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Biomedical subjects

R A Figlin

Publications and source records attributed to R A Figlin.

At least 73 records · Page 4Linked to original sources
PubMed1989

Systemic administration of recombinant methionyl human interleukin-2 (Ala 125) to cancer patients: clinical results.

Nineteen evaluable patients with advanced malignancy were treated with recombinant methionyl human interleukin-2 (Ala 125), 5 days per week by intravenous bolus. Patients were entered in five groups at starting doses ranging from 0.05 to 2.56 x 10(6) U/m2. Doses were escalated weekly as tolerated toward a potential maximal dose of 11.6 x 10(6) U/m2. Maximal tolerated dose was 3.84 x 10(6) U/m2. Dose-limiting toxicity included fatigue, rigors, nausea/vomiting, fever, and diarrhea. Other toxicities included hyperesthesias, arthralgias/myalgias, rash, fluid retention, balanitis, and mild confusion. Leukocytosis, including granulocytosis, eosinophilia, and mild lymphocytosis, was observed, as was rare mild thrombocytopenia. No partial or complete response occurred. T1/2 alpha averaged 13.4 min, with interleukin-2 detectable 2 h after doses of greater than or equal to 2.56 x 10(6) U/m2. Three patients developed anti-IL-2 antibodies without demonstrable clinical significance.

Body Weight↗
PubMed1988

Intracranial recurrence of carcinoma after complete surgical resection of stage I, II, and III non-small-cell lung cancer.

We retrospectively analyzed the risk of intracranial recurrence of cancer in 1532 patients who were surgically treated between 1977 and 1986 for Stage I, II, or III non-small-cell lung cancer, after rigorous surgical and pathological staging. This analysis was undertaken as a background for a possible randomized clinical trial of prophylactic cranial irradiation in such patients. One hundred four patients (6.8 percent) had documented first recurrences involving the brain, including 98 patients (6.4 percent) in whom the brain was the sole site of first recurrence. Sixty patients (3.9 percent) had only intracranial involvement at the time of death. Prognostic variables that had a significant effect on the time to recurrence in the brain were histologic features of the carcinoma (patients with nonsquamous-cell cancers were more at risk than those with squamous-cell cancer), the T1N1/T2N0 and T2N1 staging subsets (T1, tumor less than or equal to 3 cm in diameter; T2, tumor greater than 3 cm; N0, no regional lymph-node metastasis; N1, ipsilateral hilar-lymph-node metastasis), and initial weight loss of more than 10 percent. We conclude that prophylactic cranial irradiation would at best benefit only a very small subset of these patients. We believe, therefore, that neither prophylactic cranial irradiation nor a randomized trial is indicated in patients with non-small-cell lung cancer who have undergone complete resection.

Brain Neoplasms↗
PubMed1988

Estimating the quality of life in a clinical trial of patients with metastatic lung cancer using the Karnofsky performance status and the Functional Living Index--Cancer.

Serial assessments of Karnofsky performance status (KPS) and of the Functional Living Index--Cancer (FLIC) have been used to estimate the quality of life (QOL) of patients in a prospective, randomized trial of supportive care versus supportive care given with combination chemotherapy to patients with metastatic non-small cell lung cancer. There was a good correlation between KPS and FLIC scores at study entry, thus confirming results originally reported using the FLIC. However, a number of unexpected problems were encountered in data collection and quality control with this QOL assessment instrument. This made it impossible to look for differences in treatment effect on QOL in this clinical trial. It is believed that QOL assessment should be an integral part of cancer clinical trials; however, investigators must acknowledge the difficulties in collecting this type of data. The development of new instruments and the refinement of old ones will facilitate the collection of data for this important aspect of clinical trials research.

Aged↗
PubMed1988

Selective decrease in Leu8-negative T cell subpopulations following treatment with recombinant interferon-alpha 2a (rIFN-alpha 2a).

