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J H Edmonson

Publications and source records attributed to J H Edmonson.

At least 19 recordsLinked to original sources
PubMed1992

Granulocyte-macrophage colony-stimulating factor. Preliminary observations on the influences of dose, schedule, and route of administration in patients receiving cyclophosphamide and carboplatin.

BACKGROUND: In an attempt to learn how best to administer granulocyte-macrophage colony-stimulating factor (GMCSF), the authors performed a Phase I study of this agent. They were interested in the influences of dose, schedule, and route of administration on the effects of GMCSF in patients receiving standardized 1-day regimens of cyclophosphamide (CYCLO) and carboplatin (CBDCA). METHODS: Between June 1988 and March 1991, 57 patients with advanced cancer received GMCSF in association with CYCLO 1 g/m2 plus CBDCA 225-700 mg/m2. After the first dose escalation to 300 mg/m2 of CBDCA, patients who had previously received chemotherapy or radiation therapy were excluded. GMCSF was administered in three different doses, five different schedules, and by two different routes. Altogether, 17 different treatment groups were observed. In addition, 24-hour GMCSF serum concentration curves were charted in four patients. RESULTS: Using four sequential groups of three patients each who had received myelosuppressive treatment, treatment with CYCLO 1 g/m2 and CBDCA 225 mg/m2, the apparent superiority of daily subcutaneous injection over 30-minute daily IV infusion of GMCSF was demonstrated graphically. Subsequently, the authors observed apparent enhancement of GMCSF effects beyond those produced by the initially selected 20-day basic 10 micrograms/kg daily SC regimen beginning 2 days after chemotherapy. When administered SC every 12 hours for 14 days beginning the day after chemotherapy, GMCSF appeared to ameliorate the severity of both leukopenia and thrombocytopenia. These effects permitted escalation of the CBDCA dose to 700 mg/m2 (with 1 g/m2 of CYCLO) before cytotoxic tolerance limits were reached. Graphic small group comparisons suggest that GMCSF given SC in doses of 5 micrograms/kg twice daily may produce comparable leukocyte and platelet support after chemotherapy with lower toxicity than occurs from higher doses. Prechemotherapy priming with GMCSF twice daily for an additional 4 days (days -6 to -3) seems to ameliorate postchemotherapy cytopenias further but at the cose of some increased risk of GMCSF toxicity. Although most of the toxic effects of moderate-dose GMCSF are controlled by antihistamines and ibuprofen, oral glucocorticoids (e.g., prednisone, 10 mg twice daily during the second week of GMCSF administration) may be required in patients with serositis, pulmonary infiltrates, or severe skin eruptions. CONCLUSIONS: Our observations suggest that GMCSF should be administered SC in doses of approximately 5 micrograms/kg every 12 hours for 10-14 days beginning the day after chemotherapy. Prechemotherapy priming with these same doses for four additional days (days -6 to -3) may additionally ameliorate postchemotherapy leukopenia and thrombocytopenia, but with increased risk of toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Phase II trial of intravenous hexamethylmelamine in patients with advanced ovarian cancer.

A Phase II trial of an intravenous preparation of Hexamethylmelamine was performed in ovarian cancer. Patients who had received prior Platinum based chemotherapy and had measurable disease were eligible. Among 15 evaluable patients, there were no objective responses. Two patients did show clinical and laboratory evidence of improvement. Toxicity was predominantly nausea and vomiting with minimal other toxicity. This intravenous form of Hexamethylmelamine has not shown meaningful activity in ovarian cancer patients who have failed prior platinum treatment.

Altretamine↗
PubMed1992

Cutaneous reactions to granulocyte-monocyte colony-stimulating factor.

BACKGROUND AND DESIGN: Granulocyte-monocyte colony-stimulating factor (GMCSF) is a hematopoietic growth factor that stimulates the proliferation and differentiation of neutrophils, eosinophils, and monocytes. We reviewed the cutaneous reactions that developed in 26 patients who received GMCSF as part of a chemotherapeutic protocol. RESULTS: Fourteen patients developed immediate localized angioedematous reactions at the subcutaneous GMCSF injection site, and 21 developed generalized cutaneous reactions. Four biopsy specimens were obtained from three patients who had generalized erythrodermic reactions. All specimens showed perivascular and periadnexal lymphocytic inflammation in the dermis, and two showed perivascular and periadnexal eosinophilia. Staining for eosinophil granule major basic protein showed infiltration by eosinophils and extracellular deposition of major basic protein in three specimens from two patients with eosinophilia. Extracellular deposition of neutrophil elastase and mast cell tryptase was minimal. CONCLUSIONS: Cutaneous reactions are prominently associated with GMCSF administration. Eosinophils, known to release toxic products after being activated, may have a role in these skin reactions through stimulation by GMCSF.

