[Secondary leukemias after etoposide chemotherapy].
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Carcinoma, Bronchogenic↗
Biomedical subjects
H Poliwoda
Publications and source records attributed to H Poliwoda.
Modulation of cytostatic drugs by nifedipine in two heterotransplanted human testicular-cancer cell lines differing in their sensitivity to standard agents.
Drug resistance is an important clinical problem in testicular cancer patients with relapsed or refractory disease after first-line chemotherapy. Here we report that the relative reduction in tumour volume in nude mice heterotransplanted with either H 12.1 or H 23.1 human testicular cancer cell lines was significantly increased by addition of the calcium antagonist nifedipine to the maximum tolerated dose (MTD) of cisplatin (DDP). The mean reduction in relative tumour volume at day 30 (rVR) reached statistical significance for both cell lines following combination therapy of DDP with nifedipine compared to DDP alone (55 +/- 7% versus 12 +/- 4% for H 23.1 and 60 +/- 9% vs. DDP with nifedipine has also been confirmed in H 12.1 cells in vitro. However, in vivo, this combination was associated with a concordant increase in therapeutic toxicity. In contrast, no improvement in in vivo anti-tumour activity was obtained by combining similar dose-schedules of nifedipine with the MTD of epirubicin, or with MTDs of vinblastine or etoposide. These results are in agreement with our immunohistochemical finding that H 12.1 and H 23.1 do not over-express the Pgp 170 glycoprotein which mediates the multiple drug resistance (MDR) phenotype and involves both anthracyclines and vinblastine, but not DDP. We conclude that another Pgp-MDR modulator, nifedipine, is able to increase the anti-tumour activity of DDP in vivo and in vitro via a specific but as yet unknown mechanism, which is most likely not MDR-related. However, the increased anti-tumour activity is, in vivo, associated with a considerable increase in overall toxicity. Further studies are necessary to decrease therapeutic toxicity, before clinically relevant models for modifiers of DDP-resistance could possibly be applied to patients.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Cytokine-based biotherapy of gastrointestinal tumors.
Over the past 20 years the administration of cytokines has emerged as an important fourth modality for the treatment of human cancer. Advances in the field of therapy of gastrointestinal tumors have become a major focus of current research, given the lack of progress of conventional antineoplastic therapy in most of these tumors. Among the heterogeneous group of gastrointestinal malignancies, novel therapeutic strategies have been employed for each individual tumor type, and cytokines (interferon-alpha) have gained an established role in the treatment of advanced carcinoid tumors. Although our understanding of the mechanisms of biological response modification is still limited, further improvement in the management of gastrointestinal malignancies can be expected from multimodality therapy regimens employing cytokines in combination with other biological response modifiers, chemotherapeutic agents, active-specific immunotherapy, and immunotoxin- and radionuclide-conjugated monoclonal antibodies. A wide range of clinical and preclinical studies have been conducted in colorectal carcinoma; however, potential therapeutic benefit of cytokine-based biotherapy has not been fully defined. Therefore, largescale, i.e., multicenter, studies are required to quantify the potential therapeutic effects of cytokines in gastrointestinal tumors.
Clinical Trials as Topic↗
Long-term gonadal toxicity after therapy for Hodgkin's and non-Hodgkin's lymphoma.
