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Biomedical subjects

C G Moertel

Publications and source records attributed to C G Moertel.

At least 91 records · Page 5Linked to original sources
PubMed1986

Treatment of the malignant carcinoid syndrome. Evaluation of a long-acting somatostatin analogue.

We studied the effects of a long-acting analogue of somatostatin (SMS 201-995, Sandoz) in 25 patients with histologically proved metastatic carcinoid tumors and the carcinoid syndrome. This drug was self-administered by subcutaneous injection at a dose of 150 micrograms three times daily. Flushing and diarrhea associated with the syndrome were promptly relieved in 22 patients. All 25 patients had an elevated 24-hour urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) (mean, 265 mg per 24 hours; range, 14 to 1079), which served as an objective indicator of disease activity. Eighteen of the 25 patients (72 percent) had a decrease of 50 percent or more in their urinary 5-HIAA levels, as compared with the pretreatment values. The median duration of this biochemical response was more than 12 months (range, 1 to greater than 18). Since no serious toxicity was observed, we conclude that SMS 201-995 may be appropriate for use as early therapy in patients with symptoms due to the carcinoid syndrome who have not responded to simpler measures.

Adult↗
PubMed1986

The preoperative carcinoembryonic antigen test in the diagnosis, staging, and prognosis of colorectal cancer.

A study of preoperative carcinoembryonic antigen (CEA) levels was conducted in 319 patients with surgically treated colorectal cancer, 272 of whom had disease resectable with curative intent. Only three patients could not be completely followed. All of the remaining 316 patients have been followed for a minimum of 5 years or until death. From the standpoint of diagnosis, the CEA test was more frequently positive (greater than 5 ng/ml) in patients with advanced stage disease, with larger primary tumors, and with more differentiated histopathologic characteristics. It was grossly insensitive in diagnosis of resectable cancer (26%) and was only reasonably reliable (72%) in patients with unresectable and metastatic disease. In relationship to surgical pathology of colorectal cancer, CEA levels were significantly correlated with stage of disease and with size of the primary tumor in Dukes' B lesions, but not with extent of nodal metastasis in Dukes' C lesions. In advanced stage lesions, CEA was inversely correlated with degree of anaplasia. In the overall patient group, and also among resectable patients, the preoperative CEA level was strongly associated with survival after adjustment for the effects of a number of other prognostic factors. Within stages of resectable disease, however, CEA was not significantly associated with survival among patients with Dukes' A and B lesions or Dukes' C lesions with one to three nodes involved. CEA was found to be a significant and independent prognostic determinant only in patients with Dukes' C lesions who had four or more metastatically involved lymph nodes. Under these circumstances, a preoperative CEA level could perhaps be of some value for stratification of Dukes' C patients in randomized colorectal cancer surgical adjuvant trials. The value of this test as a prognostic guide in clinical practice, however, would seem to be limited because of a lack of sensitivity in identifying individual poor prognosis patients.

Adult↗
PubMed1986

Carcinoids: the prognostic effect of primary site histologic type variations.

Carcinoids are histologically classified as insular (A), trabecular (B) glandular (C), undifferentiated (D) or mixed. These have prognostic significance, i.e. Group 1 (most favorable, A + C); 2 (favorable, A, B, A + B); 3 (relatively unfavorable, all non A + C or A + B mixed types); and 4 (unfavorable, C, D). Midgut primaries have a better prognosis than either foregut or hindgut/cloacal primaries. Carcinoids from 114 Eastern Cooperative Oncology Group patients were studied to determine if primary site prognostic differences result from histologic prognostic group occurrence rate differences across primary sites. By primary site the following rates were observed: Foregut: 1 (0%), 2 (79.2%), 3 (12.5%), 4 (8.3%); midgut: 1 (26.7%), 2 (58.7%), 3 (6.6%), 4 (8.0%); hindgut/cloaca: 1 (0%), 2 (42.9%), 3 (42.9%), 4 (14.2%); nongut: 1 (0%), 2 (75.0%), 3 (12.5%), 4 (12.5%), p less than 0.01. The results demonstrate that primary site prognostic differences are highly dependent upon histologic prognostic group occurrence rate variations across primary sites. In addition multivariate analysis of survivorship by both histologic type (p less than 0.05) and primary site (p less than 0.05) demonstrated that each variable has independent prognostic significance.

