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)

A phase-I clinical study with coadministration of a new vinca alkaloid derivative KW-2307 with cisplatin (CDDP) at 80 mg/m2 to patients with non-small cell lung cancer was conducted by a collaborative study among 6 institutions. CDDP was given on day 1 and KW-2307 on days 1, 8 and 15, both intravenously. One 28-day course was specified to be repeated twice. The initial dose of KW-2307 was 15 mg/m2 and increased to 20 mg/m2 and then to 25 mg/m2. The numbers of enrolled subjects for each dose were 5, 8 and 12 cases, respectively, in the total 25 cases. This regimen as well as KW-2307 monotherapy induced leukocytopenia (neutropenia) as the main adverse reaction. The coadministration with CDDP tended to increase the occurrence of anorexia and nausea/vomiting. Tumor response was obtained in 5 among 24 evaluable cases (CR1, PR 4). The response rate in the cases untreated with KW-2307 and given at 20 mg/m2 or higher doses was 29.4% (5/17, 95% confidence interval of the response rate: 10.3 to 54.7%). Considering drug compliance, etc., the maximum tolerated dose in this regimen was supposed to be 25 mg/m2, and the recommended dose in phase-II study to be 20 mg/m2.
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PMID:[Phase-I clinical study of KW-2307 combined with cisplatin in non-small cell lung cancer patients]. 800 39

A late Phase II clinical study of KW-2307, a new vinca alkaloid derivative, in previously untreated patients with non-small cell lung cancer was jointly carried out in 26 medical institutions. Of 80 enrolled cases, 75 cases were eligible, and PR was attained in 23 cases (30.7%). The main adverse effect of this drug, leukopenia (neutropenia), was observed in 62.7% (83.3%) of Grade 3 and 4 cases, but they recovered rapidly. In addition to decreased hemoglobin in 67% (Grade 3 in 5.7%) of the cases, adverse effects included slight disorder of hepatic function, anorexia, nausea and vomiting, fever, general fatigue, phlebitis, paresthesia and interstitial pneumonia. Peripheral neuropathy such as paresthesia occurred rarely and was slight, if any.
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PMID:[Late phase II clinical study of KW-2307 in previously untreated patients with non-small cell lung cancer. KW-2307 Study Group (Lung Cancer Group)]. 808 45

Sixteen dogs with a histologic diagnosis of hemangiosarcoma were treated with surgery and doxorubicin/cyclophosphamide. The patients' characteristics, ie, age, size, and breed, were similar to those of previous studies. Historic controls for surgery alone were used to evaluate efficacy of the chemotherapy. The results show a trend of improved survival in dogs with localized disease (Stage I) receiving combination therapy. The median survival was 250 days, with a mean of 403 days. The survival times for dogs with stage I, II, and III disease was also improved with combination therapy, when compared to historical controls treated with surgery alone. The overall median survival was 202 days with a mean of 285 days. Toxicities included mild to moderate neutropenia (9 of 16) and clinical signs, such as lethargy, anorexia, vomiting, diarrhea, and fever (13 of 16). Three dogs had severe neutropenia requiring hospitalization and supportive care. One dog died from sepsis and related complications. Chemotherapy with doxorubicin and cyclophosphamide appears to improve survival with acceptable morbidity in patients with early stage disease.
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PMID:Chemotherapy of canine hemangiosarcoma with doxorubicin and cyclophosphamide. 811 34

A multicenter early Phase II clinical study of KW-2307, a new vinca alkaloid derivative, in patients (pts) with lung cancer was conducted in 15 hospitals. Ninety-seven pts were enrolled, among whom 95 were eligible. Seventy of the eligible pts had non-small cell cancer (NSCLC) and 25 had small cell cancer (SCLC). PR was obtained in 13 (18.6%) of NSCLC pts and 3 (12%) of SCLC pts. Only those who had no previous chemotherapy showed PR in NSCLC pts, and the response rate in these pts was 29.5% (13/44). As to the correlation between dosage and tumor effect, a better effect was exhibited at higher doses, with response rates of 21.7% (5/23) and 38.1% (8/21) at 20 mg/m2 and 25 mg/m2, respectively. The major adverse effect of this drug was leukopenia (neutropenia), which was Grade 3 or 4 in many cases. Recovery from this complication, however, was rapid. Other adverse effects included mild hepatic dysfunction, anorexia, nausea/vomiting, fever, general fatigue, phlebitis and constipation. The incidence of peripheral nervous disorder such as the paresthesia commonly observed with vinca alkaloids, was as low as 10%, and the symptoms, if any, were mild.
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PMID:[Early phase II clinical study of KW-2307 in patients with lung cancer. Lung Cancer Section in KW-2307 Study Group]. 818 36