The effects of in vivo treatment with recombinant human IFN-alpha 2a (rIFN-alpha 2a) on the distribution of T cell subpopulations were examined in 21 patients with renal cell adenocarcinoma, using two-color flow cytometry with anti-Leu8 in combination with anti-Leu2 and anti-Leu3. Other parameters indicative of immune status, such as the number and percentage of total (CD3) T cells, in vitro proliferation to mitogen, and spontaneous immunoglobulin secretion, were also measured, prior to the initiation of treatment with rIFN-alpha 2a, and during treatment. Total T cell number decreased after treatment with rIFN-alpha 2a, to a low of 54% of mean pretreatment values after 4 weeks. The CD4/CD8 ratio did not change appreciably following treatment with rIFN-alpha 2a. However, the number of Leu8-negative T cells, within both the CD4 and the CD8 T cell populations, decreased more than the number of Leu8-positive T cells. An increase in spontaneous immunoglobulin-secreting cells followed treatment with rIFN-alpha 2a.

Antibodies, Monoclonal↗
PubMed1988

Recombinant interferon alfa-2a in metastatic renal cell carcinoma: assessment of antitumor activity and anti-interferon antibody formation.

Twenty-one patients with advanced, measurable, renal cell carcinoma (RCC) were administered recombinant interferon alfa-2a (rIFN-alpha 2a) (Roferon-A; Roche Laboratories, Nutley, NJ) intramuscularly beginning at 3 x 10(6) units and escalating to 36 x 10(6) units, 5 d/wk for a total induction period of 14 weeks. rIFN-alpha 2a antibody production was measured using an enzyme immunoassay (EIA). Those sera found to be positive for presence of antibody by the EIA were tested for the presence of neutralizing antibodies (NA) by an antiviral neutralization bioassay (ANB). All patients were evaluable for toxicity, and 19 were evaluable for response and for incidence of antibody formation. Five patients (26%; 95% confidence interval, 6% to 46%) had complete responses (CR) or partial responses (PR) with a median duration of 283 days. An additional ten patients (53%) had minor tumor regressions with a median duration of 86 days. Fifty-one percent of evaluable patients are alive at 18.6 months. Antibodies to rIFN-alpha 2a as measured by the EIA, were detected in 12 (63%) patients. NA were measured in the serum of six (50%) of those EIA-positive patients. Overall, six of 19 patients (32%) developed NA. Median time to the development of antibody as measured by EIA or NA was 8 and 14 weeks, respectively. Median NA titer was 1,200 IFN neutralizing U/mL. NA-positive and -negative patients had a median duration of response of 13.7 v 9.9 months, and survival of greater than 21.3 v 18.3 months, respectively. Clinical toxicity was mild and not therapeutically limiting. Autoantibody production (ANA, rheumatoid factor [RF], Coombs' direct/indirect) occurred in both NA-positive and -negative patients. The clinical significance of the antibodies to rIFN-alpha 2a and the associated autoantibody formation remain unclear; however, presence of antibody was not associated with adverse clinical sequelae.

Adult↗
PubMed1988

Anti-interferon antibodies: a perspective.

Clinical trials with both recombinant and natural alpha and beta interferons have shown that patients may develop neutralizing antibodies to these proteins. Differences in trial design and in the sensitivity of the assays used to measure antibodies have made it difficult to evaluate the factors that influence antibody formation and the effects of these antibodies on clinical results. In several trials, neutralizing antibodies to the recombinant alpha interferons were temporally associated with decreased response to therapy in a few patients, particularly those with B-cell disorders; however, these antibodies had no effect on clinical outcome in other trials. Long periods of treatment and/or higher doses of interferons, both of which contribute to increased cumulative doses of protein, generally are associated with a higher incidence of antibody formation. The source of protein, the route of administration, and the underlying disease also may influence the development of antibodies. Further studies must assess the role of each of these factors carefully to determine which patients are most likely to develop neutralizing antibodies so that clinical effects can be quantitated and appropriate management can be recommended.

Antibody Formation↗
PubMed1988

Biotherapy with interferon--1988.

In the past decade, interferon, the first of a new class of biologic response modifiers, has undergone extensive Phase I and II clinical evaluation in a broad spectrum of cancers, including hematologic malignancies, lymphomas, and solid tumors. Interferon has been found to have important clinical activity in hairy-cell leukemia, low-grade non-Hodgkin's lymphoma, cutaneous T cell lymphoma, chronic myelogenous leukemia, previously untreated multiple myeloma, acquired immunodeficiency syndrome-related Kaposi's sarcoma, malignant carcinoid tumors, intravesically treated superficial bladder cancer, intraperitoneally treated ovarian carcinoma, renal cell carcinoma, and malignant melanoma. Recombinant DNA technology has produced molecules such as the interferons, which are antigenic and can induce antibody formation as part of a generalized immune response. The frequency of antibody occurrence, the magnitude of the antibody response, and the type of antibody induced by the interferons is thought to be related to several factors. These include the specific type of neoplasm for which interferon was administered; the specie of interferon administered; the dose, route, schedule, and duration of interferon administered; and the assay method and sampling time used to determine the antibody titer. Opinions and clinical observations about how these antibodies affect the clinical course of a disease vary among investigators. Some studies have demonstrated that antibody formation is associated with an abrogation of the clinical response, while others have not found any effects on the clinical course of a disease due to antibody presence.

