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Biomedical subjects

G E Metter

Publications and source records attributed to G E Metter.

At least 19 recordsLinked to original sources
PubMed1987

High doses of prochlorperazine for cisplatin-induced emesis. A prospective, random, dose-response study.

This study investigated the antiemetic properties of four different doses of prochlorperazine (10 mg, 20 mg, 30 mg, 40 mg) when given randomly to patients receiving four cycles of the same dose of cisplatin-based chemotherapy. Prochlorperazine was given to 71 patients by slow intravenous infusion 30 minutes before and 3 and 6 hours after the start of cisplatin chemotherapy. The higher doses of prochlorperazine proved to be effective in the control of cisplatin-induced emesis. For the 20 patients who completed all 4 study cycles of treatment, a relationship was discerned between the dose of prochlorperazine administered and the antiemetic effect. When all 71 patients were analyzed in terms of the results of the first cycle of chemotherapy, a significant dose-response effect was also found. Overall toxic reactions in 82 treatment cycles using either 30 mg or 40 mg of prochlorperazine were dystonia (1 patient), restlessness (2), hypotension (3), and drowsiness (12). This study demonstrates that higher-than-conventional doses of prochlorperazine have an impressive antinauseant effect with only moderate toxicity.

Adult↗
PubMed1987

Mitotic counts in follicular lymphomas.

Increased mitotic activity is associated with significantly shorter patient survival in some of the subtypes of diffuse non-Hodgkin's lymphomas. This study on 105 cases of follicular lymphoma was undertaken to determine the clinical significance of mitotic activity in follicular lymphomas. For each case, two pathologists independently counted mitotic figures in 20 random high-power fields. The difference of the average mitotic counts over 20 high-power fields for the two pathologists showed a Gaussian distribution with a median difference of -0.26 counts per high-power field and a standard error of 0.10 per cent. In 94 cases (91 per cent), the difference was less than two mitotic counts per high-power field, indicating good interobserver agreement. There was a statistically significant difference in mitotic counts between subtypes of follicular lymphoma as well as a gradient among subtypes, with the lowest mitotic activity in the poorly differentiated lymphocytic subtype and highest in the undifferentiated subtype. A multivariate statistical analysis of clinical and pathologic variables showed that mitotic figures were not of prognostic significance.

Humans↗
PubMed1987

Total body irradiation and high-dose etoposide: a new preparatory regimen for bone marrow transplantation in patients with advanced hematologic malignancies.

In a phase I/II study, 47 patients (median age, 24 years) with hematologic malignancies (33 patients with acute leukemia not in first remission and 14 patients with other advanced malignant hematologic disorders) were treated with total body irradiation and high doses of etoposide (VP16-213) followed by bone marrow transplantation. At the time of analysis, 21 patients were alive, and 19 of them were in continued complete remission for 101 days to greater than 40 months (median, 12 months). The actuarial disease-free survival rate of the 33 acute leukemia patients is 43% (2 SEM, 18%) and the actuarial relapse rate is 32% (2 SEM, 20%). Five of the 14 patients with the other hematologic malignancies are alive, and four of them continue to be free of disease for 8 to 27 months. Pharmacokinetic studies established a strong correlation between the administered drug doses and their plasma levels and also demonstrated complete drug clearance prior to marrow grafting. An etoposide dose of 60 mg/kg body weight was found to be the maximum tolerated dose. This new preparatory regimen was well tolerated and was not associated with specific acute or long-term regimen-related toxicities. Our data suggest that total body irradiation with high-dose etoposide presents a viable alternative to other preparatory regimens. The role of this novel combination remains to be defined by future prospective randomized trials.

Acute Disease↗
PubMed1986

What should be the morphologic criteria for the subdivision of follicular lymphomas?

