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Biomedical subjects

A Mittelman

Publications and source records attributed to A Mittelman.

At least 91 records · Page 5Linked to original sources
PubMed1990

Phase II trial of Serratia marcescens extract in recurrent malignant astrocytoma.

Nineteen assessable patients with recurrent malignant astrocytomas who had failed standard therapy (surgery, radiation, and/or chemotherapy) were treated on a phase I-II trial with a biologic extract of Serratia marcescens (ImuVert; Cell Technology, Boulder, CO) a new biologic response modifier (BRM). Two complete responses (CRs) were seen, of 63 and 77+ weeks duration. One minor response (MR) occurred, of 6 weeks duration. There were four additional stable (S) patients, with durations of 58+, 39, 12, and 7 weeks. Median time to progression and median survival in the CR plus MR patients were 63 and 129+ weeks, respectively. Overall, median time to progression and median survival were 12 and 19 weeks, respectively. Three patients are alive greater than or equal to 2.5 years from study entry. Common toxicities included transient (less than 72 hours) tenderness, induration, and erythema at the injection sites. Systemic toxicities were less frequent and included fever, chills, nausea/vomiting, headache, arthralgia, and hypotension. The response rate (CR plus MR) to this new BRM is modest (16%). However, the observation of CRs in patients with advanced recurrent malignant astrocytomas, with acceptable overall toxicity, warrants further study of this agent.

Adult↗
PubMed1989

Active specific immunotherapy with antiidiotypic antibodies in patients with solid tumors.

Tumor-associated antigens (TAA) provide appropriate targets for selective manipulation of the patient's immune response in the immunotherapy of cancer. Active specific immunotherapy utilizing antiidiotypic antibodies to anti-TAA antibodies has been implemented in phase I clinical trials both in patients with colorectal carcinoma and in those with melanoma. The theoretical basis for immunotherapy with antiidiotypic antibodies, the results of these clinical trials, and an evaluation of appropriate parameters for future clinical trials of active specific immunotherapy with antiidiotypic antibodies in patients with solid tumors are reviewed.

Animals↗
PubMed1989

Erythropoiesis in cancer patients undergoing immunotherapy.

We studied ten patients with various types of cancer who were being treated with Interleukin-2 (IL-2) and lymphokine activated killer cells (LAK). All patients developed a reticulocytopenic, normochromic, normocytic anemia. We noted some variability but no significant suppression of circulating erythroid progenitors. The levels of erythropoietin were lower than expected for the hemoglobin/hematocrit values. We could not detect Interferon or Tumor Necrosis Factor (TNF) in the serum of these patients; however, the supernatant of LAK cells did contain Interferon and TNF which could be neutralized with appropriate antibodies. These results suggest that the etiology of this anemia is multi-factorial. Administration of recombinant erythropoietin (Ep) may be of benefit in some of these patients.

Anemia↗
PubMed1989

Combination chemotherapy of cisplatin and 5-fluorouracil for advanced colorectal adenocarcinoma.

A total of 24 patients with advanced colorectal adenocarcinoma were entered into a phase I-II study of 5-fluorouracil (5-FU) and cisplatin, 21 of whom had previously received 5-FU. The starting dose of cisplatin was 20 mg/m2 diluted in 1000 cc normal saline, given over 20 h daily for 5 days, together with 600 mg/m2 5-FU diluted in 1000 cc fluid, given simultaneously over 20 h daily for 5 days. This regiment was given every 4 weeks. The dose-limiting toxicity was renal and cumulative. All 24 patients were evaluable for toxicity. Of 12 patients on the above-mentioned starting dose, 8 underwent a cisplatin dose reduction to 15 mg/m2 due to a progressive decrease in creatinine clearance following the second or third course of treatment. Of 12 patients who started cisplatin at 15 mg/m2 and 5-FU at 600 mg/m2, 11 were maintained at this dose. A WBC nadir count of less than 2000/mm3 was seen in four patients. Thrombocytopenia occurred in three patients who received 15 mg/m2 cisplatin and 600 mg/m2 5-FU. In all, 21 of the 24 patients had objectively measurable disease and were also evaluable for response as follows: 1 complete response, 2 partial responses, 1 case of stable disease, and 17 patients with progressive disease.

