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)

Because 1,2:5,6-dianhydrogalactitol (NSC-132313 (DAG; the main conversion reaction product of the treatment of dibromodulcitol by mild akali or human serum) showed considerable antitumor activity in various mouse and rat tumor systems, a phase I study in 50 patients was conducted with five daily iv treatments repeated every 6 weeks. Thrombocytopenia was the dose-limiting toxicity. At a dose of 40 mg/m2/day for 5 days, the median platelet nadir was 31,000/mm3 and occurred on day 20; the plate count returned to normal within 8 days. At the same dose, the median white blood cell (WBC) nadir was 2,300/mm3 also on day 20-, the WBC count returned to normal within 7 days. Anemia, nausea, and vomiting were usually mild to moderate. No renal, hepatic, central nervous system, cardiac, or pulmonary toxicity was identified. Antitumor effects of DAG were observed in patients with renal, bladder, and small-cell lung cancers. An iv dose of 20-30 mg/m2/day for 5 consecutive days, repeated every 5-6 weeks, was recommended for phase II studies.
J Natl Cancer Inst 1976 Jan
PMID:Phase I study of a five-day intermittent schedule for 1,2:5,6-dianhydrogalactitol (NSC-132313). 94 54

Twenty-two patients were given progressively increasing doses of Cytembena to determine toxicity patterns and to establish a dosage which produces definite but clinically tolerable toxicity when the drug is given by intravenous injections in a 5-day intensive course. Toxicity consisted primarily of nausea, vomiting, arm pain, and transiently decreased renal function. At higher doses, an "autonomic-storm" phenomenon was observed consisting of hypertension, tachycardia, tachypnea, hyperperistalsis, frequent explosive defecation, facial flushing and paresthesias, and chest pain with accompanying ischemic EKG changes. There was no evidence of mucocutaneous, hepatic, or hematologic toxic effects. Toxicity was dose-related, first being recognized at a daily dose of 300 mg/m2 and becoming clinically intolerable at a daily dose of 475 mg/m2. No permanent damage was observed in any of the organ systems monitored. An acceptable treatment regimen for most patients is 400 mg/m2/day for 5 days. Patient discomfort can be reduced by dividing each day's dose into two intravenous injections given at an interval of at least 6 hours. Coronary artery disease and impaired renal function should be contraindications to Cytembena therapy, and caution should be employed in the patients with significant impairment of liver function. Two of 22 patients, both with far-advanced carcinoma and previous chemotherapy failures, showed a favorable objective response to Cytembena therapy. Phase II studies to assess the magnitude of the drug's antineoplastic activity seem warranted.
Cancer 1976 Mar
PMID:A phase I study of cytembena. 94 91

There has been increasing interest regarding the use of Corynebacterium parvum (CP) with other modalities in the management of primary cancer. Due to the paucity of specific information available relative to CP toxicity, a Phase I study was carried out in patients with advanced disease. The purpose of the investigation was not to evaluate the effect of CP on tumor growth. from 273 injections of CP in 40 patients it was observed that following intravenous (i.v.) infusion of CP: a) a febrile response and chills of considerable severity occured in almost all patients and did not appreciably diminish in intensity following repetitive administrations; b) nausea, vomiting, headache, and confusion were not infrequent; c) a "flu-like" syndrome lasting 24 to 48 hours occurred following almost all courses of CP; d) blood pressure elevations occurred on occasion and were related to the severity of other-side-effects; hyper- or hypo- tension was not a problem; e) ther were no anaphalactic reactions. Pretreatment with a single administration of 100 mg of hydrocortisone prior to CP infusion markedly and in some instances dramatically diminished the toxicity and made acceptable the use of i.v. CP on an outpatient basis. The use of i.v. CP in patients with cerebral metasteses may be hazardous. Subcutaneously administered CP resulted in a significant number of undesirable local reactions. Evaluation of delayed cutaneous hypersensitivity response, immunoglobulins, complement, and E- and EAC-rosette-forming cells during CP administration failed to demonstrate significant change from injection values. Results were similar whether hydrocortisone pretreatment was or was not employed. From the standpoint of toxicity it now seems appropriate to use i.v. CP, particularly following pretreatment with hydrocortisone, in a controlled clinical trial to evaluate its therapeutic effectiveness in the management of primary cancer.
Cancer 1976 Jul
PMID:Observations following Corynebacterium parvum administration to patients with advanced malignancy. a phase I study. 94 9