With the increasing cure rate of patients treated for Hodgkin's and non-Hodgkin's lymphoma, the evaluation of late effects on gonadal function remains an important issue. The gonadal function of relapse-free long-term survivors with high-grade non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) were studied; 24 of 119 patients with NHL treated between 1980 and 1990 and 66 of 364 patients with HD treated between 1975 and 1990 at Hannover University Medical School, who were younger than 45 years of age and in complete remission at the time of evaluation for at least 24 months after completion of therapy, were included into the analysis. Of 24 patients with NHL, 1/10 women (10%) and only 3/14 men (21%) showed signs of gonadal dysfunction. Three of these four patients had been treated with combined modality therapy followed by maintenance COP chemotherapy, resulting in high cumulative doses of cyclophosphamide (range: 12-43 g). In comparison, 13/26 (50%) women with HD suffered from premature ovarian failure, and 26/40 (65%) men showed signs of gonadal dysfunction with significant FSH elevations. No significant difference in the incidence of gonadal toxicity existed in patients treated with combined modality who received irradiation to either supra- or infradiaphragmatic radiation fields in combination with chemotherapy (70% versus 62%). A comparison of the chemotherapy regimens used in patients with NHL or HD shows that patients from both groups had received comparable median cumulative doses of cyclophosphamide, vincristine, and adriamycin, but only patients with HD had additionally received a median cumulative dose of 13.3 g of procarbazine per patient. A tendency towards a higher incidence of gonadal toxicity with higher cumulative doses of procarbazine received was found in patients with HD. The frequency of gonadal dysfunctions is markedly lower in patients treated for non-Hodgkin's lymphoma than in patients treated for Hodgkin's disease, approximately half of whom will be affected by long-term gonadal toxicity. Although the use of more intensive radiotherapy in patients with HD compared with NHL patients makes the evaluation of the influence of radiotherapy on gonadal toxicity more difficult, the current retrospective analysis raises the concern that, in addition to infradiaphragmatic radiotherapy, the use of procarbazine in regimens for the treatment of HD, like COPP or MOPP, may be a possible explanation for the differences in gonadal toxicity observed between patients with HD and those with NHL. Regimens including procarbazine should be avoided in patients wanting to preserve fertility since alternative chemotherapies with at least equal efficacy are available.
Adolescent↗
Soluble interleukin 2 receptors abrogate IL-2 induced activation of peripheral mononuclear cells.
Soluble interleukin 2 receptors (sIL-2R) exert a potential role in immunoregulation. We investigated the in vitro effects of sIL-2R on several interleukin 2 (IL-2)-dependent cellular events. Cytotoxicity of human rIL-2-stimulated PBMC against K562 and Daudi was correlated inversely to the concentration of sIL-2R in the culture medium during rIL-2 stimulation. sIL-2R concentrations higher than 4.0 pM produced a significant loss of cytotoxicity (P < 0.01). The effect of different sIL-2R concentrations added to cultured human PBMC on secondary sIL-2R production was tested by ELISA. Secondary sIL-2R production was abrogated by high initial sIL-2R dosages whereas low initial dosages were followed by a continuing production of secondary sIL-2R after five days of culture. Proliferation of the IL-2-dependent mouse cell line CTLL-2-was suppressed by sIL-2R added to the culture medium in a dose-dependent way. The neutralizing capacity of sIL-2R strongly depended on the initial number of CTLL set in per proliferation assay. In contrast, variation of rIL-2-concentration had no significant effect on reduction of proliferation by sIL-2R. Furthermore, preincubation of sIL-2R with rIL-2 did not enhance growth suppression. These last findings indicate that there is at least no functional interaction between sIL-2R and free IL-2, whereas an interaction of sIL-2R with the membrane-bound receptor for IL-2 seems possible.
Animals↗
Induction of cytokines and cytotoxicity against tumor cells by Newcastle disease virus.
The use of NDV as biological adjuvant in vaccines against human cancer is still actual in several clinical treatment protocols. In this study, we have investigated in vitro-effects of Newcastle disease virus (NDV) strain 73-T on isolated mononuclear blood cells and cultured tumor cells. Cellular cytotoxicity of PBMC freshly isolated from healthy donors against tumor cells was enhanced significantly (p < 0.01) after coincubation of NDV with effector cells. NDV failed to enhance cytotoxicity of effector cells when PBMC were stimulated three days with 500 IU recombinant interleukin-2 (rIL-2) per ml prior to coincubation with the virus. No significant enhancement of cellular lysis was seen when only target cells were coincubated with NDV. As shown by depletion of various lymphocyte subsets, NK cells were the predominant mediator of lysis. Enhancement of cytotoxicity correlated with the induction of interferon-alpha (IFN-alpha) in PBMC by NDV. NDV also induced high amounts of tumor necrosis factor-alpha (TNF-alpha) in PBMC. Induction of interferon-gamma (IFN-gamma) was weak. A direct cytopathic effect (CPE) of NDV on different target cells was detected by colorimetric measurement of metabolic cell activity. The human tumor cell lines A-498, A-704, Caki-1, Caki-2, and K-562 and the fibroblast line MRC-5 showed progressive cellular destruction 48 h after infection with NDV, whereas PBMC and Daudi cells remained unaffected during the observation period. The nontransformed monkey kidney cell line CV-1 and the transformed monkey kidney cell line COS-1 were both lysed by NDV with marginal difference in time course of CPE. Our results indicate a reasonable potential of pleiotropic modifications of the immune response against tumors by NDV.