Adenocarcinoma↗
PubMed1989

Phase II trial of continuous-infusion iproplatin (CHIP) and 5-fluorouracil (5-FU) in advanced colorectal carcinoma.

Following the observation of antitumor activity for the combination of 5-fluorouracil (5-FU) and cisplatin in metastatic colorectal carcinoma, the combination of 5-FU and iproplatin was tested, also in colorectal carcinoma, in the hope of attaining equivalent activity without the nephrotoxicity observed with 5-FU/cisplatin. However, no responses were achieved with 5-FU/iproplatin.

Adult↗
PubMed1989

Severe intrahepatic cholestasis in patients treated with recombinant interleukin-2 and lymphokine-activated killer cells.

Immunotherapy with recombinant interleukin-2 (rIL-2) and lymphokine-activated killer cells (LAK) has become a new form of therapy that has been shown to induce remissions in patients with renal cell carcinoma and melanoma. Despite encouraging results, this form of therapy has been associated with increasing toxicity, often requiring therapy in an intensive-care unit. In this report severe intrahepatic cholestasis occurred in two patients receiving rIL-2 and LAK cells. This form of cholestasis appeared to be directly related to rIL-2 administration at a doses of 2 x 10(6) U/m2 and 3 x 10(6) U/m2 t.i.d. A liver biopsy showed moderate hepatocellular bile stasis, with lobular and portal inflammation. All other studies for potential cause of this cholestasis were negative, including studies for metastatic disease. When therapy was discontinued, evidence for cholestasis and bile stasis resolved. We conclude that rIL-2 is a drug with a potential to induce severe hepatic injury that is reversible upon cessation of therapy with rIL-2. Further care should be exercised when rIL-2 is administered to patients with abnormal liver function.

Adult↗
PubMed1989

Lack of protection against bacterial infections in patients with advanced cancer treated by biologic response modifiers.

A survey of patients with advanced cancer treated by biologic response modifiers (BRMs), including (i) recombinant interleukin-2 and lymphokine-activated killer cells, (ii) recombinant interleukin-2 and alpha interferon, and (iii) tumor necrosis factor, was done. A total of 52 patients were reviewed. A total of 73 courses of BRMs were administered. Prior to the initiation of therapy, all patients were infection free and not receiving antibiotics. Twelve patients developed bacteremia during treatment with these BRMs. Five of these 12 patients had catheter-related bacteremia. Six patients had bacteremic infections without an obvious source, and one patient had a urinary tract infection with bacteremia. Staphylococcus epidermidis accounted for six of the isolates. Other organisms were Staphylococcus aureus, group B streptococci, viridans group streptococci, and gram-negative bacilli. This was an unexpectedly high incidence of bacterial infections in patients treated with BRMs. These BRMs have been previously shown to be efficacious against infections (by bacteria and other intracellular organisms) in experimental animals. In this study BRMs did not influence host defense mechanisms or offer protection against bacterial infections.

Bacterial Infections↗
PubMed1989

Acute promyelocytic leukemia: a 5-year experience with new antileukemic agents and a new approach to preventing fatal hemorrhage.

Forty-six induction courses were administered to 32 patients with acute promyelocytic leukemia. There were 28 males and 18 females with a median age of 39.5 (range 19-68). Twelve patients were previously untreated, 32 were in relapse, and 2 were refractory to primary induction chemotherapy. Heparin 7.5-10 units/kg/h by continuous infusion, 4-6 units of platelets and 1-2 units of fresh-frozen plasma (FFP) every 12 h were given to all patients. Previously untreated patients received either daunorubicin, idarubicin or mitoxantrone in combination with cytarabine (Ara-C). For relapsed and refractory patients, regimens included amsacrine with high-dose cytarabine (Amsa/HiDac), homoharringtonine (HHT) alone, or with Ara-C, mitoxantrone and bisantrene. Hemorrhagic complications occurred in only 1 out of 46 courses (2%). Complete remission rates (CR) were as follows: previously untreated 83% (10/12), relapsed 66% (21/32), primary refractory 50% (1/2). Amsa/HiDac resulted in a 71% (10/14) CR and HHT-based regimens achieved a 46% (6/13) CR. These regimens are effective and the value of their incorporation into primary therapy should be studied. The use of heparin with platelet and FFP transfusions every 12 h reduces the risk of hemorrhage during induction therapy.

