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)

Pirarubicin, a new antineoplastic antibiotic of anthracycline derivative, was injected into the pleural cavity in 15 patients with malignant pleural effusion. The dose of pirarubicin was 40 mg or 80 mg/body. All 15 patients were evaluable for both efficacy and toxicity. Since one evaluable patient received two courses of intrapleural administration of pirarubicin, we evaluated a total of 16 courses. Overall response rate was 81.3% with 7 CR cases, 6 PR cases and 3 NR cases. As toxicities, transient elevation of fever was observed in 81.3%, chest pain in 37.5%, appetite loss in 18.8%, nausea in 12.5% and bone marrow suppression in 6.3% of 16 courses, but no alopecia was observed. Between 40 mg group (n = 8) and 80 mg group (n = 8), no significant difference was observed in response rate, response duration, survival duration or toxicities except for fever. Fever over 38 degrees C was observed in all (100%) the 80 mg group, which was significantly higher than 50% in the 40 mg group. Response duration in cases with fever over 38 degrees C (n = 12) was significantly longer than in cases with maximum fever under 38 degrees C (n = 4). Intrapleural administration of pirarubicin was considered to be effective for the treatment of malignant pleural effusion without severe toxicities.
 ...
PMID:[Intrapleural administration of pirarubicin in the treatment of malignant pleural effusion]. 165 58

Pirarubicin is a more lipophilic derivative of doxorubicin, with a higher uptake rate of cells, lower cardiotoxicity and better antitumor efficacy in preclinical models. Thirty-four patients with metastatic breast cancer were treated in a multicenter phase II study with pirarubicin (THP) using a dosage of 75 mg/m2/every 3 weeks. The patients had a median age of 56 years (range 41-73) and a performance status of WHO grade 0-2. Patients pretreated with anthracyclines, or who were older than 75 years and without sufficient bone marrow reserve were excluded. The 32 evaluable patients received a median number of 4 cycles (range 2-8). The myelosuppression was dose-limiting and led to infections (grades 1 and 2) in 5 patients. Twenty-eight patients developed leukocytopenia grade 3 and 4 toxicity and 7 patients experienced thrombocytopenia grade 1 and 2. The drug was subjectively well tolerated and nausea, vomiting and alopecia were mild. One complete remission with a duration of 15.4 months (67 weeks) and 7 partial remissions with a median duration of 9.3 months (40 weeks) were achieved, which resulted in an overall response rate of 25%. Twenty-one patients were stable for 17 weeks (median) under the treatment with pirarubicin.
 ...
PMID:Phase II study of pirarubicin in metastatic breast cancer. 220 3

A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.
 ...
PMID:A phase I study of 4'-0-tetrahydropyranyladriamycin. Clinical pharmacology and pharmacokinetics. 222 62

Fourteen patients with metastatic breast cancer previously treated with one chemotherapy regimen received Pirarubicin at a dose of 70 mg/m2 at 3-week intervals. In 7 patients the dose had to be reduced, in 1 patient to 40 mg/m2 and in 6 patients to 50-60 mg/m2. There were 1 complete and 2 partial remissions. These objective responses were observed in soft tissue, lung and pleural areas and lasted 1+; 4+ and 5+ months. Grade 3 and 4 leukopenia was found in 42%, grade 3 thrombocytopenia in 2%, grade 3 nausea/vomiting in 29% of the cycles. Grade 1 and 2 alopecia occurred in 64% of the patients, the remaining 36% of the patients did not suffer from any alopecia. No cardiotoxic side effects were observed in 13 patients. In 1 patient with severe coronary heart disease extrasystoles and reduction in left ventricular ejection fraction occurred. Pirarubicin has antitumor activity in previously treated metastatic breast cancer patients.
 ...
PMID:Phase II study of pirarubicin (THP-adriamycin) in metastatic breast cancer patients. 231 31

Pirarubicin (4'-O-tetrahydropyranyladriamycin), a new anthracyline derivative, was administered as a single agent into the pleural cavity of 42 patients (total 46 courses) with malignant pleural effusion at a dose of 20, 40, 60 or 80 mg/body. All 46 courses were evaluable for non-hematological toxicities. Fever and chest pain (> or = WHO grade 2) were seen in 67.4% and 13.0% of courses, respectively. Patients receiving a dose of 80 mg/body developed fever of > or = 39 degrees C in 45.5%, and chest pain lasting more than three days and requiring pentazocine more than three times in 36.4%. In contrast, patients receiving a dose of < or = 60 mg/body presented these toxicities in only 8.6% and 2.9%, respectively. Nausea-vomiting (> or = WHO grade 2) was observed in only 4.3% of the total 46 courses and alopecia was not observed. Thirty-eight courses (36 patients) were evaluable for hematological toxicities. Myelosuppression (leukocyte nadir count < or = 1900, WHO grade 3 or 4) was seen in four courses (10.5%), and thrombocytopenia (< or = 49,000, WHO grade 3 or 4) in only two (5.3%). Although the mean AUC (0-24) for pirarubicin in plasma during the four courses that produced myelosuppression was significantly higher than that during the 11 courses without myelosuppression, the difference in the mean dose was not significant. Furthermore, no significant correlation was shown between dose (mg/m2) and AUC in plasma. It is considered that myelosuppression is not a dose-related toxicity at a dose of 20-80 mg/body. The dose-limiting toxicity was fever or chest pain, although unexpected myelosuppression was also encountered. The maximum tolerated dose was 80 mg/body. With regard to clinical efficacy, the overall response rate was 73.7% in 38 evaluable courses (38 patients). The mean T(1/2) of pirarubicin concentration in pleural effusion and plasma was 22.1 h and 8.8 h, respectively. We recommend a dose of 40 or 60 mg/body pirarubicin for this pleurodesic treatment.
 ...
PMID:Intrapleural pirarubicin (4'-O-tetrahydropyranyladriamycin) for treatment of malignant pleural effusion. 889 73