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Biomedical subjects

R G Hahn

Publications and source records attributed to R G Hahn.

At least 235 records · Page 13Linked to original sources

Clinical trial of cisplatin and intensive course 5-fluorouracil for the treatment of advanced colorectal cancer.

A clinical trial of 5-day Cisplatin combined with loading course 5-fluorouracil (5-FU) was conducted in 37 patients with advanced colorectal carcinoma. Objective tumor responses were seen in 10 of 34 patients (29%) who had not received prior chemotherapy. The estimated median survival for previously untreated patients is 26 weeks measured from the onset of therapy. Toxicity consisted primarily of leukopenia, vomiting, and reversible renal insufficiency. This combination of cisplatin and intensive course 5-FU has demonstrated Phase II activity in patients with advanced colorectal cancer. A controlled trial is now in progress to prospectively compare this regimen with full dose single agent 5-FU.

Adult↗

A randomized comparison of cyclophosphamide, Adriamycin, and 5-fluorouracil with triethylenethiophosphoramide and methotrexate, both as sequential and as fixed rotational treatment in patients with advanced ovarian cancer.

The combinations of triethylenethiophosphoramide and methotrexate (TM) and cyclophosphamide, Adriamycin (doxorubicin), and 5-fluorouracil (CAF) were compared, both as sequential and fixed rotational treatments for advanced ovarian cancer, with L-phenylalanine mustard (L-PAM). Treatment with CAF produced a higher response rate (25% complete responses plus 31% partial responses) than treatment with L-PAM (15% complete responses plus 18% partial responses). A fixed rotation of TM and CAF resulted in longer survival (median of 15 months and 75th percentile of 27 months) than sequential treatment with TM initially, followed by CAF upon failure (median of 12 months and 75th percentile of 22 months). The fixed rotation of TM and CAF also increased progression-free survival (median of 12 months and 75th percentile of 24 months) over that achieved by initial treatment with TM (median of 6 months and 75th percentile of 15 months) or L-PAM (median of 9 months and 75th percentile of 21 months). Most patients (96%) on the fixed rotation were treated with both TM and CAF. Fewer patients (62%) on the sequential schedule with TM actually received both combination regimens, and even fewer patients (37%) beginning on CAF ever crossed over to TM. Patient age of 50 years or younger was a favorable prognostic factor for response, survival, and time to first treatment failure (progression-free survival). Disease Stage IIIA or IIIB, surgery including a bilateral salpingo-oophorectomy plus hysterectomy, and treatment within 6 months of initial diagnosis were favorable predictors for both survival and time to first treatment failure. Ambulatory performance status and well-differentiated disease were favorable prognostic factors for survival. Patients with unevaluable disease failed later than those with evaluable disease who, in turn, failed later than patients with measurable disease.

Adenocarcinoma↗

Malignant germ cell tumors of the mediastinum.

A review of 56 cases of primary malignant germ cell tumors of the mediastinum revealed that, as with benign teratomas, the tumors occurred in young adults (mean age 29 years) but that the sex distribution differed (86% male and 14% female). A single germ cell element was found in 37 (66%) of the tumors, and various combinations were present in the remaining 19 (34%). The tumors were classified among five recognized types of germ cell tissues. There were 24 seminomas (22 pure and two with mature teratomas), 17 embryonal carcinomas (nine pure and eight with mixtures), five teratomas, seven choriocarcinomas (three pure and four with mixtures), and three pure yolk sac tumors. Most (86%) of the patients were symptomatic at the initial examination, with chest pain, cough, and loss of weight being the most frequent presenting symptoms. The standard posteroanterior and lateral roentgenograms were the most helpful diagnostic tool, showing evidence of an anterior mediastinal mass in 53 patients. The diagnosis was established by surgical exploration of the mediastinum or by biopsy of a lymph node in 55 patients. Of the 55, 24 (43.6%) had complete resection of the tumor and 31 (56.4%) had incomplete resection or biopsy alone. The overall prognosis for mediastinal germ cell tumors is poor, partly because the tumors are far advanced at the time of diagnosis but also because some of the tumors that contain embryonal cell carcinoma, choriocarcinoma, and yolk sac elements are very aggressive. Factors that were prognostic in patients with seminoma--such as age, presence of the superior vena caval syndrome, lymphadenopathy, evidence of hilar disease on the chest roentgenogram, and resectability--were not predictive in patients with other types of malignant germ cell tumors. Although aggressive combination chemotherapy may represent a significant treatment modality for nonseminomatous mediastinal tumors, the present study spanned many years in which no chemotherapy was available. Patients in the later years of the study received combination chemotherapy with various treatment regimens. No conclusions concerning specific chemotherapy, therefore, can be derived from this study.

