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Cancer Jun 2003Previous research has shown oprelvekin (recombinant human interleukin-11 [rhIL-11]) to be effective in reducing the requirements for platelet transfusions after... (Comparative Study)
Comparative Study
BACKGROUND
Previous research has shown oprelvekin (recombinant human interleukin-11 [rhIL-11]) to be effective in reducing the requirements for platelet transfusions after myelosuppressive chemotherapy in patients who have previously experienced thrombocytopenia. The economic consequences of the routine use of this platelet growth factor and the usual standard of platelet transfusions for prophylaxis of severe chemotherapy-induced thrombocytopenia have not been compared.
METHODS
The authors constructed a decision-analytic model to compare the alternatives of rhIL-11 versus usual care using probability, outcome, and cost data from previously published clinical trials and their own institutional sources. They incorporated the costs of platelet transfusions and adverse events from rhIL-11 into the analysis. Quality-of-life outcomes were not considered. The pharmacoeconomic analysis was based on the criterion of cost minimization from the payer's perspective.
RESULTS
The expected cost of the usual care strategy for prophylaxis of severe thrombocytopenia (transfusion when platelets < 20000 microL(-1)) was US dollars 3495 for a 3-week cycle of chemotherapy. The prophylactic rhIL-11 strategy was more expensive, with an expected cost of US dollars 5328 over the same time period. Nonetheless, it was associated with fewer platelet transfusions, avoiding an average of 6.7 U compared with usual care. The savings from avoidance of platelet transfusion and adverse reactions to transfusion from the use of rhIL-11 were not offset by the substantial cost of the pharmaceutical. The greater expected costs from the rhIL-11 strategy were relatively insensitive to the unit price and efficacy of rhIL-11 and the costs of platelet transfusions and monitoring.
CONCLUSIONS
From the payer's perspective, rhIL-11 cannot be considered a cost-saving clinical strategy compared with routine platelet transfusions for patients with severe chemotherapy-induced thrombocytopenia.
Topics: Antineoplastic Agents; Costs and Cost Analysis; Humans; Interleukin-11; Models, Theoretical; Platelet Transfusion; Recombinant Proteins; Thrombocytopenia
PubMed: 12784347
DOI: 10.1002/cncr.11447 -
Arthritis Research 2001Interleukin-11 (IL-11) is a pleiotropic cytokine that regulates the growth and development of hematopoietic stem cells and decreases the proinflammatory mediators of... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Results of a phase-I/II randomized, masked, placebo-controlled trial of recombinant human interleukin-11 (rhIL-11) in the treatment of subjects with active rheumatoid arthritis.
Interleukin-11 (IL-11) is a pleiotropic cytokine that regulates the growth and development of hematopoietic stem cells and decreases the proinflammatory mediators of cytokine and nitric oxide production. In animal models of arthritis, treatment with recombinant human IL-11 (rhIL-11) reduces both the level of synovitis and the histologic lesion scores in the joints. The goal of this phase-I/II study in adults with rheumatoid arthritis (RA) was to evaluate the safety and clinical activity of different doses and schedules of rhIL-11 in patients with active RA for whom treatment with at least one disease-modifying antirheumatic drug had failed. This was a multicenter, randomized, placebo-controlled trial that evaluated the safety and tolerability of rhIL-11 in 91 patients with active RA. rhIL-11 was administered subcutaneously; patients were randomized into one of five treatment groups (ratio of rhIL-11 to placebo, 4:1). Patients were treated for 12 weeks with either 2.5 or 7.5 microg/kg of rhIL-11 or placebo twice per week or 5 or 15 microg/kg of rhIL-11 or placebo once per week. The status of each subject's disease activity in accordance with the American College of Rheumatology (ACR) criteria was assessed before, during, and after completion of administration of the study drug. Administration of rhIL-11 was well tolerated at all doses and schedules. The most frequent adverse event was a reaction at the injection site. The data suggest a statistically significant reduction in the number of tender joints (P < 0.008) at the 15 microg/kg once-weekly dose schedule but showed no overall significant benefit at the ACR criterion of a 20% response. The trial showed rhIL-11 to be safe and well tolerated at a variety of doses and schedules over a 12-week treatment period in patients with active RA. The only adverse event clearly associated with rhIL-11 administration was reaction at the injection site.
Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Injections, Subcutaneous; Interleukin-11; Joints; Male; Middle Aged; Recombinant Proteins; Treatment Outcome
PubMed: 11438043
DOI: 10.1186/ar309 -
American Journal of Hematology Mar 2001The objective of this research was to determine whether rhuIL-11 is an effective treatment in patients with refractory immune thrombocytopenic purpura (ITP). Platelet... (Clinical Trial)
Clinical Trial
The objective of this research was to determine whether rhuIL-11 is an effective treatment in patients with refractory immune thrombocytopenic purpura (ITP). Platelet production is decreased in certain cases of refractory ITP. IL-11 stimulates megakaryocytopoiesis in vitro and was licensed for its clinical effects to ameliorate chemotherapy-induced thrombocytopenia. A pilot study was initiated, intending to enroll 12 patients with ITP. These patients were to receive rhuIL-11 (Neumega) at a dose of 50 microg/kg subcutaneously daily for 21 consecutive days and be observed afterward for 21 additional days. CBC with platelets were obtained twice weekly with visits and physical examinations weekly. The study was terminated after 7 patients were enrolled because of toxicity and lack of efficacy. All 7 patients had had ITP for >9 years and had failed splenectomy, intravenous gammaglobulin, corticosteroids, and a variety of other treatments. The patients at entry all had platelet counts <20,000/microl; 5 of 7 had counts <10,000/microl. The maximal median increase for any day of the study was 6,000/microl. No patient achieved a count of 30,000/microl, and only 3 patients achieved (once each) a platelet count >20,000/microl. Substantial toxicity was seen. The nadir hemoglobin decrease was a mean of 2 g/dl. rhuIL-11 was not effective at increasing the platelet count in any of these patients with refractory ITP. Toxicity was substantial. The lack of platelet response to rhuIL-11 in this study does not exclude the possibility of better effects at other doses and/or in less refractory patients.
Topics: Adolescent; Adult; Hematopoiesis; Hemoglobins; Humans; Immunoglobulins, Intravenous; Interleukin-11; Megakaryocytes; Middle Aged; Pilot Projects; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Treatment Outcome
PubMed: 11279623
DOI: 10.1002/1096-8652(200103)66:3<172::aid-ajh1041>3.0.co;2-q -
Oncology (Williston Park, N.Y.) Sep 2000Safety data from two randomized phase II and one abbreviated phase III placebo-controlled, double-blind clinical studies in adult patients with nonmyeloid malignancies... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Safety data from two randomized phase II and one abbreviated phase III placebo-controlled, double-blind clinical studies in adult patients with nonmyeloid malignancies indicate that recombinant human interleukin-11 (rhIL-11, also known as oprelvekin [Neumega]) has an acceptable toxicity profile as therapy for the mitigation of chemotherapy-induced thrombocytopenia. Preliminary data also indicate that rhIL-11 is well tolerated by pediatric patients with similar types of cancers. Adverse events associated with rhIL-11 are generally mild or moderate, reversible with drug discontinuation, and easily managed. Many of the common adverse events of rhIL-11--including edema, dyspnea, pleural effusions, conjunctival injection, and in some patients, atrial arrhythmia--occur in association with fluid retention. However, these adverse events can be medically managed and need not limit the use of rhIL-11, particularly if ameliorative measures, such as salt restriction and occasional prophylaxis with a potassium-sparing diuretic to minimize peripheral edema, have been instituted along with close monitoring of fluid and electrolyte status. Such measures are suggested for any patient treated with a diuretic, especially patients with cancer who are receiving multiple medications that complicate overall care. Administration of sequential cycles of rhIL-11 treatment does not appear to result in an increased incidence of adverse events or bone marrow exhaustion. rhIL-11 does not appear to interact adversely with concomitantly administered chemotherapeutic agents or agents commonly used for supportive care, including granulocyte colony-stimulating factor (G-CSF, filgrastim [Neu-pogen]).
