PubMed Health⌕ Search

Biomedical subjects

C G Moertel

Publications and source records attributed to C G Moertel.

At least 127 records · Page 7Linked to original sources
PubMed1983

Treatment of the carcinoid tumor and the malignant carcinoid syndrome.

Certainly in treatment of the carcinoid tumor surgery has a well-established curative and palliative potential. The primary challenge is a knowledgable marriage between stage of disease and aggressiveness of operative procedure. Nonsurgical treatment of the malignant disease per se has thus far not produced optimum results and, in the opinion of this author, should still be confined to a clinical research setting. It would seem very doubtful, however, that the more mundane types of trials, empirically testing drug after drug and arbitrarily concocted drug combinations, is the most productive road to follow. There is an evident need for more sophisticated approaches to this tumor, which has unique metabolic characteristics that should be pharmacologically exploitable. Past experience has indicated that such a setting may permit dramatic therapeutic accomplishment. There is a strong need for animal models or established cell lines which would facilitate preclinical therapeutic exploration. The carcinoid syndrome presents an unparalleled opportunity for fundamental physiologic observations and for experimental therapeutic study that can have applicability not only in palliating the syndrome itself but also in the management of other pathophysiologic states that may involve more subtle abnormalities of the same hormonal mechanisms. The patient with the carcinoid tumor should not just be a fascinating curio for grand rounds exhibition. He should be a focal point for research involving an experienced, multidisciplinary clinical team supported by devoted basic scientists. If our patient resources and efforts can be concentrated in this manner, the carcinoid should be a strong candidate for the next medically curable human cancer.

Adult↗
PubMed1983

Colorectal cancer: chemotherapy as surgical adjuvant treatment.

As we view our past accomplishments in chemotherapy of colorectal cancer, it would seem clear that none of our approaches for any stage of this disease can be regarded as optimal for clinical practice or even as having any established benefit. The use of chemotherapy in the routine clinical practice setting for this disease provides little or no value to the patient today and is a distinct disservice to the patient of tomorrow. Nevertheless, the failure of past accomplishment should not lead to therapeutic nihilism. The major human problem which this disease presents demands intensive and sophisticated clinical research efforts. It would also seem obvious that these efforts require coordination of all concerned disciplines. Such a team effort should include not only the surgeon, medical oncologist, and the radiation therapist but also the laboratory scientist. With integrated and concentrated effort, a foundation can be laid for realistic optimism regarding improvement in therapy for colorectal cancer in the years immediately ahead.

Antineoplastic Agents↗
PubMed1983

Pharmacokinetics of mitomycin C in patients receiving the drug alone or in combination.

We have characterized plasma pharmacokinetics in 30 patients receiving mitomycin C (mitomycin) in doses ranging from 6 to 20 mg/m2 by iv bolus injection, either alone or in combination with other chemotherapeutic drugs. Plasma elimination of the drug was described by a two-compartment model in all but three cases, giving mean values for alpha-half-life of 8.2 mins, beta-half-life of 51.8 mins, and total body clearance of 332.9 ml/min/m2. The mean urinary excretion was 8.1% of the total dose administered. We did not detect alterations in pharmacologic parameters related to liver dysfunction, dose of mitomycin, and concomitant administration of other cytotoxic drugs.

Adult↗
PubMed1983

Treatment of metastatic carcinoid tumor with dactinomycin or dacarbazine.

We studied the effect of two single drugs on patients with metastatic carcinoid tumors. All patients had symptomatic and measurable disease and all had elevations of urinary 5-hydroxy indole acetic acid excretion. Seventeen patients were treated with dactinomycin at a dose of 12-15 micrograms/kg/day for 5 days repeated every 4-5 weeks. One partial response was achieved. Fifteen patients were treated with dacarbazine (DTIC) at a dose of 250 mg/m2/day for 5 days every 4-5 weeks. Two partial responses were achieved. The median times to tumor progression were 10 weeks with dactinomycin and 18 weeks with DTIC. Median survival times were 28 and 47 weeks, respectively. Dactinomycin given by this schedule appears to have only limited activity as a single-agent treatment in malignant carcinoid tumor. DTIC, although showing only a slightly better response rate, perhaps warrants further investigation in view of our more favorable interval to tumor progression and survival experience and in view of this drug's more established activity in the closely related islet cell carcinoma.

Adult↗
PubMed1982

A clinical trial of amygdalin (Laetrile) in the treatment of human cancer.

