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Biomedical subjects

K Margolin

Publications and source records attributed to K Margolin.

66 records · Page 4Linked to original sources
PubMed1989

Refractory metastatic breast cancer: salvage therapy with fluorouracil and high-dose continuous infusion leucovorin calcium.

Sixty women with metastatic breast cancer refractory to at least one chemotherapeutic regimen were treated with fluorouracil (FUra) and high-dose continuous infusion folinic acid (leucovorin calcium). One complete remission lasting 8.7 months and nine partial remissions ranging in duration from 1.3 to 12.8 months were observed, for an objective response rate of 17% (95% confidence interval for response, 8% to 27%). Nine of the ten responding patients had metastatic disease that had objectively progressed on previous chemotherapy with a FUra-containing regimen. This program was well tolerated, with toxicities consisting mainly of stomatitis and granulocytopenia. These results suggest that augmentation of the reduced folate levels of metastatic breast carcinomas may enhance the effectiveness of the fluoropyrimidines in this disease.

Adenocarcinoma↗
PubMed1989

A phase II study of interleukin-2 and lymphokine-activated killer cells in patients with metastatic malignant melanoma.

Thirty-six patients with metastatic melanoma were entered into a study of the therapeutic efficacy of adoptive immunotherapy with high-dose interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells. Thirty-two patients who received all components of the therapy are evaluable for response, and all patients are evaluable for toxicity. Sites of disease included lung, liver, subcutaneous nodules, and intra-abdominal metastases. One complete response (CR) and five partial responses (PRs) resulted from treatment (19% response rate). The median response duration was 5 months, with the durable CR continuing at 31+ months and one durable PR continuing for 13 months. Sites of response included lung, liver, subcutaneous nodules, and lymph nodes. Response, response duration, or site of response did not correlate with the total dose of IL-2 administered, rebound lymphocytosis, or the number of LAK cells infused. Toxicity included hypotension, fluid retention with a "capillary leak syndrome" in most patients, and transient multiorgan dysfunction that resolved promptly after the completion of therapy. Adverse cardiac events occurred in 16% of patients, with one myocardial infarction leading to a death. This study confirms the activity of the initial IL-2/LAK cell regimen in metastatic melanoma reported by Rosenberg et al, supporting the concept of adoptive immunotherapy as an important new treatment approach for this disease.

Adult↗
PubMed1988

Apheresis techniques in lymphokine-activated killer cell production.

Adoptive transfer of autologous lymphokine-activated killer cells (LAK) in conjunction with recombinant interleukin-2 (rIL-2) has been reported to produce significant regression in metastatic disease in patients with advanced cancer. In an effort to confirm the results reported by the Surgery Branch of the National Cancer Institute, the same IL-2/LAK regimen was used in cancer patients at six extramural cancer centers. In this report we will review our experience with mononuclear cell removal from the blood of cancer patients using apheresis technology and extracorporeal handling of these cells to generate a selective, highly cytotoxic cell population.

Adult↗
PubMed1988

Etoposide (VP-16) and cytosine arabinoside in the treatment of relapsed small-cell lung cancer.

Seventeen patients with small-cell lung cancer refractory to combination chemotherapy were entered in a study of VP-16 and infusional Ara-C. All patients were evaluable for response and 14 were evaluable for toxicity (three deaths that occurred after the first cycle of therapy were due to progressive tumor, and toxicity could not be evaluated in these three patients). Ara-C was given as a continuous intravenous infusion of 45 mg/m2/day for 72 h; VP-16 was given as three daily intravenous bolus doses of 50 mg/m2 at hours 12, 36, and 50 of the 72-h Ara-C infusion. Because of excessive myelotoxicity in the first six patients, the last 11 patients began treatment at a lower dose of Ara-C, 25 mg/m2/day. Six of 17 patients had previously been exposed to VP-16 as part of their initial chemotherapy regimen. The 17 patients received 32 cycles of therapy. Myelotoxicity was severe, with nadir granulocyte counts less than 500/microliters or platelet counts less than 30,000/microliters in four treatment cycles (including two at the lower Ara-C dose). No patient experienced an objective response to this therapy. We conclude that the combination of VP-16 and infusional Ara-C at these doses is excessively toxic and does not warrant further investigation in refractory small-cell lung cancer.

Aged↗
PubMed1988

High-titer, high-thermal-amplitude cold autoagglutinin not associated with hemolytic anemia.

An example of an unusual cold autoagglutinin is reported. The antibody was monoclonal IgMKappa able to fix complement, and, in the presence of albumin, had both a high titer (greater than 4,096 at 4 degrees C) and a wide thermal range (4-37 degrees C). The patient was closely followed over a 3-year period with no evidence of hemolysis ever documented, despite a persistently positive direct antiglobulin test and the presence of the cold autoagglutinin. In contrast to previous reports regarding cold-agglutinin disease, this case demonstrates that in vivo hemolysis is not always associated with cold autoagglutinins that in vitro show a high thermal range in the presence of albumin.

Agglutinins↗
PubMed1987

Renal, volume, and hormonal changes during therapeutic administration of recombinant interleukin-2 in man.