The members of the Pathology Panel for Lymphoma Clinical Studies undertook a collaborative study with the hope of resolving some of the controversies regarding the criteria and methods for the subclassification of follicular lymphomas (FLs). A group of 105 patients with FL were subclassified by seven hematopathologists according to two methods. In the first method, cases were subclassified according to the Rappaport, Lukes and Collins, and Working Formulation systems. In each of these systems, FLs are subclassified by estimation of the different cell populations, without actual counting of cells. In the second method, precise counts of different cells were made according to the standard and modified Berard methods. With this counting method, diagnoses were independently derived, based on counts provided by the seven pathologists, for large cleaved (LC), small noncleaved (SNC), and large noncleaved (LNC) cells. To ascertain what method and which criteria are most useful in predicting survival, we made clinicopathologic correlations. When the subjective (first method) diagnoses were rendered, and when the consensus diagnoses of the seven pathologists were used, there were no significant differences in survival among patients with the different subtypes. On the other hand, when we used the counting method of Berard (second method) and the cut-off points for the cell counts suggested by him for the subclassification, we were able to divide the patient population into prognostic subgroups. Because the cut-off points proposed by Berard are not derived objectively, we made statistical comparisons of survival curves to determine cut-off points (and thus to establish objective criteria). We found that the patient population could be separated into at least two prognostic groups, for SNC and/or LNC and for SNC + LNC + LC cells. The cut-off points which we derived differed with cell type, however. Until the usefulness of these new cut-off points is established, we recommend that the cut-off points and the counting method of Berard be used for the subclassification of FL. Because the choice of treatment for the different subtypes of FL is totally dependent on the histologic diagnosis, and because of the variability among the diagnoses of pathologists, treatment planning is difficult.

Age Factors↗
PubMed1985

Experience with continuous regional chemotherapy and hepatic resection as treatment of hepatic metastases from colorectal primaries. A prospective randomized study.

Sixty-five patients with hepatic metastases from colorectal primaries were studied in a prospective randomized fashion. The five patients with solitary metastases all had resection of metastases and 50% were randomized to pump therapy. Of the 16 patients with multiple resectable metastases, 7 had pump only and 9 had resection plus pump. Although the difference was not significant, there was a trend of improved survival for the patients with resection plus pump. For the patients with unresectable disease, those patients with positive portal nodes had poor survival matching those patients with extra hepatic metastases. Patients with unresectable disease treated with pump had a 73% therapeutic response rate and a median survival of 22 months. Significant complications included chemical hepatitis and biliary stenosis. The long-term efficacy of continuous hepatic artery infusion versus the hazards of treatment and the financial cost will need further investigation.

Chemical and Drug Induced Liver Injury↗
PubMed1985

Morphological subclassification of follicular lymphoma: variability of diagnoses among hematopathologists, a collaborative study between the Repository Center and Pathology Panel for Lymphoma Clinical Studies.

A collaborative study between the Repository Center for Lymphoma Clinical Studies and the members of the lymphoma pathology subcommittee of the major cooperative oncology groups was undertaken in an effort to ascertain the reproducibility and the interobserver agreement for the cytologic diagnosis of follicular lymphomas. A group of 105 patients with follicular lymphomas were subclassified by seven hematopathologists according to two methods. In the first method, cases were subclassified according to the Rappaport, Lukes, and Collins, and Working Formulation systems. In these systems, follicular lymphomas are subclassified by estimation of the different cell populations without the actual counting of cells. With this method, great variability in diagnosis was noted. For example: (1) The consensus diagnosis was that of poorly differentiated lymphocytic lymphoma (PDL) in 39 cases, but among the individual pathologists the number of cases thus diagnosed ranged from 24 to 65; (2) In 40 cases, the consensus diagnosis was follicular lymphoma, mixed-cell type; however, all seven pathologists independently agreed on this subtype in only one case; (3) A major disagreement was noted in 39 cases (37%), in which both diagnostic extremes (small cleaved and large noncleaved) were expressed. In the second method, only precise counts of different cells were made, according to a modification of the method recommended by Berard. With this counting method, diagnoses were independently derived based on the counts provided by the seven pathologists for large cleaved, small noncleaved, and large noncleaved cells. The variability in the results was wide also with this second method. For example, the average number of large cells found by each pathologist was ascertained, and the ranges were determined. The average range was 28 cells, which was considered high. The same determinations were performed only for large noncleaved cells, and the range was found to be 15 cells, which was also considered high. When the diagnoses derived from counts of only large noncleaved cells were compared with the traditional, more subjective diagnoses, fairly close agreement was obtained. In summary, the great variability in diagnoses of follicular lymphomas among pathologists may be attributed to the difficulties inherent in accurate determination of cell size and of the precise percentages of different cells. Until solutions to these problems are developed, one can subclassify follicular lymphomas according to the Berard method or the estimation method.

