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)

Intra-arterial hepatic chemotherapy (IAHC) with adriamycin (ADM) has not increased its therapeutic index. For our preclinical studies, we selected pirarubicin (THP), an ADM derivative with faster cellular uptake. In rabbits with VX2 tumor in the liver we compared plasmatic and cellular pharmacokinetics of ADM and THP after i.v. and IAH therapy. For ADM, there were no differences in plasma and heart concentrations, with only a slight increase in tumoral levels after IAH compared to i.v. administration; on the other hand, with IAH THP, there was important reduction in systemic exposure with a major increase in tumoral drug distribution. In the phase I study, involving nine patients with implanted catheters, the starting dose of THP was 30 mg/m2 with a 10 mg/m2 intrapatient escalation every 3 weeks in the absence of toxicity. Pharmacokinetics were compared for i.v. and IAH administration in seven patients. The limiting toxicity was neutropenia and the maximal tolerated dose (MTD) ranged from 50 to 110 mg/m2. Moderate nausea-vomiting (grade 1-2) and alopecia (grade 1) occurred at the MTD. No arterial occlusion, gastroduodenal ulcer, hepatitis, or sclerosing cholangitis were seen. In the phase II study, in colorectal cancer patients (CRC) with metastasis confined to the liver, patients were enrolled until June 1990. THP (40 min infusion every 3 weeks) was initiated at 60 mg/m2 with 10 mg/m2 increment until grade 2 hematotoxicity. The median MTD was 85 mg/m2 (range of 60-120 mg/m2), and the median number of cycles was 7 (range of 2-11) with cumulated doses from 180 to 1,030 mg/m2. Grade 2-4 neutropenia was reached in 15 patients. Other toxicities included two arterial occlusions, one episode of gastritis, but no hepatic toxicity and no heart failure. Antitumor effect (in 18 patients) included 1 CR, 5 PR, 3 MR, 6 NC, and 3 PD. The median survival was 18+ months and 1-year survival was 73% +/- 12%. Seven patients had extrahepatic progression at this time. In conclusion, besides 5-FU or Fudr, THP is active in IAHC (probably in relation with high local extraction) on CRC liver metastases usually unresponsive to ADM. It can be given in an outpatient setting with minimal toxicity.
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PMID:Intra-arterial hepatic chemotherapy with pirarubicin. Preclinical and clinical studies. 229 52

The recent successes being achieved with combination chemotherapy regimens, such as FAMTX (fluorouracil [5-FU], doxorubicin, methotrexate), EAP (etoposide, doxorubicin, cisplatin), and ELF (etoposide, leucovorin, 5-FU), strongly indicate that gastric cancer is chemosensitive. With these regimens, objective remission rates of more than 50% were recorded, including approximately 10% complete remissions (CRs). Moreover, some of these CRs were histopathologically confirmed. The finding that locally advanced disease (LAD) and technically unresectable disease could be rendered resectable by preoperative chemotherapy (EAP) was important. Thirty-six patients with LAD had been treated in a phase II trial with preoperative EAP, inducing 24 (70%) overall remissions (two clinical CRs, six pathologic CRs, 16 partial remissions [PRs] in 35 evaluable patients. Twenty-one patients were disease-free after chemotherapy with or without second-look surgery. The median survival time was 18 months for all patients and 24 months for disease-free patients. At 30+ months, 21% of all patients are still living disease-free. The expected survival of patients with unresectable LAD is approximately 4 to 6 months without any treatment and 6 to 9 months with standard chemotherapy. Compared with the latter results, the preoperative use of effective regimens (eg, EAP) seems to improve prognosis of patients with LAD. Moreover, such a multimodal approach may increase the number of long-term survivors among patients with resectable gastric cancer, especially those whose stage indicates a high risk of relapse (stages IIIa or IIIb). However, partly because of the severe toxicities (myelosuppression, nausea/vomiting), a considerable number of patients cannot be treated with these new regimens for the following reasons: Two of three patients with gastrointestinal disease are older than 60 years. Nontumorous diseases of the cardiovascular system, kidney, and others are frequent in this age group and may complicate or even prevent treatment with aggressive regimens. Considering the predominantly palliative treatment intentions in far advanced (metastasized) gastric cancer, regimens with low toxicities and acceptable activity should be preferred. For these reasons, we developed and investigated the combination ELF in a phase II trial in elderly patients (greater than 65 years) and in patients with cardiac risks who could not be treated with anthracyclines. The overall response rate in 51 evaluable patients was 53% (27 of 51) including six clinical CRs (12%). The median remission duration was 9.5 months and the median survival time was 11 months. Tolerability was excellent. Only 16% and 4% of patients, respectively, experienced WHO grades 3 and 4 leukopenia. Nausea/vomiting and mucositis/stomatitis were mild.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:New developments in the treatment of gastric carcinoma. 230 69