Changes in blood pressure, renal function, and fluid balance were studied in 12 patients receiving intravenous recombinant interleukin-2 (IL-2) (100,000 units/kg every eight hours) over five days for treatment of metastatic melanoma and renal and colorectal cancers. The IL-2 regimen produced progressive hypotension, azotemia, and sodium avidity (fractional excretion of sodium = 0.20 +/- 0.07 percent) despite massive fluid administration (mean: 18.4 liter per five days) and weight gain (mean: 4.0 kg). Plasma renin activity rose. Hypoalbuminemia developed rapidly (3.6 +/- 0.1 g/dl to 2.2 +/- 0.1 g/dl, p less than 0.01) with widespread edema formation despite normal central venous pressures. Hematocrit did not change during the IL-2 period, consistent with a "capillary-leak." Hemodynamic and renal functional changes reversed after the IL-2 regimen was discontinued, but hypoalbuminemia and elevated urinary n-acetyl-glucosaminidase levels persisted after six days. These studies demonstrate widespread hemodynamic and vascular effects of IL-2 administration that limit its safe use and suggest a possible role for the lymphokine in mediating cardiovascular instability under other circumstances, such as endotoxic shock.

Adult↗
PubMed1987

Preliminary analysis of a randomized comparison of 5-fluorouracil versus 5-fluorouracil and high-dose continuous-infusion folinic acid in disseminated colorectal cancer.

In this study, 50 patients were randomly assigned to treatment with 5-fluorouracil (FUra) or FUra plus high-dose continuous-infusion folinic acid. Five of 27 evaluable patients in the FUra group versus 10 of 21 patients in the FUra plus folinic acid arm of the study had objective partial remissions, P = 0.02. Time to progression was 3.9 months for FUra and 8.0 months for FUra and folinic acid, P = 0.006; however, median survivals (11.9 versus 14.5 months) were not different in this crossover study. Toxicity in both treatment arms was mild, although patients receiving FUra plus folinic acid experienced significantly more stomatitis than patients treated with FUra alone. This study suggests that high-dose, continuous-infusion folinic acid, which produces a steady-state level of biologically active folates of 10 microM, significantly increases the therapeutic activity of FUra.

Adenocarcinoma↗
PubMed1986

High-dose continuous infusion folinic acid and bolus 5-fluorouracil in patients with advanced colorectal cancer: a phase II study.

Encouraging results have recently been reported for studies using folinic acid in combination with 5-fluorouracil (5-FU) in the treatment of patients with gastrointestinal (GI) malignancies. Thirty-six patients with advanced colorectal cancer with unequivocal evidence of progression while treated with fluoropyrimidines were treated with a six-day continuous infusion of 500 mg/m2/d of folinic acid initiated 24 hours before a five-day course of 5-FU administered as an intravenous (IV) bolus of 370 mg/m2/d. An initial dose of 250 mg/m2/d of 5-FU was used in patients previously treated with ionizing radiation and/or a nitrosourea. Three objective partial responses were observed. The overall median duration of survival was 8.1 months. Toxicity was acceptable and not in excess of that expected for 5-FU alone.

Adult↗
PubMedDate not supplied

Outpatient subcutaneous interleukin-2 and interferon-alpha for metastatic renal cell cancer: five-year follow-up of the Cytokine Working Group Study.

PURPOSE: A phase II trial of outpatient subcutaneous (SC) interleukin-2 (rIL-2) plus interferon-alpha (IFN-alpha 2B) was performed in patients with metastatic renal cell cancer. A 5-year follow-up of that Cytokine Working Group study is presented. PATIENTS AND METHODS: Forty-seven patients meeting eligibility criteria of previous Cytokine Working Group studies were treated on an outpatient basis with SC rIL-2 (Chiron, Emeryville, CA), 5 x 10(6) IU/m2/dose q 8 hr x 3, then daily, 5 days per week, and IFN-alpha 2B (Schering-Plough, Kenilworth, NJ), 5 x 10(6) IU/m2/dose three times weekly for 4 weeks. After a 2- to 4-week break, patients were scheduled to continue treatment for up to six cycles. RESULTS: There were two complete and six partial responders (17% response rate, 95% CI: 8%-31%). Median duration of response was 12 months (range 1-49+ months), with complete responses of 15 and 49+ months. Responding sites of disease included lung, nodes, soft tissue, bone, and liver. Dose and schedule were adjusted to control toxicity at grade 2/3 levels, with 50% requiring dosage alterations. Grade 2/3 toxicity included fatigue, nausea/vomiting, diarrhea, anorexia, fluid overload, rash, CNS, injection site pain, chest pain/palpitations (including atrial fibrillation requiring treatment, two patients), and hypotension. Grade 4 toxicity included dehydration (seven patients), vomiting (one patient), and irreversible renal failure with crescentic glomerulonephritis requiring dialysis (one patient). CONCLUSION: SC rIL-2 plus IFN-a2B is tolerated in the outpatient setting with frequent dose adjustments. The overall response rate of this regimen is similar to that seen with high-dose rIL-2 alone; however, the response duration appears to be shorter.

Adult↗