Cell Count↗
PubMed1985

Cyclophosphamide versus 5-fluorouracil, doxorubicin, and mitomycin C (FAM') in the treatment of hormone-resistant metastatic carcinoma of the prostate: a preliminary report of a randomized trial.

There is no evidence that combination chemotherapy is superior to single agents in the treatment of advanced, hormone-resistant carcinoma of the prostate. We are reporting the preliminary results of a randomized trial comparing cyclophosphamide (CTX) with a combination of 5-fluorouracil, doxorubicin and mitomycin C (FAM'). Thirty-one patients were randomized and 30 of them were evaluable for response. Sixteen patients were treated with CTX and 14 with FAM'. On the CTX arm, eight (50%) of the patients had stable disease (SD) and eight (50%) had progressive disease (PD). On the FAM' arm, one (7%) patient had partial response (PR), five (36%) patients had SD and eight (57%) failed to respond. The difference in response rates between the two regimens was not significant (P greater than .72). The median time to progression (MTP) of all patients treated with CTX was six weeks and the MTP of patients treated with FAM' was 16 weeks (P less than .007). This difference in MTP could be explained in part by the unequal time to reevaluation between the two regimens. The MTP of the responders on CTX however, was 13 weeks, while for FAM' it was 33 weeks (P = .014). This difference suggests that FAM' has superior activity to CTX. Pain alleviation was seen in 25% of patients treated with CTX and in 64% of those treated with FAM' (P less than .01). Toxicity was tolerable on both regimens. We conclude that CTX and FAM' have similar response rates. Patients treated with FAM' enjoyed longer MTP and greater pain alleviation than those treated with CTX.

Adenocarcinoma↗
PubMed1984

Effects of amphotericin B with combination chemotherapy on response rates and on survival in non-small cell carcinoma of the lung.

Thirty-seven patients with non-small cell carcinoma of the lung were randomized to receive doxorubicin, lomustine, hexamethylmelamine, and methotrexate (ACHM) or ACHM plus amphotericin B (AMB). The complete plus partial response rate was 39% for ACHM plus AMB, compared to 23% for ACHM alone. However, the median duration of complete or partial response was only 3.0 months with ACHM plus AMB, compared to 7.0 months with ACHM. Most importantly, median survival was only 4.0 months with ACHM plus AMB, compared to 8.0 months with ACHM (P = 0.08; two-tail test). Myelosuppression was enhanced by the addition of AMB. Although AMB has biological and antitumor activity in certain clinical circumstances, it does not appear to have a meaningful role in palliative therapy of patients with non-small cell bronchogenic carcinoma.

Altretamine↗
PubMed1983

Malignant lymphoma, mixed cell type, diffuse.

This retrospective study of diffuse mixed (DM) cell lymphoma was undertaken as a collaborative study between the Repository Center for Lymphoma Clinical Studies and four cooperative oncology groups (CALGB, ECOG, SECSG, SWOG), and was based on 62 patients from the files of the Repository Center. We wanted to ascertain whether there were any significant clinical differences among the various morphological subtypes of this lymphoma. All patients were treated according to different protocols of the Cooperative Oncology Groups sponsored by the National Cancer Institute. In 16 patients (26%), the malignant lymphoma (ML) had morphological features consistent with follicular center cell origin (FCC); in 34 patients (55%), the ML did not have features of follicular center cell type (non-FCC), but had morphology described for peripheral T-cell-derived ML. In 8 of the patients (13%), no agreement could be reached by the 7 histopathologists who participated in the study, and these were classified as unresolved; the remaining 4 (6%) were unclassifiable. We compared the survival times of the 16 patients having the morphological features of the FCC subtype with the survival times of the 34 patients with the non-FCC subtype and found that patients with FCC lived longer (p = 0.07 Cox's regression). In the FCC group, all patients who had complete remissions (CR) were alive; however, their survival times were similar to those who had a partial or no response (p = 0.32). In contrast, in the non-FCC group, the median survival was 20 mo, and patients with a CR had a significantly longer survival than did incomplete responders (p = 0.003). According to these results the non-FCC diffuse mixed cell lymphoma appears to be a high-grade malignant lymphoma, whereas the FCC type is not.

B-Lymphocytes↗
PubMed1982

Serum levels of carcinoembryonic antigen and a tumor-extracted carcinoembryonic antigen-related antigen in cancer patients.

