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Biomedical subjects

C G Moertel

Publications and source records attributed to C G Moertel.

At least 73 records · Page 4Linked to original sources

Hepatoma in the noncirrhotic liver.

The pathologic features, clinical presentation and natural history of hepatocellular carcinoma (HCC) developing in the noncirrhotic liver were studied in 61 patients against a background of 63 patients seen concurrently with HCC complicating cirrhosis. Noncirrhotic HCC had a bimodal age distribution, with females predominating the first age-clustering (10-50 years) and males predominating the second age-clustering (50-90 years). Cirrhotic HCC had a unimodal age distribution (40-90 years) with male dominance throughout. Estrogen exposure was noted in 57% of the noncirrhotic HCC women overall and in 80% of those in the younger age-clustering. The majority of noncirrhotic HCC presented with a single hepatic mass or a dominant primary with satellite lesions in contrast to the usual multinodular or diffuse disease seen with cirrhosis. Twenty-nine noncirrhotic patients survived complete resection of disease limited to the liver and exhibited a median survival of 2.7 years with a 5-year survival of 25%. Low histologic grade, minimal necrosis, and the absence of hemoperitoneum, hepatomegaly, and adjacent organ involvement were all favorable prognostic variable. Patients with metastatic or locally unresectable noncirrhotic HCC had a median survival of 9 months, and 24% survived in excess of 2 years. This survival experience is significantly more favorable than cirrhotic HCC patients, who had only a 1.2-month median and a 3% 2-year survival. Low histologic grade, mild mitotic activity and the presence of some fibrosis within the specimen were associated with a favorable outcome in advanced noncirrhotic HCC. The favorable prognosis and heterogeneous composition of the noncirrhotic, when compared to the cirrhotic HCC cohort, may be important considerations in the design and evaluation of future clinical trials.

Actuarial Analysis↗

Chemotherapy of malignant hepatomas with sequential intraarterial doxorubicin and systemic 5-fluorouracil and semustine.

Twenty patients with malignant hepatoma were treated with sequential intraarterial doxorubicin (72-hour continuous infusion) followed by systemic 5-fluorouracil (5-FU) and semustine (methyl CCNU). Objective tumor responses were seen in three patients (15%). The durations of response were 6, 19, and 27+ months, respectively. Median patient survival was 7 months. A variety of problems were encountered with the use of transcutaneous angiographic catheters for doxorubicin administration, including inability to adequately perfuse the liver, sepsis, and catheter dislodgement during chemotherapy infusion. Although some patients experienced palliation of reasonable duration, we do not believe that the overall results warrant further studies of this regimen.

Adult↗

Recombinant leukocyte A interferon with doxorubicin. A phase I study in advanced solid neoplasms and implications for hepatocellular carcinoma.

A pilot study was performed on seven patients with advanced solid neoplasms. They received recombinant leukocyte interferon A (rIFN-alpha A) 12 X 10(6) U/m2 intramuscularly daily for 5 days plus doxorubicin, 25 mg/m2 IV on day 3 of each monthly cycle (Roferon-A, Hoffman-LaRoche, Nutley, NJ). Because of side effects, the dose was not increased above the initial level. There was a striking partial response of biopsy-confirmed hepatocellular carcinoma for 6+ months along with a decrease in alpha-fetoprotein from 39,000 to 202 ng/mL. The doxorubicin dose is approximately 33% to 42% of the typical single-agent dose, thus suggesting that the clinical toxicity from these two agents is additive.

Adult↗

Carcinoid tumor of the appendix: treatment and prognosis.