Aged↗
PubMed1986

Gallbladder adenocarcinoma: prognostic significance of tumor acid mucopolysaccharide content.

The gall bladder mucosa is composed of neutral mucopolysaccharide and protein radical containing secretory cells, protein radical containing migratory cells, and neutral and acid mucopolysaccharides plus sialic acid containing goblet cells. The prognostic significance of histologic or histochemical parameters in gall bladder adenocarcinoma (GBA) are unknown. To determine if histochemical acid mucopolysaccharide content in GBA has prognostic value, GBA histologic sections from 26 advanced stage disease patients participating in Eastern Cooperative Oncology Group (ECOG) treatment study EST-2273 were stained with alcian blue at pH. 1.0, assessed by a pathology panel for either high (greater than 50%) or low (less than 50%) acid mucopolysaccharide content, and correlated with patient survival. Initial panel unanimous concurrence rate on acid mucopolysaccharide content was 88.9%. Median survival times from the start of chemotherapy to date of death for high acid mucopolysaccharide content GBA was 14 weeks versus five weeks for the low content GBA (P less than 0.0001). The results indicate that high acid mucopolysaccharide content in GBA significantly improves prognosis. ECOG recommends stratification by acid mucopolysaccharide content in future GBA treatment investigations.

Adenocarcinoma↗
PubMed1986

Clinical trial of cisplatin and intensive course 5-fluorouracil for the treatment of advanced colorectal cancer.

A clinical trial of 5-day Cisplatin combined with loading course 5-fluorouracil (5-FU) was conducted in 37 patients with advanced colorectal carcinoma. Objective tumor responses were seen in 10 of 34 patients (29%) who had not received prior chemotherapy. The estimated median survival for previously untreated patients is 26 weeks measured from the onset of therapy. Toxicity consisted primarily of leukopenia, vomiting, and reversible renal insufficiency. This combination of cisplatin and intensive course 5-FU has demonstrated Phase II activity in patients with advanced colorectal cancer. A controlled trial is now in progress to prospectively compare this regimen with full dose single agent 5-FU.

Adult↗
PubMed1986

A phase II study of combined 5-fluorouracil, doxorubicin, and cisplatin in the treatment of advanced upper gastrointestinal adenocarcinomas.

In a phase II study of 67 patients with upper gastrointestinal carcinomas and measurable disease without previous chemotherapy, we have evaluated the combination of intensive course 5-fluorouracil (5-FU) (300 mg/m2/d for five days) doxorubicin (40 mg/m2 on day 1), and cisplatin (60 mg/m2 on day 1). Courses were repeated every 5 weeks. Among 26 patients with gastric carcinoma, a 50% regression rate was obtained with a median survival for all patients of 9 months. Among 29 patients with pancreatic carcinoma, the regression rate was 21% and the median survival was 4 months. Regressions were also observed in smaller numbers of patients with carcinomas of the gallbladder and ampulla of Vater, as well as in cholangiocellular carcinoma of the liver. Toxic reactions were usually clinically tolerable and consisted primarily of nausea, vomiting, stomatitis, diarrhea, leukopenia, and alopecia. Phase III studies are in progress to place the value of this experimental regimen into clinical perspective.

Adenocarcinoma↗
PubMed1985

A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma. Fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin.

Three hundred five patients with advanced pancreatic and gastric carcinoma were randomly assigned to treatment with fluorouracil, fluorouracil plus doxorubicin (Adriamycin) (FA), or fluorouracil plus doxorubicin plus mitomycin (mitomycin C) (FAM). All regimens were equivalent with regard to patient survival. There is no reasonable likelihood that either the FA or FAM regimen could produce a meaningful survival advantage over fluorouracil alone. Interval to disease progression, objective response rates, and palliative effects (improved performance, body weight, or symptoms) were essentially equivalent among the three regimens. With regard to toxicity, the FAM regimen produced more anorexia, nausea, vomiting, leukopenia, thrombocytopenia, and cumulative bone marrow suppression. Fluorouracil alone produced more stomatitis and diarrhea. Because of a failure to produce improved survival or palliation, unrewarded toxicity, and excessive cost, neither the FA nor FAM regimen can be recommended for the treatment of advanced pancreatic or gastric cancer.

