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)

Fifteen patients were treated in a Phase I study of intracarotid carboplatin (200-400 mg/m2) in 5% dextrose and water infused over 15 to 30 minutes through a transfemoral catheter with a 0.2-micron inline filter. This study was done because intravenous carboplatin has less neurotoxicity than cisplatin and is active against brain tumors. Eleven men and four women ranging in age from 37 to 72 years (median, 59 years) were treated. The Eastern Cooperative Oncology Group performance status was 1 in 3, 2 in 4, and 3-4 in 8 patients. Eight patients had one to three previous chemotherapy regimens; previous radiotherapy had failed in 13 patients. The response of patients in the Phase I study follows: glioblastoma, 6 failed; not evaluated because of early death from pulmonary embolus, 1; recurrent Grade II and III glioma, 1 stable (minor response with neurologic improvement) and 2 failed; malignant oligodendroglioma, 1 failed; brain metastases from nonsmall cell lung cancer, 1 partial remission, 1 stable (minor response), and 1 failed; brain metastases from unknown primary, 1 stable (minor response with neurological improvement). Median survival was 9 weeks. Nausea was mild to moderate. One patient had granulocytopenia, and 2 had thrombocytopenia (mild). At 200 mg/m2 (2 patients), 1 had a focal seizure. At 300 mg/m2 (9 patients), 2 with abnormally small arteries had severe pain early in the treatment and posttreatment ipsilateral conjunctival edema, decreased vision, and cerebral edema (with partially reversible increased hemiparesis); 1 other had mild decrease in ipsilateral vision and 1 had transient aphasia on removal of the catheter (possibly the result of a vascular spasm).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I study of intracarotid administration of carboplatin. 131 64

A phase II clinical study of 254-S, a new anticancer platinum complex, for primary lung cancer was conducted by the 254-S Lung Cancer Study Group consisting of 15 institutions nation-wide. Considering the results of the phase I clinical study, 254-S was administered at 100 mg/m2 by intravenous drip infusion and this administration was repeated at least 2 times at 4-week intervals. Of 75 patients registered, 61 patients consisting of 22 with small cell lung cancer (SCLC) and 39 with non-small cell lung cancer (NSCLC) were evaluable for complete tumor response. Partial response (PR) was obtained in 17 patients, for a 27.9% response rate. The response rate for SCLC was 40.9% (9 PR in 22 patients) and that for NSCLC was 20.5% (8 PR in 39 patients). In SCLC patients with no prior chemotherapy, a 50.0% (5 PR in 10 patients) response rate was obtained. In those with prior chemotherapy, the response rate was 33.3% (4 PR in 12 patients). In NSCLC patients with no prior chemotherapy, a 22.6% (7 PR in 31 patients) response rate was obtained. In hose with prior chemotherapy, the response rate was 12.5% (1 PR in 8 patients). Major toxic effects observed were hematotoxicity such as thrombocytopenia and leukopenia, and gastrointestinal toxicity such as nausea, vomiting and anorexia. Nephrotoxicity observed was mild and infrequent in spite of the low-volume hydration performed. Based on these results, it was concluded that 254-S is a useful anticancer agent for the treatment of primary lung cancer.
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PMID:[A phase II clinical study of cis-diammine glycolato platinum, 254-S, for primary lung cancer]. 131 98

Forty-two patients with unresectable non-small cell lung cancer (NSCLC) were treated with carboplatin (300, 350 or 400 mg/m2) and 21 days of oral etoposide (50 mg/m2/day). Thirty-three patients were evaluable for response (too early to assess the remaining patients) and 9 patients (27%) achieved a partial remission. Median survival was 29 weeks (range, 4+ to 71+ weeks). The primary toxicity was myelosuppression. Leukocyte and platelet count nadirs occurred between days 22 and 29. In cycle 1, median leukocyte nadir was 2.8 x 10(9)/l and the platelet nadir was 142 x 10(9)/l. Nonhematologic toxicities were modest and included alopecia in all patients, mild nausea, mild to moderate diarrhea, and an occasional increase in serum creatinine. Carboplatin plus oral etoposide is a tolerable outpatient regimen with modest activity against unresectable NSCLC.
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PMID:Carboplatin plus oral etoposide in the management of unresectable non-small cell lung cancer. Preliminary results of a Vanderbilt trial. 132 13