Forty-eight patients with a variety of advanced solid tumors were treated with a combination of adriamycin 50 mg/m2, and cis-diamminedichloroplatinum 50 mg/m2, every 2 to 4 weeks. Fifteen patients responded with a greater than 50% regression of measurable tumor; six with lung cancer; one, carcinoma of the breast; one, ovary; one, cervix; one, prostate; one, testis; one, maxillary sinus; and one, salivary gland, plus one patient with chemodectoma and one with adenocarcinoma of unknown primary. Responses lasted 1 to 18 months, with a median of 6 months. An additional six patients, including two with adenocarcinoma of the lung three with carcinoma of the cervix, and one with embryonal cell testicular carcinoma improved (25-50% regression of the tumor). Toxicity encountered included myelosuppression, azotemia, alopecia, nausea, vomitting, and stomatitis. Severe hematologic toxicity occurred only in those with compromised marrow function or with concurrent active hepatitis. Major potentiation of toxicity by the combination does not appear to have occurred.
Cancer 1976 Jul
PMID:Combination chemotherapy with adriamycin and cis-diamminedichloroplatinum in patients with neoplastic diseases. 98 19

A toxicologic evaluation of dianhydrogalactitol in man was completed for a 5- and a 10-day schedule. The maximum tolerated dose was 30 mg/m2/day for the 5-day schedule and 21 mg/m2/day for the 10-day schedule. Dose-limiting myelosuppression occurred with both schedules, with leukopenia and thrombocytopenia being observed at median Days 15 and 19 respectively for the 5-day course and median Days 22 and 26 of the 10-day course. Nausea was infrequent and mild. Responses were obtained in one patient with laryngeal carcinoma and in one patient with adenocarcinoma of the lung.
Cancer Treat Rep 1976 May
PMID:Phase I evaluation of dianhydrogalactitol (NSC-132313). 99 Nov 50

The efficacy and tolerability of aminoglutethimide for the treatment of Cushing's syndrome was assessed in 66 cases three of which are described in the present paper. Aminoglutethimide provided palliation from the signs and symptoms of hypercorticism in 13 of 21 patients with metastatic adrenocortical carcinoma and four of six patients with ectopic ACTH production due to metastatic carcinomas. All six of the patients with adrenal adenomas showed clinical and biochemical improvement, while 14 of the 33 patients with bilateral adrenal hyperplasia of pituitary origin improved. Adverse reactions attributed to aminoglutethimide such as drowsiness, rash, and nausea occurred in 58 per cent of cases. These data suggest that aminoglutethimide has a place in controlling the signs and symptoms of adrenocorticoid excess in patients with Cushing's syndrome due to malignancy and is effective preoperative therapy for patients with adrenal adenomas and bilateral hyperplasia.
 ...
PMID:Aminoglutethimide in the treatment of Cushing's syndrome. 99 60

One hundred and nine adult patients with metastatic carcinoma were treated at 3-4-week intervas with a combination of adriamycin (40 mg/m2 given iv on Day 1) and cyclophosphamide (200 mg/m2/day given orally in divided doses on Days 3-6). Ninety-two of 96 patients who had an adequate trial (minumum of two courses or progression of disease after one course) had follow-up observations of tumor sites and were considered evaluable for response. Overall objective response rates by tumor type were as follows: stage III or IV ovarian adenocarcinoma, 61% (14 of 23 patients); endometrial adenocarcinoma, 67% (four of six patients); cervical adenocarcinoma, 33% (one of three patients); prostatic adenocarcinoma, 18% (two of 11 patients); testicular carcinoma, 33% (one of three patients); lung carcinoma, 21% (four of 19 patients); renal adenocarcinoma, 14% (one of seven patients); gastrointestinal adenocarcinoma, 18% (two of 11 patients); melanoma, 25% (one of four patients); and miscellaneous tumors, no responses in five patients. In patients with ovarian adenocarcinoma who had not previously received any cytotoxic chemotherapy the response rate was 80% (12 of 15 patients) with 33% five of 15 patients achieving complete clinical remission. CRs in these patients have now been maintained for periods ranging from 7 to 12 months. The major toxic effects were mild to moderate leukopenia, alopecia, and nausea with vomiting. Hemorrhagic cystitis was observed in three patients. The combination of adriamycin and cyclophosphamide is an effective treatment for carcinoma of the breast (reported elsewhere), ovary, and endometrium and should be considered for initial chemotherapy in patients with these tumors. Further investigations of its use for melanoma and carcinoma of the lung, prostate, kidney, and gastrointestinal tract are also warranted.
Cancer Treat Rep 1976 Jan
PMID:Combination chemotherapy with adriamycin (NSC-123127) and cyclophosphamide (NSC-26271) for solid tumors: a phase II trial. 100 May 20

