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)

The efficacy of trofosfamide (Ixoten; Noristan), a derivative of cyclophosphamide, was investigated in 76 patients. Those with solid tumours were given 50 mg/kg in 6 divided doses in 48 hours; those with chronic lymphatic leukaemia were treated with 100 mg orally 3 times a day for up to 10 weeks. Side-effects of treatment included leucopenia, thrombocytopenia, a fall in the haemoglobin level, haematuria and occasional alopecia. Nausea was never severe, and occurred in only half of the patients on a high dose and in none of the patients on a low dose. A therapeutic effect was observed in patients with breast cancer, cancer of unknown origin and pancreatic cancer. Twenty-one of 24 patients with chronic lymphatic leukaemia (all of whom had aggressive disease) responded to treatment, and complete remission (including normal bone marrow), was achieved in 5 of these patients.
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PMID:Trofosfamide in the treatment of patients with cancer. A pilot trial. 35 87

In a multicentre study patients with liver metastases stratified to the histology of the primary tumour were investigated. A total of 102 patients with colorectal adenocarcinoma, non-small-cell lung cancer, pancreatic cancer, primary liver carcinoma and malignant melanoma were treated with the thioether lipid ilmofosine. The drug was administered orally as a tablet at a dosage of 150-300 mg/day (75 mg/tablet). The tolerability of ilmofosine was poor. There was a dose-limiting gastrointestinal toxicity with nausea, vomiting and loss of appetite (WHO grade II-IV) in 67% of patients. During the period of therapy (1-29 weeks, 8.5 weeks mean) no complete remission and no partial response were observed. We thus conclude that treatment with oral ilmofosine is not effective in patients with liver metastases due to various malignancies.
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PMID:Treatment results of the thioether lipid ilmofosine in patients with malignant tumours. 132 33

MK-329 is a nonpeptidal, highly specific cholecystokinin (CCK) receptor antagonist, with affinity for pancreatic and gallbladder CCK receptors similar to CCK itself. MK-329 and its progenitor, asperlicin, can inhibit the growth of CCK receptor-positive human pancreatic cancer in athymic mice. Based on these activities and the ability of MK-329 to transiently increase food intake and enhance morphine analgesia in murine models, we conducted an open trial of MK-329 in 18 patients with advanced pancreatic cancer in whom the CCK receptor status of the tumors was unknown. Tumor response, pain control, and nutritional parameters (hunger rating, caloric intake, body weight, and anthropometrics) were serially assessed. The results of the study failed to demonstrate any impact of MK-329 on tumor progression, pain, or nutrition. Toxicity was mild and limited to nausea, vomiting, diarrhea, and abdominal cramps, with 17 of 18 patients able to tolerate treatment. While a role for MK-329 in the management of patients with advanced pancreatic cancer cannot be supported by the results of this trial, additional studies of this agent in patients with known CCK receptor-positive tumors, at escalated doses, and possibly in conjunction with other growth antagonists, appear warranted.
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PMID:A pilot clinical trial of the cholecystokinin receptor antagonist MK-329 in patients with advanced pancreatic cancer. 155 66

We conducted a phase I trial of fluorouracil (5-FU), leucovorin, (LCV), and recombinant interferon-alpha-2b (rIFN-alpha-2b). The doses of each of the three agents were escalated sequentially. 5-FU and LCV were administered by IV bolus, weekly for 6 weeks and rIFN-alpha-2b was administered by subcutaneous injection, three times weekly for 6 weeks. Twenty-nine patients with advanced cancer (75% colon or pancreatic cancer) were treated. Partial remissions were observed in three patients (10%) with previously untreated colon cancer, colon cancer refractory to 5-FU plus LCV and previously untreated pancreatic cancer, respectively. An additional three patients with pancreatic, prostate, and rectal cancer had a 50% reduction in tumor markers but no change in objective tumor measurements. The toxicity of this regimen was tolerable. The most common toxicities were diarrhea, fatigue, flu-like symptoms, nausea/vomiting, and mucositis. However, no fatal or life-threatening toxicities were observed. We conclude that the combination of 5-FU, LCV, and rIFN-alpha-2b can be safely administered and recommend further evaluation of this regimen in patients with tumors of gastrointestinal origin using doses of 5-FU 600 mg/m2, LCV 500 mg/m2, and rIFN-alpha-2b 10 x 10(6) U.
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PMID:A phase I trial of fluorouracil, leucovorin, and recombinant interferon alpha-2b in patients with advanced malignancy. 155 45