On the basis of preclinical data showing synergy between 5-fluorouracil (5-FU), leucovorin (LV) and IFN-alpha-2a, a phase I study was carried out to determine the maximum tolerable dose (MTD) of IFN-alpha-2a with this combination in patients with gastrointestinal malignancies. The treatment consisted of 370 mg/m2 5-FU and 200 mg/m2, LV on days 1 to 5, and IFN-alpha-2a on days 1 to 5 of the first week of chemotherapy and on days 1, 3, 5 of each subsequent week, on a 28-day cycle. Six patients with colorectal, 3 with pancreas, 2 with oesophagus, 2 with hepatocellular and one with gastric cancer were treated. At level III (5 x 10(6) U/m2) all patients experienced grade 3 or 4 toxicity during the first 56 days of treatment and the MTD was declared level II. Grade 3 toxicity comprised of anorexia, mucositis, diarrhoea, and fatigue; in one instance, grade 4 neutropenia occurred. Ten patients were evaluable for response, one patient with an oesophageal cancer had a minor response and one patient with rectal cancer and liver metastases had a radiological complete response lasting 3 months. The recommended dose for this schedule in phase II studies is 5-FU 370 mg/m2, LV 200 mg/m2, and IFN-alpha-2a 4 x 10(6) U/m2.
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PMID:A phase I study of escalating interferon alpha-2a combined with 5-fluorouracil and leucovorin in patients with gastrointestinal malignancies. 821 38

An early phase II study of irinotecan (CPT-11) in patients with advanced or recurrent breast cancer was undertaken by a cooperative study group of 15 institutes in Japan. CPT-11 was administered by intravenous drip-infusion. The administration schedules were 100 mg/m2 weekly (regimen A), 150 mg/m2 biweekly (regimen B), and 200 mg/m2 every 3-4 weeks (regimen C). There were 4 partial responses (PRs), 12 cases with no changes (1 minor response) and 9 cases of progressive diseases with a response rate of 16% (4/25). One out of 7 patients on regimen A and 3 patients out of 15 patients on regimen C achieved PR with a response rate of 14% and 20%, respectively. In three out of 4 PRs, prior chemotherapy, endocrinotherapy or radiotherapy had failed. Major adverse reactions were leukopenia 28/33 (85%), neutropenia 19/25 (76%), anemia 15/33 (46%), nausea/vomiting 28/33 (85%), anorexia 25/33 (76%), diarrhea 22/33 (67%) and alopecia 20/33 (61%). The incidence of leukopenia and thrombocytopenia seemed to be higher in regimen C than regimen A, and diarrhea was also more severe in regimen C than regimen A. The recovery of leukopenia was delayed in some patients on regimen C. The results suggested that CPT-11 was effective against advanced or recurrent breast cancer. The recommended administration schedule for a late phase II study was thought to be 100 mg/m2 weekly, considering efficacy and safety.
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PMID:[An early phase II study of CPT-11 (irinotecan hydrochloride) in patients with advanced breast cancer]. 829 19

Ten HTLV-I-associated myelopathy (HAM) patients (four men and six women aged 38 to 58 years) with Expanded Disability Status Scale (EDSS) scores ranging from 4.0 to 8.5 entered an open-label zidovudine study. A high-dosage induction (2 g/d for 4 weeks) was followed by 1 g/d for 20 weeks. Five patients were natives of the Caribbean island Hispaniola, and one each was from Colombia, Cuba, El Salvador, Jamaica, and the United States; all were positive by polymerase chain reaction, and nine had positive Western immunoblots for HTLV-I. Side effects included anxiety, insomnia, gastric upset, anorexia, and loss of taste. Preexisting leg cramps were increased in two and headaches in one. Hemoglobin decreased from a mean of 13.5 to 11.8 g/dl and the hematocrit from 40.7% to 34.9% at 8 weeks, and then stabilized. Neutropenia appeared regularly but did not necessitate drug withdrawal. Mean EDSS scores changed little for the group as a whole, but the seven ambulatory patients improved objectively, with their scores dropping from 5.5 to 4.0 and none worsening. Timed gait improved by at least 50%. Following withdrawal, four of the five who had improved regressed. Zidovudine appears to be safe in subjects with HAM who have no other major health problems and should be investigated further.
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PMID:High-dose zidovudine induction in HTLV-I-associated myelopathy: safety and possible efficacy. 841 77