Adenocarcinoma↗
PubMed1985

High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison.

It has been claimed that high-dose vitamin C is beneficial in the treatment of patients with advanced cancer, especially patients who have had no prior chemotherapy. In a double-blind study 100 patients with advanced colorectal cancer were randomly assigned to treatment with either high-dose vitamin C (10 g daily) or placebo. Overall, these patients were in very good general condition, with minimal symptoms. None had received any previous treatment with cytotoxic drugs. Vitamin C therapy showed no advantage over placebo therapy with regard to either the interval between the beginning of treatment and disease progression or patient survival. Among patients with measurable disease, none had objective improvement. On the basis of this and our previous randomized study, it can be concluded that high-dose vitamin C therapy is not effective against advanced malignant disease regardless of whether the patient has had any prior chemotherapy.

Aged↗
PubMed1985

A pilot study to determine clinical tolerability of intensive combined modality therapy for locally unresectable gastric cancer.

Eighteen patients with unresectable carcinoma of the stomach whose known malignant disease was confined to structures immediately adjacent to the primary tumor and could be encompassed within a radiotherapy field were treated with an intensive sequential combined modality regimen. The regimen consisted of 5-FU plus adriamycin chemotherapy, followed by high dose megavoltage radiation therapy with 5-FU given as a radiation sensitizer, followed by maintenance chemotherapy with 5-FU plus adriamycin plus methyl CCNU (FAMe). Our primary objective was to determine patient tolerability. Severe and prolonged anorexia, nausea, and decreased performance status occurred during and after high dose radiotherapy given twice daily in 150-170 cGy (rad) fractions when given with 5-FU. Lengthening intervals between treatment segments, and the use of one daily dose of radiation therapy combined with 5-FU or two fractions daily without 5-FU seemed to decrease nutritional complications. Control of tumor at the primary site appeared to be achieved in most patients. Distant metastases represented the predominant mode of treatment failure with only two patients currently without progression of malignant disease. Our treatment regimen as initially conceived was too toxic for general use. Improved therapeutic results in locally unresectable gastric cancer will require the development of more effective therapy for occult distant metastases.

Adenocarcinoma↗
PubMed1985

Clinical trial of adjuvant chemotherapy after surgical resection of colorectal cancer metastatic to the liver.

Adjuvant chemotherapy consisting of 5-fluorouracil and semustine was given to 26 patients who had undergone resection (with curative intent) of hepatic metastatic lesions from a primary colorectal carcinoma. Our objective was to obtain preliminary observations regarding the effectiveness of this regimen for improving the long-term survival associated with hepatic resection alone in these patients (the overall 5-year survival after hepatic resection is 25% at our institution). At the time of analysis, the malignant disease had progressed in 19 of our patients, and 17 patients had died. For all patients who receive adjuvant chemotherapy, the median duration of survival is 34 months, and the estimated 5-year survival is 15%. Statistical analysis indicated no significant advantage in survival for the study patients in comparison with 26 control patients who were treated with hepatic resection only and were closely matched for prognostic factors. Because 5-fluorouracil plus semustine conferred no apparent beneficial effects as an adjuvant treatment in this exploratory study, we do not recommend a definitive randomized trial of this regimen.

Adult↗
PubMed1985

A controlled evaluation of recent approaches to biochemical modulation or enhancement of 5-fluorouracil therapy in colorectal carcinoma.

