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Biomedical subjects

R M Simon

Publications and source records attributed to R M Simon.

At least 55 records · Page 3Linked to original sources
PubMed1980

Curability of advanced Hodgkin's disease with chemotherapy. Long-term follow-up of MOPP-treated patients at the National Cancer Institute.

The results of treatment of 198 patients with Hodgkin's disease with MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) were analyzed. Eighty percent attained complete remission, and 68% of patients achieving a complete remission have remained disease free beyond 10 years from the end of treatment. Results of autopsy on patients who died of other causes while in clinical complete remission did not show evidence of residual tumors except in one patient. Asymptomatic patients and patients with mixed-cellularity or lymphocytic-depleted Hodgkin's disease do significantly better than symptomatic patients and those with nodular sclerosing histologic type. Advanced Hodgkin's disease appears to be curable by chemotherapy.

Adolescent↗
PubMed1980

Nodular histiocytic lymphoma: an aggressive nodular lymphoma with potential for prolonged disease-free survival.

Nodular histiocytic lymphoma (NH) is uncommon, and its natural history is not well defined. Of 473 patients with non-Hodgkin's lymphoma, we found 16 (3.4%) with NH. Most patients (13/16) presented with pathologic stage (PS) III or IV disease, including 7 with liver involvement. One patient (PS III) was initially treated with cyclophosphamide alone, and 4 patients received only radiotherapy, and none were long-term survivors. Eleven patients received combination chemotherapy, and 8 achieved complete remission. Only one of these patients relapsed and died at 19 mo; the other 7 continue in complete remission without maintenance therapy with a minimum followup of 4.5 yr. The survival of the entire group of patients with NH is intermediate between that of the other nodular lymphomas and diffuse histiocytic lymphoma. Nine of 16 patients had either a repeat lymph node biopsy during the course of their disease or lymph node examination at autopsy. Lymph node histology in the majority converted to a diffuse, less differentiated subtype of lymphoma. NH has a natural history similar to that of diffuse histiocytic lymphoma and should be approached with the same therapeutic strategy.

Humans↗
PubMed1979

Cryptococcal meningitis and internal ophthalmoplegia.

A 17-year old girl received prednisone and azathioprine for the treatment of systemic lupus erythematosus. She developed a fever and hallucinations 18 months later; cryptococcal meningitis was diagnosed. An internal ophthalmoplegia with loss of accommodation and dilation of the pupils developed together with bilateral lateral rectus palsy. Treatment with intravenous amphotericin resulted in disappearance of papilledema, muscle palsy, and internal ophthalmoplegia. We believe that the internal ophthalmoplegia was secondary to involvement of the accommodative and pupillary fibers of both third nerves at the base of the brain.

Adolescent↗
PubMed1979

Delata-9-tetrahydrocannabinol as an antiemetic in cancer patients receiving high-dose methotrexate. A prospective, randomized evaluation.

Fifteen patients with osteogenic sarcoma receiving high-dose methotrexate chemotherapy were studied in a randomized, double-blind, placebo-controlled trial of oral and smoked delta-9-tetrahydrocannabinol (THC) as an antiemetic. Each patient served as his or her own control. Fourteen of 15 patients had a reduction in nausea and vomiting on THC as compared to placebo. Delta-9-tetrahydrocannabinol was significantly more effective than placebo in reducing the number of vomiting and retching episodes, degree of nausea, duration of nausea, and volume of emesis (P less than 0.001). There was a 72% incidence of nausea and vomiting on placebo. When plasma THC concentrations measured less than 5.0 ng/mL, 5.0 to 10.0 ng/mL, and greater than 10.0 ng/mL, the incidences of nausea and vomiting were 44%, 21%, and 6%, respectively. Delta-9-tetrahydrocannabinol appears to have significant antiemetic properties when compared with placebo in patients receiving high-dose methotrexate.

Adolescent↗
PubMed1979

Histologic grade in advanced ovarian cancer.