Based on promising results with 5-FU/FA or 5-FU/IFN-alpha in colorectal cancer, a pilot study was initiated to evaluate the effects of the combination 5-FU/FA/interferon alfa (IFN-alpha) in patients with advanced pancreatic cancer. Patients received 9 million units (MU) IFN-alpha subcutaneously three times a week or 6 MU IFN-alpha once a week; 500 mg/m2 5-FU via an intravenous bolus 1 hour after the initiation of a 2-hour infusion of 500 mg/m2 of FA, once a week. Fourteen patients, all previously untreated with chemotherapy, were enrolled; 13 (two females/11 males) were evaluable for response and toxicity (one too early). The median performance status was 80% (range, 60 to 100) and the median age 62 years. Besides the inoperable primary tumor, metastatic sites were liver, lung, and peritoneum. Three of 13 patients had a partial remission, three of 13 patients a minor response, and four of 13 patients no change. Three patients had progressive disease. Until now, no complete remission was seen. Median duration of response was 4+ months; median survival has not been reached yet. Of all patients there were three instances of World Health Organization grade 3 toxicity: fatigue (one of 13), nausea (one of 13), and diarrhea (one of 13); grade 4 toxicity did not occur. Although overall toxicity was moderate, most patients experienced a reduction of well-being. Therefore in all patients the dose of IFN was reduced (from 3 x 9 MU/week to 1 x 6 MU/week). Our preliminary data suggest that biochemical modulation of 5-FU with FA and IFN-alpha (reduced dosage) is effective in pancreatic cancer with moderate toxicity, warranting further study.
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PMID:Combination fluorouracil, folinic acid, and interferon alfa-2a: an active regimen in advanced pancreatic carcinoma. 155 50

Cancer of the pancreas is rising in incidence and will strike 27,000 Americans this year. There is no curative therapy for most patients, so palliation of symptoms should be the prime concern. Severe pain is very common, and often difficult to treat. Neurolytic celiac plexus block (NCPB) is claimed by some to be the most effective way to treat pancreatic cancer pain (PCP), yet only a minority of patients undergo this procedure. We have reviewed the literature on NCPB to determine if it has been adequately evaluated in the management of PCP. There have been 15 published series since 1964 on NCPB for PCP. A total of 480 patients with cancer of the pancreas were reported; at least a satisfactory response to NCPB was reported in 418 (87%). We found major deficiencies in these reports. None described the pre-NCPB analgesic history. Post-NCPB data were also limited. No information was given concerning post-NCPB analgesic dosages, and only 4 series stated that most patients did not require opiates. Information on whether NCPB was effective until death was lacking or incomplete in 12 series. Many claimed additional benefits of NCPB such as decreased nausea, decreased constipation, and increased appetite, but none provided any data to support these claims. We conclude that the data available on NCPB for PCP are insufficient to judge for efficacy, long-term morbidity, or cost effectiveness, and rigorous evaluation of the technique is required.
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PMID:Has the analgesic efficacy of neurolytic celiac plexus block been demonstrated in pancreatic cancer pain? 169 55

Fifteen patients with invasive bladder cancer were treated with selective intra-arterial cisplatin and external beam radiotherapy (30.6 Gy over 3 weeks) prior to a planned cystectomy. Cisplatin, in total 200 mg, was administered via bilateral internal iliac artery infusion during the course of radiotherapy. Seven patients were evaluated for local response. Partial response (PR) was revealed in 4, and minor response (MR) in 3. Ten patients received total cystectomy, and pathological effects by the criteria adipted by Japanese Urological Association and The Japanese Society of Pathology, were as follows: Ef. 3 in 1 case, Ef. 2 in 6. Ef. 1b in 1 and Ef. 1a in 2. Down staging was observed in 8 patients from the clinical to the pathological stage. Thirteen patients are alive for 21 months. Two patients have died (1 lung infarction, 1 pancreatic cancer). Though nausea and sciatica-like pain were observed in some cases, there was no severe systemic side effects such as bone marrow suppression and renal toxicity. From these results it is concluded that this therapeutic modality could be effective in the preoperative work-up of candidates for total cystectomy, and also that it could be useful in the treatment of patients in whom total cystectomy is contraindicated.
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PMID:[Intra-arterial cisplatin and concurrent radiation for invasive bladder cancer]. 177 Jun 97

