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Biomedical subjects

J R Quesada

Publications and source records attributed to J R Quesada.

At least 19 recordsLinked to original sources
PubMed1990

Durable complete remissions after 2'-deoxycoformycin treatment in patients with hairy cell leukemia resistant to interferon alpha.

The efficacy of interferon alpha in treatment of hairy cell leukemia is well established. Our experience with low doses of 2'-deoxycoformycin, a competitive inhibitor of adenosine deaminase, showed that it was also effective against hairy cell leukemia in 10 of 11 patients studied whose disease was resistant to interferon alpha. Ten patients entered complete remission after five to 12 doses of 2'-deoxycoformycin (4 mg/m2 every other week), and one patient did not respond. No relapses were observed after median follow-up of 18.5 months; unmaintained complete remissions lasted from more than 10 to more than 30 months. The study demonstrated that 2'-deoxycoformycin induces a high rate of durable, unmaintained complete remissions in patients with hairy cell leukemia resistant to interferon alpha.

Adult↗
PubMed1989

Role of interferons in the therapy of metastatic renal cell carcinoma.

The prognosis of metastatic renal cell carcinoma continues to be dismal because of the lack of effective systemic therapies. To date, existing chemotherapy and hormonal therapy have produced disappointing results. However, alpha interferon and other biologic response modifiers have recently shown evidence of modest but consistent activity. This review summarizes results obtained with alpha interferon alone or in combination in the treatment of advanced renal carcinoma. It is hoped that future development of this field of cancer therapy may result in further improvements in the clinical management of these patients.

Antineoplastic Agents↗
PubMed1989

Biologic response modifiers in cancer therapy: a review.

Biologic response modifiers have expanded the therapeutic horizon of medical oncology. These agents, procedures, and interventions are likely to become an established fourth modality of cancer therapy in the near future. This is a succinct review of the most prominent areas of clinical research and the results obtained, including cytokines (interferons, interleukins), growth factors, monoclonal antibodies, adoptive immunotherapy, and tumor vaccines.

Humans↗
PubMed1988

Recombinant interferon gamma in hairy cell leukemia, multiple myeloma, and Waldenstrom's macroglobulinemia.

Fifteen patients with multiple myeloma, five with hairy cell leukemia, and five with Waldenstrom's macroglobulinemia were treated with recombinant interferon gamma (rINF-gamma) to determine the antitumor activity of this agent. The rIFN-gamma was administered by daily intramuscular injection at doses ranging from 0.125 to 0.5 mg/m2. No responses were observed in patients with multiple myeloma, although in one patient the disease has remained stable for over 16 months. Minimal improvement in some hematologic indexes were observed in three of five patients with hairy cell leukemia. One partial remission and one minor response were documented in two of the five patients with Waldenstrom's macroglobulinemia. In five patients, an increase in normal serum immunoglobulins was observed. These results suggest that there is only minimal activity of rIFN-gamma as a single agent in neoplasms of B-cell origin.

Adult↗
PubMed1988

Interferon therapy for metastatic renal cell carcinoma.

We have used multiple interferon protocols to treat 274 patients who had metastatic renal cell carcinoma. Leukocyte (alpha) interferon in 50 patients produced 3 complete responses (CR) and 10 partial responses (PR), a 26% response rate that was nearly matched among the next 89 patients treated with recombinant alpha interferon (2 CR, 17 PR, 21%). Other types and combinations of interferon, even when coupled with cytotoxic chemotherapy or other biologic agents, did not produce better results. Interferon has definite activity against renal cell carcinoma, but clinical experience has not yet defined the optimal type, dose, and treatment schedule.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Recombinant interferon alpha and gamma in combination as treatment for metastatic renal cell carcinoma.

Fifty-three patients with metastatic-renal cell carcinoma received treatment with combinations of recombinant alpha (rIFN-alpha-2a) and gamma (rIFN-gamma) interferons on three different treatment schedules. On treatment schedule A, 13 patients received i.m. rIFN-alpha-2a and rIFN-gamma simultaneously at a 1:1 ratio by dose units (2 X 10(6) U/m2), equivalent to a 1:10 ratio by protein weight. Results included severe constitutional symptoms in 62% of the patients and no partial remissions (PR) or complete remissions among 10 evaluable patients. On treatment schedule B, 25 patients received an i.m. injection of rIFN-alpha-2a and rIFN-gamma simultaneously at a 1:1 ratio by protein weight (2 X 10(6) U/m2 and 2 X 10(5) U/m2, respectively). This schedule was well tolerated, allowing a 25-50% increment in over 75% of the patients. Four patients (16%) achieved PR. On treatment schedule C, 15 patients received alternating weekly therapy: first rIFN-gamma (5 X 10(6) U/m2 daily for 7 days) followed by rIFN-alpha-2a (10 X 10(6) U/m2 daily for 7 days). One of 13 evaluable patients in treatment schedule C achieved an 80% tumor reduction and was rendered free of disease after the primary tumor was resected. Toxicity was similar in nature to that of rIFN-alpha-2a or rIFN-gamma separately. The toxicity of treatment schedule A suggested additive toxic effects. No distinct synergistic antitumor effect was observed.