Adult↗
PubMed1989

High-dose, potentially myeloablative chemotherapy and autologous bone marrow transplantation for patients with advanced Hodgkin's disease.

Twenty three patients with Hodgkin's disease were treated with BCNU (carmustine), etoposide, and cyclophosphamide at doses of 450-600 mg/m2, 1500-2000 mg/m2, and 120 mg/kg respectively. Bone marrow refrigerated at 4 degrees C for 2-5 days or cryopreserved at -80 degrees C was used to reconstitute bone marrow function. The median age was 28 (range 16-48), and the median Karnofsky performance status was 70. Nineteen patients had progressive disease while on chemotherapy. The median number of prior regimens was three (1-7), and the median number of prior chemotherapy drugs was 10 (range 4-12). Ten patients had received at least two of the drugs used in this study and four had had all three. Indicator lesions included lung (10), peripheral lymph nodes (9), retroperitoneal nodes (8), liver (3), and chest wall masses (2). Ten patients achieved a complete remission (43.5%; 95% confidence limits 23-64%), and five patients had a partial remission (21.7%; 95% confidence limits 5-39%). The median duration of complete remission was 6 months (range 2-13+ months). Responses were shorter in duration for patients with primary refractory disease. Liver function abnormalities were noted in nine (39%) cases. Post transplant, the recovery time was 18 days (range 11-43) for WBC and 24 days (11-77) for platelets. Two patients died of septic episodes while neutropenic. The median number of RBC units used was seven (range 1-45). Ten patients had evidence of pulmonary dysfunction. In seven patients there was symptomatic improvement with steroid therapy, but three patients who were not treated with steroids died as a result of interstitial pneumonia. Future programs should consider bone marrow transplantation in patients with Hodgkin's disease earlier in the course of disease, at the time of minimal residual disease, and employ newer, potentially less toxic drugs.

Adolescent↗
PubMed1989

Treatment of patients with HIV thrombocytopenia and hemolytic uremic syndrome with protein A (Prosorba column) immunoadsorption.

Both antibodies and circulating immune complexes (CIC), which bind to platelets and induce the destruction and clearance of platelets by the reticuloendothelial system, are found in patients with human immunodeficiency virus (HIV) and immune thrombocytopenic purpura (ITP). IgG and CIC were removed from patients' plasma by extracorporeal immunoadsorption using protein A-silica columns (PROSORBA columns). Of the 36 HIV-positive ITP patients treated, 29 received more than one treatment and were evaluated for response. Sixteen patients showed more than a 50% increase in their platelet counts. Platelet-associated IgG (PAIgG) and/or platelet-directed IgG and CIC were elevated in all patients. After four to eight treatments, 16 of 29 patients showed a 170% to 430% increase in platelet counts. A decrease in CIC and PAIgG was noted in responding patients. The median duration of response to date was 8 to 12 months. This treatment was associated with immune modulation and the development of an anti-F (ab')2 antibody response. The antibody functions by complexing with both platelet-binding IgG and CIC, neutralizing their binding capacity for platelets and enhancing their clearance from the circulation. Nine patients with mitomycin-C-induced hemolytic uremic syndrome (HUS) were also treated with PROSORBA columns. Pretreatment platelet counts were markedly reduced while a definite increase in platelet counts was observed upon completion of therapy. There was a decrease of hemolysis and stabilization of renal function in three patients. PROSORBA column treatment has demonstrated marked activity against both HIV-ITP and HUS, and has successfully freed patients from the bleeding diathesis associated with these syndromes.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Protein A immunotherapy in the treatment of cancer: an update.