The histologic grade of epithelial ovarian tumors was found to be a major prognostic factor for survival in patients with advanced (stage III-IV) disease. In addition, a grading system based on cytologic detail (modified Broders' grades I-IV) identified groups with a differential response to chemotherapy. The overall improvement in survival observed with combination chemotherapy was related primarily to an increased survival of patients with grade II and III lesions. Although the survival of patients with grade I lesions was markedly better than for patients with grade IV lesions, in neither case was it influenced by the choice of single-agent or combination chemotherapy. In prospective clinical trials in advanced disease, modified Broders' grades should be included as a separate stratification factor.

Altretamine↗
PubMed1979

Treatment of osteogenic sarcoma. II. Aggressive resection of pulmonary metastases.

Thirty-nine patients with osteogenic sarcoma were treated in a prospective protocol involving the use of adjuvant high-dose methotrexate, frequent screening for pulmonary metastases, and aggressive resection of all metastatic disease whenever possible. Twenty-two of these 39 patients have had recurrence and in 20 patients evidence of metastatic disease was confined to the lungs. Eighteen of the patients had thoracotomy, and in 11 patients all known disease was resected. Although four of these patients have required further thoracotomies, all 11 patients have no evidence of disease. Thus, of the original 39 patients, 30 (76.9%) are now alive and 28 (71.8%) have no evidence of disease, with a median followup of 27 months. Survival is significantly improved compared to historical control patients (P less than 0.001; one-sided Kruskal-Wallis test).

Antineoplastic Agents↗
PubMed1979

Treatment of osteogenic sarcoma. I. Effect of adjuvant high-dose methotrexate after amputation.

Thirty-nine patients with extremity osteogenic sarcoma and no discernible metastases were treated with amputation and postoperative adjuvant high-dose methotrexate with leucovorin rescue. One half of the patients were also randomized to receive bacillus Calmette-Guérin by a multiple-puncture technique. Results have been analyzed with a minimum followup of 10 months and a median followup of 27 months. Actuarial analysis estimates that 38% of current protocol patients remain continuously free of disease for 24 months compared to only 17.4% of historical control patients (P = 0.029; one-sided generalized Kruskal-Wallis test). Bacillus Calmette-Guérin administered by a multiple-puncture technique had no effect on disease-free interval. Minor differences between current protocol and historical control patients with regard to race, age, histologic type, and site and size of primary tumors do not affect the difference in disease-free interval between these two patient groups. However, current patients had somewhat lower grade lesions and consideration of the patients with grade III and IV lesions only, lessens the difference between current and historical control patients (P = 0.11; one-sided generalized Kruskal-Wallis test). High-dose methotrexate was administered with virtually no morbidity and no deaths. The small differences observed in this study between protocol patients treated with surgery plus high-dose methotrexate and historical control patients treated with surgery alone point to the need for a prospective randomized study to establish the role of high-dose methotrexate in the adjuvant treatment of patients with osteogenic sarcoma.

Adolescent↗
PubMed1978

Advanced ovarian adenocarcinoma. A prospective clinical trial of melphalan (L-PAM) versus combination chemotherapy.

Eighty patients with advanced ovarian adenocarcinoma were treated in a prospective, randomized trial comparing a four-drug combination--hexamethylmelamine, cyclophosphamide, methotrexate and 5-fluorouracil--with the oral alkylating agent, melphalan. Treatment with the four-drug combination was associated with a significantly increased overall response rate (75 vs. 54 per cent) (P less than 0.05), more complete remissions (33 vs. 16 per cent) and longer median survival (29 vs. 17 months) (P less than 0.02) but more severe toxicity than occurred with melphalan. Patients with minimal residual disease had a significantly higher overall response rate than patients with extensive residual disease (84 vs. 53 per cent) (P less than 0.05). Patients with advanced disease who achieved a complete remission documented by peritoneoscopy or laparotomy (or both) have a median survival that will exceed three years. The four-drug regimen is more effective than melphalan in the management of advanced ovarian adenocarcinoma.

Adenocarcinoma↗
PubMed1978

Increasing incidence of Gram-positive sepsis in cancer patients.