Adult↗
PubMed1991

Does histologic grade in soft tissue sarcoma influence response rate to systemic chemotherapy?

To assess whether chemosensitivity in metastatic soft tissue sarcoma (STS) is influenced by the histologic grade of the tumor, the authors retrospectively analyzed tumor responses to doxorubicin-based chemotherapy in four prospective studies conducted at the Mayo Clinic, Rochester, Minnesota, between 1976 and 1984. A total of 131 patients with metastatic STS were included in these trials. All pathologic material was reviewed by one pathologist (H.M.R.) and graded according to the four-tier grading system of Broders. One hundred and sixteen patients were accepted for analysis. Objective regression rates according to grade were as follows: Grade 4, 55% (22 of 40 patients); Grade 3, 23% (7 of 31 patients); Grade 2, 19% (5 of 27 patients); and Grade 1, 0% (0 of 3 patients). Fifteen nongradable sarcomas were analyzed separately (27% [4 of 15]). In contrast to several reports suggesting that grade does not effect response, the authors found differences in response rates to be statistically significant for Grade 2 versus Grade 4 (P = 0.003) and Grade 3 versus Grade 4 (P = 0.006), but not for Grade 2 versus Grade 3 (P = 0.7). Additional comparisons adjusted for the histologic type of STS, chemotherapeutic regimen, performance status, age, and prior treatment confirmed these results. These results suggested that, in addition to being an important prognostic factor for survival in newly diagnosed STS, histologic grade may correlate with the probability of response and should be considered a stratification factor in future studies.

Adolescent↗
PubMed1991

A phase II evaluation of menogaril in cisplatin-refractory advanced ovarian carcinoma. A collaborative trial of the North Central Cancer Treatment Group and the Mayo Clinic.

Forty-one women with advanced, recurrent epithelial ovarian carcinoma (in whom prior chemotherapy with a platinum-based regimen failed) were treated with menogaril 200 mg/m2 intravenously every 4 weeks in a Phase II trial. Partial responses were seen in two of 19 (10.5%) measurable disease patients and three of 12 (25%) nonmeasurable but evaluable patients, an overall objective response rate of 16.1% (95% confidence interval, 5% to 34%). Median time to progression for all patients was 2 months and median survival, 5 months. Toxicities were acceptable and consisted primarily of leukopenia and gastrointestinal toxicity. Twenty-nine percent of the patients had venous irritation or painful phlebitis at the intravenous injection site. Menogaril, as administered in this protocol, had modest antineoplastic activity in previously treated ovarian carcinoma patients. The responses were of short duration, and there appeared to be no survival advantage with menogaril treatment.

Adult↗
PubMed1991

Phase II evaluation of menogaril in patients with advanced cervical carcinoma. A collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic.

Fourteen patients with advanced/recurrent squamous cell carcinoma of the uterine cervix received menogaril, 200 mg/m2 by one hour intravenous infusion at four-week intervals. No objective regressions were observed. Median time to progression was less than two months and median survival was seven months. All patients experienced neutropenia. Platelet toxicity was negligible. Venous irritation and phlebitis occurred at the infusion site in 43% of patients. Menogaril as administered in this protocol is ineffective in treating previously irradiated advanced/recurrent squamous cell carcinoma of the uterine cervix and warrants no further investigation in this disease at the dosage and administration schedule used in this protocol.

Adult↗
PubMed1991

Phase I-II study of pibenzimol hydrochloride (NSC 322921) in advanced pancreatic carcinoma.

Pibenzimol is a fluorescent molecule known to bind to double stranded DNA. It also induces prolongation of the G2 phase of the cell cycle, inhibition of DNA replication and cessation of the growth of some cells in late S phase after DNA content has been doubled. It has been shown to increase the life span of mice bearing intraperitoneally implanted L1210 and P388 leukemia. These factors coupled with the affinity of pibenzimol for pancreatic tissue led us to conduct a phase I-II trial of pibenzimol hydrochloride in patients with advanced pancreatic cancer. Twenty-six patients were treated with a five day continuous infusion of pibenzimol at a dose ranging from 6-28 mg/m2/d. There were no treatment related deaths. Major toxicity was hyperglycemia which was self-limited. No objective responses were noted.

Adult↗
PubMed1991

5-Fluorouracil plus leucovorin in women with metastatic breast cancer. A phase II study.