Levels of carcinoembryonic antigen (CEA) and a tumor-extracted CEA-related antigen (TEX) were determined in sera from patients with carcinomas of the breast, colon, lung, head and neck, and a number of miscellaneous categories. The purpose of this study was to compare the levels of each antigen at various stages of malignant disease. Competitive radioimmunoassays developed in our laboratory were shown to be sufficiently specific to detect either of these two antigens independent of each other. The results indicate that: (a) with our specific assays, CEA was not significantly elevated in smoker controls, but TEX was elevated in 29% of smoker controls; (b) TEX was equivalent to CEA as a tumor marker for colonic cancer. TEX was better than CEA as a marker for lung cancer and, based on limited data, there is a possibility that TEX is a significantly better tumor marker than is CEA in early lung cancer; (c) TEX was superior to CEA as a tumor marker for breast and head and neck cancers; (d) there is a strong indication that serial determinations of TEX can be used as effectively as CEA in the monitoring of disease progress. These preliminary results must be confirmed by increasing the number of cancer patients and including nonmalignant disease controls.

Antigens↗
PubMed1980

Chemotherapy of advanced prostatic cancer with adriamycin, BCNU, and cyclophosphamide.

A phase II trial of Adriamycin, BCNU, and cyclophosphamide was performed in 29 patients with advanced prostatic carcinoma (Southeastern Cancer Study Group protocol SEG 76 PR 0102P). Therapy consisted of BCNU 100 mg/m2, plus cyclophosphamide, 300 mg/m2 i.v., on day 1, followed by Adriamycin, 30 mg/m2 i.v., on day 2. Therapy was repeated every four weeks. In 27 evaluable patients refractory to prior estrogen therapy, one patient had a complete response, six patients had partial responses, and two patients had objective improvement (complete plus partial response rate 26%, and overall response rate 33%). Responders had a median time to progression of disease of 5.5 months, compared with a median time to progression of 4.0 months for those patients with stable disease. The median survival of responders was 9.3 months, compared with 6.7 months for stable disease and 3.9 months for patients with progression. Patients with higher pretreatment performance status did not have higher response rates. No life-threatening toxicity was observed. Only five patients had nadir platelet counts below 50,000/mm3, and only six patients had nadir granulocyte counts below 750/mm3. This regimen palliates the effects of hormone-resistant metastatic prostatic carcinoma.

Carmustine↗
PubMed1978

Adriamycin, bleomycin, and CCNU as effective induction chemotherapeutic agents in advanced squamous cell carcinoma (COG Protocol 7333).

Twenty-six member institutions of the Central Oncology Group entered 154 patients in this two-armed, phase III study comparing the effects of adriamycin, bleomycin, and CCNU against a variety of squamous cell carcinomas. The combination of adriamycin and bleomycin produced a 43% overall response rate in primary tumors of the head and neck, which included two complete responses. This compares favorably to the results obtained with methotrexate and other agents previously reported. The combination of adriamycin and bleomycin will probably be the most useful for induction chemotherapy because both drugs have cumulative toxicities and the duration of response to this combination is short.

Aged↗
PubMed1978

Yoshi 864 (1-propanol, 3,3'-iminodi-, dimethanesulfonate [ester], hydrochloride): a phase II study in solid tumors.

Two hundred and eight acceptable patients were treated with Yoshi 864 (2 mg/kg/day by iv push X 5 days repeated once every 6 weeks). Toxicity was minimal. There was an overall response rate of 11%. Cross resistance with other alkylating agents may not be present. Because of its lack of toxicity, Yoshi 864 should be further evaluated in chronic myelocytic leukemia, lymphomas, and carcinomas of the ovary and bladder where significant responses were seen. It should also be evaluated in combinations as a replacement for other alkylating agents which cause more nausea and vomiting.

Alkylating Agents↗
PubMed1977

Adjuvant chemotherapy with 5-fluorouracil after surgical resection of colorectal carcinoma (COG protocol 7041). A preliminary report.