Three hundred thirty-five previously untreated patients with advanced colorectal carcinoma were randomly assigned to treatment with 5-fluorouracil (5-FU) alone, 5-FU plus N-(phosphonacetyl)-L-aspartic acid (PALA), 5-FU plus high-dose thymidine, 5-FU plus levamisole, or 5-FU plus methyl CCNU, vincristine, and streptozotocin (MOF-Strept). Dosages were designed to produce definite toxicity in the majority of patients, although the nature of dose-limiting reactions varied considerably among regimens. 5-FU alone and 5-FU plus levamisole produced mucocutaneous reactions, diarrhea, and leukopenia; 5-FU plus PALA produced primarily mucocutaneous reactions and diarrhea; 5-FU plus thymidine produced leukopenia with occasional neurotoxicity and hypotension; and MOF-Strept produced substantial nausea and vomiting with both thrombocytopenia and leukopenia. Objective response rates among patients with measurable disease varied from 12% (5-FU plus PALA) to 34% (MOF-Strept), but none of the regimens were significantly superior to 5-FU alone. Both interval to progression and survival were comparable among the five regimens with no reasonable chance that any combination regimen could produce as much as a 50% improvement when compared with 5-FU alone. Whereas we observed definite modulation of 5-FU dose--toxicity relationships, particularly with the thymidine and PALA combinations, this did not result in a detectable improvement in therapeutic effect. None of the combination regimens, administered in the dosages and schedules we used, can be recommended as standard therapy of advanced colorectal carcinoma.

Aged↗
PubMed1985

Treatment of locally unresectable cancer of the stomach and pancreas: a randomized comparison of 5-fluorouracil alone with radiation plus concurrent and maintenance 5-fluorouracil--an Eastern Cooperative Oncology Group study.

One hundred ninety-one patients with pathologically confirmed, locally unresectable adenocarcinoma of the stomach (57 patients) and pancreas (91 patients), were randomly allocated to therapy with 5-fluorouracil (5-FU) alone, 600 mg/m2 intravenously (IV) once weekly, or radiation therapy, 4,000 rad, plus adjuvant 5-FU, 600 mg/m2 IV, the first three days of radiotherapy, then follow-up maintenance 5-FU, 600 mg/m2, weekly. Forty-three patients (22%) could not be analyzed because of ineligibility or cancellation, thus 148 patients were evaluable. The median survival time was similar for both treatment programs and for both types of primary carcinoma, and was as follows: gastric primary carcinoma, 5-FU, 9.3 months; 5-FU plus radiotherapy, 8.2 months; pancreatic primary carcinoma, 5-FU, 8.2 months; 5-FU plus radiotherapy, 8.3 months. Substantially more toxicity was experienced by patients treated with the combined modality arm than by those patients receiving 5-FU alone. Severe or worse toxicity experienced by patients with gastric primary carcinoma treated by 5-FU was 19%, and the combined modality arm was 31%. The toxicity experienced by patients with pancreatic primary carcinoma treated with 5-FU was 27%, and the combined modality arm was 51%. Significant prognostic variables included: weight loss in stomach-cancer patients; and performance status, degree of anaplasia, and reduced appetite in pancreas-cancer patients.

Adenocarcinoma↗
PubMed1984

Eastern Cooperative Oncology Group experience with chemotherapy for inoperable gallbladder and bile duct cancer.

In a prospective randomized Eastern Cooperative Oncology Group (ECOG) study, 53 eligible and evaluable patients with advanced gallbladder carcinoma and 34 with advanced bile duct carcinoma were treated with oral 5-fluorouracil (5-FU) or with oral 5-FU plus streptozotocin (Stz) or oral 5-FU + Methyl-CCNU (MeCCNU). Severe toxicity occurred in 2 of 30 patients receiving 5-FU (7%), in 14 of 26 receiving 5-FU + Stz (54%), and in 12 of 31 receiving 5-FU + MeCCNU (39%). Five of 53 patients with gallbladder carcinoma (2/18 [11%] on 5-FU, 2/16 [12%] on 5-FU + Stz, and 1/19 [5%] on 5-FU + MeCCNU) had objective response to treatment. There was no significant difference between treatments with respect to response or survival. Three of 34 patients with bile duct cancer (1/12 [8%] on 5-FU, 0/10 on 5-FU + Stz, and 2/12 on 5-FU + MeCCNU) had objective response to treatment. There was no significant difference between treatments with respect to response or survival. Patients with prior chemotherapy were randomized between MeCCNU alone and Stz alone. Among such patients, only 1 of 17 patients who had prior chemotherapy with other agents responded to MeCCNU alone, and none of 14 patients responded to Stz alone.

Antineoplastic Combined Chemotherapy Protocols↗