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Biomedical subjects

C G Moertel

Publications and source records attributed to C G Moertel.

At least 145 records · Page 8Linked to original sources

Streptozocin alone compared with streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma.

To evaluate the treatment of advanced islet-cell carcinoma, we randomly assigned 84 patients to streptozocin alone or streptozocin plus fluorouracil. Each regimen was given in five-day courses. The most frequent toxic effects were nausea and vomiting, mild and reversible renal toxicity, and bone-marrow depression with the combination regimen. The combination had advantages over streptozocin alone in overall rate of response (63 vs. 36 per cent) and in rates of complete response (33 vs. 12 per cent). There was no evidence of a preferential response among types of functional tumors. Objective responses were generally of long duration (median, 17 months) and of substantive clinical benefit. Treatment with the combination also yielded a survival advantage over treatment with streptozocin alone (medians, 26 and 16 1/2 months), but this difference is not statistically significant. In spite of gastrointestinal side effects, streptozocin combined with fluorouracil appears to be a valuable treatment for advanced islet-cell carcinoma.

Adenoma, Islet Cell↗

Chemotherapy of advanced esophageal carcinoma: Eastern Cooperative Oncology Group experience.

In a Phase II study, patients with measurable metastatic or recurrent esophageal carcinoma randomly received after Adriamycin (ADR), 60 mg/M2 I.V. q three weeks, or methotrexate (MTX), 40 mg/M2 I.V. q one week, or 5-fluorouracil (5-FU), 500 mg/m2 I.V. x 5 days q five weeks. Objective partial response rates for 72 patients were 5% for ADR (one of 20), 12% for MTX (three of 26), and 15% for 5-FU (four of 26). There were no complete responses. Median duration of response was 13 weeks. Median survival was 14 weeks (eight weeks for ADR, 14 weeks for MTX, and 15 weeks for 5-FU). Factors of liver metastasis, adjacent anatomic involvement, time from initial diagnosis to study entry, and prior radiation were found to be significant determinants of survival. Adriamycin did not appear to benefit patients with advanced measurable squamous cell carcinoma of the esophagus. Methotrexate and 5-fluorouracil showed comparable activity and survival, although methotrexate was slightly more toxic.

Antineoplastic Agents↗

Rectal cancer following colectomy for polyposis.

Reevaluation of 178 patients treated for multiple colonic polyposis by abdominal colectomy and restoration of bowel continuity confirmed that patients with both rectal and colonic polyps are at substantial risk of having rectal cancer develop postoperatively. Rectal cancer has not occurred in any of 35 patients who had no rectal polyps preoperatively. However, 46 (32%) of 143 patients with multiple colorectal polyposis have had cancer develop during a median follow-up of nearly 20 years. Multivariate analysis showed a highly significant association between the number of rectal polyps present preoperatively and decreased survivorship free of rectal cancer (P less than .001), and a strong correlation between the presence of cancer in the resected colon and subsequent development of rectal carcinoma (P less than .01). No correlation could be established between low anastomosis and prevention of rectal carcinoma. The risk of cancer developing in the retained segment of large bowel can be established only by extended postoperative observation.

Actuarial Analysis↗

Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group.

The prognostic effect of weight loss prior to chemotherapy was analyzed using data from 3,047 patients enrolled in 12 chemotherapy protocols of the Eastern Cooperative Oncology Group. The frequency of weight loss ranged from 31 percent for favorable non-Hodgkin's lymphoma to 87 percent in gastric cancer. Median survival was significantly shorter in nine protocols for the patients with weight loss compared to the patients with no weight loss. Chemotherapy response rates were lower in the patients with weight loss, but only in patients with breast cancer was this difference significant. Decreasing weight was correlated with decreasing performance status except for patients with pancreatic and gastric cancer. Within performance status categories, weight loss was associated with decreased median survival. The frequency of weight loss increased with increasing number of anatomic sites involved with metastases, but within categories of anatomic involvement, weight loss was associated with decreased median survival. These observations emphasize the prognostic effect of weight loss, especially in patients with a favorable performance status or a limited anatomic involvement with tumor.

Activities of Daily Living↗

Correlation of histopathologic characteristics of primary tumor and uninvolved regional lymph nodes in Dukes' class C colonic carcinoma with prognosis.

