 31 patients during the first course of treatment using a HPLC method. Carzelesin exhibited linear pharmacokinetics. The concentration of U-76,074 (active metabolite) extended above the lower limit of quantitation (1 ng ml(-1)) for short periods of time and only at the higher dose levels. There was no relationship between neutropenia and the AUC of the prodrug Carzelesin, but the presence of detectable plasma levels of the active metabolite U-76,074 was usually associated with a substantial decrease in ANC values.
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PMID:Phase I study of Carzelesin (U-80,244) given (4-weekly) by intravenous bolus schedule. 1018 90


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