Adolescent↗

The family physician as a legal consultant.

Family physicians have a responsibility to their peers and patients to participate in malpractice litigation in a manner that ensures that evidence is properly and thoroughly evaluated. Family physicians have not routinely involved themselves as expert witnesses in medical malpractice litigation because of lack of training, misconceptions about their role, and distrust of attorneys. The role of expert medical witness requires an ability to interact with attorneys, witnesses, and courts of law as well as a clear understanding of the malpractice process and the law that governs such proceedings. Philosophical differences, rationale for participation, and the malpractice process are discussed in this paper, and guidelines for the expert witness are presented.

Consultants↗

Phase II trial of PCNU in advanced colorectal carcinoma. An Eastern Cooperative Oncology Group pilot study.

PCNU, a chloroethylnitrosourea with high alkylating activity, low carbamoylating activity, optimal octanol: water partition coefficient, and broad activity in animal systems was administered to 30 evaluable patients with measurable advanced colorectal carcinoma by brief intravenous infusions every 6 weeks. The initial dose was 75 or 100 mg/m2, with escalation or reduction for toxicity, and a total of 64 evaluable courses were given. Half of the patient population had received no prior chemotherapy. Two objective partial responses occurred. The response rate was 6.7% with a 95% confidence interval of 0.8-22.1%. Thrombocytopenia was dose-limited and leukopenia was relatively mild. Gastrointestinal toxicity was less severe than expected for clinically available nitrosoureas. In colorectal carcinoma, PCNU has limited clinical activity that does not appear to be superior to that of other nitrosoureas.

Adenocarcinoma↗

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↗

Compliance difficulties with progestin-supplemented estrogen replacement therapy.

Forty postmenopausal women were studied prospectively while undergoing estrogen replacement therapy (ERT). Eighteen women with an intact uterus were cycled with additional progestin therapy. All but three women of the estrogen-progestin group elected to discontinue therapy because of undesirable "physiologic" withdrawal bleeding. Future progestin-ERT recommendations should take these results into consideration. Wide-scale re-education of patients and physicians will be necessary if the existing recommended regimens are to be observed. Alternatively, new or different pharmacologic agents and regimens will be necessary to achieve the postulated benefits of progestin-ERT without undesirable side effects.

Aged↗

Cyclophosphamide, doxorubicin, and cisplatin combined in the treatment of advanced sarcomas.

Twenty-five patients with evaluable histologically confirmed inoperable metastatic sarcomas were treated once every four weeks with cyclophosphamide, doxorubicin, and cisplatin in doses of 400, 40, and 60 mg/m2, respectively. Cyclophosphamide and doxorubicin were given by rapid intravenous injection followed immediately by cisplatin by slow intravenous infusion (2-6 hr) in 1 liter of 0.45% saline with mannitol added. Leukopenia, alopecia, and vomiting were common side effects and three patients refused further treatment because of vomiting following their initial courses. No drug-related deaths occurred and we removed no one from the study because of toxicity problems. Among the 9 patients who experienced objective tumor regression were 2 of 2 with hemangiosarcoma, 3 of 5 with malignant fibrous histiocytoma, 3 of 5 with osteosarcoma, and 1 of 1 with pleomorphic liposarcoma of bone. Although not therapeutically gratifying, these results appear to be better than any previously observed at our institution.

Adolescent↗

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↗

Phase II study of PALA and AMSA in advanced renal cell carcinoma.