Ninety-two patients with Dukes' class C colonic carcinoma, divided equally into those who survived 5 years or more and those surviving less than 5 years after resection for cure, underwent evaluation of multiple histopathologic characteristics of the primary tumor and the uninvolved regional lymph nodes. These characteristics were analyzed by the chi-square test for correlation with survival. A statistically significant correlation (P less than 0.05) in the group who survived 5 years or more was observed for Broders' grades 1 and 2, tumor not involving serosa, and a pushing tumor margin. Of the 14 patients who had a pushing tumor margin and tumor not involving serosa, 12 (86%) survived 5 years or more. Seven patients had an infiltrating tumor margin and peritumor venous invasion, and of this group, only one (14%) survived 5 years or more. Histopathologic characteristics of host immune reaction at the tumor or in the uninvolved regional lymph nodes did not correlate with survival.

Colonic Neoplasms↗

Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial.

One hundred and fifty patients with advanced cancer participated in a controlled double-blind study to evaluate the effects of high-dose vitamin C on symptoms and survival. Patients were divided randomly into a group that received vitamin C (10 g per day) and one that received a comparably flavored lactose placebo. Sixty evaluable patients received vitamin C and 63 received a placebo. Both groups were similar in age, sex, site of primary tumor, performance score, tumor grade and previous chemotherapy. The two groups showed no appreciable difference in changes in symptoms, performance status, appetite or weight. The median survival for all patients was about seven weeks, and the survival curves essentially overlapped. In this selected group of patients, we were unable to show a therapeutic benefit of high-dose vitamin C treatment.

Aged↗

Nonspecific immune determinants in the patient with unresectable gastrointestinal carcinoma.

Assays of immune function (recall skin tests to microbial antigens; total circulating lymphocytes, T-cells, B-cells; lymphocyte blastogenesis with PHA, Con A, and pokeweed mitogens; and serum immunoglobulins IgA, IgM, IgG) were obtained in 408 patients with unresectable gastrointestinal carcinoma. The overall patient population, in comparison to normal controls, was characterized by reduced response to recall skin tests, reduced total lymphocyte and T-cell counts, reduced lymphocyte blastogenesis assays, increased B-cell counts and increased IgA and IgM. Significant immunosuppression was associated with prior radiation or chemotherapy, and with impaired patient performance status. There was no apparent correlation between extent of clinically evident malignant disease and immune function within this patient population. No assay of immune function matched the prognostic value of the more readily available and less expensive determinations of performance status, serum alkaline phosphatase, or SGOT. Only reactivity to recall skin tests had a significant correlation to patient survival independent of performance status. Among patients with little or no disability, only intensity of skin test reactivity correlated significantly with survival; and among those with greater disability, there was correlation only with proportion of skin tests positive. The combination of candida and streptokinase antigens provided the best recall skin test survival correlation. Adding a third, fourth, or fifth antigen did not add to prognostic value. From an overall standpoint, the immune determinants which we studied do not appear to provide useful additions to the evaluation of the patient with unresectable gastrointestinal cancer.

Age Factors↗

A phase I study of chlorozotocin (NSC 178248).

Chlorozotocin was administered by rapid intravenous infusion to 35 patients with advanced cancer on either single-day of five-consecutive-day schedules. Total doses per course ranged from 12.5 to 200 mg/m2. On either administration schedule, dose limiting toxicities were thrombocytopenia and leukopenia at total doses of 150 mg/m2 to 200 mg/m2. Repetitive courses of drug may produce progressive impairment of renal and bone marrow function. Nausea and vomiting were infrequent and mild without definite relationship to dose. Minor reversible nondose related increases in SGOT and in serum creatinine occurred at all doses on both schedules. The plasma half-life of intact N-nitroso groups averaged 9.5 minutes after rapid intravenous administration of doses up to 40 mg/m2 and 12.5 minutes after doses of 150 or 200 mg/m2. No differences between plasma half-lives were seen between identical doses given on the first and fifth days of the five-day schedule. Objective tumor regression was noted in one patient with bronchogenic large cell carcinoma and one patient with metastatic melanoma.

Adult↗

Delta-9-tetrahydrocannabinol as an antiemetic for patients receiving cancer chemotherapy. A comparison with prochlorperazine and a placebo.