Adjuvants, Immunologic↗
Human antibodies to recombinant interleukin-2 in patients with hypernephroma.
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Antibodies↗
Hepatic and serologic toxicity of systemic interleukin-2 and/or interferon-alpha. Evidence of a risk-benefit advantage of subcutaneous therapy.
A total of 107 cancer patients were treated with 148 cycles of subcutaneous (SC) immunotherapy employing interleukin-2 (rIL-2) and/or interferon-alpha (rIFN-alpha). The systemic toxicities of SC cytokine therapy were retrospectively evaluated with regard to hepatic and metabolic adverse effects, and compared to adverse effects previously reported upon high- or intermediate-dose intravenous (IV) rIL-2 therapy. Our study cohorts consisted of 15 patients who received SC rIL-2 at doses of 4.8-14.4 million IU/m2/day on 5 days per week for a total of 8 weeks, 20 patients who received rIFN-alpha 2b at 3.0-6.0 million U/m2/day thrice weekly for a total of 6 weeks, and 72 patients who were given SC rIFN-alpha 2b at 6.0 million U/m2/day thrice weekly plus SC rIL-2 at 14.4-18.0 million IU/m2/day on days 1 and 2, followed by 4.8 million IU/m2/day, 5 days per week for 6 consecutive weeks. These treatment regimens were well tolerated in the outpatient setting; no toxic deaths occurred, and none of the patients developed life-threatening toxicity. Upon SC rIL-2/rIFN-alpha combination therapy, we observed mild decreases in plasma protein and albumin levels (mean nadir +/- standard deviation, 67 +/- 5 g/L and 38.8 +/- 3.9 g/L, respectively), minor albeit significant increases in serum total bilirubin levels (mean peak +/- standard deviation, 7.8 +/- 3.1 mumol/L), serum aspartate aminotransferase (25.9 +/- 9.9 U/L), alanine aminotransferase (42.0 +/- 45.9 U/L), alkaline phosphatase (301 +/- 255 U/L), lactate dehydrogenase (230 +/- 64 U/L), gamma-glutamyl transpeptidase (147 +/- 141 U/L) activities and triacylglyceride (2.6 +/- 0.9 mmol/L) concentrations. Cholinesterase activities (mean nadir +/- standard deviation, 42.6 +/- 13.7 kU/L), and serum cholesterol levels (4.4 +/- 0.9 mmol/L) decreased upon SC rIL-2/rIFN-alpha combination therapy. These mild clinical side effects and laboratory changes were in marked contrast to a multitude of dose-limiting and life-threatening adverse reactions described upon IV rIL-2 therapy. It is concluded that low-to intermediate-dose SC rIL-2/rIFN-alpha combination therapy as used in this study, can be given in the outpatient setting with good practicability and excellent safety.
Adult↗
Cardiotoxicity of 5-fluorouracil in combination with folinic acid in patients with gastrointestinal cancer.
BACKGROUND: Cardiotoxicity related to the widely used cytotoxic compound 5-fluorouracil (5-FU) is rare compared with the frequency observed with the use of anthracyclines. More effective protocols incorporating active biomodulatory compounds like folinic acid (FA) or combination chemotherapy change type and severity of toxicity as well. The objective of the current study was to assess cardiotoxicity of the combination 5-FU and folinic acid. METHODS: The authors' multicenter experience with 390 patients treated for advanced gastrointestinal cancer with intermediate-dose folinic acid and 5-FU was reviewed. RESULTS: The overall risk of cardiotoxicity was 3%, which is not significantly higher than that reported with 5-FU alone. Eight of 53 patients with a history of cardiac disease reported cardiac symptoms (15.1%), compared with 5 of 337 patients (1.5%) with a no history of cardiac disease. Median time to symptoms was 3 days (range, 2-6). Nine patients had symptoms resembling myocardial ischemia, one patient died due to assumed myocardial infarction related closely to fluorouracil treatment, four patients had supraventricular arrhythmia, and one patient had congestive heart failure. A history of cardiac disease was the only risk factor associated with cardiotoxicity. Relapses were frequent on reinstitution of therapy despite cardiac symptoms in the preceding cycle. Therapeutically or prophylactically administered nitrates had no significant effect. CONCLUSION: Physicians should be aware of the cardiotoxic properties of active fluorouracil treatment. The combination of 5-FU and leucovorin does not differ from single-agent therapy in frequency or type of cardiotoxicity. Close monitoring of patients is mandatory, especially for those patients at high risk for cardiac side effects. Treatment should be discontinued if coronary symptoms develop, because neither effective treatment nor prophylaxis exists for such symptoms.