The results of an ongoing trial randomizing patients with progressive, metastatic breast carcinoma between tamoxifen (Tam, NSC-180973) and Tam plus fluoxymesterone (Flu) (7 mg/m2 bid) are reported. Each patient received a single dose level of Tam in the range of 2-100 mg/m2 bid. The combination had a higher response rate overall (45% vs 28%) and when only the patients' soft tissue sites were analyzed (54% vs 9%, P=0.04). The time to treatment failure was longer for the combination among those patients with a response or disease stabilization (P=0.08). Response rates with Tam doses less than 12 mg/m2 bid were also higher than with doses greater than or equal to 12 mg/m2 for all patients in the study (62% vs 30%, P=0.025) and for those where only soft tissue sites were evaluable (43% vs 29%, P=0.07). Side effects were mild and consisted primarily of transient hematologic suppression, nausea, masculinization, hepatic enzyme elevations, and edema. The latter three were observed only with the Flu regimen. Leukopenia and thrombocytopenia were more frequent at Tam doses less than 12 mg/m2 bid whereas nausea was more common at higher doses. Tam doses as high as 100 mg/m2 bid were well tolerated. Tam amy be more effective at low doses, has only mild side effects, and is well tolerated at doses up to 100 mg/m2 bid. Combining Tam with Flu appears to enhance the therapeutic effectiveness.
Cancer Treat Rep 1976 Oct
PMID:Evaluation of tamoxifen dose in advanced breast cancer: a progress report. 102 Dec 26

Thirty-two patients with stage D carcinoma of the prostate were treated with oral estramustine phosphate at a dose of 15 mg/kg/day from 3 to 15 months. Objective remissions, reduction of greater than 50 percent of measurable lesions such as soft tissue masses, lymph nodes, and prostatic masses, were seen in seven of 32 patients (22 percent response rate). Subjective response, ie, relief of pain, weight gain, sense of well being, snd improved performance status, occurred in all objective responders and in seven other patients with stable disease (15 of 32 patients = 47 percent). No hematologic, hepatic, or renal toxic effects were observed. Transient nausea occurred early in one half of the patients and nausea and vomiting was dose limiting in only two patients. Oral estramustine phosphate is well tolerated and worthy of further clinical use.
Cancer Chemother Rep
PMID:Oral estramustine phosphate (NSC-89199) in the treatment of advanced (stage D) carcinoma of the prostate. 109 69

Sixty-nine patients with advanced gastrointestinal carcinomas were given adriamycin intravenously at a dose level of 40-75 mg/m once every 3 weeks. Toxic effects included nausea, vomiting, diarrhea, stomatitis, alopecia, leukopenia, thrombocytopenia, and minor ECG changes. There was a slight trend toward move severe leukopenia in patients with markedly abnormal liver function test (serum glutamic oxaloacteic transaminase and alkaline phosphatase). Of the 57 pateints with colorectal cancer treated with adriamycin, four (7%) showed partial objective responses. In a controlled comparison of adriamycin versus 5-fluorouracil (5-FU) in patients with previously untreated large bowel carcinoma, three of 23 patients (13%) receiving adriamycin showed partial objective responses as compared with six of 25 patients (24%) receiving 5-FU. The median duration of response with adriamycin was 3 months com pared to over 6 months with 5-FU. Four of eight patients with gastric carcinoma showed partial objective responses. No responses were noted in a small number of patients with pancreatic and gallbladder carcinomas. Adriamycin would not seem to have any role in the treatment of advanced colorectal carcinoma. Our results, however, would justify further evaluation of this agent in gastric carcinoma.
Cancer Chemother Rep
PMID:Adriamycin (NSC-123127) therapy for advanced gastrointestinal cancer. 109 99


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