The antiemetic activity and side-effects of delta-9-tetrahydrocannabinol (THC) were evaluated in 116 patients (median age 61 years) receiving combined 5-fluorouracil and semustine (methyl CCNU) therapy for gastrointestinal carcinoma. In a double-blind study, patients were randomized to receive THC, 15 mg orally three times a day, prochlorperazine, 10 mg orally three times a day, or placebo. The THC had superior antiemetic activity in comparison to placebo, but it showed no advantage over prochlorperazine. Central nervous system side-effects, however, were significantly more frequent and more severe with THC. With the dosage and schedule we used, and in our patient population of largely elderly adults, THC therapy resulted in an overall more unpleasant treatment experience than that noted with prochlorperazine or placebo. Although THC may have a role in preventing nausea and vomiting associated with cancer chemotherapy, this role must be more clearly defined before THC can be recommended for general use.

Adult↗

Chemotherapy of gastric and pancreatic carcinoma: a controlled evaluation of combinations of 5-fluorouracil with nitrosoureas and "lactones".

By random assignment a total of 176 eligible patients with advanced nonmeasurable pancreatic carcinoma were treated with 5-fluorouracil (5-FU) either alone or in combination with a nitrosourea (streptozotocin), in combination with a "lactone" (spironolactone), or in combination with both. By random assignment a total of 179 patients with advanced nonmeasurable gastric carcinoma were treated with 5-FU either alone or in combination with a nitrosourea (methyl CCNU), in combination with a lactone (testolactone), or in combination with both. The median survival period for all pancreatic carcinoma patients was 17 weeks, and for all gastric carcinoma patients 30 weeks. The addition of the nitrosoureas or the lactones or a combination of both produced no improvement in length of patient survival for either primary carcinoma when compared to treatment with 5-FU alone.

Adenocarcinoma↗

A comparative clinical and immunological assessment of methanol extraction residue of Bacillus Calmette-Guérin versus placebo in patients with advanced cancer.

Eighty-four patients with advanced cancer refractory to conventional therapeutic modalities were randomly assigned in double-blind fashion to one of three intradermal treatment regimens: "high"-dose methanol extraction residue fraction of Bacillus Calmette-Guérin (MER) (2.0 mg); "low"-dose MER (0.5 mg); or 0.9% NaCl solution placebo. Toxicity, consisting primarily of cutaneous inflammation and ulceration, was limited to patients receiving MER and was most severe with the high-dose regimen. Pretreatment clinical and immunological parameters were comparable between patient groups. Although a significant number of patients had increases in various immune parameters according to the criteria used, there was no appearent advantage to MER given in either dosage schedule compared to placebo. Patient survival was not affected by either MER regimen compared to placebo. This investigation failed to demonstrate any significant clinical or immunological benefit from MER given in two dosage regimens in patients with advanced cancer with the laboratory methodology used and emphasizes the importance of appropriate controls in evaluating immunostimulants in humans.

BCG Vaccine↗

Combination chemotherapy trials in metastatic carcinoid tumor and the malignant carcinoid syndrome.

One hundred eighteen patients with metastatic carcinoid tumor were randomized to treatment with streptozotocin combined with cyclophosphamide or with 5-fluorouracil (5-FU). Commonly experienced side effects were nausea, vomiting, leukopenia, thrombocytopenia, and nephrotoxicity. Objective response rates among eligible and evaluable patients treated with the 5-FU combination was 14 of 42 (33%) and with the cyclophosphamide combination, 12 of 47 (26%). Among those patients with carcinoids primary to the small bowel the respective response rates were 44% and 37%. The overall response rates for patients with carcinoids of pulmonary or unknown origin were only 12% and 17%. There was no significant difference in patient survival between the two treatment arms. Among 11 patients who received crossover therapy with 5-FU alone there were two responders. There were no responders among eight patients treated with cyclophosphamide alone. Urinary 5HIAA excretion proved to be a useful biologic marker in these patients that correlated well with the observed measurements of tumor bulk. Median survival times from the diagnosis of unresectable malignant disease related to sites of origin of carcinoid tumor were the following: small bowel, 28.4 months; pancreas, 24.0 months; lung, 15.1 months; and unknown origin, 9.0 months. Metastatic carcinoid tumor is a malignant disease susceptible to chemotherapeutic approaches and continued investigation of the therapy of these neoplasms should be strongly encouraged.

Adolescent↗