Protein A, a naturally occurring Staphylococcus aureus cell surface protein, has the unusual property of binding circulating immune complexes and immunoglobulin G with high avidity. CIC have played a major role in cancer-associated immunosuppression. Thus, removal of the immunosuppressive agents, ie, the CIC, may lead to a modulation of the immunosuppression and a liberation of the immune system to perform an antitumor effect. In animal studies, protein A has been used in extracorporeal immunoadsorption columns and treatments have resulted in tumor shrinkage and antiviral responses. Our group developed a multicenter clinical trial to assess toxicity and antitumor responses with this biologic response modifier alone. This is an update of our original trial. We have now treated 142 patients for a total of 1,306 treatments. The patients consisted of 74 males and 68 females. Their age ranged from 7 to 83 years, with a mean of 50 years. The Karnofsky performance index values ranged from 40 to 95, with a mean of 80. Patients who received seven or more treatments were considered eligible for tumor response assessment, and all patients with one or more treatments were eligible for toxicity assessment. Thus, there were 101 patients eligible for tumor response and 142 eligible for toxicity response. The total response rate was 22 patients or 21.8% (partial remission [PR], 12 patients, 12%; less than PR, 10 patients, 10%). Response rates were similar in the 13 treatment centers. Toxicity was assessed in 142 patients. One thousand three hundred six treatments were assessed for treatment toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗
PubMed1989

Treatment of patients with advanced cancer using multiple long-term cultured lymphokine-activated killer (LAK) cell infusions and recombinant human interleukin-2.

Escalating doses of recombinant human interleukin-2 (rIL-2) were combined with long-term cultured rIL-2 activated killer cells to treat patients with disseminated melanoma, renal cell cancer, and colon cancer. Twenty-four patients were entered, 12 with renal cell cancer, 8 with colon cancer, and 4 with melanoma; 23 were evaluable for efficacy and toxicity. The (dose-related) toxicities were moderate to severe and consisted of fever, chills, rigors, weight gain, hypotension, mild confusion, elevation of liver enzymes and serum creatinine, thrombocytopenia, and eosinophilia. No cardiac events (arrhythmias or myocardial infarction) were recorded. None of the patients were admitted to the intensive care unit, and no deaths occurred. Two partial responses were observed, one at relatively low doses of rIL-2 in a patient with renal cell carcinoma and one at the highest dose level in a patient with malignant melanoma. The maximally tolerated dose level of rIL-2 for this study was 6 X 10(6) U/m2 i.v./day. The recommended dose for further studies is 3 X 10(6) U/m2 i.v./day in three divided doses.

Adult↗
PubMed1988

Endoscopic surveillance of patients following a curative resection for colorectal cancer.

From 1974 to 1985, 161 patients were followed by at least one colonoscopy following a polypectomy for an adenomatous polyp. These patients had had a previous curative resection performed for colorectal carcinoma. The median follow-up time after surgery was 54 months. A polyp within 65 cm from the anal verge or from a permanent colostomy was considered detectable by the flexible sigmoidoscope. Seventy-one patients (44%) were found to have adenomatous polyp(s) within 65 cm during the follow-up period. This incidence was influenced by the type of colorectal resection performed. In 36 of 41 patients (88%) undergoing a right hemicolectomy, the adenomatous polyp(s) was found within 65 cm from the anal verge. This was an incidence statistically and significantly higher than the incidence in patients undergoing other types of surgical resections. There were no differences in age, sex, or Dukes' stages according to the type of surgical resection performed. In summary, the present study demonstrates that there is a role for postoperative surveillance by the 65 cm flexible sigmoidoscope. This surveillance can be performed with great safety especially in patients following a right hemicolectomy; significantly more of these patients have adenomatous polyps within reach of the 65 cm flexible sigmoidoscope.