Because leucovorin increases the antitumor activity of 5-fluorouracil (5-FU) in multiple tumor model systems, we performed a clinical trial to evaluate this combination in women who had received one or no prior chemotherapy regimens for metastatic breast cancer. Thirty-six women with measurable metastatic disease were treated with five consecutive days of i.v. leucovorin, 500 mg/m2/day infused over 30 min, followed 1 h later by i.v. bolus 5-FU, 375 mg/m2/day. Repeat cycles were planned at 4-week intervals. Tumor regression occurred in 10 of 36 patients (28%; 95% confidence interval, 14-45%) with a median time to disease progression (TTP) of 8.7 months (range 3.2-16.8 months) in the responding patients. The median TTP and survival for all patients were 3.0 and 12.4 months, respectively. Among 30 patients who had received prior 5-FU, tumor regressions were seen in seven (23%; 95% confidence interval 10-42%). The major dose-limiting toxicity in this study was mucositis, affecting 89% of the patients. Other toxicities were tolerable in the majority of patients. Although the role of leucovorin in breast cancer clinical practice remains undefined, the data from this trial support the hypothesis that leucovorin enhances the cytotoxic activity of 5-FU against human breast cancer.

Adult↗
PubMed1990

Papillary serous carcinoma of the peritoneum. A review of 33 cases treated with platin-based chemotherapy.

Thirty-three patients were identified who had papillary serious carcinoma of the peritoneum (PSCP). The gross operative specimens, histopathologic condition, and treatment records were reviewed. The median age at presentation was 60 years (age range, 22 to 78 years). Abdominal pain and distention were the most common presenting symptoms. All patients had a total abdominal hysterectomy and bilateral salpingo-oophorectomy, and all but two had debulking surgery. All patients had disease involving the omentum, the abdominal and pelvic peritoneum, and the surface of the ovaries, but none had intrinsic disease of the ovaries. Eight patients had disease outside of the abdominal cavity. Seven of these patients had malignant pleural effusions. All patients received platin-based chemotherapy. Sixteen patients underwent second-look laparotomy, two had no evidence of disease, and one had microscopic disease only. The median survival time for all patients was 17 months. Three patients are alive 6 to 7 years after the initial diagnosis. In conclusion, long-term survival can be achieved in some PSCP patients by debulking surgery and platin-based chemotherapy.

Abdominal Pain↗
PubMed1990

Randomized comparison of doxorubicin and vindesine to doxorubicin for patients with metastatic soft-tissue sarcomas.

Two treatment regimens for metastatic soft-tissue sarcomas were compared in a randomized trial in the cooperative group setting. Histopathologic diagnosis was affirmed by pathology reference panel review in 72% of the 347 patients. In 21% of patients, the reference panel affirmed the diagnosis of soft-tissue sarcoma but disagreed as to type; 7% of patients were ineligible based upon cell type. Of 298 patients evaluable, measurable tumor regression (partial or complete response) occurred in 17% of patients to doxorubicin (70 mg/m2 intravenously) and 18% of patients to doxorubicin (70 mg/m2 intravenously) and vindesine (3 mg/m2 intravenously), each given every 3 weeks. No difference existed in complete response (4% for doxorubicin, 6% for doxorubicin and vindesine) or median survival (9.4 months for doxorubicin, 9.9 months for doxorubicin and vindesine). Overall, 60% of those patients on doxorubicin and vindesine and 46% on doxorubicin experienced a severe or worse toxicity of treatment (P = 0.01). With greater toxicity and lack of any gains in efficacy, the results do not support use of the combination of doxorubicin and vindesine for metastatic soft-tissue sarcomas.

Adult↗
PubMed1988

Phase II studies of bleomycin, cyclophosphamide, doxorubicin and cisplatin, and bleomycin and cisplatin in advanced cervical carcinoma.

In a randomized phase II trial of two cisplatin-based chemotherapy regimens, 45 patients with advanced cervical carcinoma received a combination of bleomycin, cyclophosphamide, doxorubicin, and cisplatin (BCAP), and 45 others received bleomycin plus cisplatin (BP). BCAP was repeated every 4 weeks, and BP was given at 3-week intervals. Although 19 of 43 (44%) evaluable patients receiving BCAP and 16 of 42 (38%) evaluable patients receiving BP experienced tumor regression, only 22% of those receiving BCAP and 21% of those on BP survived 1 year after beginning treatment. Among bidimensionally measurable patients, 15 of 27 (56%) and 8 of 25 (32%) receiving BCAP and BP, respectively, achieved tumor regression. One patient died of bleeding resulting from severe myelosuppression on BCAP, and two others succumbed to pulmonary toxicity of bleomycin on the BP regimen. Although active against cervical carcinoma, these regimens have limited therapeutic value at this advanced stage of the disease.

