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Biomedical subjects

J Aisner

Publications and source records attributed to J Aisner.

At least 181 records · Page 10Linked to original sources

Cyclophosphamide and dimethylsulfoxide in the treatment of squamous carcinoma of the lung. Therapeutic efficacy, toxicity, and pharmacokinetics.

To determine whether dimethylsulfoxide (DMSO) can potentiate antitumor activity of cyclophosphamide (CYC) in patients with squamous cell carcinoma of the lung, 14 patients were treated with 5 l of a 5% or 6% DMSO solution PO over 3 days and 1,500 mg CYC/m2 IV as a 60-min infusion on the third day of treatment. Serial blood, CSF, and urine samples were collected to assess the pharmacokinetics of CYC. Courses were repeated every 3-4 weeks. No antitumor responses were observed. Toxicity was mainly hematologic and similar to that of CYC alone. There was one death from infection during granulocytopenia. Nonhematologic toxicity was moderate to severe and included nausea (14 patients) and vomiting (five patients). The plasma pharmacokinetics of CYC in this study are similar to previously reported results for CYC alone, but the 24-h urinary excretion of CYC in our study is much lower than previously reported. Further studies in tumors more responsive to CYC may be warranted.

Adult↗

Long-term follow-up patients with leukemia receiving platelet transfusions: identification of a large group of patients who do not become alloimmunized.

Alloimmunization is the major complication of platelet transfusion therapy in patients with acute leukemia. To evaluate whether alloimmunization continues to be a long-term problem in patients surviving induction therapy, 114 patients with acute nonlymphocytic leukemia (ANLL) who survived more than 6 mo and who received multiple courses of chemotherapy and abundant platelet transfusions were studied. Clinical response to random donor platelets and lymphocytotoxic antibody (LCTAb) were measured pretreatment and serially throughout the study period. Fourteen patients (12%) were alloimmunized upon admission, 34 (30%) patients became alloimmunized during remission induction therapy, and 66 (58%) patients did not become alloimmunized during that period. Sixty-one of these 66 patients (92%) never became alloimmunized and responded to random donor platelets during their subsequent course despite the fact they received multiple further platelet transfusions, whereas the alloimmunized patients tended to remain alloimmunized for their entire clinical course. There was no difference in age or sex between groups, and prognostic factors predicting alloimmunization could not be detected. In greater than 90% of patients not alloimmunized at admission, the presence or absence of LCTAb after induction predicts later alloantibody production. This information can be used to plan the type of platelet transfusions (HLA-matched or random donor) needed for subsequent maintenance and induction therapy. It may also help to identify a group of patients to whom more aggressive maintenance chemotherapy may be more safely administered.

Acute Disease↗

Phase II trial of methyl-G (methylglyoxal bis-guanylhydrazone) in patients with metastatic renal cell carcinoma.

Fourteen patients with metastatic renal cell carcinoma received methyl-G weekly at a starting dose of 600 mg/m2 (five patients) and 500 mg/m2 (nine patients) intravenously. All 14 patients are evaluable for response and toxicity. No antitumor responses were observed. Six patients achieved stabilization of disease for 8 to 42 weeks. Toxicity was nonhematologic and included nausea or vomiting (35%), fever with shaking chills (28%), diarrhea (21%), myalgia (63%), paresthesia (49%), and bilateral foot drop (7%). Methyl-G does not appear to have activity against renal cell carcinoma.

Adenocarcinoma↗

Alloimmunization following platelet transfusion: the absence of a dose-response relationship.

A major concern about the use of prophylactic platelet transfusions is the development of alloimmunization. To determine whether the rate of alloimmunization is related to the number of platelet transfusions, we measured the development of lymphocytotoxic antibody in the first 2 mo of induction therapy in patients with acute nonlymphocytic leukemia. All patients received prophylactic random donor platelets and packed red blood cells during induction. No patient had lymphocytotoxic antibody present at admission. One hundred and six patients received an average of 9.3 platelet transfusions (range 2-34) containing an average of 61 U (range 9-236). The rate of alloimmunization was 38% overall and correlated with refractoriness to platelet transfusions. Ten of 19 patients receiving less than or equal to 4 transfusions became immunized, compared with 30/87 patients receiving less than 4 transfusions. There was no relationship between the number of platelet transfusions given and the rate of severity of alloimmunization, suggesting prophylactic platelets need not be withheld expressly to prevent alloimmunization.

Adult↗

Chemotherapy versus chemoimmunotherapy for small-cell undifferentiated carcinoma of the lung.

