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Biomedical subjects

C G Moertel

Publications and source records attributed to C G Moertel.

At least 109 records · Page 6Linked to original sources
PubMed1984

Primary liver cancer. An Eastern Cooperative Oncology Group Trial.

One hundred ninety-two patients with unresectable primary liver cancer studied by members of the Eastern Cooperative Oncology Group (ECOG) were evaluable in a prospectively randomized clinical trial. Patient discriminants such as performance status were carefully evaluated to assess their influence on prognosis and to evaluate the importance of patient status on response and survival. Patients who were totally bedridden or with signs of overt liver failure were not entered on study. The median survival time for all evaluable previously untreated patients was 17 weeks (19 weeks for North American and European, and 10 weeks for South African black patients). Among the South African patients, however, there was a significantly larger proportion with an initially poor performance status. Prognostic variables (performance status, jaundice, and reduced appetite) dominate any differences among the treatments studied. Among North American and European patients on intravenous (IV) 5-fluorouracil (5-FU) + Methyl-CCNU (MeCCNU) + Adriamycin (ADM, doxorubicin), the 19% response rate is offset by 63% with severe toxicity and a median survival time of only 17 weeks, making this treatment unacceptable clinically. The median survival time of North American and European patients treated with IV 5-FU +/- MeCCNU was 28 weeks in contrast to a median survival time of 12 weeks with ADM (P less than or equal to 0.01). EST 2273 was the ECOG study of patients with primary liver cancer. The results of the first part of the trial were published in 1978. This report updates those findings and reports the results of patients entered subsequently on the second part of that study after it was amended in 1979. With more than 300 evaluable patients in EST 2273, this duet of studies is the largest ever conducted in patients with primary liver cancer, and draws a new baseline from which to measure the disease and its response to treatment.

Adenoma, Bile Duct↗
PubMed1984

Carcinoma of the anal canal. A clinical and pathologic study of 188 cases.

Among 188 patients presenting with carcinoma of the anal canal the predominant cell types were squamous cell (56%) and nonkeratinizing basaloid (35%). Thirteen patients who had predominantly small (less than or equal to 2 cm) and only superficially invasive squamous cell lesions were treated with local excision, and although one required later abdominal perineal (AP) resection for local recurrence, all were apparently cured. Local excision should be preferred as initial treatment for such lesions. One hundred eighteen patients with squamous cell and nonkeratinizing basaloid carcinomas were primarily treated with AP resection. The operative mortality rate was 2.5%. Among 114 patients who survived surgery and had adequate follow-up, 40% developed recurrent disease, and 71% have survived 5 or more years. Pathologic staging based on depth of tumor invasion and regional nodal involvement was strongly predictive of survival as was tumor histology with progressively poorer survival rates from low-grade squamous cell to high-grade squamous cell to nonkeratinizing basaloid types. Tumor size was inversely related to prognosis and was strongly associated with stage. Squamous cell anal carcinoma was dominantly a local disease with approximately 70% of patients presenting with tumor apparently limited to the bowel wall, only 20% with regional node involvement and only 2% with distant metastasis. Even among those patients who recurred after AP resection approximately 80% had all known disease still limited to the pelvic area. Corresponding figures for nonkeratinizing basaloid tumors were 50 percent presenting limited to the bowel wall, 30% with regional nodes, 20% with distant metastasis, and 60% with initial recurrence limited to the pelvis. Among the 13 patients studied with small cell anal carcinoma, the authors found the disease to be very virulent either initially presenting with or rapidly evolving into diffuse dissemination. Only one of the seven patients who could be treated surgically survived 5 years. As is true for small cell carcinomas primary to other sites, this neoplasm should be regarded as a systemic disease. With these findings as a foundation, possible future strategies for management of anal carcinoma are discussed.

Adult↗
PubMed1984

Treatment of psoriasis with N-phosphonacetyl-L-aspartate.

