Chemotherapy myelosuppression with

L. E. Friberg, A. Henningsson, H. Maas, L. Nguyen, and M. O. Karlsson, Model of chemotherapy-induced myelosuppression with parameter consistency across drugs. J Clin Oncol 20 4713 721 (2002). 

AML accounts for most cases of acute leukemia in adults, and occurs with increasing frequency in elderly patients. It accounts for only 15% to 20% of the acute leukemias in children, but is responsible for 30% of leukemia-related mortality. With recent advances in chemotherapy and supportive care, 65% to 85% of all patients achieve CR and 20% to 40% become long-term survivors. " Overall, the median duration of remission is 1 to 2 years. " In patients older than age 60 years, the percentage of patients achieving a CR is lower (39% to 64%), and the median duration of remission is shorter than 1 year. In contrast to ALL, effective therapies used in AML cause severe and often prolonged myelosuppression, with the exception of tretinoin. As a result, patients with AML, particularly patients older than age 60 years, are at greater risk for treatment-related fatal infectious and bleeding complications. 

A related anthracenedione, mitoxantrone, has been approved for use in AML. Mitoxantrone has limited ability to produce quinone-type free radicals and causes less cardiac toxicity than does doxorubicin. It produces acute myelosuppression, cardiac toxicity, and mucositis as its major toxicities the drug causes less nausea and vomiting and alopecia than does doxorubicin. It is also used as a component of experimental high-dose chemotherapy regimens, with uncertain efficacy. 

The incidence of neutropenia has also been investigated in combination schedules. Patients who receive paclitaxel in combination with cyclophosphamide have severe neutropenia more often than with monotherapy (72% of patients). Paclitaxel given as a 24-hour infusion before cyclophosphamide is more likely to cause severe neutropenia compared with patients who receive cyclophosphamide first [54 ]. Conversely, in studies of paclitaxel and cisplatin combination chemotherapy, myelosuppression is worse when paclitaxel is given after cisplatin rather than before. This appears to be due to reduced plasma clearance of paclitaxel when cisplatin is administered first... 

The National Comprehensive Cancer Network (NCCN) recommends an anemia work-up for patients with hemoglobin of less than 11 g/dL (110 g/L or 6.8 mmol/L). Patients who are symptomatic or asymptomatic with significant risk factors (e.g., extensive transfusion history, myelosuppressive chemotherapy, etc) may qualify for treatment with erythropoietic agents such as epoetin-alfa or darbepoetin. Data do not support the use of one agent over another they are both equally effective in treating this type of anemia.12 Table 63-4 provides dosing recommendations for chemotherapy-related anemia. 

Myelosuppression is one of the most common dose-limiting side effects of cancer drugs that cause myelosuppression. Myelosuppression may occur several days to several weeks after treatment and varies with the chemotherapy drugs used. WBCs, in particular, neutrophils, are the first cell line that is decreased because of their rapid proliferation and short life span of 6 to 12 hours. Platelets, with a life span of 9 to 11 days... 

JP is receiving a highly myelosuppressive chemotherapy regimen for the next 3 days for his lymphoma. The chemotherapy orders specify ifosfamide, carboplatin, and etoposide. The goal of this cycle of chemotherapy is to put the cancer into remission so that his lymphoma can be cured with a bone marrow transplant. 

Provide patient education regarding common toxicities associated with chemotherapy, such as nausea/vomiting, mucositis, myelosuppression, and alopecia. 

Overall survival is affected by the success of the initial surgery to debulk the tumor to less than 1 cm of disease and response to first-line chemotherapy. The CA-125 level should be monitored with each cycle, and at least a 50% reduction in CA-125 after four cycles of taxane/platinum chemotherapy is related to an improved prognosis. Patients who achieve a complete response should have follow-up examinations every 3 months, including CA-125 determination, physical examination, pelvic examination, and appropriate diagnostic scans (e.g., CT scan, MRI, or PET scan) and should be evaluated for the detection of disease. Evaluate patients for resolution of any residual chemotherapy-related side effects, including neuropathies, nephrotoxicity, ototoxicity, myelosuppression, and nausea/vomiting. 

Because of the need for repeated venous access, a central venous catheter or infusion port is placed prior to starting treatment. These devices are useful not only for delivery of chemotherapy but also to support patients during periods of myelosuppression. Infection and bleeding complications are the primary cause of mortality in patients with leukemia. 

GM-CSF was approved in 1991 by the United States Food and Drag Administration (FDA) to support transplant associated neutropenia and mobilize stem cells. In Europe, it is also approved for prophylactic treatment following dose intensive chemotherapy. However, the rate of absolute neutrophil count (ANC) recovery in response to treatment with GM-CSF in patients receiving myelosuppressive chemotherapy or in the... 

In an effort to overcome the lack of solubility, poor penetration across the blood-brain barrier and decreased delivery of conventional systemic agents by a compromised intratumoral blood supply, several studies have evaluated various combinations of BCNU alone or with other agents delivered intraarterally. Unfortunately, response rates and median survival times observed in patients treated with intraarterial chemotherapy have not been significantly different than those seen in patients treated with standard intravenous nitrosurea-containing regimens, while increased rates of toxicity such as leukoen-cephalopathy, retinal injury, edema, myelosuppression, sepsis, and thrombotic complications have been noted (40-46). 

B. Indications and use Filgrastim is indicated to lessen neutropenia associated with myelosuppressive chemotherapy, bone marrow transplantation, and severe... 

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. 

Cancer patients treated with myelosuppressive cancer chemotherapy... 

Granulocyte colony-stimulating factor (G-CSF filgrastim) Neutropenia Cancer patients treated with myelosuppressive cancer chemotherapy... 

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. 

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