Adult↗
Single-agent carboplatinum for advanced seminoma. A phase II study.
BACKGROUND: To reduce the side effects of cisplatin-based combination chemotherapy, the activity of carboplatinum was evaluated in patients with advanced seminoma. METHODS: Forty-two evaluable patients with advanced seminoma (defined as abdominal lymph nodes > 5 cm or supradiaphragmatic or visceral disease) received single-agent carboplatinum at a dose of 400 mg/m2 intravenously every 4 weeks for a maximum of six cycles. The median follow-up was 31 months (18-67 months). RESULTS: Thirty patients (71%) achieved a complete remission (CR; 21 chemotherapy alone, 9 with additional surgery), 8 patients (19%) a partial remission (PR), and 4 patients had disease progression (10%). Patients with metastases confined to the lymph nodes had a significantly higher remission rate than patients with visceral metastases (97% versus 50%; P < 0.002). Elevation of lactate dehydrogenase or human chorionic gonadotropin before radiation therapy had no influence on response rate. Eight patients have relapsed (five from CR and three from PR). All 12 patients failing carboplatinum therapy received cisplatin-based combination regimens. Ten patients achieved a stable favorable response (eight CR, two PR), whereas two patients died of their disease. Currently, 30 patients (71%) are continuously free from progression (25 CR, 5 PR), and 40 patients are alive (survival 93%). Toxicity was mild with no neurotoxicity or nephrotoxicity. CONCLUSIONS: The use of up-front carboplatinum therapy appears not to compromise the ultimate curability of patients with advanced seminoma. Randomized trials, however, will have to demonstrate the effectiveness of carboplatinum with regard to survival, and help to identify prognostic subgroups of patients who require up-front cisplatinum-based combination chemotherapy.
Adult↗
Neuropsychiatric symptoms during treatment with interleukin-2 and interferon-alpha.
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Cognition Disorders↗
Analysis of a non-ras 21-kDa protein in patients with metastatic testicular germ-cell tumors.
A novel protein of 21 kDa (p21) has been detected in the sera of patients with different solid tumors. The serum levels of this p21 protein were measured in seven patients with metastatic testicular germ-cell tumors before and after chemotherapy using an enzyme-linked immunosorbent assay. In five out of six patients who responded to chemotherapy a concomitant decrease of p21 serum levels was found. The decrease of p21 was in accordance with the decline of the established tumor markers alpha-fetoprotein, human chorionic gonadotropin beta-subunit and lactate dehydrogenase in three patients with non-seminomatous tumors and with the decline of lactate dehydrogenase and the clinical response in two patients with seminoma. In one patient the predicted decline of p21 did not occur despite the patient's clinical response to chemotherapy. In the seventh patient, who relapsed directly after chemotherapy, no decline of either p21 levels or tumor markers was observed. The absolute amount of the p21 protein prior to chemotherapy did not correlate with the patients' tumor burden. Elevated levels of p21 were found in patients with seminomatous and non-seminomatous germ-cell tumors. Since seminoma patients do not secrete tumor markers like alpha-fetoprotein or human chorionic gonadotropin beta, the determination of p21 levels may help to evaluate the efficacy of chemotherapy in patients with seminomatous as well as in patients with marker-negative non-seminomatous germ-cell tumors. The biological role of p21 and its clinical significance will be further investigated.
Adult↗
Comparison of 5 vs 10 micrograms/kg per day of GM-CSF following dose-intensified chemotherapy with cisplatin, etoposide, and ifosfamide in patients with advanced testicular cancer.