Topics: Antineoplastic Agents; Arrhythmias, Cardiac; Blood Platelets; Colony-Stimulating Factors; Double-Blind Method; Drug Combinations; Drug Interactions; Dyspnea; Edema; Humans; Hypokalemia; Interleukin-11; Platelet Activation; Recombinant Proteins; Safety; Thrombocytopenia
PubMed: 11033837
DOI: No ID Found -
Oncology (Williston Park, N.Y.) Sep 2000Placebo-controlled clinical trials of recombinant human interleukin-11 (rhIL-11, also known as oprelvekin [Neumega]) in patients with nonmyeloid malignancies have... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Placebo-controlled clinical trials of recombinant human interleukin-11 (rhIL-11, also known as oprelvekin [Neumega]) in patients with nonmyeloid malignancies have demonstrated significant efficacy in preventing postchemotherapy platelet nadirs of < or = 20,000/microL, and reducing the need for platelet transfusions while continuing chemotherapy without dose reductions. The likelihood of requiring a platelet transfusion in rhIL-11-treated patients receiving chemotherapy is approximately 40% lower than the risk for untreated patients. Treatment with rhIL-11 appears to accelerate earlier recovery to platelet counts of 20,000/microL, 50,000/microL, and 100,000/microL, suggesting that patients treated with rhIL-11 are more likely to be able to receive their next chemotherapy cycle in a timely fashion. rhIL-11 shows sustained efficacy over multiple cycles of full-dose chemotherapy. Activity has also been demonstrated in pediatric patients with solid tumors. The use of rhIL-11 in combination with granulocyte colony-stimulating factor (G-CSF, filgrastim [Neupogen]) may also produce a synergistic hematopoietic effect, resulting in earlier neutrophil recovery. The recommended adult dose regimen for rhIL-11 is 50 micrograms/kg administered subcutaneously once daily beginning 6 to 24 hours after the administration of chemotherapy until a postnadir platelet count of > or = 50,000/microL is reached. The recommended pediatric dose of rhIL-11 is 75 micrograms/kg subcutaneously, once daily beginning 6 to 24 hours after the administration of chemotherapy until a postnadir platelet count of > or = 50,000/microL is reached. The administration of rhIL-11 for greater than 21 days has not been studied and therefore is not recommended.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blood Platelets; Bone Marrow; Breast Neoplasms; Colony-Stimulating Factors; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Female; Granulocyte Colony-Stimulating Factor; Hematopoiesis; Humans; Interleukin-11; Middle Aged; Recombinant Proteins; Thrombocytopenia; Treatment Outcome
PubMed: 11033836
DOI: No ID Found -
Oncology (Williston Park, N.Y.) Sep 2000Thrombocytopenia occurs at various grades of severity in patients with nonmyeloid malignancies undergoing chemotherapy with myelosuppressive agents. Frequently, it is... (Review)
Review
Thrombocytopenia occurs at various grades of severity in patients with nonmyeloid malignancies undergoing chemotherapy with myelosuppressive agents. Frequently, it is the major dose-limiting hematologic toxicity, especially in the treatment of potentially curable malignancies such as leukemia, lymphomas, and pediatric cancers. This is becoming increasingly important given the recent trend toward the use of dose-intensive combination chemotherapy regimens facilitated by supportive hematopoietic colony-stimulating factors to prevent chemotherapy-induced febrile neutropenia. The standard preventive measure against chemotherapy-induced depression of platelets in subsequent treatment cycles has been dose reduction and/or dose delay. However, follow-up data from studies in various populations of patients with cancer suggest a correlation between delivery of lower than intended doses and poor outcomes, including reduced disease-free periods and overall survival. Other consequences of thrombocytopenia include the need for platelet transfusions and subsequent exposure to the risk of numerous complications, including bacterial and viral infections; febrile, nonhemolytic transfusion reactions; and transfusion-induced immunosuppression. Furthermore, a large proportion of multitransfused patients become refractory to subsequent infusions. Refractoriness to platelet transfusions is quickly becoming more prominent. The availability of a platelet growth factor--recombinant human interleukin-11(rhIL-11, also known as oprelvekin [Neumega])--provides an effective means of preventing chemotherapy-induced thrombocytopenia and accelerating platelet recovery, thereby facilitating the administration of full doses of chemotherapy during subsequent cycles and avoiding the need for rescue with platelet transfusions.