Seven patients with severe psoriasis were treated with the aspartate carbamylase inhibitor N-phosphonacetyl-L-aspartate (PALA). Three patients showed a definite improvement lasting up to 3 months after each course of therapy. Three other patients showed more limited responses of shorter duration, and one patient experienced progressive worsening of his psoriasis while on the study. Psoriatic arthritis did not appear to be improved by the PALA therapy. Side effects were usually mild and limited to skin irritation and diarrhea. The development of alternate schedules of administration may lead to a more useful treatment response in patients with severe psoriasis.

Adult↗
PubMed1984

A phase II study of chlorozotocin in advanced large bowel carcinoma. A cooperative study between two institutions.

Mayo clinic and georgetown university carried out a cooperative phase II study of chlorozotocin in measurable advanced large bowel carcinoma. Of 78 evaluable patients randomized, 39 received low-dose (120 mg/m2 if previously untreated, 100 mg/m2 if previously treated) and 39 high-dose (200 mg/m2 if previously untreated, 175 mg/m2 if previously treated) chlorozotocin intravenously at 6-week intervals. Both groups were comparable in regard to age, prior treatment, treating institution, site of metastases, and performance scores. Overall response rate was 8%, including 5% in low-dose patients and 10% in high-dose patients. Toxicity was mild to moderate, with gastrointestinal toxicity substantially, and hematologic toxicity somewhat less, than seen with other nitrosoureas. Time to progression and survival showed no significant difference between patients treated on the low- and high-dose schedules. As chlorozotocin produced less nausea and vomiting than other nitrosoureas, even in the high-dose regimen, it should be considered for evaluation in neoplasms where nitrosoureas have shown more activity than in colorectal carcinoma.

Adenocarcinoma↗
PubMed1984

A phase II study of the combination, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and N-(phosphonacetyl)-L-aspartate (PALA), in patients with advanced large bowel cancer.

A phase II study of BCNU and PALA was undertaken in advanced large bowel carcinoma. Thirty patients with advanced metastatic colorectal carcinoma were treated with the combination BCNU (200 mg/m2) every 6 weeks, and PALA (5.0 g/m2) every 3 weeks. Fifteen patients had received no prior chemotherapy and 15 had been previously treated with one or more cytotoxic agents. Only one patient met the criteria for a partial response, and this response was of only 3 months' duration. It would seem unlikely that the combination of BCNU and PALA holds the potential of response greater than BCNU alone and that further trials of this treatment regimen for this tumor type seem unwarranted.

Adenocarcinoma↗
PubMed1984

Clinical trial of sequential N-phosphonacetyl-L-aspartate, thymidine, and 5-fluorouracil in advanced colorectal carcinoma.

Preclinical studies have demonstrated enhanced cytotoxic effects of 5-fluorouracil (5-FU) when given in conjunction with N-phosphonacetyl-L-aspartate (PALA) or thymidine in several murine systems. Early clinical studies have demonstrated significant delayed depletion of pyrimidine nucleotides in tumor biopsy specimens following systemic PALA administration and prolonged serum levels of 5-FU after thymidine administration. Each of these biochemical effects would be anticipated to augment the cytotoxic activity of 5-FU. A phase II trial of a timed sequential administration schedule of PALA, thymidine, and 5-FU was conducted in 37 patients with advanced measurable colorectal cancer. Ten of 37 patients (27%) experienced objective tumor responses with a median response duration of 22 weeks, and 18 patients (49%) had stable disease for a median duration of 20 weeks. Six of 13 patients (46%) with anaplastic histology and/or rapidly progressive tumors experienced high-quality tumor responses. Leukopenia and neurologic side effects were the primary toxicities, including one death caused by sepsis. This regimen has demonstrated striking alteration in the 5-FU dose-effect relationship and definite antitumor activity in patients with advanced colorectal cancer. Further trials in patients with anaplastic carcinomas of the colon or other anatomic sites should be considered.

Adult↗
PubMed1984

Combined 5-fluorouracil and radiation therapy as a surgical adjuvant for poor prognosis gastric carcinoma.