Ninety-two evaluable patients with measurable renal cell carcinoma participated in a phase II trial of PALA (1500 mg/m2/day for 5 days every 3 weeks) versus AMSA (120 mg/m2 every 4 weeks). No complete responses occurred; objective partial response rates were 5% for PALA and 3% for AMSA. Treatment did not influence survival, but ambulatory patients survived longer than did nonambulatory patients. Mucocutaneous and acute gastrointestinal toxicity occurred with PALA, while hematologic toxicity predominated in AMSA treatments. At these schedules neither drug has significant single-agent activity in renal cell carcinoma.

Adenocarcinoma↗

Primary anterior mediastinal seminoma.

A review of the Mayo Clinic experience with primary anterior mediastinal seminomas involved 17 patients who had pure anterior mediastinal seminomas and four who had mixed germ-cell tumors containing seminomas. At follow-up, of the 17 patients with pure anterior mediastinal seminoma, nine had no evidence of disease and eight had died of metastatic disease. Of the four patients with mixed germ-cell tumor containing seminoma, two were alive at follow-up and two had died of metastatic disease. In the group with pure anterior mediastinal seminoma, these factors seemed to have been associated with a greater potential for progression of disease: older than 35 years of age, presentation with fever, superior vena caval syndrome, supraclavicular or cervical adenopathy, and roentgenographic evidence of hilar disease.

Adolescent↗

Randomized clinical trial of megestrol acetate versus tamoxifen in paramenopausal or castrated women with advanced breast cancer.

Fifty-five women with progressive metastatic breast cancer who were paramenopausal (1 to less than 5 years since last menstrual period) or castrated were randomized to receive either megestrol acetate (150 mg/m2 daily in three divided doses) or tamoxifen (10 mg twice daily). The regression rate (complete plus partial) was higher for tamoxifen (26%) than for megestrol acetate (14%), but not significantly so. Analysis of time to treatment failure showed no significant difference (medians: megestrol acetate, 65 days; tamoxifen, 58 days). There was survival advantage associated with megestrol acetate (P = 0.02 after adjustment for stratification factors) that is difficult to interpret given the results of analysis of regression and time to treatment failure for the two agents.

Adult↗

An evaluation of early or delayed adjuvant chemotherapy in premenopausal patients with advances breast cancer undergoing oophorectomy: a later analysis.

In 1977 we reported our results of an ongoing randomized clinical trial evaluating early or delayed adjuvant chemotherapy utilizing 5-flourouracil, cytoxan and prednisone in premenopausal patients with recurrent or advanced breast cancer. At that time the group receiving early systemic chemotherapy was shown to have an improved progression-free interval and appeared to have a trend toward improved survival. The results of subsequent analysis after over 4 more years of follow-up indicate however, that while early employment of systemic chemotherapy does indeed prolong the progression-free interval, and while this advantage has been maintained, there is no survival advantage shown for either group of patients.

Adult↗

A preliminary assessment of factors associated with recurrent disease in a surgical adjuvant clinical trial for patients with breast cancer with special emphasis on the aggressiveness of therapy.

Two hundred ninety-three patients were randomly assigned to three treatment regimens following mastectomy for operable but prognostically unfavorable breast cancer: L-PAM, CFP, or CFP with radiation therapy. For premenopausal patients an increased risk of recurrence was associated with the presence of unfavorable local signs, large number of lymph nodes involved, greater body weight, younger age, and L-PAM treatment. For the postmenopausal patients only three factors were associated with an increased risk of recurrent disease: large tumor size, large number of lymph nodes involved, and inner/central location of the primary lesion. Specifically, the treatment employed has shown no effect. Of particular importance is the fact that for neither group of patients does our experience presently demonstrate clear association of recurrent disease with the level of drug dose administered. Furthermore, evidence suggests that although patients who experience little or no myelosuppression have significantly worse disease-free intervals than patients who experience moderate or severe myelosuppression, here is no benefit for severe myelosuppression over moderate, myelosuppression.

Adult↗