Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon-alpha (IFN-a) or 2'-deoxycoformycin (pentostatin; DCF) have each been shown to be highly active in hairy-cell leukemia (HCL). In this phase II study of the Leukemia Cooperative Group of the European Organization for Research and Treatment of Cancer (EORTC), the efficacy and toxicity of DCF were investigated in patients who were resistant to IFN-a treatment. Resistance was defined as: (1) progressive disease (PD) under IFN-a therapy for more than 2 months; (2) stable disease (SD) after more than 6 months of IFN-a treatment; (3) relapse within 3 months of discontinuing IFN-a; and (4) intolerance to IFN-a because of World Health Organization (WHO) grade 3 or 4 toxicity. DCF was applied at a dosage of 4 mg/m2 weekly x 3, then 4 mg/m2 every other week x 3. Responders were given a maintenance therapy once per month for a maximum of 6 months. At the time of report, 33 patients with resistant disease were evaluable for response and toxicity. Median duration of IFN-a therapy before DCF administration was 14.7 months (range, 1 to 41 months). Complete remissions (CRs) were achieved in 11 patients and partial remissions (PRs) in 15, resulting in a total response rate of 78.8%. Median interval between beginning of DCF therapy to best response was 3.9 months with a range from 2.0 to 7.0 months. Two patients who achieved PR have relapsed 7 and 14 months after cessation of DCF therapy. The median duration of response was over 11.5 months (range, over 3.0 to over 24.0 months). Three patients died within the first 6 weeks of DCF treatment: one of drug-unrelated cardiomyopathy and two of fungal pneumonia. The patients with early death (n = 3) and nonresponsive disease (n = 4) received IFN-a treatment for a longer period (median, 18.0 months) than did the 26 responsive patients (median, 10.0 months). Major side effects included nausea, skin rash, and infections and were otherwise mild. Thus, DCF is highly active in patients with HCL resistant to IFN-a.
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PMID:Response to pentostatin in hairy-cell leukemia refractory to interferon-alpha. The European Organization for Research and Treatment of Cancer Leukemia Cooperative Group. 278 73

The use of alpha interferon (alpha IFN) and, more recently, of the purine analogues deoxycoformycin (dCF) and 2-chlorodeoxyadenosine (2-CdA) has dramatically improved the prognosis of patients affected by hairy cell leukemia (HCL). DCF has been shown to induce an higher and more durable response rate than IFN, with only moderate myelosuppression and relatively few side effects. In this paper, we report our experience with dCF in a series of 38 HCL patients who had progression of their disease after IFN therapy. Serum interleukin-1 beta (IL-1 beta), soluble interleukin-2 receptors (sIl-2R) and Tumor Necrosis Factor alpha (TNF alpha) levels were also evaluated before, both during and after treatment in order to monitor clinical response. Two schedules of treatment were employed: 23 patients were treated with the EORTC protocol and the following 15 with the NCI regimen. The overall response rate was 94.7%; no significant differences in response rates were observed between the two schedules. In respect to toxicity, we recorded nausea and in two cases a cutaneous rash. Four patients experienced localized herpes zoster and one had a fungal pneumonia. Median overall survival after therapy is 38.5 months, 55 percent of patients enrolled in the EORTC schedule and 77% of those who received the NCI program are currently in CCR at 3 years. Serum IL-1 beta and sIL-2R levels significantly decreased after treatment, while no significant changes in serum TNF alpha levels were observed. In our study, dCF was confirmed as an effective agent in HCL, inducing an high response rate with only moderate side effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Deoxycoformycin induces long-lasting remissions in hairy cell leukemia: clinical and biological results of two different regimens. 782 42

We carried out a phase I/II trial of adding 2-weekly docetaxel to cisplatin plus fluorouracil (CF) therapy (2-weekly DCF regimen) in esophageal cancer patients to investigate its safety and antimetastatic activity. Patients received 2-weekly docetaxel (30 mg/m(2) [dose level (DL)1] or 40 mg/m(2) [DL2] with a 3 + 3 design in phase I, on days 1 and 15) in combination with fixed-dose CF (80 mg/m(2) cisplatin, day 1; 800 mg/m(2) fluorouracil, days 1-5) repeated every 4 weeks. The primary endpoint was dose-limiting toxicity (DLT) in phase I and central peer review-based response rate in phase II. At least 22 responders among 50 patients were required to satisfy the primary endpoint with a threshold of 35%. Sixty-two patients were enrolled in phase I and II. In phase I, 10 patients were enrolled with DLT of 0/3 at DL1 and 2/7 in DL2. Considering DLT and treatment compliance, the recommended phase II dose was determined as DL1. In phase II, the response rate was 62% (P < 0.0001; 95% confidence interval, 48-75%); median overall survival and progression-free survival were 11.1 and 5.8 months, respectively. Common grade 3/4 adverse events were neutropenia (25%), anemia (36%), hyponatremia (29%), anorexia (24%), and nausea (11%). No febrile neutropenia was observed. Pneumonitis caused treatment-related death in one patient. The 2-weekly DCF regimen showed promising antimetastatic activity and tolerability. A phase III study comparing this regimen with CF therapy is planned by the Japan Clinical Oncology Group. This study was registered at the UMIN Clinical Trials Registry as UMIN 000001737.
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PMID:Phase I/II trial of 2-weekly docetaxel combined with cisplatin plus fluorouracil in metastatic esophageal cancer (JCOG0807). 2504 Oct 52