Efficacy of a 48-hour infusion of 5-FU in patients with stage IV gastric cancer was investigated. A one-cycle regimen consisted of a 48-hour infusion of 5-FU (30 mg/kg/24 hours) every week for 6 weeks. Fourteen patients with stage IV gastric cancer who underwent absolutely non-curative gastrectomy, received 5-FU infusion postoperatively. Ten of the 14 received more than 2 cycles. Survival rates in these patients (group I) were evaluated by Kaplan-Meier method and compared with those of matched pair controls (group II) who received other anticancer agents. Side effects were generally mild. Nausea during infusion was observed in only 3 cases. The 50% survival period was 393 days in group I and 135 days in group II, respectively. The survival curve in group I was significantly higher than in group II (p = 0.05). From these results, this treatment is considered to be very effective.
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PMID:[Efficacy of a 48-hour infusion of 5-fluorouracil in patients with stage IV gastric cancer after palliative gastrectomy]. 236 35

A 52-year-old woman with bilateral liver metastasis originating from rectal cancer was treated with transarterial infusion of cisplatin, MMC, 5-FU and ADM after abdomino-peritoneal resection of the rectum. Cisplatin was infused continuously for 72 hours up to a 150 mg of dose through a Port-A-Cath which was inserted via gastro-duodenal artery at operation. The side effects observed were nausea, vomiting and leukopenia, but renal dysfunction was not encountered. Histology of the rectal lesion revealed poorly differentiated adenocarcinoma. The liver lesions were followed up by Echo, CT and angiography after chemotherapy, which demonstrated remarkable reduction in size or disappearance of the tumors.
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PMID:[A case report of bilateral liver metastasis from rectal cancer effectively treated with continuous infusion of anti-cancer drugs through hepatic artery]. 250 76

It is very common for intraarterial infusion therapy of some anticancer agent to be effective against hepatocellular carcinoma. In this case, the patient was a 74-year-old man who suffered from very advanced hepatocellular carcinoma with tumor thrombus of the intrahepatic portal vein and IVC. He was treated with intraarterial infusion of CDDP, Etoposide, 5-FU, through a catheter placed in the proper hepatic artery. CDDP (30 mg/day) and Etoposide (60 mg/day) were given once every 5 days, and then 5-FU(250 mg/day) was infused daily for 26 days. The patient underwent this protocol study twice in 3 months. After the intraarterial infusion, transarterial embolization using CDDP (100 mg) powder added to lipiodol and aluminum stearate as suspension was done a month later. The tumor regression rate was 84% after intraarterial infusion of CDDP, Etoposide and 5-FU. The tumor thrombus in the intrahepatic portal vein and IVC had completely disappeared. We could not find lipiodol accumulated in the tumor after TAE. Thus, we assumed that the remaining tumor was a necrotic scar and that a complete response was obtained in the patient. There were some side effects, such as nausea, vomiting, pancytopenia and gastritis but no severe complication occurred.
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PMID:[A case of hepatocellular carcinoma effectively treated by intraarterial infusion of CDDP and other agents]. 255 Dec 53

Although a 39-year-old male received the curative operation of total gastrectomy for advanced scirrhous carcinoma of the stomach, recurrence of cancer was occurred soon after the surgery, accompanied by hemorrhagic diathesis from DIC. The abdominal CT scan examination revealed the rapid enlargement in the size of the several lymphnodes around the abdominal aorta, and the blood chemistry tests showed marked increase of the serum CEA value. The sequential chemotherapy with intermediate dose of MTX and 5-FU in conjunction with OK-432 was started to treat the case. This chemotherapy was carried out once a week for 5 times and consequently DIC was led to the perfect remission. Furthermore, CEA level decreased within normal range, and the size of the enlarged lymphnodes at paraaortic area diminished remarkably. Although he complained of nausea and loss of appetite during the treatment, no severe adverse effects such as granulocytopenia, diarrhea, or loss of hair were observed. The successful result in this patient suggests that sequential therapy of intermediate dose of MTX and 5-FU with administration of OK-432 may be effective in the treatment of advanced scirrhous carcinoma of the stomach.
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PMID:[Effect of sequential MTX/5-FU therapy for a case of disseminated intravascular coagulation syndrome associated with recurrence of gastric cancer--a case report]. 255 83

Twenty patients with primary hepatic carcinoma (PHC) treated by hepatic arterial embolization in our department from Dec. 1986 to Mar. 1987 are reported. There were 15 males and 5 females. The ages ranged from 34 to 75 years with an average of 50.7. Preoperative diagnosis and localization of the tumor were done by AFP, B-us, CT and angiography (right lobe 15 cases, left lobe 1 case, both lobes 4 cases). Celiac and superior mesenteric angiography was carried out by femoral artery approach and then highly selective hepatic catheterization was utilized for hepatic arterial embolization. Antitumor agent (5-Fu, adriamycin), iophendylate and foamy gel sponge were used for peripheral and proximal embolization. Manifestations were improved in most of the patients after embolization, such as relief of abdominal pain, improvement of appetite, decrease of tumor size. Total necrosis of the tumor was found in 2 patients who underwent surgery 1 month after embolization. The side effects of the posthepatic embolization such as, nausea, vomiting, abdominal pain and fever could be relieved by symptomatic treatment. No severe complications, such as gangrene of the gall bladder, hepatic failure, liver abscess, intestinal necrosis or pulmonary embolization were found except 3 patients who died of renal failure after the procedure. The liver dys-function returned to normal within 2 weeks. Hepatic arterial embolization provides an alternative treatment for the patients with PHC who has compensated liver function without severe systemic diseases, especially renal endocrine problems and severe portal hypertension. They should have patent portal system as proved by angiography. The authors considered that this therapeutic embolization with hepatic chemotherapy infusion is safe and effective in the management of PHC. It may increase the resectability and provide palliative means for the advanced and terminal cases.
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PMID:[Hepatic artery embolization for primary hepatic carcinoma]. 255 66

