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

In an effort to improve the treatment of patients with refractory or recurrent lymphoma, we developed a protocol using cis-platinum combined with two other agents of known efficacy in these disorders but with differing side effects: VP-16 and MGBG. Twenty-six eligible patients were treated with this regimen. There were 15 men and 11 women with a median age of 54 years (22-73), and performance status of 1 (0-3). Their diagnoses were Hodgkin's disease 5 and non-Hodgkin's lymphoma [NHL] 21 which included 11 with diffuse histocytic lymphoma [DHL]. The median number of chemotherapy regimens was 2 (1-5); 12 also received radiotherapy. Twenty patients are evaluable for response: 15 NHL and 5 Hodgkin's disease. Three patients, all of whom had DHL entered complete remission (20%) with a median time to treatment failure of 7 1/2 months. Six NHL (40%) and one Hodgkin's disease (20%) patients entered a partial remission. There were three early deaths: one due to progressive disease, one to acute respiratory failure, and one with disease status undocumented. Toxicity included leukopenia, thrombocytopenia, anorexia, nausea, vomiting, stomatitis, alopecia, renal failure, profound peripheral neuropathy, and hypersensitivity vasculitis. Treatment was stopped because of the latter two. These agents are non-crossresistant with doxorubicin-containing regimens. The drugs are possibly synergistic and modestly active with moderate to severe toxicity.
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PMID:Cisplatin, VP-16-213 and MGBG (methylglyoxal bis guanylhydrazone) combination chemotherapy in refractory lymphoma, a phase II study. 319 89

Three patients were studied: two infants with acute monocytic leukemia who failed to respond to the initial combination therapy of daunorubicin with cytosine arabinoside, and an adolescent with relapsed acute monocytic leukemia. They were intensively treated with epipodophyllotoxin (VP-16-213) alone and subsequently had complete remission. One patient showed apparently dose-dependent cytotoxic effect. All three patients have maintained complete remission for 6, 7, and 11 months, respectively. Toxicities, including myelosuppression, alopecia, nausea, vomiting, and renal dysfunction, were well tolerated. Intensive treatment with VP-16-213 alone was thus found to have a potent therapeutic effect on acute monocytic leukemia in children. VP-16-213 deserves a further assessment in the therapeutic protocol for patients with childhood acute monocytic leukemia.
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PMID:Acute monocytic leukemia in children. Response to VP-16-213 as a single agent. 332 51

The present trial was designed to compare the effect of metoclopramide(MCP) + dexamethasone(DM) (Method A) with that of MCP + DM + lorazepam(Lor) (Method B) in the treatment of CDDP (cis-diamminedichloroplatinum)-induced nausea and vomiting in a randomized fashion. The results were collected by questionnaire given to 50 patients. The dosage of CDDP was 80-100 mg/m2. In addition, MMC and VDS, or VP-16 were used concurrently. Within 24 hours after the administration of CDDP, vomiting was not observed in 72% and 88% of the patients treated with Method A and Method B, respectively, and nausea was not noted in 48% and 68%, respectively. Marked malaise was observed in 36% of patients in the Method A group and in 12% in the Method B group. With respect to the extent of comfort, 16% of patients in the Method A group and 56% in the Method B group felt good. Sixteen percent in the Method A group and 56% in the Method B group were satisfied with the anti-emetic treatment. Thus, Method B was significantly superior to Method A with regard to the degree of comfort and treatment satisfaction.
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PMID:[Anti-emetic treatment with metoclopramide and other drugs during CDDP therapy]. 380 Apr 3

Etoposide (VP-16) is a semisynthetic epipodophyllotoxin that exhibits cell cycle phase specific cytotoxicity and enhanced effectiveness with increasing duration of drug exposure. We have therefore conducted a Phase I trial to determine the side effects, tolerable doses, and pharmacokinetic parameters of VP-16 given by continuous i.v. infusion to patients with advanced cancer. Eighteen patients were treated with varying dosages of VP-16 infused continuously for 72 consecutive hours every 28 days. Using this schedule, the maximally tolerated dosage of VP-16 was 150 mg/m2/day for patients with good performance status and 125 mg/m2/day for more debilitated cancer patients. Hematological toxicity was dose limiting with median granulocyte and platelet nadirs of 700/mm3 and 116,000/mm3, respectively, at a dose of 150 mg/m2/day. Other toxicities included only mild nausea, vomiting, and alopecia. Plasma and urine VP-16 concentrations were determined using a high-performance liquid chromatography assay. At a VP-16 dosage of 150 mg/m2/day, steady-state VP-16 concentrations were in the range of 2.1 to 7.0 micrograms/ml in all patients. Further pharmacokinetic analysis revealed that the plasma clearance of VP-16 was consistently near 25 ml/min/m2 (independent of dosage) and that renal clearance accounted for only 15% of VP-16 total plasma clearance. Patient age was found to be the most important factor correlating with plasma clearance of VP-16. Linear regression analysis also revealed that both the plasma VP-16 concentration at steady state and the concentration of VP-16 in plasma at 24 h from the start of the infusion correlated with hematological toxicity; no other patient characteristics correlated with hematological toxicity. The recommended VP-16 dose for Phase II trials of 72-h continuous infusion VP-16 is 150 mg/m2/day in patients with good performance status.
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PMID:Phase I clinical and pharmacological study of 72-hour continuous infusion of etoposide in patients with advanced cancer. 381 83