Sixty-two patients with resectable but poor-prognosis gastric carcinoma were randomized to either no surgical adjuvant therapy or treatment with 5-fluorouracil (15 mg/kg by rapid intravenous injection X 3) plus radiation (3,750 rad in 24 fractions) initiated 3 1/2 to six weeks postoperatively. Informed consent was obtained after randomization and only from the 39 randomized to treatment. Ten patients refused their treatment assignment. The five-year survival rate for patients randomized to treatment was 23%, and for those randomized to no treatment, 4% (P less than .05). Both the survival distributions and the alive-without-recurrence distributions were significantly different for the two groups (P = .024) and favored treatment assignment. When the treatment assignment group was broken down to those patients actually receiving treatment and those refusing, five-year survival rates were: treated, 20%; treatment refusal, 30%; controls, 4%; the three survival distributions were not significantly different. Thirty-nine percent of patients actually treated had a local-regional component of first clinical recurrence compared with 54% of those who received no treatment. This study does not establish 5-fluorouracil plus radiation as effective surgical adjuvant therapy for gastric cancer but suggests this approach as a possible fruitful area for continued research. This study also illustrates the potential problems that may be encountered in interpreting results when patients are randomized to a study before consent is obtained.

Adult↗
PubMed1984

Streptozocin plus fluorouracil versus doxorubicin therapy for metastatic carcinoid tumor.

EST 5275 is a phase II and III study of fluorouracil plus streptozocin (5-FU plus STZ) or doxorubicin in patients with measurable progressive carcinoid tumor. Among one hundred seventy-two cases with no prior chemotherapy and no heart disease, the response rate was 22% for 5-FU plus STZ and 21% for doxorubicin, while the median response duration and median survival were 31 weeks and 64 weeks for the combination and 26 weeks and 48 weeks for doxorubicin. Thirty-three patients who failed 5-FU plus STZ crossed over to doxorubicin and achieved an 18% response. Of the thirty-five patients who failed on doxorubicin, 29% responded to 5-FU plus STZ. Hematologic toxicity was similar for both treatments; however, the 5-FU plus STZ patients experienced more vomiting but acceptable renal toxicity. Both chemotherapy regimens have antitumor activity in carcinoid tumors.

Adult↗
PubMed1984

Metabolic studies of delta-9-tetrahydrocannabinol in cancer patients.

The metabolism of oral delta-9-tetrahydrocannabinol (THC) was studied in nine patients with gastrointestinal neoplasms receiving chemotherapy regimens containing 5-FU and semustine. Plasma levels of THC and its metabolites 11-OH-delta-9-THC (11-OH-THC) and 11-nor-9-carboxy-delta-9-THC (C-THC) were measured. Plasma levels of THC and its metabolites were quite variable among the patients studied. Plasma levels of THC and 11-OH-THC tended to peak at the same time; the C-THC levels peaked later and lasted much longer than the others. Mean half-lives of THC, 11-OH-THC, and C-THC were estimated to be 1.5, 2.1, and 4.4 hours, respectively. Multiple doses of THC did not produce a significant additive effect on the plasma concentrations of the biologically active metabolites THC and 11-OH-THC. No correlation between antiemetic effect or cannabinoid toxicity and plasma levels of the three metabolites could be made in this small number of patients.

Adult↗
PubMed1984

Evaluation of combined cyclophosphamide and methotrexate therapy in the treatment of metastatic carcinoid tumor and the malignant carcinoid syndrome.

Sixteen patients with metastatic carcinoid tumor and the malignant carcinoid syndrome were treated with combined cyclophosphamide and methotrexate therapy in a regimen previously described as highly effective. Toxicity was relatively mild and consisted primarily of leukopenia. One patient experienced some symptomatic benefit and minor reduction in hepatomegaly and 5-hydroxyindoleacetic acid excretion. None met our criteria for an objective response. Combined cyclophosphamide and methotrexate therapy does not appear to offer significant benefit for this disease.

Adult↗
PubMed1983

Assessment of weight loss, food intake, fat metabolism, malabsorption, and treatment of pancreatic insufficiency in pancreatic cancer.

