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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical pharmacology and toxicity of a novel anthracycline derivative, 4'-O-tetrahydropyranyladriamycin (THP-adriamycin), was investigated in patients with advanced malignant diseases. The starting dose was 30 mg/m2 which was escalated by increments of 10 mg/m2. Twelve patients with a median age of 42 (range, 19-69) years and a median Eastern Cooperative Oncology Group performance score of 2 (range, 1-2) were entered into the study. The diagnoses included four testicular cancers, two breast cancers, two small cell lung cancers, two acute myeloid leukemias, one colon cancer, and one hemangiosarcoma. THP-adriamycin was given as an i.v. bolus injection every 3 weeks. Evaluable were 18 courses for general toxicity, 16 courses for hematological toxicity, and 16 courses for pharmacokinetics. THP-adriamycin had a short initial half-life of 1.4 +/- 0.3 min (mean +/- SD) due to rapid cellular uptake. Peak concentrations in unseparated blood cells were reached 5 min after drug injection and remained higher than in plasma throughout the observation period of 72 h. The half-lives of THP-adriamycin in plasma were 19 +/- 2.8 min in an intermediate and 13 +/- 1.6 h in the terminal phase. A linear correlation was observed between the dose and the areas under the concentration curves for THP-adriamycin in plasma (r2 = 0.97) and blood cells (r2 = 0.99). The volume of distribution was 2124 +/- 221 liters/m2 and the total clearance rate 115 +/- 11 liters/m2h. THP-adriamycin was metabolized to Adriamycin, THP-adriamycinol, and adriamycinol. The major metabolite was Adriamycin with a terminal half-life in plasma of 33 +/- 10 h. The area under the curve of Adriamycin was also correlated to the administered dose (r2 = 0.96). Since excessive peak concentrations of Adriamycin were avoided, the treatment with THP-adriamycin might be an alternative to continuous infusions or weekly administrations. The maximum tolerated dose was 70 mg/m2, and the dose-limiting toxicities were leukopenia and thrombocytopenia. Anemia, nausea, and vomiting were mild to moderate, and no other toxicity was observed. All side effects were dose dependent and reversible. In a patient with breast cancer, a disease stabilization was achieved lasting for 9 weeks. No objective remission was observed. We suggest 60 mg/m2 in pretreated or poor risk and 70 mg/m2 in untreated or good risk patients every 3 weeks for further clinical trials.
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PMID:Clinical pharmacology and toxicity of 4'-O-tetrahydropyranyladriamycin. 381 48

Mitoxantrone (Novantrone), is an anthracenedione which in preclinical studies demonstrated a spectrum of antitumor activity similar to the anthracyclines, but with less cardiotoxicity. Novantrone is a cytotoxic agent that produces dose-dependent myelosuppression. When administered to patients intravenously every three weeks, white blood cell (WBC) and platelet nadirs occurred between days 8 and 15 with hematologic recovery by day 22. In multiple clinical trials in over 4450 patients, including 372 patients in randomized trials against Adriamycin, Novantrone was consistently associated with a reduced incidence of moderate and severe acute side-effects. In four randomized trials the adverse experience profile associated with Novantrone was superior to that of Adriamycin with statistically significant lower incidences of mucositis/stomatitis, nausea, vomiting and alopecia. Novantrone was less cardiotoxic than Adriamycin and cardiac events were rare in patients without predisposing risk factors. The high level of activity combined with improved patient tolerance and decreased toxicity make Novantrone a promising agent for patients requiring cytotoxic chemotherapy.
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PMID:Mitoxantrone: an overview of safety and toxicity. 389 76

Preliminary analysis of adjuvant chemo-endocrine therapy for 193 breast cancer patients was performed. The patients consisted of 38 cases of Stage I, 124 cases of Stage II and 31 cases of Stage III. Therapeutic regimen was randomly divided into three groups; (1) Tamoxifen (TAM), (2) TAM + ftorafur (FT-E) and (3) TAM + FT-E + Adriamycin. Side effects among the three therapeutic groups were comparatively studied. Anorexia and nausea were observed in 1.4%, 17.1% and 60% of the patients, respectively. Leucopenia of less than 3,000 and alopecia were remarkably seen in the patients treated with regimen 3. Liver dysfunction was observed in 10.9% of group 1, 29.5% of group 2 and 13.3% of group 3, respectively. Gastrointestinal symptoms and liver dysfunction were important side effects.
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PMID:[Preliminary report of adjuvant chemo-endocrine therapy for breast cancer]. 391 52