Antibody Formation↗
PubMed1987

Application of a new method for detecting the phenotype of target binding cells.

A new method was developed for detecting the phenotype of target binding cells (TBC) in a single-cell assay system. This methodology was evaluated during a clinical trial of recombinant interferon alfa-2a (rIFN alfa-2a) for the treatment of 10 metastatic renal cell carcinoma patients. Total TBC with K562 targets, HNK-1+ TBC, and HLA-DR+ TBC were quantitated during rIFN alfa-2a therapy. A significantly increased proportion of lymphocytes bound to target cells on day 9 of therapy bore the HNK-1 marker. This proportion subsequently declined to pretreatment levels. Total TBC paralleled the rise and fall in HNK-1+ TBC. HLA-DR+ TBC binding to targets remained constant and low throughout therapy. These findings suggest that rIFN alfa-2a early in therapy (day 9) caused the recruitment of additional HNK-1+ cells into binders. However, with continued therapy, this proportion reverts to pretreatment levels. The results of this clinical trial served to illustrate the ability of the modified single-cell assay system to detect TBC phenotype.

Antibodies, Monoclonal↗
PubMed1987

Phase II study of betaseron (beta ser17-interferon) as treatment of advanced malignant melanoma.

Betaseron (beta ser17-interferon) was administered to 19 patients (17 evaluable) with advanced melanoma by two schedules. Patients received either 30 X 10(6) units (mU) by intravenous bolus 5 days a week for 2 weeks followed by 2 weeks rest, or 30 mU daily for 5 days in week 1, 60 mU daily for 5 days in week 2, then twice-weekly doses escalating from 90 to 270 mU. Toxicity commonly included malaise, fatigue, fever, and weight loss. Mild hematologic, gastrointestinal, and hepatic toxicity were also seen, as well as an episode of atrial fibrillation in a patient with mitral valvular disease. No responses to therapy occurred.

Adult↗
PubMed1985

Treatment of renal cell carcinoma with alpha (human leukocyte) interferon and vinblastine in combination: a phase I-II trial.

Twenty-four patients with measurable metastatic renal cell carcinoma were treated in a phase I-II trial with alpha (human leukocyte) interferon (alpha IFN) and vinblastine (VBL) in combination. Patients received 3 X 10(6) IU/day of alpha IFN im 5 days/week and VBL iv weekly (at a starting dose of 0.15 mg/kg), with doses modified for toxicity. All patients were evaluable for toxicity; 23 patients were evaluable for response. An objective response rate of 13% was observed (three partial responses). An additional 22% of patients had minimal responses (five patients). The occurrence of nausea, vomiting, thrombocytopenia, hepatic dysfunction, and fever was comparable to that seen in previous studies of alpha IFN alone. Granulocytopenia, neurotoxicity, and malaise, however, occurred with increased frequency and severity. alpha IFN and VBL administered in combination in this dose schedule demonstrated activity similar to but toxicity greater than that seen in previous trials of alpha IFN alone.

Adult↗
PubMed1985

Phase II trial of alpha-lymphoblastoid interferon given weekly as treatment of advanced breast cancer.

Eighteen patients with advanced breast cancer refractory to first-line chemotherapy and hormonal therapy (or estrogen receptor-negative) were treated with human alpha-lymphoblastoid interferon (Wellferon) in a dose of 30 X 10(6) U/m2 im weekly. None of 15 patients receiving three or more doses achieved a partial or complete response. Toxicity was substantial and included fatigue, malaise, fever, hematologic suppression, nausea/vomiting, and diarrhea.

Adult↗
PubMed1983

Phase II trial of alpha (human leukocyte) interferon administered daily in adenocarcinoma of the colon/rectum.

