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Biomedical subjects

C G Moertel

Publications and source records attributed to C G Moertel.

At least 181 records · Page 10Linked to original sources
PubMed1976

A phase I study of cytembena.

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.

Acrylates↗
PubMed1976

The effect of measuring error on the results of therapeutic trials in advanced cancer.

In this study, 16 experienced oncologists each measured 12 simulated tumor masses employing their usual clinical methods. Unknown to the oncologists, two pairs of these tumors were identical in size. This permitted a total of 64 measurement comparisons of the same investigator measuring the same size mass and 1920 comparisons of different investigators measuring the same size mass. If a 50% reduction in the product of perpendicular diameters is accepted as a criterion, the objective response rate due to measuring error alone was 7.8% by the same investigator and 6.8% by different investigators. If a 25% reduction criterion is used, the respective "placebo" response rates were 19% and 25%. In the clinical setting it is recommended that the 50% reduction criterion be employed and that the investigator should anticipate an objective response rate of 5 to 10% due to human error in tumor measurement.

Clinical Competence↗
PubMed1976

Sequential and combination chemotherapy of advanced gastric cancer.

One hundred and forty-six previously untreated patients with advanced gastric cancer were assigned at random to therapy with the following regimens: 1) Methyl CCNU alone; 2) Methyl CCNU with cyclophosphamide induction; 3) 5-fluorouracil (5-FU) + methyl CCNU; and 4) 5-FU + methyl CCNU with cyclophosphamide induction. Cyclophosphamide induction produced an objective response rate of only 8%. In addition, it added to hematologic toxicity and detracted from the therapeutic activity of subsequent treatment. Methyl CCNU was relatively ineffective therapy with an overall objective response rate of 8%. The response rate to 5-FU + methyl CCNU without cyclophosphamide induction was 40% and this was significantly superior to all other regimens. The survival time of all patients treated with 5-FU + methyl CCNU was significantly superior to that of all patients treated with methyl CCNU alone.

Adenocarcinoma↗
PubMed1976

Phase I study of a five-day intermittent schedule for 1,2:5,6-dianhydrogalactitol (NSC-132313).

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.

Adolescent↗
PubMed1976

Who responds to sugar pills?

Among 288 cancer patients undergoing controlled trials of oral analgesics there were 112 who received 50% or greater pain relief from placebo formulations. Patients who responded to placebo had a greater response rate to active drugs. They also had a higher incidence of central nervous system side effects to placebo. Patient groups showing as increased placebo response included those with a high level of education, farmers, those with a professional occupation, women working outside the home, and patients who were widowed, separated, or divorced. Those resistant to placebo were patients with a low educational level, unskilled workers, housewives, married women without children, and smokers. It is theorized that placebo response is a type of autohypnosis phenomenon resulting from exaggerated oral-dependency needs. Particularly vulnerable to placebo effect is the very self-sufficient individual with heavy responsibilities who is thrust into the unaccustomed dependency of disabling illness.

Aged↗
PubMed1976

Ultrastructural cytochemistry of platelets and megakaryocytes in the carcinoid syndrome.

Platelets and megakaryocytes from 11 patients with the carcinoid syndrome have been studied by transmission electron microscopy. Cells fixed in phosphate-buffered glutaraldehyde are oval to discoid, with pseudopods, a dilated open-channel system, and a prominent dense tubular system as defined by peroxidase activity and alkaline bismuth stain. Atypical with hexagonal lattices and treaded substructures and large (diameter greater than 0.5 mum), phosphatase-positive, debris-containing vacuoles are four times more numerous than in normal platelets. Incubation of platelets in a 0.05% suspension of latex results in particle incorporation into phagosomes and the debris-containing vacuoles. Molybdate-dichromate stain reveals two classes of dense bodies, one of which (with a reticular core) is 20 times more numerous than in normal platelets. Bone marrow megakaryocytes lack both dense bodies and debris vacuoles analogous to those found in circulating platelets. These results suggest autophagy or endocytosis abnormalities and provide evidence for multiple types of dense bodies in carcinoid platelets.

Acid Phosphatase↗
PubMed1976

Nitrosoureas: useful agents for the treatment of advanced gastrointestinal cancer.

Patients with a wide range of gastrointestinal cancers have been treated with nitrosoureas by the Eastern Cooperative Oncology Group. Methyl-CCNU, CCNU, and streptozotocin have been evaluated as single agents in the treatment of colorectal carcinoma. Methyl-CCNU has had an extensive trial in gastric carcinoma as a single agent and in combination with 5-fluorouracil (5-FU). It has also been used to treat pancreatic carcinoma and, in a few patients, carcinoma of the biliary tract. In gastric cancer it would appear that a synergistic effect on response rates has resulted from the combination of methyl-CCNU and 5-FU. The addition of cyclophosphamide to this combination as an induction agent detracted significantly.

Clinical Trials as Topic↗
PubMed1976

Phase II studies of dianhydrogalactitol and VP-16-213 in colorectal cancer.

