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Biomedical subjects

P Chang

Publications and source records attributed to P Chang.

At least 307 records · Page 17Linked to original sources

A phase II study of intravenously- administered methyl CCNU in the treatment of advanced sarcomas.

Thirty-two patients with advanced, inoperable nonhematologic soft-tissue and osseous sarcomas were treated with Methyl CCNU administered via controlled intravenous infusion in doses of 130-170 mg/m2 every 6 weeks in a Phase II trial. All 28 evaluable patients were no longer responsive to adriamycin. Greater than 50% tumor regression was seen in one of two patients with chondrosarcoma and one of five patients with rhabdomyosarcoma. Less than 50% tumor regression occurred in one of five patients with rhabdomyosarcoma, one of two patients with malignant giant cell tumor, and one of three patients with malignant fibrous histiocytoma. Stabilization of previously advancing disease occurred in two of seven patients with leiomyosarcoma. The drug preparation was well tolerated. Nausea and vomiting occurring in three of 32 patients. Major toxicity was myelosuppression, characterized chiefly by thrombocytopenia with lesser degrees of leukopenia. This drug preparation appears to have activity in this group of tumors.

Clinical Trials as Topic↗

A comparison of cyclophosphamide, vincristine, and prednisone (COP) with nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) in the treatment of nodular, poorly differentiated, lymphocytic lymphoma.

This study was designed to test the efficacy and toxicity of COP (cyclophosphamide, vincristine, and prednisone) and MOPP (nitrogen mustard, vincristine, prednisone, and procarbazine) in 13 previously untreated patients with disseminated, nodular, poorly differentiated, lymphocytic lymphoma, and to test for patient cross-resistance to the regimens. Complete remission was initially achieved in six of eight patients on COP and three of five on MOPP. Three patients were crossed over to the alternative induction regimen because of progressive disease after an initial partial response; one was crossed over because of toxicity. On crossover, four patients achieved complete remission, two on either regimen. Durations of unmaintained complete remission range from 6-46+ months, with 8/13 still in their first complete remission. Only one patient has died, while in remission, from progressive Kaposi's sarcoma; one was lost to follow-up while in complete remission at 44 months; the others (85%) remain alive 33-54 months from the initiation of chemotherapy. MOPP was significantly more toxic with respect to thrombocytopenia, duration of myelosuppression, and cumulation of toxicity. Because of its more acceptable toxicity, COP is recommended as initial therapy for patients with nodular, poorly differentiated, lymphocytic lymphoma. MOPP or another regimen of non-crossresistant combination chemotherapy would be more appropriate for primary treatment failures.

Adult↗

Combination chemotherapy with adriamycin and streptozotocin. I. Clinical results in patients with advanced sarcoma.

In a prospectively randomized study, 17 evaluable patients treated with adriamycin alone, 60 mg/m2 intravenously every 3 wk, were compared with 14 patients treated with adriamycin in the same dose and schedule plus streptozotocin. 500 mg/m2/day intravenously for 5 days every 3 wk. All patients had advanced sarcomas, but none had previously received either adriamycin or streptozotocin. Objective responses were seen in 9 patients on the single drug arm (4 with more than 50% tumor shrinkage and 5 with stabilization of disease), and in 8 patients given the combination drug arm (2 with more than 50% tumor shrinkage and 6 with stabilization of disease). Duration of response and survival from treatment for both treatment groups were similar. Transient hepatic dysfunction, renal function abnormalities, and nausea with vomiting were additive in the combination drug arm, the last two limiting therapy most. Leukopenia, thrombocytopenia, and mucositis appeared to be synergistically increased in patients receiving both adriamycin and streptozotocin. Patients with abnormal pretreatment renal function were able to tolerate the combination therapy without undue incidence of severity of renal toxicity. Patients who developed transient streptozotocin-related renal dysfunction were able to tolerate further doses of streptozotocin after their renal parameters normalized. Adriamycin in combination with streptozotocin did not offer any therapeutic advantage over adriamycin alone.

Adolescent↗

Combination chemotherapy with adriamycin and streptozotocin. II. Clincopharmacologic correlation of augmented adriamycin toxicity caused by streptozotocin.

Plasma pharmacokinetics were compared in patients with advanced sarcomas receiving adriamycin, 60 mg/m2 intravenously (iv) on day 1 every 3 wk in combination with streptozotocin, 500 mg/m2/day iv on days 1 to 5 every 3 wk, and patients receiving adriamycin alone in the same dose and schedule. The combination-treated group had greater adriamycin drug exposure (concentration X time) when serial plasma levels were analyzed by fluorescence assay and by radioimmunoassay (RIA). The plasma t 1/2 of adriamycin equivalents measured by fluorescence assay was also significantly prolonged in the combination-treated group. These changes correlated well with an increase in adriamycin-related toxicity--mucositis and myelosuppression-seen in the patients who received the combination drug therapy. Plasma streptozotocin kinetics and the incidence of streptozotocin-related side effects--hepatic and renal function abnormalities--were those published for streptozotocin alone. Evidence is presented to support the hypothesis that the increased incidence of adriamycin side effects is due to streptozotocin-related hepatic dysfunction, affecting both the detoxification and excretion of adriamycin. Combination of other drugs with adriamycin should take into account their potential for inducing hepatic dysfunction which may affect the therapeutic index of adriamycin.

Adolescent↗

The endogenous reverse transcriptase activity of Gibbon ape lymphoma virus: characterization of the DNA product.