Forty-seven previously untreated patients with histologically or cytologically proven non-small cell lung cancer were treated with ICE (ifosfamide/cisplatin/etoposide). Patients received ifosfamide 4 g/m2 with mesna uroprotection on day 1, and cisplatin 25 mg/m2/d and etoposide 100 mg/m2/d on days 1, 2, and 3; courses were repeated every 28 days. Premedication with prochlorperazine, dexamethasone, and high-dose metoclopramide was given to prevent nausea; lorazepam was added on days 2 and 3 only. Thirty-four men and 13 women (median age, 60 years) received a total of 146 treatment cycles. One patient had stage IIIA disease, seven had IIIB disease, and 39 had hematogenous metastases. Forty-six patients were evaluable for response and toxicity. One patient suffered a myocardial infarction on day 7 that was judged unrelated to treatment. Two patients suffered early death from toxicity and have been classified as nonresponders. Three patients achieved complete response (median, 42+ weeks) and 14 patients achieved partial response (median, 29+ weeks; range, 10 to 82+), for an overall response rate of 37% (95% confidence limits, 23% to 51%). The median survival of the entire group is 26 weeks (1 to 82+). The median nadir granulocyte count was 0.275 x 10(9)/L (range, 0 to 2.3 x 10(9)/L), and there were 14 episodes (in 11 patients) or neutropenia-associated fever, one of which resulted in death. Seven of these patients had not had the required protocol dose reduction for nadir neutrophil count in the preceding cycle. The median nadir platelet count was 120 x 10(9)/L (range, 13 to 385 x 10(9)/L), and three patients required platelet transfusions. Eleven patients had RBC transfusions. Only ten patients had grade 2 gastrointestinal toxicity. Five patients had microscopic hematuria, and one patient had central nervous system toxicity.
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PMID:Ifosfamide, cisplatin, and etoposide (ICE) in the treatment of advanced non-small cell lung cancer. 132 13

Eleven inoperable patients with non-small cell lung cancer were treated as a maintenance therapy with oral etoposide 25 mg daily. The toxicity appeared during the chemotherapy were assessed in all cases, but the blood concentration of the drug were measured in 5 cases on the first and the seventh day of treatment. While the peak plasma level (Cmax) was 0.92 +/- 0.43 microgram/ml on the first day and 1.02 +/- 0.30 micrograms/ml on the seventh day of chemotherapy, AUC was 12.3 +/- 5.41 micrograms.hr/ml and 11.9 +/- 4.52 micrograms.hr/ml on the first and the seventh day, respectively. Cumulative effect of the drug did not exist, since in any of these two measurements there was no significant statistical difference between values obtained on the first and on the seventh day. Regarding the toxicity of the drug, bone marrow suppression with abnormal reduction of peripheral white blood cells was observed. Though grade 2 adverse reaction was found in 6 cases, stopping drug administration for 2 weeks, enabled to re-administer the drug. Alopecia and liver or renal injury were not observed, and in spite of the presence of nausea and anorexia in one case, maintenance therapy could continue in all cases. Based on these results we concluded that etoposide can be safely administered as a maintenance therapy on out-patient basis.
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PMID:[Pharmacokinetic study and side effects of chronic daily administration of oral etoposide]. 132 70

We treated 34 chemotherapy-naive patients with stage IIIb or IV non-small cell lung cancer with trimetrexate 150-200 mg/m2 intravenously over 30 minutes every two weeks. Six of 31 evaluable patients (19%) achieved a partial response. The major toxic effects from this regimen were myelosuppression, nausea/vomiting, and skin rash. We conclude that this well-tolerated schedule of trimetrexate has significant activity as a single agent against non-small cell lung cancer.
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PMID:Phase II trial of trimetrexate for unresectable or metastatic non-small cell bronchogenic carcinoma. 133 71