Three hundred five patients with advanced pancreatic and gastric carcinoma were randomly assigned to treatment with fluorouracil, fluorouracil plus doxorubicin (Adriamycin) (FA), or fluorouracil plus doxorubicin plus mitomycin (mitomycin C) (FAM). All regimens were equivalent with regard to patient survival. There is no reasonable likelihood that either the FA or FAM regimen could produce a meaningful survival advantage over fluorouracil alone. Interval to disease progression, objective response rates, and palliative effects (improved performance, body weight, or symptoms) were essentially equivalent among the three regimens. With regard to toxicity, the FAM regimen produced more anorexia, nausea, vomiting, leukopenia, thrombocytopenia, and cumulative bone marrow suppression. Fluorouracil alone produced more stomatitis and diarrhea. Because of a failure to produce improved survival or palliation, unrewarded toxicity, and excessive cost, neither the FA nor FAM regimen can be recommended for the treatment of advanced pancreatic or gastric cancer.
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PMID:A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma. Fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin. 257 57

Continuous arterial infusion chemotherapy is associated with a significantly greater tumor response rate, though patients must be hospitalized for a long time. This paper describes techniques and our experience with arterial continuous infusion chemotherapy for outpatients using implantable port and ambulatory pump. Eleven patients (liver metastasis of colorectal cancer, hepatocellular carcinoma and local recurrence of rectal cancer) were treated with continuous arterial infusion chemotherapy at our outpatient clinic. The chemotherapy infusions were carried out repeatedly for 5.7 months on average (10-2 months) with 5-FU or CDDP. Total periods of infusions were 64.8 days on the average (136-24 days). The infusion dose and frequency of drug refilling were limited by pump quality. A major complication occurred only in one patient who developed arterial thrombosis. Minor complications were mainly gastrointestinal symptoms (nausea, vomiting) and abdominal pain, which were easily corrected with drugs. The tumor responses were as follows: PR 1 case, MR 1 case, NC 7 cases and PD 2 cases. Home arterial continuous infusion chemotherapy reduced the hospitalized period and helped patients return to work. Therefore it may well contribute to improve the quality of life of cancer patients.
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PMID:[Continuous arterial infusion chemotherapy in cancer cases followed as outpatients]. 278 3

Malignant intra-abdominal neuroendocrine tumors are rare; consequently, a standard chemotherapeutic protocol for patients with unresectable disease has not been established. This prompted a review of our experience with dimethyltriazeno imidazole carboxamide (dacarbazine) (DTIC) treatment for these tumors. From 1976 to 1986, 14 patients were treated with DTIC for metastatic neuroendocrine tumors. There were seven men and seven women whose ages ranged from 19 to 76 years. Diagnoses included eight nonfunctioning islet-cell carcinomas, three retroperitoneal neuroendocrine tumors, two glucagonomas, and one ileal carcinoid. Before DTIC chemotherapy, four patients were treated with streptozotocin and 5-FU, and one was treated with cytoxan and methotrexate without response. Two patients who were initially treated with DTIC with no response were subsequently treated with streptozotocin and 5-FU without benefit. Standard treatment with DTIC consisted of monthly cycles of 250 mg/m2/day administered intravenously for 5 days. Seven patients had an objective response to DTIC with both improvement in quality of life and a decrease of more than 50% in tumor size on computerized tomography (CT) or liver scanning. Response duration ranged from 1 to 10 years. One patient with a glucagonoma was treated for two years and had no evidence of disease at laparotomy 7 years later. Four patients with nonfunctioning islet cell carcinoma had a positive response to DTIC, but three of these patients had tumor recurrence 3 to 6 years after treatment. Two patients with retroperitoneal neuroendocrine tumors had a positive response to DTIC treatment. One patient with a glucagonoma and one with a nonfunctioning islet-cell tumor had equivocal responses with transient clinical improvement but no objective changes in tumor size. Five patients did not respond; two were given DTIC therapy as a last resort and died 1 and 12 days later. Of the other three patients, two died 6 months and one 2 years after treatment. DTIC chemotherapy was effective in 50% of patients with intra-abdominal neuroendocrine tumors. Although DTIC therapy was associated with nausea, no major gastrointestinal, hematologic, or renal complications were noted. This favorable experience with DTIC chemotherapy for nonresectable intra-abdominal neuroendocrine tumors indicates that further clinical evaluation and use are warranted.
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PMID:DTIC therapy in patients with malignant intra-abdominal neuroendocrine tumors. 282 70


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