Nineteen patients with metastatic adenocarcinoma of the colon or rectum were treated with alpha (human leukocyte) interferon (alpha IFN). Patients received 3 X 10(6) IU/day of interferon im 5 days/week. Eighteen patients are evaluable for response and toxicity. There were no objective responses. All evaluable patients demonstrated progression of disease during therapy. Toxicity consisted primarily of mild granulocytopenia, thrombocytopenia, fatigue, weakness, and fever. This trial demonstrates that while alpha IFN can be administered safely as scheduled, this regimen has no activity against adenocarcinoma of the colon/rectum.

Adenocarcinoma↗
PubMedDate not supplied

Current management of renal cell carcinoma.

Renal cell carcinoma is the most common malignancy of the kidney and accounts for about three percent of all adult neoplasms. This article reviews the clinical presentation, diagnosis, staging, and treatment of this disease.

Adult↗
PubMedDate not supplied

Treatment of metastatic renal cell carcinoma with high-dose bolus interleukin-2 in a non-intensive care unit: an analysis of 124 consecutively treated patients.

PURPOSE: In prior studies of high-dose interleukin-2 (IL-2) therapy in the treatment of metastatic renal cell carcinoma, the majority of patients were asymptomatic (65% of patients had Eastern Cooperative Oncology Group [ECOG] scores of 0 [no cancer-related symptoms]). These studies demonstrated that an ECOG score of 0 predicted an objective antitumor response to IL-2 (P = 0.03). The current study determined the response frequency to high-dose IL-2 therapy in a primarily symptomatic patient population (ECOG = 1 [presence of cancer-related symptoms] for 57.3% of patients). The IL-2 therapy was administered in a non-intensive care unit (non-ICU). PATIENTS AND METHODS: In this single-institution study of high-dose IL-2 therapy, 124 patients were consecutively enrolled and treated with the drug. Antitumor responses and safety were assessed by radiographic methods and the occurrence of grade 3 and 4 adverse events, respectively. RESULTS: The frequency of objective responses was 14.5% (18 of 124 patients). Seven patients (5.6%) and 11 patients (8.9%) experienced complete responses (CRs) and partial responses (PRs), respectively. Two of 7 patients (28.6%) with CR and 7 of 11 patients (63.6%) with PR had ECOG scores of 1. The median response duration is 18 months for all responders (CR plus PR). The median survival duration is 15 months for all patients. It was not possible to estimate the median survival duration for all responders because the majority of responding patients were alive at close of study. All patients with CR and 5 patients with PR were alive at close of study. The frequency of grade 3 and 4 adverse events was comparable to or less than published data and IL-2 was safely administered in a non-intensive care unit. CONCLUSION: The frequency of objective antitumor responses in patients with ECOG scores of 1 suggests that high-dose IL-2 therapy may have comparable effectiveness in symptomatic and asymptomatic patients. High-dose IL-2 can be administered in a non-ICU setting with acceptable toxicity and the chance of clinical benefit.

Adult↗
PubMedDate not supplied

Oral dolasetron mesylate in patients receiving moderately emetogenic platinum-containing chemotherapy. Oral Dolasetron Dose Response Study Group.

PURPOSE: This double-blind, dose-response study was conducted to assess the safety and efficacy of four oral doses of dolasetron mesylate for preventing acute emesis in cancer patients receiving their first course of moderately emetogenic platinum-containing chemotherapy. PATIENTS AND METHODS: Patients were randomized to receive a single oral dose of 25, 50, 100, or 200 mg dolasetron 30 minutes before receiving IV carboplatin (275-400 mg/m2)- or cisplatin (20-50 mg/m2)-containing chemotherapy, then monitored for nausea and vomiting for 24 hours. RESULTS: Three hundred seven cancer patients from 32 sites completed the study. There was a statistically significant dose response across the four doses for complete response (no emetic episodes or rescue medication): 44.7%, 71.3%, 73.2%, and 82.5% for the 25, 50, 100, or 200 mg doses of dolasetron, respectively. Patients' nausea severity and patient satisfaction visual analogue scale scores also showed a statistically significant trend with dose. All doses of dolasetron were well tolerated. The most common adverse events were headache (17.6%) and dizziness (2.0%). DISCUSSION: This study demonstrates the safety and antiemetic efficacy of oral dolasetron mesylate in patients receiving moderately emetogenic platinum-containing chemotherapy with the highest antiemetic activity observed at 200 mg.

Administration, Oral↗