In a long-term study of 150 unselected patients with carcinoid tumors of the appendix, we found that the neoplasms were usually less than 1.0 cm in largest dimension and discovered as an incidental finding during surgery performed for other reasons. Metastases were observed with none of the 127 appendiceal carcinoids less than 2.0 cm in largest dimension, with 3 of the 14 lesions greater than or equal to 2.0 cm but less than 3.0 cm in greatest dimension, and with 4 of the 9 lesions greater than or equal to 3.0 cm. Paradoxically, the patients with the larger tumors and metastases were younger than those with smaller and clinically benign tumors. The median age of patients with tumors greater than or equal to 2.0 cm was 31 years and that of those with metastases was 29 years, as compared with a median age of 42 years in patients with nonmetastasizing tumors less than 2.0 cm. We conclude that simple appendectomy is adequate treatment for patients with apparently localized tumors less than 2.0 cm in largest dimension. We have not observed any recurrences or metastases among 122 such patients followed for a median time of more than 26 years. Simple appendectomy is probably also appropriate treatment for lesions greater than or equal to 2.0 cm in elderly patients or in those at high operative risk. Right hemicolectomy seems justified only in young patients with tumors greater than or equal to 2.0 cm who have a low risk of operative morbidity or mortality. Vascular involvement and invasion of the mesoappendix are features that may favor a more radical approach.

Adolescent↗

Colorectal cancer. Dukes' stage, tumor site, preoperative plasma CEA level, and patient prognosis related to tumor DNA ploidy pattern.

Flow cytometric DNA histograms of colorectal carcinomas from 264 patients were evaluated for the association of tumor site, Dukes' stage, tumor grade, and preoperative carcinoembryonic level with patient survival. The DNA nondiploid carcinomas were significantly more common from the left (descending and sigmoid) colon and the rectum. A poorer prognosis was found for patients with DNA nondiploid cancers than for patients with DNA diploid cancers. This was particularly true for patients with Dukes' stages B2 and C tumors with a small number (one to three) of lymph nodes with metastatic deposits. The DNA nondiploid cancers also had a relatively poorer prognosis in patients with unresectable disease. In a Cox multivariate analysis model, the DNA pattern was an independent prognostic variable for this group of 264 patients with resected colorectal carcinoma.

Carcinoembryonic Antigen↗

Gallbladder adenocarcinoma: the prognostic significance of histologic grade.

Gallbladder adenocarcinoma (GBA) postresection 5-year survival rates are less than 5%, but when histologically confined to the mucosa or submucosa, survival rates of 64% (5 years) and 44% (10 years) have been reported. Whether any other histologic features of GBA have prognostic significance is unknown. This investigation was conducted to determine if GBA histologic grade correlates with survival. Thirty patients with advanced stage GBA participating in Eastern Cooperative Oncology Group (ECOG) treatment protocol EST-2273 served as the study material. Using glandular tumor grade criteria recommended by others, a panel of 7 ECOG pathologists categorized the GBA as either predominantly low or high histologic grade. Each patient's GBA histologic section measured no less than 1.0 X 1.0 cm. Predominant grade was defined as being that grade present in greater than 75% of the histologic section. Patient survival times by grade were calculated from date of initiation of chemotherapy until date of death. The 13-week low grade GBA patient survival was significantly longer than the 7-week high grade GBA patient survival (p less than 0.01). Stratification of patients by either high or low predominant histologic grade is recommended in future GBA treatment studies.

Adenocarcinoma↗

Alpha-fetoprotein associated with islet cell tumors.

Elevated serum levels of alpha-fetoprotein (AFP) (100-1,000 ng/ml) were found in three patients with islet cell tumors. Serial levels correlated with progression of disease, suggesting that AFP could be a useful tumor marker substance for islet cell tumors. Survey sera from an expanded pool of 23 patients with islet cell tumors and nine with carcinoid tumors did not identify additional cases, however, suggesting that elevated AFP levels in these classes of Apudomas are uncommon. Nonetheless, the distinction from other AFP-producing tumors such as hepatocellular carcinoma is clinically important and warrants an awareness of the rare association of AFP with these tumors.

Adenoma, Islet Cell↗

A randomized clinical trial of combination chemotherapy in advanced colorectal cancer.