Topics: Antineoplastic Agents; Bone Marrow; Colony-Stimulating Factors; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Immunosuppression Therapy; Interleukin-11; Maximum Tolerated Dose; Neoplasms; Opportunistic Infections; Platelet Transfusion; Recombinant Proteins; Survival Rate; Thrombocytopenia
PubMed: 11033835
DOI: No ID Found -
Oncology (Williston Park, N.Y.) Sep 2000
Review
Topics: Antineoplastic Agents; Blood Platelets; Colony-Stimulating Factors; Dose-Response Relationship, Drug; Hematopoiesis; Humans; Interleukin-11; Maximum Tolerated Dose; Megakaryocytes; Recombinant Proteins; Thrombocytopenia
PubMed: 11033833
DOI: No ID Found -
Blood May 1996We performed a phase I trial of recombinant human interleukin-11 (rhIL-11) in women with breast cancer. Cohorts of three to five women were accrued to five dosage levels... (Clinical Trial)
Clinical Trial
We performed a phase I trial of recombinant human interleukin-11 (rhIL-11) in women with breast cancer. Cohorts of three to five women were accrued to five dosage levels of rhIL-11 (10, 25, 50, 75, and 100 micrograms/kg/d). rhIL-11 alone was administered by a daily subcutaneous injection for 14 days during a 28-day prechemotherapy "cycle 0." Patients (pts) subsequently received up to four 28-day cycles of cyclophosphamide (1,500 mg/m2) and doxorubicin (60 mg/m2) chemotherapy followed by rhIL-11 at their assigned dose (days 3 through 14). Sixteen pts (13 stage IV, 3 stage IIIB) were accrued to this study. Median age was 53 years and median Eastern Cooperative Oncology Group Performance Status was 0. A grade 3 neurologic event was seen in 1 pt at 100 micrograms/kg. Because of the degree of grade 2 constitutional symptoms (myalgias/arthralgias and fatigue) at 75 micrograms/kg, dose escalation was stopped and 75 micrograms/kg was the maximally tolerated dose. No other grade 3 or 4 adverse events related to rhIL-11 were seen. The administration of rhIL-11 was not associated with fever. Reversible grade 2 fatigue and myalgias/arthralgias were seen in all pts at 75 micrograms/kg. Weight gain of 3% to 5% associated with edema was seen at doses > 10 micrograms/kg but a capillary leak syndrome was not seen. rhIL-11 alone was associated with a mean 76%, 93%, 108%, and 185% increase in platelet counts at doses of 10, 25, 50, and 75 micrograms/kg, respectively. No significant changes in leukocytes were seen. A mean 19% decrease in hematocrit was observed. Acute-phase proteins increased with treatment at all doses. Compared with patients at the 10 micrograms/kg dose, patients receiving doses > or = 25 micrograms/kg experienced less thrombocytopenia in the first two cycles of chemotherapy. We conclude that rhIL-11 has thrombopoietic activity at all doses studied, is well tolerated at doses of 10, 25, and 50 micrograms/kg, and at doses > or = 25 micrograms/kg has the potential to reduce chemotherapy-induced thrombocytopenia in this model.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cohort Studies; Female; Humans; Injections, Subcutaneous; Interleukin-11; Middle Aged; Recombinant Proteins; Thrombocytopenia
PubMed: 8611685
DOI: No ID Found