Despite the increasing use of granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of chemotherapy-induced neutropenia, few studies have focused on the activity and toxicity of the different clinically used dosages of GM-CSF. Forty-four patients with "poor-risk" (advanced disease, according to the Indiana University classification) testicular cancer were treated with a dose-intensified chemotherapy regimen of cisplatin (30 mg/m2), etoposide (200 mg/m2), and ifosfamide (1.6 g/m2), given on days 1-5 for a total of four cycles at planned intervals of 21 days. Patients (pts) received GM-CSF, either 10 (22 pts; 70 cycles evaluable) or 5 micrograms/kg body wt. daily s.c. (22 pts; 72 cycles evaluable), starting the first day after chemotherapy for 10 consecutive days. Overall, 34 patients (78%) achieved a favorable response (CR or PR with negative tumor markers), six patients (14%) failed this chemotherapy regimen, and four patients (9%) died of therapy-related complications. The durations of both neutropenia and thrombocytopenia increased with the number of treatment cycles given. The duration of granulocytopenia after the fourth PEI cycle was significantly shorter for patients receiving 10 micrograms/kg than for those with 5 micrograms/kg per day of GM-CSF (9 vs 13 days; p < 0.05). The median duration of thrombocytopenia < 20,000/microliters after the fourth cycle of PEI was also significantly reduced in favor of patients receiving 10 micrograms/kg of GM-CSF (4 vs 9 days; p < 0.02). However, there were no differences in the frequency of severe infections or in the achieved dose intensity. Five patients (11%) discontinued GM-CSF due to side effects (three anaphylactoid-type reactions, one myalgia and fever, one cutaneous toxicity). No difference in the frequency of side effects was seen between patients receiving 5 and those receiving 10 micrograms/kg per day of GM-CSF. The dose of 5 micrograms/kg per day of GM-CSF may be sufficient to ameliorate neutropenia following standard-dose chemotherapy, while higher dosages of GM-CSF may be advantageous in patients receiving repetitive cycles of dose-intensified chemotherapy.
Antineoplastic Combined Chemotherapy Protocols↗
Interleukin-2 in combination with interferon-alpha and 5-fluorouracil for metastatic renal cell cancer.
Recent clinical trials for the biological therapy of solid tumours have used recombinant human cytokines in combination with conventional chemotherapy. In patients with progressive metastatic renal cell carcinoma, we established a three-drug combination comprising interferon-alpha (IFN-alpha), interleukin-2 (IL-2) and 5-fluorouracil (5-FU), using a regimen which allows outpatient therapy. Treatment consisted of 8 weeks each of IFN-alpha [6-9 MU/m2 once to three times weekly subcutaneously (sc)] combined sequentially with IL-2 (5-20 MU/m2 thrice weekly sc for 4 weeks) and 5-FU [750 mg/m2 intravenously (i.v.) weekly for 4 weeks]. Among the first 35 patients treated, there were 4 complete (11.4%) and 13 partial responders (37.1%), with an overall objective response rate of 48.6% (95% confidence interval 32-66%). Regressions occurred in local relapse, in lung, lymph node, bone, pleural, renal and thyroid metastases. Median response duration was calculated at 7+ months. An additional 13 patients (37.1%) were stable throughout therapy and thereafter (median of 6+ months). Response rate of this three-drug combination regimen compared favourably with single agent IFN-alpha (objective response rate approximately 16%) and against the sc IFN-alpha/IL-2 combination (objective response rate approximately 28%). Systemic toxicity was mild to moderate with no severe 5-FU-related mucositis and no dose-limiting adverse effects of sc IL-2. While the exact mechanisms of the potentially additive or synergistic effects of 5-FU and IFN-alpha/IL-2 remain to be established in more detail, it appears that the sequential use of IFN-alpha/IL-2 and IFN-alpha/5-FU in metastatic renal carcinoma further enhances the therapeutic index of IFN-alpha/IL-2-based biological therapy. Based on the present data, combined biochemotherapy may be a promising new approach to the therapy of advanced renal cancer.
Adult↗
Titanocendichloride activity in cisplatin and doxorubicin-resistant human ovarian carcinoma cell lines.
The activity of a new organometallic compound, titanocendichloride, was evaluated in doxorubicin- and cisplatin-resistant human ovarian carcinoma cell lines in vitro. Titanocendichloride showed no cross resistance to doxorubicin in two multidrug resistant sublines of A2780. Furthermore, the cell line A2780 CP3, which is about 20-fold resistant to cisplatin was only 2.5-fold resistant to titanocendichloride, indicating a lack of cross resistance between the two metal compounds. These results were confirmed in vivo where titanocendichloride showed a much stronger inhibitory effect in cisplatin-resistant human ovarian carcinoma xenografts than cisplatin.
