Anemia chemotherapy-induced

Groopman JE, Itri LM. Chemotherapy-induced anemia in adults Incidence and treatment. J Natl Cancer Inst 1999 91(19) 1616-1634. 

Aranesp, Darbepoetin alfa Amgen, Inc. Anemia associated with chronic renal failure Chemotherapy-induced anemia in patients with non-myeloid malignancies Sept. 2001 July 2002... 

Erythropoietin Erythropoietin (EPO) (Fig. 4.8) is a glycoprotein produced by specialized cells in the kidneys. It has 166 amino acids and a molecular weight of approximately 36kDa.EPO stimulates the stem cells of bone marrow to produce red blood cells. It is used to treat anemia and chronic infections such as HIV and cancer treatment with chemotherapy where anemia is induced. Patients feel tired and breathless owing to the low level of red blood cells. EPO can be prescribed instead of blood transfusion. 

Sequential determination of platelet counts in patients receiving vincristine during early studies unexpectedly occasionally revealed thrombocytosis, which could not be accounted for by systemic response to treatment alone 10,11). Ultimately shown to most likely be the result of increased megakaryocytic endomitosis II), the observation led to the use of vincristine, and later vinblastine, both alone and bound to platelets, in a variety of thrombocytopenic disorders. These include idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, and chemotherapy-induced microangiopathic hemolytic anemia. 

Amgen has recently introduced darbe-poetin Aranesp), a long-acting version of human erythropoietin. With two additional N-linked carbohydrate chains, darbepoetin contains more sialic acid than epoetin alfa and has an approximately threefold longer half-life, which leads to less frequent dosing than epoetin alfa. Darbepoetin is approved for both the treatment of anemia due to chronic renal failure and the treatment of chemotherapy-induced anemia. 

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. 

Jumbe, N., B. Yao, R. Rovetti, G. Rossi, and A.C. Heatherington. 2002. Clinical trial simulation of a 200-microg fixed dose of darbepoetin-a in chemotherapy-induced anemia. Oncology (WiUiston. Park) 16 37-44. 

Recombinant human erythropoietin (epoetin and darbepoetin) provides effective therapy with a very favorable risk-benefit ratio in hemodialysis patients with end-stage chronic renal insufficiency, and in patients with progressive renal insufficiency who are not yet being dialysed (1). It improves cognitive function and the quality of life of patients with chronic uremia (2-5) and is very effective in children with chronic renal graft rejection and anemia (6). It also offers new opportunities for treating anemia in non-uremic patients. In patients with chemotherapy-induced anemia, epoetin increases hemoglobin concentration, reduces transfusion requirements, and improves quality of life (7,8). The response rate to epoetin in patients with multiple myeloma and anemia, which is 55-85% (9), increases when GM-CSF or G-CSF is... 

Kunikane H, Watanabe K, Fukuoka M, Saijo N, Furuse K, Ikegami H, Ariyoshi Y, Kishimoto S. Double-blind randomized control trial of the effect of recombinant human erythropoietin on chemotherapy-induced anemia in patients with non-small cell lung cancer. Int J Clin Oncol 2001 6(6) 296-301. 

Data was pooled from three clinical trials (547 patients) studying the use of darbepoetin alfa in the treatment of chemotherapy-induced anemia. Serial PK and PD (Hgb concentrations) measurements were collected throughout the studies and merged into a single database along with patient-relative covariates. A population PK/PD model was developed that simultaneously modeled darbepoetin alfa... 

Epoetin alpha (e.g., Epogen) Epoetin alpha is recombinant human erythropoietin. Erythropoetin, which is synthesized in the kidney in response to hypoxia or anemia, stimulates erythropoiesis. Epoetin alpha is indicated for anemia in patients with chronic renal failure, because these patients are unable to synthesize erythropoetin to correct the anemia. Additional uses include correcting zidovudine (AZT)-induced anemia in HIV-infected patients and chemotherapy-induced anemia in cancer patients (unlabelled use). Several weeks of therapy are required before the hematocrit levels rise, therefore, this drug cannot replace transfusions for the acute treatment of severe anemia. Epoetin alpha should not be used in patients with uncontrolled hypertension because the elevation in hematocrit may exacerbate hypertension. 

Persistent or recurrent cutaneous T-cell lymphoma Prevention of severe chemotherapy-induced thrombocytopenia Moderate to severe active rheumatoid arthritis Moderate to severe active rheumatoid arthritis Anemia related to AZT therapy in HIV-infected patients Anemia associated with chronic renal failure... 

Henry DH, Gordan LN, Charu V, et al. Randomized, open-label comparison of epoetin aha extended dosing (80 000 U Q2W) vs weekly dosing (40 000 U QW) in patients with chemotherapy-induced anemia. Curr Med Res Opin 2006 22 1403-1413. 

Henry DH, Dahl NV, Auerbach MA. Thrombocytosis and venous thromboembolism in cancer patients with chemotherapy induced anemia may be related to ESA induced iron restricted erythropoiesis and reversed by administration of IV iron. Am J Hematol 2012 87(3) 308-10. 

Finally, the successful use of vincristine in the treatment of drug-induced microangiopathic hemolytic anemia, a disease resembling the hemolytic uremic syndrome rarely seen subsequent to administration of mitomycin C or other chemotherapy has been described in two patients with this disorder (79). 

Oprelvekin has thrombopoietic activity and has been licensed to prevent severe thrombocytopenia and reduce the need for platelet transfusion after myelosuppressive chemotherapy (1). Common adverse effects included myalgia and arthralgias, fatigue, headache, and conjunctival injection. Peripheral edema, dyspnea, pleural effusions, tachycardia, and anemia were supposedly the result of oprelvekin-induced fluid retention (SEDA-20, 336) (SEDA-21, 376). Atrial flutter or fibrillation were sometimes noted. 

When drug-induced megaloblastic anemia is related to chemotherapy, no real therapeutic option is available, and the anemia becomes an accepted side effect of therapy. If drug-induced megaloblastic anemia results from cotrimoxazole, a trial course of folinic acid, 5 to 10 mg up to four times a day, may correct the anemia. Folic acid supplementation of 1 mg every day often corrects the drug-induced megaloblastic anemia produced by either phenytoin or phenobarbital, but some clinicians suggest that supplementation of folic acid may decrease the effectiveness of the antiepileptic medications. ... 

Myelosuppressant chemotherapy, in bone marrow transplantation, to reduce length of drug-induced neutropenia (aplastic anemia, hairy cell leukemia, AIDS)... 

Control of anemia with darbepoetin alfa has been reported in association with cancer chemotherapy, treatment of renal insufficiency, to control anemia due to inflammatory bowel disease, and in diabetes-induced anemia. However, this appears to be the first time it has been used successfully to control a drug-induced anemia. 

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