Adult↗
PubMed1979

Complete responders to chemotherapy in metastatic breast cancer. Characterization and analysis.

Four hundred thirty-eight patients with metastatic breast cancer treated with nine prospective randomized trials were reviewed to analyze, characterize, and compare those with complete regression (CR) (N=49 [11%]) with those with noncomplete regression (non-CR) (N=389 [89%]). Site of dominant disease was identical in the CR and non-CR patients. However, CR was statistically more likely when the disease-free interval and the postmenopausal status was five years or less. Survival and time to progression occurred at sites of prior dominant disease, except that relapses occurred in the CNS in 14%. Six CR patients received prolonged chemotherapy and were believed to be "cured" when treatment was discontinued; however, all except one have had relapses.

Antineoplastic Agents↗
PubMed1979

Pulmonary resection for metastatic nonosteogenic sarcoma.

Analysis was made of 112 patients who underwent resection of metastatic pulmonary noldules for nonosteogenic sarcoma at the Mayo Clinic from 1950--76. The 5-year post-thoracotomy survival was 29% with a median survival of 18 months. There has been no substantial change between 1950 and 1976 in post-thoracotomy survival among all patients who received this operation here. Prognosis was especially grim (p less than 0.01) for patients with pre-thoracotomy disease-free intervals of less than 12 months, and for those experiencing extrathoracic recurrences vs. further pulmonary recurrent tumor (p = .01) following thoracotomy. The following discriminants were not significantly associated with postthoracotomy survival: age, sex, histology, number of lesions fully excised, or site of lung lesions. We conclude that the therapeutic value of thoracotomy in the treatment of metastatic nonosteogenic sarcomas has not changed here during the past quarter of a century. Whether the recent more common use of thoracotomy in metastatic disease of this type is therapeutically worthwhile cannot be clearly determined from the data available.

Humans↗
PubMed1979

Different chemotherapeutic sensitivities and host factors affecting prognosis in advanced ovarian carcinoma versus minimal residual disease.

Treatment of patients with advanced ovarian carcinoma (stages IIIB and IV) using either cyclophosphamide alone (1 g/m2) or cyclophosphamide (500 mg/m2) plus adriamycin (40 mg/m2) by iv injection every 3 weeks each produced partial regression in approximately one third of the patients. Survival curves and time-to-progression curves for the two regimens were nearly identical in these patients with advanced disease. These same regimens produced different results when used monthly in patients who had minimal residual disease (stages II and IIIA). In patients with minimal residual disease the therapeutic index of the combination regimen was superior to that of cyclophosphamide alone. Prognosis was better overall among patients with minimal residual disease than among patients with advanced disease. Within the minimal-disease group grossly complete excision of tumor prior to chemotherapy was associated with still better prognosis. Among patients with advanced disease, prognosis was significantly better for older patients despite their generally less favorable performance scores. Much of this prognostic superiority appeared to be related to menopausal status and presumably to the depletion of endogenous estrogens in the older patients.

Cyclophosphamide↗
PubMed1978

Repeated adjuvant chemotherapy with phenylalanine mustard or 5-fluorouracil, cyclophosphamide, and prednisone with or without radiation, after mastectomy for breast cancer.

172 patients who had had mastectomy for breast cancer were treated by repeated adjuvant chemotherapy, either with phenylalanine mustard (P.A.M.) or a combination of cyclophosphamide, 5-fluorouracil, and prednisone (C.F.P.) with and without radiotherapy. Tumours recurred significantly more frequently and mortality tended to be higher in P.A.M.-treated patients than in patients on other treatment. The interval between surgery and disease recurrence was significantly shorter for P.A.M.-treated premenopausal but not postmenopausal patients than for patients of equivalent menstrual status treated with C.F.P. with or without radiation. The associations in premenopausal patients between the mode of treatment and both survival and the disease-free interval were significant before and after adjustment for variations between the treatment groups in the number of involved lymph nodes and the size of the primary tumour.

Adult↗
PubMed1978

A preliminary study of cyclophosphamide (NSC-26271), adriamycin (NSC-123127), imidazole carboxamide (NSC-45388), and actinomycin D (NSC-3053) with or without MER-BCG in patients with advanced sarcomas.

Polychemotherapy for soft tissue sarcomas has been reported to produce response rates ranging from 24--60% (1, 2). Immunotherapy has reportedly prolonged survival after surgery for some tumors and enhanced the effectiveness of chemotherapy (3, 4). This report summarizes our preliminary experience with the combination of cyclophosphamide, adriamycin, imidazole carboxamide (DTIC), and actinomycin D (CAIA) with or without methanol extraction residue of BCG (MER) in patients with advanced sarcomas.

Adult↗