Animals↗
Lack of therapeutic efficacy of tamoxifen in advanced renal cell carcinoma.
In the present study, we treated a total of 62 patients with advanced renal cell carcinoma with high-dose tamoxifen (100 mg/m2/day). Patients were treated in the outpatient setting, and were evaluated 8-12 weeks after initiation of therapy or sooner, when clinical disease progression was evident; a total of 15 patients were seen at short regular intervals for evaluation of clinical and laboratory parameters. Of these 62 patients, 59 were evaluable for treatment response, survival and systemic toxicity. One partial remission was achieved (1.7%; 95% confidence interval, 0.04-9.09%), response duration was 3 months. 10 patients presented with stable disease, for a median duration of 4.0 months, and 48 patients exhibited disease progression upon and after therapy. Systemic toxicity was significant; severe fatigue occurred in 5% of patients, and moderate anaemia, dyspnea, alopecia and malaise in almost 20% of patients. Antineoplastic efficacy of tamoxifen at this dosage in this cohort of patients was at best marginal and well in the range associated with the occurrence of spontaneous remissions. Toxicity was substantial, and it was not balanced by therapeutic benefit. This is consistent with the known lack of therapeutic efficacy of endocrine therapy in advanced renal cell carcinoma.
Adult↗
Bilateral testicular tumours: prevalence and clinical implications.
In a series of 773 patients with the diagnosis of a testicular germ cell tumour, treated at Hannover University Medical School between 1972 and 1985 and with a median follow-up of 9 years (60-210 months), bilateral testicular tumours occurred in 27 (3.5%) patients. None of 157 patients receiving chemotherapy for metastatic disease of the first tumour developed a metachronous bilateral tumour. Of 24 patients with metachronous tumours 23 had stage I and 1 patient had stage II at the time of initial diagnosis. The second testicular tumour was stage I in 18 patients, stage II in 5 and stage IV in 1 patient. 3 patients (13%) relapsed after treatment for their second germ cell tumour (surveillance 13 patients, radiotherapy 7 patients, lymph node dissection 2 patients and chemotherapy 2 patients), 1 of which died after refusing further treatment. The cure rate was 96% in patients with bilateral disease. Routine biopsy of the contralateral testis to identify existing carcinoma in situ (CIS) is recommended. Patients with CIS must be informed about their increased risk of a second testicular tumour. Irradiation of CIS or close clinical follow-up might both constitute appropriate strategies for the management of these patients.
Humans↗
Clinical and preclinical evaluation of recombinant PEG-IL-2 in human.
High dose interleukin-2 alone or in combination with lymphokine activated killer (LAK) cells has demonstrated antitumor activity in a variety of malignant diseases. The currently formulated recombinant human interleukin-2 (IL-2) has limited solubility and short circulatory half life resulting in limited bioavailability. To improve the bioavailability of IL-2 the protein was covalently bound to activated Polyethylenglycol (PEG). We designed a phase I/II trial to evaluate the bioactivity of PEG-IL-2 in man, given as intravenous (iv) bolus injection every two weeks, and to determine safety, efficacy, and the maximum tolerated dose (MTD) in patients with advanced malignancies. Assessment of cytokine levels, phenotypic analyses and differential blood counts were performed to investigate the effects of PEG-IL-2 in-vivo. To compare in-vitro PEG-IL-2 activity to activities of IL-2 we evaluated proliferation, cytotolytic activity, morphology, and phenotype of cytokine activated lymphocytes. Among seven patients treated with PEG-IL-2, there was no objective remission, three patients exhibited stabilisation of disease. Four patients presented with further disease progression. Treatment-related toxicity was mild to moderate (mainly WHO grades I and II) in patients receiving dose levels up to 10 x 10(6) IU/m2 (maximum tolerated single dose in the outpatient setting). No toxic deaths occurred. In comparison to IL-2, the pharmacokinetic profile of PEG-IL-2 exhibited increased plasma levels and a decreased clearance (alpha and beta half-life estimates of 4 and 14 hours, respectively). The analysis of a variety of immunologic parameters demonstrated that PEG-IL-2 has significant biologic activity both in vitro, and in man.
Adult↗