Phase II chemotherapy trials of dianhydrogalactitol and VP-16-213 were conducted in patients with metastatic colorectal cancer who had measurable malignant disease which served as indicators of response to therapy. Dianhydrogalactitol was given in a 5-day course at a dosage of 30 mg/m2/day. Toxic reactions included nausea, vomiting, leukopenia, thrombocytopenia, and anemia. There was a definite tendency to a compounding of hematologic toxicity with repeated courses. No evidence of objective therapeutic response was observed among 30 patients treated. VP-16-213 was given at a dosage of 130 mg/m2 on Days 1, 3, and 5. Toxic reactions included nausea, vomiting, alopecia, leukopenia, thrombocytopenia, and anemia. Hematologic toxicity was more severe in patients with elevated serum bilirubin levels. No evidence of objective therapeutic response was observed among 28 patients treated.

Adenocarcinoma↗
PubMed1975

A double-blind comparison of intensive course 5-flourouracil by oral vs. intravenous route in the treatment of colorectal carcinoma.

This radomized double-blind study was designed to compare the therapeutic effectiveness of the oral and i.v. routes for 5-FU administered in intensive courses to 100 patients with metastatic adenocarcinoma of the large bowel, treated to equivalent levels of toxicity. An oral dose of 20 mg/kg day times 5 was found to produce comparable G.I., mucocutaneous, and hematologic side effects to a dose of 13.5 mg/kg day times 5 by rapid i.v. injection. Courses were repeated at 5 weeks. Nine of 47, or 19.1%, treated by the oral route have shown objective response, compared to 14 of 53, or 26%, treated by the i.v. route. If malignant hepatomegaly is considered alone, the response rates are 8 of 23, or 34.8%, by the oral route, and 7 of 22, or 31.8%, by the i.v. route. The mean duration of response for the oral group, 11.1 weeks, was shorter than for the i.v. route, 20 weeks, a statistically significant (p less than 0.02) difference. Serial serum 5-FU levels after two doses of 5-FU were determined by microbiological assay in 19 patients. For i.v. administration the curves were comparable among different patients as well as in the same patient. There was striking variability, however, for oral administration.

Adenocarcinoma↗
PubMed1975

Clinical management of advanced gastrointestinal cancer.

Although advanced gastrointestinal cancer is the most commonplace problem encountered by the medical oncologist, this group of diseases has proved exceedingly resistant to past chemotherapy efforts. 5-Fluorouracil (5-FU), accepted by some as standard treatment, had provided only infrequent, incomplete, and fleeting antitumor effects, which are probably more than counterbalanced by its gastrointestinal, mucocutaneous, and hematologic antihost effects. There is no evidence that any manipulation of route or schedule of administration provides any improvement in the therapeutic ratio of 5-FU. There is no evidence that this drug contributes to patient survival when used at any stage of any type of gastrointestinal carcinoma. The search for alternative single drugs to 5-FU has been disappointing. The nitrosoureas and Mitomycin C produce occasional regressions, but they do not match the meager effectiveness of 5-FU; and they, in addition, present the difficult problem of cumulative bone marrow suppression. Recent trials with combination regimens have given some indication that the long stalemate in chemotherapy of gastrointestinal cancer may be breaking. Substantial improvements in frequency of tumor regression have been recorded for gastric carcinoma with combinations of 5-FU and BCNU, 5-FU and methyl CCNU, and 5-FU, Mitomycin C, and cytosine arabinoside; for colorectal carcinoma, with the combination of 5-FU, methyl CCNU, and vincristine; and for carcinoid tumors and islet cell carcinomas, with the combination of 5-FU and Streptozotocin. There are also suggestion that such combination chemotherapy with response rates in the 30 to 50% range may produce increased survival when compared to the untreated patient and patients treated with single-drug regimens. While the accomplishments of chemotherapy for the gastrointestinal cancer patient remain less than spectacular there is nevertheless realistic hope that a respectable contribution can now be made to multidisciplinary efforts applied at a stage of disease with minimal tumor burden.

Adenoma, Islet Cell↗
PubMed1975

The urinary excretion of nucleosides of ribonucleic acid by patients with advanced cancer.

By means of a sensitive and specific method utilizing gas-liquid chromatography, the excretion levels for three nucleosides, degradation minor base products of ribonucleic acid, primarily transfer ribonucleic acid, were determined in 24-hour urine specimens from over 200 patients with solid tumor malignancies. These nucleosides were N2,N2-dimethylguanosine, l-methylinosine, and pseudouridine. When compared to normal control values, elevated levels of these compounds were found for patients in each of several tumor types studied. Increases in pseudouridine excretion suggest increased tumor transfer ribonucleic acid turnover; in addition, for the methylated nucleosides, higher than normal values may reflect enhanced transfer ribonucleic acid methylase activity of the neoplastic cells.

Chromatography, Gas↗
PubMed1975

Oral benzquinamide in the treatment of nausea and vomiting.

The clinical antiemetic effect of bezquinamide by oral route at a dosage of 100 mg 3 times daily was evaluated by a controlled double-blind method in 183 studies of patients treated with 5-fluorouracil. The incidence of nausea and vomiting in benzquinamide-treated patients was equal to that in placebo-treated patients and significantly higher than that in patients treated with prochlorperazine, 10 mg 3 times daily. Sedation was the only significant side effect observed, and this occurred at essentially equal rates in benzquinamide- and prochlorperazine-treated patients.

Clinical Trials as Topic↗