Adult↗
PubMed1988

Phase II trial of fludarabine phosphate (F-Ara-AMP) in patients with advanced breast cancer.

Eighteen patients with advanced breast cancer were entered into a phase II study of fludarabine phosphate. Fludarabine phosphate was given by continuous infusion for 5 days, at a starting dose of 20 mg/m2 per day for patients previously treated with two or more regimens and 25 mg/m2 per day for minimally treated patients with less than two prior regimens; therapy was repeated every 3-4 weeks. Of the 18 patients, 11 had undergone more than two prior regimens and 7 patients had undergone one prior regimen. One patient achieved a partial response (PR) for 22 months. Myelosuppression was the most common toxicity observed. Four patients developed mild nausea and vomiting and two developed a nonspecific dermatitis that resolved spontaneously. No renal, hepato-, or neurotoxicity was observed. Our study demonstrates that in heavily pretreated patients, fludarabine phosphate given on this schedule has minimal efficacy in treating advanced breast cancer. This drug might possibly have shown more activity in a previously nontreated patient population. However, patients with advanced breast cancer, who have not undergone previous treatment are not often encountered.

Adult↗
PubMed1988

Phase I clinical trial and human pharmacokinetics of 2,4-diamino-5-adamantyl-6-methyl pyrimidine ethane sulfonate (DAMP-ES): a lipid-soluble antifolate.

A phase I and pharmacokinetic study of a novel lipid-soluble antifolate, 2,4 diamino-5-adamantyl-6-methyl pyrimidine ethane sulfonate (DAMP-ES) has been carried out on two schedules: I--daily x5; II--24-h continuous infusion. In schedule I, doses of 10-90 mg/m2 per day were evaluated. Dose-limiting toxicity was hematologic, but nausea and vomiting, skin rash, diarrhea, anorexia, alopecia, mucositis, and neurotoxicity were also noted. In schedule II, doses of 192 and 240 mg/m2 were evaluated. Dose-limiting toxicity was neurotoxicity, but hematologic toxicity was also marked. Recommended starting doses for phase II studies are 75 mg/m2 per day for 5 days or 192 mg/m2 by continuous infusion for 24 h. Pharmacokinetic studies indicated a beta-phase plasma half-life of 12.4-24 h and a large and variable volume of distribution.

Adamantane↗
PubMed1988

Treatment of bowel obstruction after operation for colorectal carcinoma.

Operative therapy is beneficial in patients with bowel obstruction after operation for colorectal carcinoma. The cause of the bowel obstruction is more likely to be benign following colorectal carcinoma than following other malignancies. Also, the period of preoperative nasogastric suction can safely be extended to 3 to 4 days in these patients, since a resolution rate of 28 percent can be achieved with minimal risk of strangulation.

Adenocarcinoma↗
PubMed1988

Endoscopy versus double-contrast barium enema in the evaluation of patients with symptoms suggestive of colorectal carcinoma.

Two hundred seventy-six patients with positive findings on a stool guaiac test, hematochezia, a change in bowel habits, or a family history of colorectal carcinoma were referred to the colorectal clinic for further investigation. There were 105 men and 171 women. All patients underwent examination with the 65 cm flexible sigmoidoscope. Patients with no abnormalities on endoscopy underwent a double-contrast barium enema. If the barium enema revealed a polyp or other suspicious pathologic process, the patient was referred for colonoscopy. In 258 patients, findings of barium enema and flexible sigmoidoscopy were in agreement. The findings in 178 of these examinations were completely negative, and in the remaining 80 cases flexible endoscopy and barium enema revealed diverticulosis. In an additional 18 patients, negative findings on flexible sigmoidoscopy were followed by positive findings on barium enema. Thirteen of these 18 patients (72 percent) had negative findings on colonoscopies and therefore had false-positive findings on barium enema. In the remaining five patients (28 percent), an unsuspected colonic carcinoma or premalignant polyp was discovered on barium enema and documented by colonoscopy. Also, in four of these five patients, colonoscopy found additional polyps that were not seen on barium enema.

Barium Sulfate↗