Chloroquinoxaline sulfonamide (CQS) is a halogenated heterocyclic sulfanilamide identified by the in vitro human tumor colony-forming assay as an active agent in a variety of human solid tumors. In this phase I study, 182 courses of CQS were administered intravenously every 28 days to 88 patients at doses ranging from 18 to 4870 mg/m2. Hypoglycemia associated with hyperinsulinemia was the dose-limiting adverse effect at 4870 mg/m2. Supraventricular tachyarrhythmias were observed at doses > 4000 mg/m2. Less common reactions included infusion site phlebitis, nausea, anemia, alopecia, perioral numbness, and diarrhea. Cumulative toxicity was not observed. Minor objective antitumor responses were noted in 7 patients; 6 of the 7 responses occurred in patients with non-small cell lung cancer. Results of pharmacokinetic studies were consistent with the preclinical observations that CQS is highly bound to plasma protein. Plasma elimination followed a two-compartment model; the mean t 1/2 alpha was 2.7 +/- 0.3 h and the t 1/2 beta was 52 +/- 6 h (+/- SE). The total body clearance and the volume of distribution at steady state of CQS both increased with the dose (distribution at steady state, 3.7-10.5 liter/m2; total body clearance, 53-264 ml/h/m2 for doses of 18-4060 mg/m2) and may reflect saturation of the protein binding and "free" drug clearance. Although inactive against common animal tumors in preclinical screening systems both in vitro and in vivo, CQS has demonstrated definite activity in the human tumor stem cell colony-forming assays, as well as modest anticancer activity in this phase I study in patients with advanced solid tumors. The pharmacokinetic results and the limiting effect of transient hypoglycemia suggest that considerably higher cumulative doses of CQS could be administered using a more frequent dosing schedule.
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PMID:Phase I clinical and pharmacological study of chloroquinoxaline sulfonamide. 142 6

Twenty-eight patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) received neoadjuvant chemotherapy with cisplatin (120 mg/m2 on days 1 and 29) and vinblastine (4 mg/m2 weekly for 6 weeks). At the completion of induction chemotherapy, all patients were assessed for resectability. Those patients judged to be resectable underwent thoracotomy. All remaining patients received thoracic radiation therapy (5500 cGy) followed by additional chemotherapy in those patients responding to neoadjuvant treatment. There were 15 partial responses to neoadjuvant chemotherapy for an overall response rate of 54% (95% confidence interval, 36% to 71%). Only five partially responding patients (18%) were thought to have had sufficient tumor regression to allow for a potentially curative resection. However, a complete resection was done in only two patients. Overall median survival was 12 months (range, 4 to 72 months) with 1-year, 2-year, and 3-year survival rates of 54%, 39%, and 11%, respectively. The primary toxicity associated with neoadjuvant chemotherapy was moderate to severe (Eastern Cooperative Oncology Group Grade 3 or 4) nausea and emesis in 25% of patients. Hematologic toxicity was relatively modest; only one patient had Grade 4 leukopenia (less than 1000/microliter). Fever and neutropenia were uncommon, and there were no documented septic episodes or treatment-related deaths. Compared with historic controls treated with radiation therapy alone, cisplatin-based neoadjuvant chemotherapy appeared to improve the median and long-term survival of Stage III NSCLC patients modestly.
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PMID:Neoadjuvant cisplatin plus vinblastine chemotherapy in locally advanced non-small cell lung cancer. 165 2