Twenty-eight patients with refractory advanced malignancies were treated with a 24-hour infusion of 5-fluorouracil (5-FU), leucovorin (LV), and N-(phosphonacetyl)-L-aspartic acid (PALA) weekly. Twenty-seven patients were evaluable to assess toxicity and antitumor activity. The PALA was administered as an intravenous bolus over 15 minutes at a fixed dose (250 mg/m2) 24 hours before the start of the 5-FU and leucovorin infusions. Initially the dose of 5-FU was 750 mg/m2; this was increased incrementally to 2600 mg/m2. The LV was administered in a fixed dose of 500 mg/m2 concurrently with the 5-FU over a 24-hour period. This regimen was repeated weekly. Diarrhea, stomatitis, nausea, and vomiting were among the dose-limiting toxicities. Others were hand-foot syndrome, hair loss of the scalp and eyelashes, overall weakness, rhinitis, and chemical conjunctivitis. The maximum tolerated dose of 5-FU in this combination and schedule was 2600 mg/m2. Seven of 14 patients treated with 2600 mg/m2 were able to tolerate the chemotherapy on a weekly basis without interruption. The other seven patients required dose reductions, but most received 5-FU at a dose of 2100 mg/m2. Twenty-three of 27 patients were treated previously. Eight patients had a partial response; five of these were treated previously. A complete response was observed in one patient with pancreatic carcinoma, previously untreated. The overall response rate for patients treated with 2100 or 2600 mg/m2 of 5-FU was nine of 18 patients (50%). Three of four previously untreated patients with pancreatic cancer responded to this treatment (two responded partially, and one had a complete response). One of three heavily pretreated patients with non-small cell lung cancer had a partial response as did a patient with breast cancer. Four of ten patients with colorectal cancer responded to the treatment (four partial responses), of whom three had been treated previously.
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PMID:A phase I, II study of high-dose 5-fluorouracil and high-dose leucovorin with low-dose phosphonacetyl-L-aspartic acid in patients with advanced malignancies. 187 76

A new dosage form of cisplatinum (CDDP), lactic acid oligomer microspheres incorporating cisplatinum (CDDP-ms), is designed to slowly release 70% of contained CDDP. CDDP-ms's acute toxicity is as low as 57% of the toxicity of CDDP aqueous solution, and its therapeutic efficacy is statistically significantly strong as compared with that of CDDP aqueous solution, when examined with experimental peritoneal carcinomatosis induced by mouse M5076 ovarian sarcoma. Clinical trials were carried out in 10 patients with malignant ascites (gastric cancer 6, pseudomyxoma peritonei 2, colon cancer 1, pancreas cancer 1) and in one patient with pleural effusion (lung cancer). CDDP-ms at 100 mg/person in terms of CDDP was injected at bolus into the affected cavity. In the 10 patients with ascites, 7 responded completely, two partially and one did not respond. The patient with pleural effusion responded partially. The response rate was 91%. Five of the 11 patients complained of temporary nausea or vomiting. In 5 patients fever higher than 38 degrees C was seen. No other side effect such as kidney, nor liver-damage or blood cell count abnormality was noted.
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PMID:[Intracavitary microspheres incorporating cisplatinum in the treatment of malignant effusions--clinical trials]. 238 51

Since 1984, 13 patients were entered into our study and 12 patients have completed one or more cycles of treatment with mixed bacterial vaccine (MBV), a natural biologic response modifier derived from Streptococcus pyogenes and Serratia marcescens. Eight patients with refractory malignancy were treated with MBV only (0.1 ml intravenously [IV]) twice weekly for 3-16 weeks (colorectal cancer, pancreatic cancer, chronic lymphatic leukemia, hepatoma [two patients], sarcoma [three patients]). Four patients with advanced non-small cell lung cancer were treated with MBV in combination with low-dose cyclophosphamide, day 1; cisplatin, day 15; and MBV, 0.1 ml IV, days 5, 7, and 9. Two patients in this study received cyclophosphamide and cisplatin alone. The cycle was repeated every 28 days. Plasma interferon levels, interleukin-2 production by peripheral lymphocytes, and lymphocyte subpopulations were monitored. Interferon levels and interleukin-2 production showed increased or sustained values in general. In some patients, B-cells and helper T-cell populations increased, whereas T-suppressor cell numbers declined. With one exception, side effects were mild and consisted of fever greater than 37.8 degrees C (nine of 13), chills (11 of 13), increased respiratory rate (nine of 13), minor changes in blood pressure (seven of 13), and nausea (three of 13). One patient with non-small cell lung cancer had a partial response. Two patients with non-small cell lung cancer and one patient with refractory malignancy had stable disease and performance status at the end of 8 weeks of treatment; one patient with refractory malignancy was stable at the end of 4 weeks of treatment. In this pilot study, cancer patients treated with MBV showed objective evidence of immune stimulation with acceptable toxicity.
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PMID:Effect of the mixed bacterial vaccine on the immune response of patients with non-small cell lung cancer and refractory malignancies. 245 82


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