One hundred seventy-eight patients with cancer were treated with amygdalin (Laetrile) plus a "metabolic therapy" program consisting of diet, enzymes, and vitamins. The great majority of these patients were in good general condition before treatment. None was totally disabled or in preterminal condition. One third had not received any previous chemotherapy. The pharmaceutical preparations of amygdalin, the dosage, and the schedule were representative of past and present Laetrile practice. No substantive benefit was observed in terms of cure, improvement or stabilization of cancer, improvement of symptoms related to cancer, or extension of life span. The hazards of amygdalin therapy were evidenced in several patients by symptoms of cyanide toxicity or by blood cyanide levels approaching the lethal range. Patients exposed to this agent should be instructed about the danger of cyanide poisoning, and their blood cyanide levels should be carefully monitored. Amygdalin (Laetrile) is a toxic drug that is not effective as a cancer treatment.

Adolescent↗
PubMed1982

Human colorectal carcinoma: patterns of sensitivity to chemotherapeutic agents in the human tumor stem cell assay.

The human tumor stem cell assay (HTSCA) was applied to 103 primary and metastatic colorectal carcinomas. Thirty-four carcinomas could not be evaluated for colony formation (clonogenicity) because of microbial contamination. Of the remaining 69 carcinomas, 18 (26%) demonstrated clonal growth in vitro. Colony formation did not correlate with the clinicopathologic stage of the tumor, the histological grade of the tumor, the method used to disperse the solid tumors into single cells (mechanical or enzymatic), or cell viability (exclusion of trypan-blue) prior to plating. The in vitro chemotherapy sensitivity data of the 18 tumors which formed colonies indicated that most tumors were generally resistant to chemotherapeutic drugs and that a few tumors were sensitive to multiple agents. Use of the human tumor stem cell assay may facilitate an individualized approach to clinical chemotherapy of colorectal carcinoma for certain patients.

Adenocarcinoma↗
PubMed1982

A prospective controlled evaluation of combined pelvic radiotherapy and methanol extraction residue of BCG (MER) for locally unresectable or recurrent rectal carcinoma.

Forty-four patients with unresectable primary, residual, or recurrent colorectal carcinoma confined to the pelvis were randomized to treatment with split course megavoltage radiotherapy alone (5,000 rad given over 7 weeks) or in combination with the intradermal administration of the methanol extraction residue of BCG (MER) over an eight-month period. No improvement was observed in frequency of symptomatic palliation, interval to progression, or survival among patients receiving MER. Furthermore, there was no evidence of enhanced immunological status in patients receiving MER as compared to those receiving radiation alone. Although temporary pain relief was seen in 94% of patients with pretreatment pelvic or perineal pain, 37 patients (84%) have experienced subsequent progressive malignant disease. Regional recurrences within the radiotherapy port were observed in 28 of 31 patients who were evaluable for analysis of pattern of sites of initial progression. Eleven of the 28 patients with local failure also had distant metastasis at the time of tumor progression. There was no discernible clinical value associated with MER treatment in combination with radiotherapy as employed in this study. The high frequency of pelvic recurrence following radiotherapy at the dose and schedule we employed highlights the need for more effective treatment strategies for this group of patients.

Aged↗
PubMed1982

Phase II trial of doxorubicin therapy for advanced islet cell carcinoma.

Twenty evaluable patients with advanced islet cell carcinoma were treated with doxorubicin at a dosage of 60 mg/m2 every 3-4 weeks. Toxicity was clinically tolerable and characteristic of doxorubicin therapy. Although all patients had previously been treated with other chemotherapy regiments, four (20%) had objective therapeutic responses persisting for 2-301/2 months. Doxorubicin has definite therapeutic activity in islet cell carcinoma and is currently being evaluated in combination chemotherapy regimens.

Adenoma, Islet Cell↗
PubMed1982

Pilot study of PALA and 5-FU in patients with advanced cancer.

A pilot study was carried out among 21 patients with advanced solid tumors to establish appropriate dose levels of PALA and 5-FU given on a 5-day schedule to produce definite but tolerable clinical toxicity. While dermatitis, diarrhea, leukopenia, and thrombocytopenia were observed, stomatitis was the dose-limiting side effect. The recommended initial dose levels for further clinical trials are 625 mg/m2 of PALA daily x 5 and 250-300 mg/m2 of 5-FU daily x 5, with courses repeated at 4-week intervals. Studies were also conducted to establish the time course of anticipated increased incorporation of 5-FU into cellular RNA following treatment with PALA. In murine P388 leukemia, PALA increased tritiated 5-FU incorporation by as much as 70%, the effect being maximal within 1 hour and maintained up to 25 hours. It was not possible to demonstrate increased tritiated 5-FU uptake into normal human leukocyte RNA from patients receiving combination chemotherapy with PALA and 5-FU, perhaps because of low rates of RNA synthesis.

Adult↗
PubMed1982

A phase II study of aziridinylbenzoquinone (AZQ) in advanced large bowel carcinoma.