Following extensive phase II trials of the combination of dacarbazine and interferon-alpha 2a we performed a prospective, randomized, controlled trial of this combination versus dacarbazine alone as systemic therapy for symptomatic, measurable metastatic malignant melanoma. The two treatment arms were well matched for age, sex, performance, status, relapse-free survival, prior therapy and sites of disease. Therapy consisted of dacarbazine given in combination in escalating doses of 200 mg/m2, 400 mg/m2 and 800 mg/m2 i.v. every 3 weeks, or alone at 800 mg/m2 i.v. every 3 weeks. Interferon was administered subcutaneously starting at 3 mU daily on days 1-3, 9 mU daily on days 4-70, then 9 mU three times per week. Therapy was continued for at least 6 months unless overt progressive disease was observed. Eighty seven patients were randomized to the combination and 83 patients to dacarbazine alone. Response rates were respectively, complete 7% and 2%, and partial 14% and 15%, for a total response rate of 21% (95% confidence limits 13-31%) and 17% (95% confidence limits 10-27%). Median duration of response was 258 and 286 days, and survival of the whole groups 229 and 269 days respectively. Toxicity was worse in the combination arm, with more patients experiencing fatigue, nausea and anorexia, flu-like symptoms and neutropenia. However quality of life was not significantly different in either group, except that fatigue, as measured at week 12 by LASA scales, and activity, as measured by the functional living index, were both improved in the combination.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interferon-alpha 2a does not improve response or survival when combined with dacarbazine in metastatic malignant melanoma: results of a multi-institutional Australian randomized trial. 851 52

A late phase II clinical trial of RP56976 (docetaxel), derived from Taxus baccata was performed to evaluate anti-tumour activity, time to progression and clinical toxicity in patients with advanced or recurrent breast cancer. The patients, between 15 and 80 years old with performance status (PS) of 0-2, received at least two cycles of docetaxel 60 mg m-2 intravenously at 3-4 week intervals. Of the 81 patients enrolled, the 72 eligible for the study were given a total of 327 cycles, with a median of four cycles each. Five patients obtained a complete response (CR) and 27 a partial response (PR); the response rate (RR) was 44.4% (95% confidence interval 32.7-56.6%). A relatively high RR of 9/28 (32.1%) was observed in patients who had received prior chemotherapy involving anthracyclines. The dose-limiting toxicity was grade 3-4 leucocytopenia or neutropenia, found in 78.9% and 85.9% patients respectively. Other severe (grade > 3) toxicities included alopecia (38%), anorexia (18.3%), nausea/vomiting (11.3%), and fatigue (9.9%). Hypersensitivity reactions, oedema and skin toxicity were not severe and were reversible. One therapy-related death occurred 10 days after the initial dose was given. These findings indicate that docetaxel has potent activity against metastatic breast cancer, and that the dose of 60 mg m-2 is safe.
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PMID:A late phase II study of RP56976 (docetaxel) in patients with advanced or recurrent breast cancer. 854 8

Carboxyamido-triazole (CAI) is a synthetic inhibitor of non-excitable calcium channels that reversibly inhibits angiogenesis, tumor cell proliferation, and metastatic potential. Inhibition of calcium influx and calcium-dependent events is a potential common mechanism underlying these effects of CAI. The cytostatic and antiangiogenic properties of CAI led to its development for clinical investigation. In a Phase I clinical trial open to patients with refractory solid tumors, 49 patients received p.o. administered CAI daily or every other day. Two oral formulations, PEG-400 CAI solution and a gelatin capsule containing CAI in PEG-400, were tested. All administered dosages of CAI yielded plasma concentration at or above the range demonstrated to be effective in inhibiting signaling and cancer progression in vitro and in preclinical models (1 microgram/ml, 2.3 microM). Toxicity of p.o. administered CAI most commonly consisted of dose-related grade 1-2 nausea, vomiting, and occasional anorexia. CAI administration at bedtime ameliorated gastrointestinal complaints in many patients; others required addition of simple antiemetic regimens, usually consisting of metoclopropamide or prochlorperazine. Gastrointestinal complaints were the cause for compliance-limiting toxicity at 175 mg/m2/day of the liquid formulation and 125 mg/m2/day of the gelatin capsule formation. Reversible and rare sensory axonal neuropathy (grade 3, 1 patient) and neutropenia (grade 4, 1 patient) were dose-limiting toxicities observed at the 330 mg/m2 every-other-day liquid CAI dose level. No evidence of cumulative end organ damage or central nervous system injury was observed. Disease stabilization and improvement in performance status was observed. Disease stabilization and improvement in performance status was observed in 49% of evaluable patients who had disease progression before CAI. Disease stabilization and associated improvement in performance status was seen in patients with renal cell carcinoma (7 months), pancreaticobiliary carcinomas (3, 5, and 5 months), melanoma (7 months), ovarian cancer (7 months), and non-small cell lung cancer (3 months). The recommended Phase II doses from this trial are 150 mg/m2/day in the liquid formation and 100 mg/m2/day in the gelatin capsule formation.
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PMID:Clinical investigation of a cytostatic calcium influx inhibitor in patients with refractory cancers. 856 73


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