Thirty-eight patients with small-cell carcinoma were treated with cyclophosphamide, Adriamycin, and VP16-213 + or - MER. Response and survival of the six patients who received radiotherapy prior to entering the study were inferior compared with patients who received chemotherapy alone. Of 32 previously untreated patients, 13 had limited and 19 had extensive disease. Ninety-seven percent of these 32 responded and 63% achieved complete remission (CR). All patients with limited disease had a response and 77% achieved CR. Patients with extensive and limited disease had 91/2 months (range 1-26 months) and 14 months (range 31/2 -42 + months) median survival, respectively. The median survival for all complete responders irrespective of extent of disease was 16 months (range 6 - 42 + months). Three patients with limited disease are disease free more than 34 + months and off all therapy 10 + to 18 + months. Eighteen of 38 patients required antibiotics for fever during neutropenia. Eight patients had MER fevers and nine had serious infections. There were four drug-related deaths. MER therapy did not influence response rate, drug toxicity, or survival, but did add morbidity. This combination chemotherapy alone is an effective treatment for previously untreated small-cell lung cancer patients regardless of extent of disease.

Aged↗

Platelet transfusion therapy. One-hour posttransfusion increments are valuable in predicting the need for HLA-matched preparations.

Seventy-nine platelet transfusions to 73 thrombocytopenic patients with cancer were analyzed to determine whether a platelet count obtained one hour after transfusion could help differentiate between alloimmunization and other clinical factors that result in rapid platelet destruction. These transfusions were selected because 18- to 24-hour increments were inadequate in response to fresh, random donor platelets. A corrected count increment (Cl) (Cl=[posttransfusion count-pretransfusion count]Xbody surface area [sq m]/platelets transfusedX10'') at one hour of 10X103/microliter or greater was associated with absence of lymphocytotoxic antibody, whereas increments of less than 10X103/microliter were generally associated with high levels of strongly cytotoxic antibody. HLA-matched transfusions produced no improvement in increments when the previous one-hour Cl had been 10X103/microliter or greater, whereas in the other group significantly better increments were obtained. A one-hour posttransfusion count is a simple test that correlates well with the presence of antibody against HLA antigens, is valuable in predicting the need for HLA-matched platelets, and helps avoid wasteful, empirical use of such transfusions.

Adult↗

Pericardial window for malignant pericardial effusion.

Seventeen patients with malignant pericardial effusion were treated by the creation of a pericardial window. This was done through a subxiphoid approach in 13 patients and through limited anterior thoracotomy or sternotomy incisions in 4. There were no deaths and no major complications attributable to the operation. In all patients, relief of the cardiac compression caused by the effusion was immediate and complete. No patient showed a clinically significant recurrence of the effusion, although 1 patient who had received irradiation required pericardiectomy for constriction 5 months later. Survival was determined principally by the extent of the primary malignancy. Six patients died of the primary tumors within 30 days, but 6 survived 3 to 12 months and 2 are alive at 8 and 21 months. It is concluded that creation of a pericardial window, preferably by the subxiphoid approach, is the treatment of choice for malignant pericardial effusion. The procedure provides an accurate diagnosis, carries virtually no mortality or morbidity, and affords immediate and long-lasting relief of cardiac compression.

Adult↗

Phase I trial of pentamethylmelamine in patients with previously treated malignancies.

Pentamethylmelamine (PMM), a demethylated soluble analog of hexamethylmelamine, was given to 35 patients with solid tumors in a phase I clinical trial. Thirty patients were given single doses ranging from 80 to 2000 mg/m2 in a 2-hour infusion every 3 weeks. Once a maximum tolerated dose was defined for this schedule, an additional five new patients plus four patients who had already received PMM were treated on a multiple-dose schedule of PMM given three times a week every Monday, Wednesday, and Friday (M-W-F) for 4 weeks. Dose-limiting toxic effects for the single-dose schedule were in the central nervous system and gastrointestinal tract, manifested by nausea (60%), vomiting (49%), somnolence (37%), depression (6%), and headache (6%). Other toxic effects observed on this schedule included anorexia (34%), diarrhea (7%), and diaphoresis (21%). The toxic effects were first observed in mild form at 400 mg/m2/dose and became progressively more severe and prolonged with each dose escalation; they were considered intolerable at the 2000-mg/m2 dose level in all patients treated. The nine patients receiving the multiple-dose schedule were given PMM at a dose of 1000 mg/m2 three times a week (M-W-F). This level produced dose-limited nausea and vomiting in all patients so that no patient completed greater than 3 weeks of treatment on this schedule. One patient developed PMM-related visual hallucinations. PMM produced no hematologic, hepatic, renal, allergic, or acute side effects; no alopecia was observed. Minor tumor regressions of 1 month's duration were seen in two patients, one with pleural mesothelioma and one with a parotid gland tumor. The recommended doses for solid tumor phase II studies are 1500 mg/m2 given as a 2-hour infusion every 3 weeks and 1000 mg/m2 given three times a week (M-W-F), repeated at 3-week intervals.