In 12 patients with biopsy-proven pancreatic ductal adenocarcinoma, the following were determined: (1) whether decreased food intake, malabsorption, or altered fat metabolism were associated with weight loss; (2) the effect of pancreatic extract as treatment for malabsorption; and (3) the accuracy of the triolein breath test for detection of steatorrhea. Weight loss occurred in 11 patients and only in patients who had either malabsorption (n = 5), low coefficients of caloric consumption (n = 2), or both (n = 4). Nine patients had fat malabsorption, six had protein malabsorption, and caloric consumption was decreased in seven patients. Metabolism of oleic acid was significantly decreased (P less than 0.01) compared to normal subjects and correlated with basal metabolic rates (r = 0.6; P less than 0.05) which were within the range of normal values for age and sex. Body weight loss correlated only with coefficients of fat and protein absorption (r = 0.59; P less than 0.05). Treatment of patients with pancreatic extract resulted in significant improvement in absorption in those with moderate to severe fat or protein malabsorption (coefficient of absorption less than 80%) but no significant improvement occurred in patients with mild fat or protein malabsorption. The triolein breath test was abnormal in all patients with fat malabsorption and predicted improvement of fat absorption in five of six patients with steatorrhea who were treated with pancreatic extract. Thus, in pancreatic cancer, weight loss is associated with malabsorption; exogenous pancreatic extract significantly improves moderate to severe fat or protein malabsorption, and the triolein breath test detects fat malabsorption and predicts the treatment response to pancreatic extract.

Adult↗
PubMed1983

Carcinoids: the association of histologic growth pattern and survival.

There are five generally accepted carcinoid histologic growth patterns, i.e., insular, trabecular, glandular, undifferentiated, and mixed. To determine their possible prognostic significance, a panel of pathologists studied the growth patterns of 138 carcinoids collected from an Eastern Cooperative Oncology Group carcinoid advanced stage disease chemotherapy investigation. Survival times were measured from date of initial pathologic diagnosis of carcinoid disease to date of either death or last follow-up. Significant differences were observed in survival times between the five major growth patterns (P less than 0.001). Within the mixed growth pattern group, significant differences in survival time were also observed (P approximately 0.05). In decreasing order of median survival time in years, the growth patterns ranked as follows: mixed insular plus glandular, 4.4; insular, 2.9; trabecular, 2.5; mixed insular plus trabecular, 2.3; three pooled low incidence rate mixed growth patterns, 1.4; glandular, 0.9; and undifferentiated, 0.5. Histologic growth patterns are recommended as a stratification factor in future studies of this disease.

Aged↗
PubMed1983

Surgical treatment of functioning metastatic carcinoid tumors.

Thirteen patients with functioning carcinoid syndrome and hepatic metastases were surgically treated. Localized hepatic metastases were resected in five patients, and diffuse hepatic metastases were treated with hepatic artery ligation in eight. There were no postoperative deaths, and follow-up ranged from six to 46 months. All patients were symptom-free after operation. In all patients with resection, levels of 5-hydroxyindoleacetic acid (5-HIAA) returned to normal or near normal, whereas in patients who underwent hepatic artery ligation, the average reduction in 5-HIAA level was 76%. Three patients died during the follow-up period--two of metastatic carcinoids and one without evidence of disease. The mean duration of response was 36 months for resection and 4.8 months for hepatic artery ligation. The addition of postoperative intra-arterial chemotherapy and sequential systemic chemotherapy may enhance the response to hepatic artery ligation.

Aged↗
PubMed1983

A phase II study of alanosine in advanced large bowel carcinoma.

Thirty patients with advanced metastatic colorectal adenocarcinoma were treated with alanosine at a dose of 160 mg/m2 daily for 5 days every 4 weeks. Sixteen patients had received no prior chemotherapy and 14 had been previously treated with one or more cytotoxic agents. No patient met the criteria for a complete or partial response. The major toxicity was stomatitis.

Adenocarcinoma↗