Carcinoma, Renal Cell↗
PubMed1988

Phase I study of recombinant methionyl human consensus interferon (r-metHuIFN-Con1).

Consensus interferon (r-metHuIFN-Con1) is the product of a gene constructed to code for the most frequent amino acid residues known to occur in subspecies of alpha interferons. Twenty-one patients with advanced malignancy entered this phase I trial with dosing levels of 3, 7.5, 15, 30, and 45 mcg/m2/day given intramuscularly on days 1-5 and 8-10 of each 28-day cycle. The initial dose was randomly given by intravenous, intramuscular, or subcutaneous injection to facilitate pharmacokinetic studies. Vomiting and diarrhea were dose-limiting at 45 mcg/m2/day, preventing completion of therapy. Malaise, flu-like symptoms, nausea, and headache were frequent but tolerable at a dose of 30 mcg/m2/day. Patients were able to escalate to 45 mg/m2/day, suggesting tachyphlaxis to these toxicities. The initial distribution phase (T1/2 alpha) was 4.9-9.0 minutes with a T1/2 beta of 34-415 minutes in three patients for whom sequential values could be determined. r-MetHuIFN-Con1 was absorbed after both subcutaneous and intramuscular administration. 2'5'-Synthetase levels increased following treatment, although no consistent pattern was noted. One partial response was seen in a patient with gastrointestinal carcinoma. The recommended phase II starting dose of r-metHuIFN-Con1 is 30 mg/m2/day using this schedule by any of these routes of administration.

Adolescent↗
PubMed1987

Phase II studies of recombinant human interferon gamma in metastatic renal cell carcinoma.

Thirty-three patients with metastatic renal cell carcinoma were treated with recombinant human interferon gamma (rIFN gamma) in two sequential, nonrandomized phase II studies. Fifteen patients received rIFN gamma by daily i.m. injection in doses ranging from 0.25 to 1.0 mg/m2, and 18 patients received it by daily continuous i.v. infusion in doses ranging from 0.01 to 0.05 mg/m2. Partial remissions were achieved by one of 14 (7%) evaluable patients in the i.m. study and in one of 16 in the i.v. study (6%). The incidence of clinical toxicity was similar for both studies. Toxicity was severe in patients receiving rIFN gamma by the i.m. route at 1.0 mg/m2 and by the i.v. route at 0.05 mg/m2. Toxicity includes constitutional symptoms (fatigue, anorexia, weight loss), leukopenia, abnormalities in liver function tests, and hypertriglyceridemia. At the doses and schedules used, rIFN gamma had minimal therapeutic activity as a single agent in metastatic renal cell carcinoma.

Carcinoma, Renal Cell↗
PubMed1987

Alpha interferon production in patients with hairy cell leukemia: correlations with disease activity and remission status.

Nineteen patients with hairy cell leukemia (HCL) were studied for in vitro production of alpha interferon (IFN alpha). The patients were divided into three groups. The first group consisted of 8 patients with active disease, all of whom showed a severe deficiency in IFN alpha production (no detectable titers in 6 and less than 40 units/ml in the other 2) compared to normal controls (range: 320-10,500 units/ml; median: 2,560 units/ml). The second group consisted of 6 patients who achieved a partial remission (PR) after IFN alpha treatment. These 6 patients had normal numbers of mononuclear cells in the peripheral blood, but still had deficient IFN alpha production (titers of IFN alpha were below 10 units/ml in 5 of the 6 patients). The third group consisted of 5 patients in complete remission (3 after IFN alpha treatment and 1 each after splenectomy and infection). This group had IFN alpha production that was not significantly different from that of controls 35 years or older (median: 640 units/ml; range 60-2,560 units/ml for patients vs. 1,513 units/ml; range 320-5,120 units/ml for controls; p greater than 0.05). These data show a direct relationship between the activity of HCL and the capacity to produce IFN alpha in vitro. The data also suggest that deficiency of endogenous production of IFN alpha may be relevant to the induction and sustenance of remissions in this disease and that relapses may be partly associated with failure to fully restore endogenous IFN alpha production.