Ifosfamide is an oxazaphosphorine alkylating agent with a broad spectrum of antineoplastic activity. It is a prodrug metabolised in the liver by cytochrome P450 mixed-function oxidase enzymes to isofosforamide mustard, the active alkylating compound. Mesna, a uroprotective thiol agent, is routinely administered concomitantly with ifosfamide, and has almost eliminated ifosfamide-induced haemorrhagic cystitis and has reduced nephron toxicity. Therapeutic studies, mostly noncomparative in nature, have demonstrated the efficacy of ifosfamide/mesna alone, or more commonly as a component of combination regimens, in a variety of cancers. In patients with relapsed or refractory disseminated nonseminomatous testicular cancer, a salvage regimen of ifosfamide/mesna, cisplatin and either etoposide or vinblastine produced complete response in approximately one-quarter of patients. As a component of both induction and salvage chemotherapeutic regimens, ifosfamide/mesna has produced favourable response rates in small cell lung cancer, paediatric solid tumours, non-Hodgkin's and Hodgkin's lymphoma, and ovarian cancer. Induction therapy with ifosfamide/mesna-containing chemotherapeutic regimens has been encouraging in non-small cell lung cancer, adult soft-tissue sarcomas, and as neoadjuvant therapy in advanced cervical cancer. As salvage therapy, ifosfamide/mesna-containing combinations have a palliative role in advanced breast cancer and advanced cervical cancer. Ifosfamide/mesna can elicit responses in patients refractory to numerous other antineoplastic drugs, including cyclophosphamide. With administration of concomitant mesna to protect against ifosfamide-induced urotoxicity, the principal dose-limiting toxicity of ifosfamide is myelosuppression; leucopenia is generally more severe than thrombocytopenia. Reversible CNS adverse effects ranging from mild somnolence and confusion to severe encephalopathy and coma can occur in approximately 10 to 20% of patients after intravenous infusion, and the incidence of neurotoxicity may be increased to 50% after oral administration because of differences in the preferential route of metabolism between the 2 routes of administration. Other adverse effects of ifosfamide include nephrotoxicity, alopecia, and nausea/vomiting. In general, intravenously administered mesna is associated with a low incidence of adverse effects; however, gastrointestinal disturbances are common following oral administration. Thus, ifosfamide/mesna is an important and worthwhile addition to the currently available range of chemotherapeutic agents. It has a broad spectrum of antineoplastic activity and causes less marked myelosuppression than many other cytotoxic agents. At present, the role of ifosfamide/mesna in refractory germ cell testicular cancer is clearly defined; however, its overall place in the treatment of other forms of cancer awaits delineation in future well-controlled comparative studies.
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PMID:Ifosfamide/mesna. A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer. 172 Mar 82

In a dose escalation study, CIS-diamminedichloroplatinum II (cisplatin) was combined with a standard dose of external beam irradiation in 15 patients with localized non-small cell lung cancer (NSCLC) and 16 patients with fixed or recurrent localized adenocarcinoma of the rectum. Cisplatin was given 5 days a week during irradiation using an outpatient portable infusion pump system, at doses of 3.2 mg/m2/24 hr in 15 patients, 4.0 mg/m2/24 hr in 13 patients, and 5.0 mg/m2 24 hr in 3 patients. Twelve of 15 patients with NSCLC received 66 Gy in 33 fractions in 6 1/2 weeks; one received 46 Gy followed by a surgical resection; for the other two patients treatment was discontinued after 50 Gy and 64 Gy, respectively, because they developed distant metastases. The 16 patients with rectal carcinoma received a preoperative dose to the pelvis of 45 Gy in 25 fractions in 5 weeks. Of 12 patients who underwent laparotomy, 10 had a surgical resection, 2 with close or positive surgical margins. Four patients who had resections received an intraoperative electron boost. Of the two patients who did not undergo resection at laparotomy, one received an intraoperative electron boost, the other a boost with interstitial iridium-192. Among the four patients with rectal adenocarcinoma who were not candidates for surgery because of advanced local disease, two had further external beam therapy up to 59.4 Gy, and two had no further therapy. Major toxicity was site-specific, with esophagitis predominating in the patients with NSCLC, diarrhea in the patients with rectal carcinoma, and nausea experienced by both. Cisplatin dose and toxicity seemed to be related. The maximum tolerated dose for low-dose continuous infusion cisplatin given 5 days/week in these patients was 3.2 mg/m2/24 hr combined with 66 Gy in patients with NSCLC and 4.0 mg/m2/24 hr combined with 45 Gy in patients with rectal carcinoma.
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PMID:Low-dose continuous infusion cisplatin combined with external beam irradiation for advanced colorectal adenocarcinoma and unresectable non-small cell lung carcinoma. 165 11


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