A review of the agents causing septicemia in cancer patients during a nine-year period (1968--76) revealed that Gram-positive organisms (especially S aureus) have become the most frequent isolates during the last two years. This unanticipated increase (P less than 0.001) in the number of Gram-positive isolates could not be related to horizontal transmission nor to changes in patient characteristics or therapy.

Adolescent↗
PubMed1978

Failure of immunotherapy with neuraminidase-treated tumor cell vaccine in mice bearing established 3-methylcholanthrene-induced sarcomas.

C3H/HeJ mice bearing MC-80 fibrosarcomas were given immunotherapy consisting of multiple injections of a Vibrio cholerae neuraminidase (VCN)-treated tumor cell vaccine at a site remote from the established tumor. In five separate experiments we were unable to show either partial or complete tumor regression or prolongation of survival for vaccine-treated mice compared to appropriate controls. Further, the use of BCG in addition to VCN-treated tumor cells failed to show any therapeutic efficacy. We could not confirm the successful immunotherapy results reported by others despite multiple efforts of reproduce the immunotherapy model as carefully and precisely as possible.

Animals↗
PubMed1978

"Concentration x time" methotrexate via a subcutaneous reservoir: a less toxic regimen for intraventricular chemotherapy of central nervous system neoplasms.

Neurotoxicity associated with intrathecal methotrexate therapy has been shown to correlate with elevated concentrations of the drug in the cerebrospinal fluid as well as with the total cumulative dosage. In our study 19 patients with meningeal leukemia were randomized to receive courses of intraventricular methotrexate via an Ommaya reservoir consisting of either single injections of 12 mg/sq m/dose or a low-dose "concentration x time" (C x T) schedule of 1 mg every 12 hr for 3 days. There were no significant differences between the two treatment groups in the rate of remission induction, the number of relapses, or the durations of remission. The mean (+/- 1 SD) cumulative methotrexate dose was 66 +/- 41 mg/sq m in the C x T group and 173 +/- 64 mg/sq m in the 12 mg/sq m/dose group (p less than 0.005). Neurologic toxicity occurred in one of the eight patients in the C x T group and in seven of ten patients in the 12 mg/sq m/dose group (p less than 0.05). These observations suggest that the C x T dosage schedule is less neurotoxic and equally effective in the treatment of central nervous system leukemia.

Adolescent↗
PubMed1978

Lack of therapeutic synergism between vincristine and methotrexate in L1210 murine leukemia in vivo.

In vivo studies were performed in mice bearing L1210 ascites tumor to examine the interaction of vincristine (VCR) at doses of 0.15 and 1.5 mg/kg with methotrexate (MTX) at doses of 0.5, 5, 50, and 350 mg/kg. The combination was administered on Days 2, 6, and 10 after tumor inoculation. VCR was given either concurrently with MTX or preceding it by 30, 60, or 120 minutes. VCR administered at a dose of 0.15 mg/kg achieved a peak peritoneal fluid concentration of 1.4 micron declining with a half-life (T1/2) of 33.5 minutes and produced no in vivo augmentation of MTX uptake. VCR administered at a dose of 1.5 mg/kg achieved a peak peritoneal fluid concentration of 16.5 micron declining with a T1/2 of 24.9 minutes and produced significant in vivo augmentation of MTX uptake when given concurrently with the MTX and 30 minutes prior to MTX at a dose of 350 mg/kg. No other interval was associated with augmented MTX uptake. When animal survival was evaluated, no therapeutic synergism was observed at any dose level of either drug in any schedule. In fact, VCR (0.15 and 1.5 mg/kg) and MTX at doses of greater than or equal to 50 mg/kg produced toxic synergism which adversely affected survival. Since the drug doses studied are comparable with those used in "high-dose" clinical protocols, individual tumor evaluation is indicated to support the use of these drugs in combination.

Animals↗
PubMed1978

Note on the design of multi-institution three-treatment studies.