A Phase II clinical trial of NK 171 (Etoposide), a semisynthetic podophyllotoxin, was undertaken in 56 patients with advanced malignant lymphoma and 36 patients with acute leukemia. The dosage of NK 171 was 110-130 mg/m2 day p.o. or 80-100 mg/m2 day i.v. for 5 consecutive days. Of the 92 patients, 23.9% obtained a complete or partial remission. By tumor type, good responses were obtained in non-Hodgkin's lymphoma (34%, 17/50), Hodgkin's disease (25%, 1/4), AML (21.4%, 3/14), and CML-BC (25%, 1/4). Side effects included leukopenia (78.4%), alopecia (62.0%), anorexia (40.2%), nausea (30.4%) thrombocytopenia (25.6%) and fever (16.3%). These results demonstrated NK 171 to be an effective agent against malignant lymphoma and acute myeloblastic leukemia.
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PMID:[Phase II study of NK 171 (etoposide) on malignant lymphomas and acute leukemia. A cooperative study group on NK 171 in hematological malignancies]. 395 73

Phase II study of Etoposide administered intravenously and orally was performed in 163 patients with urologic malignancies for the clinical evaluation of responses and adverse effects. The eligibility of the patients and evaluation of the responses were carried out according to the general criteria proposed by Koyama and Saito. Out of the 163 patients registered in the study, it was possible to evaluate 141. In the cases of intravenous administration, the response rates were 16.7% in testicular cancer mostly refractory to prior therapy, 15.6% in bladder cancer, 7.7% in prostatic cancer, and 0% in renal cell route. The overall response rate was 11.1%. Toxicities were noted in the gastrointestinal tract, the rates being 54.4% for anorexia, 35.4% for nausea and 17.7% for vomiting. Alopecia was observed at a high incidence of 72.1%. Myelosuppression leukopenia and thrombocytopenia were the other prominent adverse effects.
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PMID:[Collaborative phase II study of etoposide (NK-171). Urological Cooperative Study Group of etoposide (NK-171)]. 404 Sep 86

Eighteen patients with advanced and heavily pretreated squamous cell carcinoma of the head and neck were treated with etoposide (VP-16). Of 16 patients evaluable for response, two (13%) achieved partial response lasting 3 to 4 months, and five (31%) achieved stable disease status lasting 2 to 7 months. One patient achieved a partial response in regional lymph nodes and the primary site, while a second patient achieved a partial response of a regional lymph node recurrence. Toxicity was significant but acceptable, consisting mainly of leukopenia and alopecia. Thrombocytopenia and mild nausea were also seen. VP-16 demonstrated modest activity in this disease and might be considered for further trials.
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PMID:Phase II study of etoposide (VP-16) in the treatment of advanced head and neck cancer. 406 73

The effect and toxicities of Cis-containing combination chemotherapy were tested in 28 patients with primary lung cancer. All patients were treated with 80 mg/m2 Cisplatinum on the first day and 750 mg ftorafur p.o. every day. In addition to these drugs, patients with squamous cell cancer were treated with continuous subcutaneous infusion of 4 mg/m2 Peplomycin for 5 days and one shot i.v. of 4 mg MMC. Patients with adeno- and large cell cancer were treated with 30 mg/m2 Adriamycin and 4 mg MMC, while patients with small cell cancer were given 150 mg/m2 VP-16 p.o. for 5 days. The following results were obtained. Of 22 evaluable patients, overall response rate was 50%. In each histologic type, response rate was 50% (5/10) for squamous cell carcinoma 50% (4/8) for adenocarcinoma 33% (1/3) for large cell carcinoma and 100% (1/1) for small cell carcinoma. No CR was obtained in this series. Main side effects due to Cisplatinum were nausea, vomiting, loss of appetite, mild leukopenia and thrombocytopenia, mild elevation of serum creatinine and BUN and alopecia, all of which were transient. Interstitial pneumonitis was observed in 40% of patients with squamous cell cancer. Two patients with adenocarcinoma died within 3 weeks after treatment due to embolism of the abdominal aorta and myocardial infarction probably caused by treatment with Adriamycin.
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PMID:[CDDP-containing combination chemotherapy for advanced lung cancer]. 621 53

Twenty-three patients with non-small cell lung cancer were treated with a combination of cis-dichlorodiammineplatinum (II) 100 mg/m2 IV on day 1 and VP 16-213 80 mg/m2 IV on days 1-3. Eighteen patients are evaluable for response. Seven partial remissions with a median duration of 3 months (range, 1-13+) have been observed. Three patients exhibit stable disease, and eight patients show tumor progression. Overall survival was 5+ months (range, 1-13+); 7.5 months (range, 3-13+) for responders and 3+ months (range, 1-9+) for non-responders. Hematologic toxicity was acceptable, but poor subjective tolerance (nausea, vomiting, loss of appetite) was the main factor limiting treatment duration.
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PMID:Cis-dichlorodiammineplatinum (II) and VP 16-213 combination chemotherapy for non-small cell lung cancer. 626 80

Sixty-two patients with previously untreated limited stage small cell lung cancer were treated in a prospectively randomized trial comparing thoracic irradiation plus combination chemotherapy with VP-16-213, vincristine (Oncovin), cyclophosphamide, and Adriamycin (VOCA) or those same four drugs plus low-dose (40 mg/m2) cisplatin (VOCAP). The addition of the cisplatin in eight courses of planned chemotherapy did not significantly improve either time to tumor progression of survival or alter sites of disease progression. It did, however, worsen the degree and frequency of nausea, vomiting, and myelosuppression. We did not identify any benefit from the usage of low-dose cisplatin as employed in this study.
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PMID:An evaluation of low-dose cisplatin as part of combined modality therapy of limited small cell lung cancer. 626 70


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