Neutropenia chemotherapy-induced

NEUPOGEN Filgrastim (G-CSF) Amgen Chemotherapy-induced neutropenia, bone marrow transplantation, chronic severe neutropenia, peripheral blood progenitor cell transplant... 

Esser, M. and Brunner, H. 2003. Economic evaluations of granulocyte colony stimulating factor in the prevention and treatment of chemotherapy-induced neutropenia. Pharmacoeconomics 21(18), 1295-1313. 

Chemotherapy-induced neutropenia Neutropenia during bone marrow transplant Severe chronic neutropenia Autologous or allogeneic bone marrow transplantation Mobilization of autologous PBPCs after chemotherapy Persistent or recurrent cutaneous T cell lymphoma Feb. 1991 June 1994 Dec. 1994 Dec. 1995 April 1998 Feb. 1994... 

Unlabeled uses Lithium carbonate (300 to 1,000 mg/day) has improved the neutrophil count in patients with cancer chemotherapy-induced neutropenia, in children with chronic neutropenia, and in AIDS patients receiving zidovudine. 

Filgrastim is a recombinant human G-CSF (produced in E. coli), approved for chemotherapy-induced neutropenia since 1991. Although the 18.8 kDa recombinant product is not glycosylated and contains an additional N-terminal methionine residue (due to expression in E. coli), it displays biological activity indistinguishable from native G-CSF. The product is presented in freeze-dried format and contains buffer elements as well as sorbitol and Tween as excipients. 

Lo N, Cullen M. Antibiotic prophylaxis in chemotherapy-induced neutropenia time to reconsider. Hematol Oncol 2006 24 120-5. 

G. Other applications Leukine has been effective in producing increases in normally functioning neutrophils, eosinophils, and monocytes in AIDS patients and patients with leukopenia. Leukine may prolong survival when used as adjuvant therapy in patients with stage III or IV malignant melanoma. Leukine has also been effective in abrogating chemotherapy-related neutropenia in cancer patients, with a reduction in the severity and duration of chemotherapy-induced myelosuppression. 

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. 

F. Role in therapy According to the manufacturer, until now, filgrastim was the only prescription drug shown to decrease risk of infection and hospitalization as a result of chemotherapy-induced neutropenia. The burden of daily dosing (up to 14 consecutive days), however, led many physicians to delay intervention until a patient developed a neutropenic infection. 

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. 

Bhana N Granulocyte colony-stimulating factors in the management of chemotherapy-induced neutropenia Evidence based review. Curr Opin Oncol 2007 19 328. [PMID 17545795]... 

The CSFs prevent chemotherapy-induced neutropenia. They stimulate hematopoiesis in marrow failure. The CSFs promote cell differentiation, assist in marrow transplantation, stimulate monocyte anticancer effects and augment effector cell function. 

Like G-CSF and pegfilgrastim, GM-CSF also reduces the duration of neutropenia after cytotoxic chemotherapy. It has been more difficult to show that GM-CSF reduces the incidence of febrile neutropenia, probably because GM-CSF itself can induce fever. In the treatment of chemotherapy-induced neutropenia, G-CSF, 5 g/kg/d, or GM-CSF, 250 g/m2/d, is usually started within 24-72 hours after completing chemotherapy and is continued until the absolute neutrophil count is >... 

Fig. 15.5 Upper Prospective simulation of sustained plasma levels of pegfilgrastim in simulated neutropenic monkeys. Symbols indicate observed values in normal monkeys dashed lines indicate simulated values during chemotherapy-induced neutropenia. The...

Dale D. Current management of chemotherapy-induced neutropenia the role of colony-stimulating factors. Semin. Oncol. 2003 30 3—9. 

Holmes FA, Jones SE, O Shaughnessy J, et al. Comparable efficacy and safety profiles of once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy-induced neutropenia a multicenter... 

Chemotherapy-induced neutropenia/autologous bone marrow transplantation/chronic severe neutropenia/acute myeloid leukemia E. coli... 

Vidal Pan C, Gonzalez Quintela A, Roman Garcia J, MiUan I, Martin Martin F, Moya Mir M. Cephapirin-induced neutropenia. Chemotherapy 1989 35(6) 449-53. 

A 40-year-old woman with metastatic breast cancer received cychc snbcntaneons G-CSF for chemotherapy-induced neutropenia. After 5 months she had a pruritic rash at injection sites. She did not change the injection sites and the lesions recnrred after each injection. Biopsy showed a lichenoid reaction and the lesions healed with residual pigmentation after topical steroid application and G-CSF discontinuation. GM-CSF was well tolerated. 

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