Attention has recently focused on the appropriate use of statistics for the analysis of end results from clinical trials, with a corresponding lack of emphasis concerning the experimental design of such studies. In this paper, a particular design for a three-treatment multi-institution clinical trial is reviewed due to its recent increase in popularity. Although it may appear desirable at first, further investigation indicates that several difficulties may arise in the subsequent analysis and interpretation of the data. Defects of the design are discussed, and an alternative design is recommended.

Clinical Trials as Topic↗
PubMed1977

Bone marrow involvement in breast cancer: effect on response and tolerance to combination chemotherapy.

Forty-three patients with metastatic breast cancer who had not received prior chemotherapy were divided into two groups on the basis of whether or not a bone marrow examination revealed tumor. Both groups were treated with combination chemotherapy regimens and were analyzed with regard to response and toxicity parameters. The positive marrow group had a response rate similar to that of the negative marrow group (67% vs 71%), and a slightly shorter median time to progressive disease (240 vs 258 days) and median duration of remission (213 vs 243 days). The positive marrow group had higher requirements for hematologic support and tended to have more infectious complications. The data suggest that metastatic breast cancer patients with a bone marrow examination revealing tumor, although requiring more supportive care, may be treated as effectively with combination chemotherapy as those patients in whom the marrow examination does not reveal tumor.

Adult↗
PubMed1977

Thymosin reconstitution of T cell deficits in vitro in cancer patients.

Thymosin, a soluble extract of fetal calf thymus, has increased cellular immunity in children with thymic deficiency. Prior to therapy, an increase in thymus-dependent lymphocyte (T cell) levels in vitro after incubation with thymosin correlated with a rise in peripheral blood T cell levels and improvement in other parameters of cellular immunity. These correlations constituted the basis for a study of the effects of thymosin on T cell levels in vitro in cancer patients. Groups studied were 350 untreated patients with local-regional solid malignancies, 157 patients cured of these tumors, 340 patients studied at 523 intervals during radiation therapy, 80 patients receiving chemotherapy for disseminated solid malignancies, and 427 normal volunteers. Although there were significant differences among the groups in mean leukocyte, lymphocyte and T cell levels, among those with low T cell levels in each group there was a significant inverse relation between T cell levels after incubation with thymosin in vitro and initial T cell levels, with the exception of patients receiving chemotherapy. In patients receiving chemotherapy, T cell levels increased independently of initial T cell levels. These in vitro observations are consistent with evidence that a major effect of thymosin is maturation of T cell precursors; however, the effect is that of reconstitution at low T cell levels, and not of elevation to levels significantly above normal. The results provide a rationale for clinical trials with thymosin to maintain immune competence during radiation therapy and chemotherapy, and for a two-phase approach to immunotherapy of cancer utilizing thymosin for reconstitution of cellular defects followed by administration of agents that potentiate cellular immunity.

Adolescent↗
PubMed1977

Effect of thymosin in vitro on T cell levels during radiation therapy: correlations with radiation portal and initial T cell levels.

The effect of thymosin in vitro on percent T cells was determined in 388 blood specimens from patients with head and neck, mediastinal, and pelvic malignancies during radiation therapy, in 94 untreated patients with these malignancies, and 277 normal adults. Changes in percent T cell levels after incubation of lymphocytes with thymosin did not correlate with tumor histology or cumulative radiation dose, but in all groups correlated with radiation portal and initial T cell levels. T cell levels increased by a similar increment in normals and in the untreated patients. During irradiation, the mean levels after incubation with thymosin did not change in patients with head and neck and pelvic malignancies, but in patients with mediastinal malignancies the levels increased significantly more than in normals. For a given T cell level, the increase in patients with mediastinal malignancies was greater than in patients with pelvic malignancies, and as a group was greater than in patients with head and neck malignancies. The results can be explained by an increase in circulating thymosin-responsive lymphocytes during mediastinal irradiation due to suppression of a function of the thymus important for maturation of these cells, and a decrease in these cells during pelvic irradiation due to a deleterious effect on precursors in pelvic bone marrow. The results thus provide a rationale for clinical trials to assess the efficacy of thymosin in averting declines of T cell levels in patients receiving mediastinal irradiation.

Adolescent↗