Chemotherapy thrombocytopenia

Thrombocytopenia is another dose-limiting side effect of chemotherapy. The primary treatment for thrombocytopenia is platelet transfusions. The risk of bleeding is significant when platelet counts are less than 10,000/mm3 (10 x 109/L) ... 

Chemotherapy regimen that does not have significant (greater than 10%) risk of thrombocytopenia... 

Neumega Oprelvekin Genetics Institute Prevention of severe chemotherapy-induced thrombocytopenia... 

Severe thrombocytopenia and reduction of the need for platelet transfusions Chemotherapy-induced thrombocytopenia Nov. 1997... 

Neumega (rIL-11) Approved (1997) Prevention of chemotherapy-induced thrombocytopenia Genetics Institute... 

F. Role in therapy According to Micro-medex, treatment of severe chemotherapy-related thrombocytopenia is hmited to platelet transfusions. There is a need for an alternative, especially due to the frequent use of myeloid colony-stimulating factors (G-CSF, GM-CSF) to reduce febrile neutropenia although effective, their use increases the risk of acute and prolonged thrombocytopenia, and the need for platelet transfusions. Other cytokines, such as interleukin-1 and interleukin-6, have been investigated as a means of ameliorating chemotherapy-induced thrombocytopenia, but results have been equivocal. 

G. Other considerations Recombinant human oprelvekin has been designated an orphan product for use in the prevention of chemotherapy-induced thrombocytopenia. 

Interleukin-11 (IL-11, oprelvekin) Thrombocytopenia Patients with nonmyeloid malignancies who receive myelosuppressive cancer chemotherapy... 

Neutropenia is a common adverse effect of the cytotoxic drugs used to treat cancer and increases the risk of serious infection in patients receiving chemotherapy. Unlike the treatment of anemia and thrombocytopenia, transfusion of neutropenic patients with granulocytes collected from donors is performed rarely and with limited success. The introduction of G-CSF in 1991 represented a milestone in the treatment of chemotherapy-induced neutropenia. This growth factor dramatically accelerates the rate of neutrophil recovery after dose-intensive myelosuppressive chemotherapy (Figure 33-5). It reduces the duration of neutropenia and usually raises the nadir count, the lowest neutrophil count seen following a cycle of chemotherapy. 

Interleukin-11 is approved for the secondary prevention of thrombocytopenia in patients receiving cytotoxic chemotherapy for treatment of nonmyeloid cancers. Clinical trials show that it reduces the number of platelet transfusions required by... 

Tositumomab is another anti-CD20 monoclonal antibody and is complexed with iodine 131 (131I). Tositumomab is used in two-step therapy in patients with CD20-positive, follicular non-Hodgkin s lymphoma whose disease is refractory to rituximab and standard chemotherapy. Toxicities are similar to those for ibritumomab and include severe cytopenias such as thrombocytopenia and neutropenia. Tositumomab should not be administered to patients with greater than 25% bone marrow involvement. 

Issac C, Robert NJ, Bailey FA, Schuster MW, et al. 1997. Randomized placebo-controlled study of recombinant human interleukin 11 to prevent chemotherapy induced thrombocytopenia in patients with breast cancer receiving dose-intensive cyclophosphamide and doxorubicin. J Clin Oncol. 15 3368-3377. 

Tepler I, Elias L, Smith JW, Hussein M, et al. 1996. A randomized placebo-controlled trial of recombinant human interleukin-11 in cancer patients with severe thrombocytopenia due to chemotherapy. Blood. 87 3607-3614. 

Interleukin-11 is the first growth factor to gain FDA approval for treatment of thrombocytopenia. It is approved for the secondary prevention of thrombocytopenia in patients receiving cytotoxic chemotherapy for treatment of nonmyeloid cancers. Clinical trials show that it reduces the number of platelet transfusions required by patients who experienced severe thrombocytopenia after a previous cycle of chemotherapy. Although IL-11 has broad stimulatory effects on hematopoietic cell lineages in vitro, it does not appear to have significant effects on the leukopenia or neutropenia caused by myelosuppressive chemotherapy. Interleukin-11 is given by subcutaneous injection at a dose of 50 g/kg/d. It is started 6-24 hours after completion of chemotherapy and continued for 14-21 days or until the platelet count passes the nadir and rises to > 50,000 cells/ L. 

Recombinant thrombopoietin is still an investigational agent. The primary focus of current clinical trials is for the treatment of chemotherapy-induced thrombocytopenia and thrombocytopenia accompanying hematologic stem cell transplantation. Other trials are looking into the possibility of administering thrombopoietin to normal donors in order to increase the number of cells recovered by platelet apheresis. Approval of the latter application will require that thrombopoietin be shown to have an excellent short- and long-term safety profile. 

Vadhan-Raj S. Clinical experience with recombinant human thrombopoietin in chemotherapy-induced thrombocytopenia. Semin Hematol 2000 37(2 Suppl 4) 28-34. 

Three interleukins (ILs) are in use for renal cell carcinoma and malignant melanoma (IL-2), cutaneous T-cell lymphoma (denileukin), and thrombocytopenia associated with cancer chemotherapy (IL-11). These interleukins are protein products that can cause substantial multiorgan toxicity, especially cardiovascular, and limit their full clinical usefulness, which characterizes most interleukins. Denileukin is a fusion protein of IL-2 and diphtheria toxin (Table 9). 

Oprelvekin (IL-11) Neumega (Wyeth/Genetics Institute) Thrombocytopenia owing to chemotherapy... 

In a phase III trial in 190 patients with metastatic melanoma, sequential chemotherapy with dacarbazine, cisplatin, and vinblastine plus interferon alfa and aldesleukin modestly increased the response rates and produced considerably more frequent and severe adverse effects than chemotherapy alone (128). In particular, severe episodes of anemia and thrombocytopenia that required blood or platelet transfusions were 2-6 times more frequent in the chemotherapy group. 

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