In a prospectively randomized study the effect of adjuvant chemotherapy with 5-FU on survival and recurrence was analyzed in 274 evaluable patients with colorectal carcinoma who either underwent a curative or a palliative resection. In the treatment group, chemotherapy consisted of the intravenous administration of 5-FU 12 mg/kg daily for four consecutive days, then 6 mg/kg/per day on alternate days to the point of toxicity or to a maximum of 5 doses, followed by 12 mg/kg/week for one year. Drug toxicity was rarely severe and consisted of nausea and vomiting, diarrhea, stomatitis, leukopenia, and thrombocytopenia in slightly more than half of all patients. There have been no drug-related deaths. Analysis of the survival curves and disease-free interval curves reveal some evidence of drug benefit in both the curative group of resections and the palliative group of resections. However, this benefit is not significant except in those treated to toxicity. The disease-free interval after curative resection is significantly longer in patients treated with 5-FU to the point of toxicity with a white blood count less than 4,000 cells/mm3. We conclude that a preliminary analysis of the Central Oncology Group data in this trial does not make a convincing case for the use of 5-FU as an adjuvant to the surgical treatment of colorectal carcinoma.

Adenocarcinoma↗
PubMed1977

An evaluation of colon cleansing regimens.

To study the efficacy of colon cleansing regimens, 500 hospital outpatients were randomly assigned to one of four regimens. Two featured castor oil followed by phosphate enema and two used magnesium citrate and bisacodyl. For the 349 patients who completed all components of the regimens, quality of the subsequent barium enema examination was scored by three radiologists in a blind manner. Regimens featuring magnesium citrate and bisacodyl were found to be significantly superior to those featuring castor oil. Calcium bisdiocytl sulfosuccinate did not improve the quality of colon cleansing but appeared to decrease the incidence of abdominal cramping in patients receiving magnesium citrate and bisacodyl. It is hoped that the investigative approach used in this study may serve as a model for future testing of colon cleansing regimens.

Adolescent↗
PubMed1976

Studies on adriamycin using a weekly regimen demonstrating its clinical effectiveness and lack of cardiac toxicity.

Adriamycin has been given to 442 patients using the weekly regimen as initially described by Bonadonna et al. Hematologic toxicity and clinical effectiveness have been similar to those described with regimens in which the drug is given every 3 weeks. Stomatitis is more frequent with the weekly regimen than with the usual triweekly regimen. The incidence of electrocardiographic changes and arrhythmias was similar to that reported in other studies. Nine patients received between 500 and 550 mg/m2, nine between 550 and 600 mg/m2, 28 between 600 and 1000 mg/m2, and 22 between 1000 and 2500 mg/m2. None of the patients developed definite evidence of cardiomyopathy although six showed some disturbance of myocardial function. In each of the six patients, factors other than adriamycin cardiotoxicity were believed to play a major role in the myocardial abnormality. The difference between the incidence of cardiomyopathy seen in this series and that previously reported is statistically significant. The reasons for the difference are not clear but are probably related to the schedule that was used.

Adult↗
PubMed1976

DTIC (nsc-45388) and combination therapy for melanoma. I. Studies with DTIC, BCNU (NSC-409962), CCNU (NSC-79037), vincristine (NSC-67574), and hydroxyurea (NSC-32065).

A total of 270 patients with metastatic malignant melanoma were entered into a randomized chemotherapy study conducted by the Central Oncology Group (COG) over a period of 2 years (COG protocol No. 7130). The study utilized DTIC, CCNU, BCNU, vincristine, and hydroxyurea. The results of therapy with DTIC alone were compared with three combinations: (a) DTIC, CCNU, and vincristine; (b) DTIC, BCNU, and vincristine: and (c) DTIC, BCNU, and hydroxyurea. There were 243 evaluable patients out of 270. The response rate was 17.3% (42 of 243 patients) for evaluable patients and 15.5% (42 of 270 patients) for all patients entered in the study. The results showed no statistically significant difference in the response rates among the four treatment arms. However, several significant points were observed: (a) A 13% response rate was obtained using a combination of agents that included DTIC in patients who had previously shown no response to DTIC used as a single agent. (b) There was a significant difference in survival time when comparing responders to those with no change and to those with progression. (c) Toxicity was noted to be greater in responders than in nonresponders. (d) Two of the four treatment arms were considered most advantageous due to the ease of administration. These treatment arms were DTIC, BCNU, and vincristine and DTIC, CCNU, and vincristine administered in 5-day courses every 6 weeks. (e) The percentage of response and length of survival were significantly greater in patients without brain or liver metastasis. (f) In comparing men to women there was no statistically significant difference in response in rates or durations of response. (g) There was no statistically significant difference in survival when comparing site of primary lesion.

Adolescent↗