Aziridinylbenzoquinone (AZQ: NSC-182986), is a quinone derivative which has been shown to have activity in implanted murine tumor systems. Toxicity in small and large animals included hypothermia, diarrhea, anorexia, emesis, weight loss, and gastrointestinal bleeding. In addition, there was myelosuppression and elevated liver function tests. In a phase I study at the Mayo Clinic, dose-limiting toxicity was myelosuppression. Patients with prior radiation therapy or prior chemotherapy were more sensitive to this toxicity. A dose schedule of 27.5 mg/m2 q4 weeks was recommended for patients who had had no previous chemotherapy and 22.5 mg/m2 for previously treated patients or for patients who had had extensive prior radiation therapy. The objective of this study was to determine therapeutic activity for AZQ in patients with advanced colorectal adenocarcinoma.

Adenocarcinoma↗
PubMed1981

Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group.

One-hundred-ninety-four eligible and evaluable patients with histologically confirmed locally unresectable adenocarcinoma of the pancreas were randomly assigned to therapy with high-dose (6000 rads) radiation therapy alone, to moderate-dose (4000 rads) radiation + 5-fluorouracil (5-FU), and to high-dose radiation plus 5-FU. Median survival with radiation alone was only 51/2 months from date of diagnosis. Both 5-FU-containing treatment regimens produced a highly significant survival improvement when compared with radiation alone. Forty percent of patients treated with the combined regimens were still living at one year compared with 10% of patients treated with radiation only. Survival differences between 4000 rads plus 5-FU and 6000 rads plus 5-FU were not significant with an overall median survival of ten months. Significant prognostic variables, in addition to treatment, were pretreatment performance status and pretreatment CEA level.

Adenocarcinoma↗
PubMed1981

A pharmacologic and toxicological study of amygdalin.

Six patients with advanced cancer were treated with amygdalin (laetrile) at dosages similar to those employed by laetrile practitioners. Amygdalin given intravenously at 4.5 g/sq m/day was largely excreted unchanged in the urine and produced no clinical or laboratory evidence of toxic reaction. Amygdalin given orally at 0.5 g three times daily produced significant blood cyanide levels to 2.1 microgram/mL. No clinical or laboratory evidence of toxic reaction was seen in the six patients taking oral amygdalin at this dosage. One patient, however, challenged with a large intake of raw almonds, had transient symptoms of cyanide toxic reaction with escalating blood cyanide levels. This small study indicates that amygdalin in the doses employed produces few clinical side effects. A definite hazard of cyanide toxic reaction must be assumed, however, and possible long-term side effects remain unknown.

Administration, Oral↗
PubMed1981

Pharmacology of amygdalin (laetrile) in cancer patients.

Plasma and urine concentrations of amygdalin, whole-blood concentrations of cyanide, and thiocyanate concentrations in serum and urine were determined in cancer patients following intravenous (4.5 g/m2) and oral (500-mg tablet) administration of amygdalin. To measure low plasma concentrations of amygdalin following oral administration a GC/MS assay was developed. Following intravenous administration, concentrations of parent drug as high as 1,401 microgram/ml were observed, with no increase in plasma concentrations of cyanide or serum concentrations of thiocyanate. Plasma elimination of amygdalin was best described by a two-compartment open model with a mean distributive phase half-life of 6.2 min, mean elimination phase half-life of 120.3 min, and mean clearance of 99.3 ml/min. Following oral administration of amygdalin, plasma concentrations were much lower, with peak values of less than 525 ng/ml. Cyanide concentrations increased to values as high as 2.1 microgram/ml whole blood. Thiocyanate concentrations did not increase for several days, plateauing at values as high as 38 microgram/ml serum. Ingestion of almonds by two patients taking oral amygdalin increased cyanide concentrations compared with values obtained after oral amygdalin alone.

Administration, Oral↗
PubMed1981

A controlled clinical and immunological evaluation of immunotherapy with Bacillus Calmette--Guerin in patients with metastatic cancer.

One hundred thirty adult patients with metastatic solid tumors were studied to evaluate the therapeutic results, toxicity, and immunological effects of three BCG preparations given intradermally by the multiple puncture time technique on either a monthly or weekly schedule: Tice lyophilized BCG, Pasteur lyophilized BCG, and Pasteur fresh-frozen BCG. Patients were randomly assigned in a double-blind manner to receive one of the BCG preparations or saline placebo administered in an identical manner. A battery of immunological tests were performed pretreatment and serially during the investigation. None of the 82 patients with measurable indicator lesions experienced an objective tumor response, nor were there any differences in survival among patients receiving any of the BCG preparations compared to placebo. Toxicity consisted of mild to moderate local cutaneous reactions and liver function abnormalities in BCG-treated patients with no significant differences between BCG preparations. Improvements in each of the assays of immune function performed occurred with roughly equal frequency among patients receiving BCG or placebo. It was not possible to demonstrate any significant clinical or immunological benefit from BCG administration in this patient population with the methodology employed.

Adult↗