Adult↗

High-dose VP 16-213 (NSC 141540) for the treatment of patients with previously treated acute leukemia.

Thirteen patients with relapsed acute leukemia, 12 adults with acute nonlymphocytic leukemia, and one child with acute lymphoblastic leukemia were treated with VP 16-213, an epipodophyllotoxin analog, at a dose of 200-300 mg/m2/day X5 as a 2-hour intravenous infusion. Only four patients achieved bone marrow aplasia and three regenerated with leukemic cells. The fourth patient achieved a partial remission for 4 weeks. Toxicities included myelosuppression (WBC nadir 500/microliter), nausea and vomiting (70% of courses), mucositis (23%), esophagitis (12%), which contributed to death in one patient, hypotension (12%), and transient liver function abnormalities (12%). It is concluded that increasing the dose of VP 16-213 as employed in this study did not increase the therapeutic activity of VP 16-213 for the treatment of relapsed leukemia but did increase the risk of toxicity.

Adult↗

High-dose cis-diamminedichloro-platinum therapy in patients with advanced breast cancer: pharmacokinetics, toxicity, and therapeutic efficacy.

Seventeen patients with advanced breast cancer were treated with cis-diamminedichloroplatinum (DDP) 100 mg per m2 every 21--28 days. Hydration and mannitol or furosemide diuresis was given. Responses were seen in two patients (one complete, one objective) with soft-tissue metastases. There was no difference in peak plasma platinum concentration (3.91 micrograms/ml +/- 1.41 micrograms/ml), terminal plasma half-life (116--288 hours), peak concentration of unbound platinum (0.7 micrograms/ml), or 24-hour urinary platinum excretion (6.7--17.2% of administered dose) between the objective responder and the nonresponders. Toxicities included severe nausea and vomiting, renal insufficiency, high-frequency hearing loss, and peripheral neuropathies. Hematologic toxicity was mild in most patients. DDP has limited activity when used as a single agent in this dose and schedule in patients with metastatic breast cancer.

Adult↗

Meperidine for the treatment of shaking chills and fever.

Meperidine hydrochloride was evaluated in a prospectively randomized double-blind study for its effectiveness in stopping shaking chills occurring with amphotericin B infusions. Seven patients were randomized on multiple occasions for a total of 19 reactions. In the meperidine group, nine of nine reactions stopped within 30 minutes of the administration of meperidine, with a mean cessation time of 10.8 minutes. The placebo group had a mean time of 37.4 minutes to cessation of reactions with three of ten reactions subsiding spontaneously. The mean dose of meperidine hydrochloride for cessation of reaction was 45 mg. The comparisons between meperidine and placebo for cessation of reaction within 30 minutes and the mean time to cessation of reaction were significantly different. Side effects with meperidine were minimal and less severe than the shaking chills and fever seen with amphotericin B infusions. Meperidine can eliminate these reactions more effectively and more rapidly than simply discontinuing the amphotericin B.

Adult↗

Increased leukocyte alkaline phosphatase activity following transfusion of leukocytes from a patient with chronic myelogenous leukemia.

Neutrophils from a patient with chronic myelogenous leukemia and typically low leukocyte alkaline phosphatase (LAP) activity markedly increased in LAP content following transfusion to and circulation in an infected neutropenic recipient. Incubation of the recipient's serum and plasma with normal neutrophils failed to alter their LAP activity. This observation suggests that LAP activity is inducible by as yet unknown "environmental" factors, and possible mechanisms for this are discussed.

Adult↗

Invasive aspergillosis in acute leukemia: correlation with nose cultures and antibiotic use.

Aspergillosis in cancer patients is a problem. Because not all patients can undergo invasive procedures, we sought other methods for diagnosis. We reviewed the data from all patients with acute nonlymphocytic leukemia treated at our center during a 3-year period. Of 125 patients, 18 had invasive aspergillosis (cases). Eleven patients had nose cultures growing Aspergillus flavus or A. fumigatus; 10 of these 11 had aspergillosis, whereas only eight of 114 without such nose cultures had invasive disease (P less than 0.000001). Thus, A. flavus on nose culture appears "predictive" for aspergillosis. Absence of such a culture does not preclude infection. Of 125 patients, 61 had sterile nose culture(s) and 14 of the 18 cases had such a sterile nose culture. Only four of the 64 patients without sterile nose cultures developed aspergillosis (P less than 0.008), suggesting a relation between sterile nose culture and aspergillosis. Carbenicillin was used for a longer period among cases and patients with predictive nose cultures than among patients without aspergillosis. These data may help identify patients at risk of aspergillosis and help determine antifungal therapy when invasive procedures are contraindicated.

Acute Disease↗