Docetaxel, cisplatin and 5-fluorouracil (DCF regimen) are currently applied as an effective combination treatment for various human malignancies; however, the efficacy of this regimen is impaired by severe adverse events associated with it. Therefore, better-tolerated regimens with comparable efficiency are required for patients with gastric cancer. To explore such possibilities, a phase-I clinical trial was performed to evaluate the safety and tolerability of a modified regimen replacing cisplatin and 5-fluorouracil with oxaliplatin and capecitabine, respectively (DOX program). The maximum-tolerated dose (MTD) and dose-limited toxicity (DLT) of capecitabine in this regimen were determined and a dose for subsequent phase-II clinical trials was identified. A total of 24 patients with advanced gastric cancer were sequentially enrolled in the present capecitabine dose-escalation trial. The patients were treated with docetaxel and oxaliplatin at fixed doses [75 and 100 mg/m2, respectively, intravenously, on day 1 (d1)], and with capecitabine at increasing doses (1,500, 2,000 and 2,500 mg/m2, per os, d1-7). The MTD of capecitabine was 2,000 mg/m2 (d1-7), repeated every 21 days for at least two cycles. The most frequent DLTs for this regimen were leukopenia (15/24, 62.5%, all at grade-III/IV) and neutropenia (13/24, 54.2%, all at grade-III/IV), nausea (14/24, 58.3%, all at grade-III) and vomiting (13/24, 54.2%, all at grade-III). The effective rate of the DOX regimen was 75.0% (18/24). Based on the results, the combination of docetaxel (75 mg/m2, d1), oxaliplatin (100 mg/m2, d1) and capecitabine (2,000 mg/m2, d1-7) is recommended for a future phase-II trial. While these doses for the DOX regimen were generally well tolerated, the efficacy of this modified regimen in patients with advanced gastric cancer remains to be further evaluated in subsequent phase-II trials.
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PMID:Seven-day capecitabine plus docetaxel and oxaliplatin regimen for the treatment of advanced gastric cancer: A phase-I clinical trial. 2841 80

Gastric cancer is the fourth common cancer and the second leading cause of cancer death worldwide. Due to lack of adequate information on the side effects of chemotherapy regimens in treatment of gastric cancer, this study was aimed to determine the side effects of two common chemotherapy regimens of gastric cancer. This prospective study was conducted in Emam Khomeini Educational Hospital and Touba Polyclinic; both are affiliated to Mazandaran University of Medical Sciences. The frequency and severity of side effects of chemotherapy were recorded based on the National Cancer Institution (NCI) Toxicity Criteria (version 2). DCF (Docetaxel, Cisplatin, 5FU) and FOLFOX (Folinic acid, 5FU, Oxaliplatin) adverse reactions were compared using SPSS 16 software. One hundred twenty five chemotherapy cycles administered to seventy four patients were assessed. The most common used regimens were DCF (70%) and FOLFOX (16%). The incidence of vomiting was higher with DCF compared to FOLFOX (P = 0.049). In more than 50% of cycles, DCF regimen caused diarrhea, while in FOLFOX regimen it was less than 9% (P = 0.002). Stomatitis, visual changes, nausea, skin reactions, and constipation were not significantly different between the two regimens. It seems that the adverse drug reactions of FOLFOX regimen were more favorable than DCF regimen. The results of this study may help clinicians choosing a more favorable chemotherapy regimen especially in patients with a low performance status who have difficulties in tolerating a chemotherapy regimen with a more severe adverse effect profile.
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PMID:Comparison the Incidence and Severity of Side Effects Profile Of FOLFOX and DCF Regimens in Gastric Cancer Patients. 3153 Oct 83