Adult↗
PubMed1987

Mid-term observations on the efficacy of alpha-interferon in hairy cell leukemia and status of the interferon system of patients in remission.

We summarize our experience using alpha-interferon (IFN-alpha) in the treatment of 93 patients with hairy cell leukemia. Both partially purified interferon and recombinant IFN-alpha produced over 85% response rate. Equal efficacy at 12 months of treatment was found for both types of IFN-alpha. However, continuation of treatment up to 24 months with partially purified IFN-alpha resulted in an increased number of complete remissions. An increase in the number of bone marrow's hairy cells occurred in 70-80% of the patients in whom a treatment was discontinued. Only 20% of the patients required reinitiation of treatment, and in all, reinduction of remission was readily obtained. Toxicity to IFN-alpha in patients with hairy cell leukemia was minimal. IFN-alpha production by patients in remission was studied. Only those patients in complete remission showed adequate IFN-alpha production. The role of endogenous IFN-alpha in the induction and sustenance of remission in hairy cell leukemia is discussed.

Humans↗
PubMed1986

Recombinant gamma interferon induces hypertriglyceridemia and inhibits post-heparin lipase activity in cancer patients.

Animals suffering from malignancy or chronic infection develop characteristic metabolic abnormalities, including a well-defined hypertriglyceridemic state. These abnormalities have been attributed to release of one or more mediators from activated macrophages. We report that cancer patients receiving RIFN-gamma, a potent macrophage activator, at doses of greater than or equal to 0.25 mg/m2/d i.m. show marked increases in triglyceride but not in cholesterol levels (pretreatment triglyceride level of 180 +/- 190 mg/dl [mean +/- SD] vs. a day-14 level of 370 +/- 242 mg/dl, n = 23, p less than 0.001 by the paired t test). This hypertriglyceridemia was characterized by an increase in very low-density lipoproteins and a decrease in plasma post-heparin lipase activity, consistent with defective triglyceride clearance (mean pretreatment lipase level of 2.1 mumol/ml/h vs. a day-14 level of 1.2 mumol/ml/h, n = 6, p = 0.02 by the paired t test). rIFN-gamma did not directly inhibit lipoprotein lipase enzymatic activity in vitro. Other possible mechanisms of action, such as suppression of lipase by an rIFN-gamma-induced mediator released from activated macrophages, or a direct effect of interferon on lipase biosynthesis, require further investigation. Our observations provide evidence that factors produced by the immune system can regulate lipid metabolism in man.

Adult↗
PubMed1986

Psoriasis and alpha-interferon.

Two patients with metastatic renal carcinoma who were treated with recombinant-DNA-derived alpha-interferon (rIFN alpha) had exacerbation of concomitant psoriasis, and another patient experienced onset of psoriasis during treatment with rIFN alpha. This suggests that interferons may participate in the pathophysiology of psoriasis.

Acute Disease↗
PubMed1986

Treatment of hairy cell leukemia with alpha interferons.

A review of clinical research with alpha interferons in the treatment of hairy cell leukemia is presented. The results of several studies have shown that alpha interferons effectively reduce leukemic infiltrates in the bone marrow and other organs, with attendant resolution of cytopenias. Alpha interferons have shown efficacy in the treatment of patients in all clinical stages of the disease, including those previously untreated, and may become the treatment choice for hairy cell leukemia. Hairy cell leukemia will also provide a useful human clinical model in which some of the fundamental mechanisms of interferon activity can be studied.

Dose-Response Relationship, Drug↗
PubMed1986

Serologic studies in hairy cell leukemia: high prevalence of Epstein-Barr and cytomegalovirus antibodies and absence of human T-cell lymphotrophic viruses antibodies.

Serum from 60 patients with hairy cell leukemia (HCL) were studied for the presence and the titers of antibodies to Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human T-cell lymphotrophic viruses (HTLV). Eighty-three percent of the patients were seropositive for EBV, with a (reciprocal) geometric mean titer (GMT) of 960. Seventy-eight percent of the patients had antibodies to CMV with a GMT of 435. All 21 patients tested for HTLV I and HTLV III were seronegative; only one patient showed detectable antibodies to HTLV II. The potential role of these infections in the physiopathology of HCL is discussed.

Antibodies, Viral↗