Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A phase I/II study was carried out to determine the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in combination with a fixed dose of carboplatin (area under the concentration-time curve = 6 by Calvert method) given on an every-3-week schedule to patients with non-small cell lung cancer (NSCLC). Cohorts of patients were entered at increasing dose levels of paclitaxel: six at dose level I (paclitaxel 150 mg/m2), six at dose level 2 (paclitaxel 175 mg/m2), 11 at dose level 3 (paclitaxel 200 mg/ m2), 21 at dose level 4 (paclitaxel 225 mg/m2), and five at dose level 5 (paclitaxel 250 mg/m2). The patients comprised 31 men and 18 women with a median age of 62 years (age range, 46 to 81 years) and a median Southwest Oncology Group performance status of I (range, 0 to 2). Twenty-three patients had unresectable stage III NSCLC and 26 had stage IV NSCLC. Fortynine patients and 176 treatment courses are evaluable for toxicity. Grade 4 neutropenia or grade 3 arthralgias/ myalgias or sensory neuropathy were the most significant toxicities of therapy. In addition, two patients (dose levels 2 and 3) experienced acute chest pain, flushing, and hypotension, and had electrocardiogram changes during the paclitaxel infusion; one had mild creatine phosphokidnase MB elevation. Both recovered uneventfully, were not re-treated with paclitaxel, and account for two of only four hospitalizations for toxicity management in this trial. At this time, 42 patients with objectively measurable disease are evaluable for responses: two complete responses and 24 partial responses (62% objective response rate) have been observed. These data imply that the maximum tolerated dose of paclitaxel is 250 mg/m2 with dose-limiting toxicity consisting primarily of grade 3 osteo/arthralgias-myalgias or cumulative sensory neuropathy; paclitaxel at a dose of 225 mg/m2 given by 3-hour infusion combined with carboplatin at a calculated target area under the concentration-time curve of 6 is a well-tolerated outpatient treatment regimen and highly active in NSCLC; myelosuppression is mild and rarely dose limiting. Most notably, paclitaxel appears to decrease carboplatin's pharmacodynamic effects on thrombopoiesis.
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PMID:Preliminary results of a phase I/II clinical trial of paclitaxel and carboplatin in non-small cell lung cancer. 894 2

Long-acting depot forms of somatostatin analogs administered by intramuscular injections are now available for the treatment of neuroendocrine tumors (NETs). In the present study, we investigated the efficacy and tolerability of a slow-release form of lanreotide in patients with advanced NETs. From July 1996 to January 1999, 25 patients with advanced NETs (12 carcinoids, 13 endocrine pancreatic tumors) were enrolled in the study. Thirteen patients were pretreated with subcutaneous octreotide, chemotherapy, or hepatic metastasis alcoholization. All the patients had measurable disease. Seventeen patients were symptomatic and 20 patients had elevated serum and/or urine markers. Octreotide scintigraphy was positive in 23 of 25 patients. Lanreotide was administered as intramuscular injections at the dose of 30 mg every 2 weeks until there was objective, biochemical, or symptomatic tumor progression. Objective partial responses (PRs) were documented in 2 patients (8%), whereas 10 patients (40%) had tumor stabilization. The PRs were observed in patients with midgut carcinoids, of whom one was pretreated with subcutaneous octreotide. The response duration was 21+ and 24+ months in responding patients; the median duration of disease stabilization was 8.5 months (range, 4-21+). The overall biochemical response rate was 42%, including 2 complete responses (CRs) (10.5%) and 6 PRs (31.5%); all biochemical responses were observed mostly in patients with carcinoid tumors; the duration of response was 18+ and 30+ months for CRs; the median duration of biochemical response was 7 months (range, 4-18+) for PRs. The overall symptomatic response rate was 70% with a median duration of 7.5, 18, and 18+ months for diarrhea, abdominal pain, and flushing, respectively. Median duration of lanreotide treatment was 10 months (range, 2-30+). No significant side effects were reported. Depot lanreotide 30 mg shows significant efficacy in terms of objective response rate and in biochemical and symptomatic control, in pretreated patients as well as nonpretreated patients with advanced NETs. Tolerability is good, with good patient compliance.
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PMID:Long-acting depot lanreotide in the treatment of patients with advanced neuroendocrine tumors. 1095 74