The DNA product of the endogenous reverse transcriptase reaction of Gibbon ape lymphoma virus has been analyzed and characterized. Data show that in simultaneous detection assays in which the type and/or concentration of divalent cation is varied the best yield of rapidly-sedimenting DNA was obtained from reactions containing 1.5 mM Mn2+. This yield is ten-fold better than the yield observed at the optimal Mg2+ concentration (5.0mM). Evidence is presented to show that DNA synthesized at the optimal concentration of either of these cations consists of large pieces varying in size from 4 to 12S. This DNA hybridizes efficiently to homologous viral RNA (greater than 60 percent annealing) and protects at least two-thirds of GALV 70S [32P]RNA from ribonuclease digestion. The hybrids formed with homologous viral RNA are stable as evidenced by their thermal elution patterns from hydroxylapatite columns. In contrast, DNA synthesized in reactions in which the concentration of Mn2+ or Mg2+ was greater than optimal was predominantly 4S or smaller in size and displayed a low level of hybridization (less than 10 percent) to homologous viral RNA.

Animals↗

Dose and treatment factors in radiation-related pericardial effusion associated with the mantle technique for Hodgkin's disease.

A retrospective study of 83 patients with Stage I-III Hodgkin's disease treated with an upper mantle field revealed a rate of radiation-related pericardial effusion (RRP) of 28.9% (24/83). Clinical presentation was asymptomatic effusion in 10/24 and symptomatic effusion in 14/24. RRP was self-limited in all but 4 patients, who progressed to chronic effusion requiring pericardiectomy (4/24). A midplane mediastinal dose of 4000 rads in 4 weeks was given with an anteriorly weighted mantle field that resulted in an average pericardial dose of 5325 rads (1823 ret) and an average midplane cardiac dose of 4625 rads (1558 ret). The rate of RRP was correlated with increasing degree of mediastinal Hodgkin's disease. Increased incidence of RRP with increasing cardiac and pericardial dose could not be proven statistically. Factors which may facilitate pericardial effusion following a basic radiation injury are discussed.

Hodgkin Disease↗

Radiation-related pericarditis.

To determine the incidence of pericardial effusion in patients undergoing upper mantle radiation therapy, 81 patients with Hodgkin's disease, stages I to IIIB, were selected from a protocol series of 98 patients. Twenty-four patients (29.6 percent) met X-ray criteria for the presence of pericardial effusion. Eleven of the 24 also underwent right heart catheterization to confirm the presence of pericardial effusion and to define any hemodynamic abnormality. Fourteen patients were found to have transient effusion. Five of the 11 patients have had partial pericardiectomy for symptoms and signs of cardiac tamponade. There has been no evidence of recurrent Hodgkin's disease in these surgically treated patients. Ninety-two percent of the pericardial effusions occurred in the first 12 months after the end of radiation therapy. Therapeutic implications depend on elucidation of the natural history of this process. At present close follow-up is necessary with surgical intervention for signs or symptoms of cardiac tamponade.

Cardiac Catheterization↗

The surgeon, the surgery, the patient, and the disease: factors complicating colonic surgery.

A review of 231 cases of colonic operations performed during the year 1971 by, or under the supervision of, 32 attending surgeons in an 850 bed private community medical center was undertaken. The overall mortality rate was 5.6% while a 35.5% overall complication rate was also noted. Factors significantly associated with increased overall complication rate were: emergency operations, preoperative anemia (hemoglobin less than 10 gm%), preoperative hypoalbuminemia (serum albumin less than 3 gm%), preoperative obstruction, malignant lesions of the colon and ulcerative colitis, prolonged operation, operations requireing a large quantity of packed cell transfusion, coexisting hepatic disease and operations performed by surgical attending staff under 50 years of age in this institution. Each of these factors is discussed individually. Several factors that were expected to be associated with increased complication rate failed to show significant statistical correlation in this series. These are: age of the patient, coexisting diseases other than hepatic disease, absence of prophylactic parenteral antibiotics, preoperative perforations and operations involving resection of the colon. Hypotheses are offered to explain a number of unexpected poor correlations.

Colonic Diseases↗

Radiation-related pericardial effusions in patients with Hodgkin's disease.

Pericardial effusions following radiotherapy for Hodgkins Disease have previously been described as infrequent and related to the total dose of radiation received. Analysis of all chest x-rays on 81 patients who received upper-mantle radiotherapy for Hodgkins Disease at the Baltimore Cancer Research Center between 1968 and 1972 disclosed an incidence of pericardial effusions of 30.9% (25 of 81), with 13.6% (11 of 81) requiring limitation of activity (5) or pericardiectomy (6). Clinical presentation of radiation-related percardial effusions was subtle, with signs and symptoms a late finding if they occurred. Radiotherapy data was reviewed and no difference in total dose (rads) or time-dose relationships (rets) was found between the groups who did or did not develop effusions. Analysis of multiple pre-treatment clinical and pathological characteristics disclosed four parameters that were felt to be related to the development of pericardial effusions; elevated ESR, normal absolute lymphocyte count, initial presence of extensive mediastinal adenopathy and the addition of adjuvant chemotherapy. The presence of increasing combinations of these pretreatment 'risk factors' led to an increasing likelihood of developing a radiation-related pericardial effusion such that six of seven patients with all four 'risk factors' developed a pericardial effusion. Nine of 13 clinically significant effusions were associated with the addition of adjuvant chemotherapy. Possible pathogenetic mechanisms that include factors other than radiation dosage and the clinical management of radiation-related pericardial effusions are discussed.

Adult↗