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

Hepatocellular cancer provides an ideal model for studying combined modality chemotherapy and radiation interactions. We have treated 20 evaluable patients. All patients received intrahepatic arterial (IA) 5 FU (10 mg/kg/d continuous infusion times 5 minus 9 d) + Adriamycin (3-5 mg/m(2)/d bolus times 5 minus 7 d), and 1,500 and 2,100 rads whole liver radiation (300 rads/day). Additionally, 3 patients have received IA Mitomycin C (8 mg/m(2)). After this "induction" therapy patients usually received IV Adriamycin + 5FU +/- Mitomycin monthly. Objective regressions occurred in 9/20 (45%) and another 9/20 (45%) and stable disease. Median duration of response is 5+ months (range 1+ to 8 months). Improvement in liver function tests occurred in 11/19, and local symptomatic relief in 12/15. Median WBC nadir = 4,000; platelet nadir = 115,000. Mild anorexia, fever, and nausea were frequent, but no radiation hepatitis has been detected. This program seems to result in significant clinical benefit (subjective and objective) in this refractory neoplasm.
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PMID:Therapy of hepatocellular cancer with combined intrahepatic arterial chemotherapy and whole liver irradiation. 625 17

A randomized, double-blind, placebo-controlled trial of oral and smoked delta-9-tetrahydrocannabinol (THC) was performed in eight patients with resected soft tissue sarcomas who received adjuvant Adriamycin and Cytoxan chemotherapy. Each patient served as his own control. Delta-9-tetrahydrocannabinol, in comparison with a placebo, did not significantly reduce the number of vomiting and retching episodes, volume of emesis, degree of nausea, or duration of nausea. In contrast to a previous report where significant antiemetic effects of THC were observed in patients receiving high-dose methotrexate, THC did not effectively reduce emesis induced by Adriamycin and Cytoxan. These findings suggest that the antiemetic properties of THC are effective only against specific chemotherapeutic drugs.
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PMID:A prospective evaluation of delta-9-tetrahydrocannabinol as an antiemetic in patients receiving adriamycin and cytoxan chemotherapy. 626 26

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

Chemotherapy with a combination of cisplatin (60 mg/m2), Adriamycin (45 mg/m2), and etoposide (120 mg/m2 X 3) (CAV) has been evaluated in 36 patients with small-cell bronchogenic carcinoma (SCBC) after two full courses. The complete response (CR) rate was 23% in patients with extensive disease and 64% in patients with limited disease; the partial remission (PR) rate was 59% in patients with extensive disease and 22% in those with limited disease after two cycles (six weeks) of therapy. Patients with CR survived significantly longer than patients with PR (P = 0.02). Side effects were acceptable and consisted mostly of nausea, vomiting, alopecia, and myelosuppression. Thirteen patients were included into a "late intensification" program that was performed with increased doses of CAV regimen used for remission induction. This intensification of chemotherapy was carried out in a protective environment and with autologous bone marrow transfusion. In two patients with PR, CR could be obtained after late intensification and in one patient whose disease was progressing, PR had been achieved. However, excessive extramedullary toxicity of the late intensification regimen, consisting of mucositis, suggested that CAV does not appear to be the optimal therapy for further intensification.
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PMID:Cisplatin, adriamycin, and etoposide (CAV) for remission induction of small-cell bronchogenic carcinoma. 628 35

A chemotherapy regimen consisting of hexamethylmelamine (H) 150 mg/m2 orally days 1-14, cyclophosphamide (C) 500 mg/m2 IV day 1 of a 28-day cycle with Adriamycin (A) 40 mg/m2 IV day 1 alternating with cis-diamminechloroplatinum (C-P) 50 mg/m2 IV day 1 every other cycle was administered to 29 patients with advanced epithelial ovarian cancer. Toxicity to this regimen included alopecia, nausea, and vomiting in all patients. Mild paresthesias occurred in four patients. Hematologic toxicity required only minimal dose modification. There was no cardiac, renal, or auditory toxicity. The clinical response rate of 55% and median survival of 14 months compare favorably with that of other reported series. This chemotherapy regimen seems to be well tolerated without jeopardizing the patients' response.
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PMID:Alternating multiagent chemotherapy for advanced ovarian cancer. 629 47

Nabilone, a synthetic cannabinoid, and Prochlorperazine were compared in a double-blind crossover study of 34 patients with lung cancer undergoing a 3-day schedule of chemotherapy with Cyclophosphamide, Adriamycin and Etoposide. Symptom scores were significantly better for patients on nabilone for nausea, retching and vomiting (P less than 0.05). Fewer subjects vomited with nabilone (P = 0.05) and the number of vomiting episodes was lower (P less than 0.05); no patients on nabilone required additional parenteral anti-emetic. More patients preferred nabilone for anti-emetic control (P less than 0.005). Adverse effects common with nabilone were drowsiness (57%), postural dizziness (35%) and lightheadedness (18%). Euphoria was seen in 14% and a "high" in 7%. Erect systolic blood pressure was lower in nabilone patients on Day 1 (P = 0.05) but postural hypotension was a major problem in only 7%. Nabilone is an effective oral anti-emetic drug for moderately toxic chemotherapy, but the range and unpredictability of its side-effects warrant caution in its use.
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PMID:Anti-emetic efficacy and toxicity of nabilone, a synthetic cannabinoid, in lung cancer chemotherapy. 631 40


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