One hundred and sixty-five patients with advanced colorectal cancer were entered into a prospectively randomized trial of combination chemotherapy comparing three 5-fluorouracil plus methyl CCNU (FM)-based regimens: FM plus ICRF-159 (FMI), FM plus triazinate (FMT), and FM plus vincristine (FMV). Patients were stratified according to performance status, anatomic site of primary indicator lesion, and prior chemotherapy. Those with abnormal kidney or liver function were randomized between FMI and FMV because triazinate depends on both hepatic and renal mechanisms for elimination. There were no significant differences between the treatment regimens in objective response rate (11%-17%), interval to progression (median, 10-14 weeks), or survival (median, 5-6 months). The primary side effect observed was hematologic toxicity, which tended to increase in severity with repeated courses of therapy. Although ICRF-159 and triazinate have been shown to have limited single-agent phase II activity against colorectal cancer in previous trials, neither agent combined with 5-fluorouracil plus methyl CCNU has an improved treatment effect compared with FMV. We do not recommend the further use of these regimens in the treatment of advanced colorectal cancer.

Adult↗

Phase II clinical trial of triazinate in combination with mitomycin C for patients with advanced gastric cancer.

Thirty-three patients with advanced measurable gastric cancer were treated with a combination of mitomycin C and triazinate. Twenty-nine of these patients had failed prior chemotherapy. Nine patients (27%) had an objective tumor response (median duration, 10 weeks). Median survival of all patients treated was 21 weeks. This study demonstrates that carefully selected patients with advanced gastric cancer who have failed a trial of chemotherapy, but are still ambulatory and maintaining adequate nutrition are appropriate subjects for studies of new treatment regimens. Based on the observed objective tumor response rate and median patient survival, further studies of these drugs in combination for the treatment of advanced gastric cancer are indicated.

Adenocarcinoma↗

The other CHOP.

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Breast Neoplasms↗

Treatment of metastatic islet cell carcinoma with a somatostatin analogue (SMS 201-995).

We used an octapeptide analogue of somatostatin, SMS 201-995, in dosages ranging from 150 to 450 micrograms/d administered subcutaneously in three daily doses for 1 to 16 months, to treat 22 patients with advanced malignant islet cell carcinomas. Of the 22 patients, there were 9 with gastrinomas; 3 with glucagonomas; 4 with insulinomas; 1 with ectopic production of parathyroid hormone; and 3 with mixed syndromes. The only biochemical marker in 1 patient was pancreatic polypeptide, and 1 patient had no demonstrable peptide production from the tumor. In 14 patients, dramatic decreases in the levels of circulating peptides (insulin, vasoactive intestinal polypeptide, gastrin, and glucagon) have been accompanied by major alleviations of symptoms. Steatorrhea appears to be the most significant toxicity. This analogue of somatostatin may be appropriate for use as early therapy in patients who have symptoms from syndromes related to islet cell carcinomas but in whom there is no immediate threat from tumor progression.

Adenoma, Islet Cell↗

Phase I and pharmacokinetic study of menogaril administered as a 72-hour continuous i.v. infusion.

Menogaril is a new anthracycline analog of nogalamycin. When administered as a 72-hour continuous iv infusion the dose-limiting toxic effect of menogaril was venous irritation at dose levels that cause only mild leukopenia and minimal gastrointestinal toxicity. Pharmacokinetic studies showed that the rise in plasma concentration during infusion was first-order, with a half-life of 11.9 hours. Total-body clearance of menogaril was 204 ml/minute/m2. There were no detectable metabolites of menogaril in plasma. Urinary excretion of unchanged menogaril was 17.3% of the dose and N-demethylmenogaril was 0.5% over 72 hours. Since menogaril does not appear to be metabolized, a high degree of tissue binding is likely.

Adult↗

Phase I study of two schedules of teroxirone.

Two schedules of teroxirone, a triazine triepoxide, were evaluated in a phase I study. Twenty-six patients were treated on 1 day every 5 weeks at doses of 36-2250 mg/m2. At doses greater than or equal to 1500 mg/m2, severe thrombophlebitis was seen without cytotoxic effect, and this schedule was closed. Twenty-seven patients were treated on 5 days every 5 weeks at daily doses of 16-450 mg/m2. Mild thrombophlebitis and moderate leukopenia were encountered. For phase II studies, a dose of 375 mg/m2 X 5 every 5 weeks is recommended. Pharmacologic studies showed rapid plasma elimination, which suggests the agent's possible usefulness for regional infusion.

Antineoplastic Agents↗