14.06.2010 – 08:05
New Data Confirms the Negative Impact of Febrile Neutropenia in Patients With Non-Hodgkin Lymphoma Receiving R-CHOP Chemotherapy
Data presented at the 15th European Hematology Association (EHA) congress in Barcelona, highlights the impact of febrile neutropenia (FN) on chemotherapy delivery in non-Hodgkin lymphoma (NHL) patients. The IMPACT NHL study showed that unplanned hospitalisations, delays in chemotherapy and reductions of chemotherapy dose leading to suboptimal relative dose intensity (RDI) of chemotherapy were more frequent in patients who experienced FN than those who did not.(i)
In the study, patients (>/= 18 years) with NHL were administered Cyclophosphamide ( http://www.macmillan.org.uk/Cancerinformation/Canc ertreatment/Treatmenttypes/Chemotherapy/Individualdrugs/Cyclophospham ide.aspx ), Doxorubicin, Vincristine and Prednisolone (CHOP) chemotherapy either every two weeks (CHOP-14) or every three weeks (CHOP-21) in combination with the monoclonal antibody rituximab (R). Neutropenia management and granulocyte-colony stimulating factor (G-CSF) use were entirely at the discretion of the treating physician, in order to prevent FN. A total of 1,111 patients with diffuse large B cell lymphoma were included in the current study analysis and 214 patients experienced FN.
In the R-CHOP-21 group, optimal chemotherapy dose intensity of 90% or more was maintained by three quarters (76%) of patients who did not experience FN, but only 62% of those who did experience FN, achieved this target. For the R-CHOP-14 group this was 71% and 37%, respectively. Patients were less likely to reach or maintain optimal chemotherapy dose intensity if they experienced FN. Previous data shows that a reduction in CHOP chemotherapy dose intensity below 90%(ii) may decrease survival in patients with aggressive NHL.
"These data confirm the significant impact febrile neutropenia can have on chemotherapy delivery in NHL, possibly reducing the favourable outcome of the treatment. There is a need for early prophylaxis with G-CSFs in those patients at risk," said Dr Ruth Pettengell, presenting author of the study and Senior Lecturer in Haematology and Honorary Consultant in Oncology at St George's Hospital Medical School, University of London.
Unplanned hospitalisations were also greater in patients who experienced FN (79% versus 18% in R-CHOP-21; 78% versus 21% in R-CHOP-14).
Based on these data from everyday clinical practice, the authors conclude physicians should implement guidelines on G-CSF use and G-CSF primary prophylaxis should be considered for NHL patients receiving R-CHOP-21 chemotherapy, who are assessed as having an overall FN risk of 20% or higher, and for all patients receiving R-CHOP-14.
Use of G-CSF primary phrophylaxis to prevent FN differed between the two groups; less than half of R-CHOP-21 patients (36%) were given G-CSF primary prophylaxis, compared to 84% of the R-CHOP-14 group and incidence of FN was 19% and 20% respectively.
About the Study
The aim of the IMPACT NHL study was to assess the impact of febrile neutropenia (FN) on non-Hodgkin lymphoma (NHL) patients receiving CHOP chemotherapy in combination with rituximab(R) every two (14 days) or three (21 days) weeks (current standard of care).
The study was supported by Amgen and included a total of 1,829 patients over the age of 18 with NHL receiving either R-CHOP-14 or R-CHOP-21 chemotherapy between 2005 and 2008. Centres were based in Europe (123 sites) and Australia (5 sites), with each enrolling up to 30 patients. Participating centres recorded their assessment of patients' FN risk, G-CSF use and FN incidence, as well as related outcomes such as chemotherapy delivery and unplanned hospitalisations. This current analysis is based on data from 1,111 patients with diffuse large B cell lymphoma.
G-CSFs are indicated to shorten the duration of severe neutropenia and reduce the incidence of FN.
About CHOP Chemotherapy
CHOP chemotherapy is named after the initials of the drugs used in the chemotherapy treatment. The drugs include cyclophosphamide ( h ttp://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmen ttypes/Chemotherapy/Individualdrugs/Cyclophosphamide.aspx ), doxorubicin (chemical name hydoxydaunorubicin), vincristine (used to be called Oncovin(R)) and prednisolone, which is a steroid ( http:// www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes /Supportivetherapies/Steroids.aspx ).(iii)
CHOP is given by a combination of injections into the tubing of a drip (infusion).The prednisolone is taken as tablets. In some instances CHOP chemotherapy may also be administered in combination with the monoclonal antibody rituximab (R-CHOP).
FN is an abnormally low level of neutrophils, an important infection-fighting white blood cell (WBC), in the blood stream. A low white blood cell count indicates that the immune system is not as strong as it should be, and the risk for serious infection is increased.(iv)
FN is a common and potentially dangerous side effect of myelosuppressive chemotherapy leading to a heightened risk of infection, sometimes life-threatening, among people with cancer. Severe neutropenia and/or FN may lead physicians to delay the next cycle of chemotherapy or reduce the dose given (in order to reduce further toxicity).
Granulocyte-colony stimulating factors (G-CSFs) are haematopoetic growth factors. It stimulates the bone marrow to produce more white blood cells. A major side effect of chemotherapy is the reduction in white blood cells which makes the body less able to combat infection. The use of a G-CSF after chemotherapy reduces the risk to patients of developing febrile neutropenia and reduces the duration of neutropenia.(v)
For further information please refer to the SmPC for pegfilgrastim and filgrastim - two commonly used G-CSFs.
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(i) Pettengell, R Johnson HE, Lugtenburg P, Salar A, Duehrsen U, Haioun C, Verhoef G, Rossi FG, Schwenkglenks M, Bendall K, Szabo Z, Jaegar U. IMPACT NHL-FN vs no FN analysis in DLBCL patients. Poster presented at EHA Congress 2010 Jun 14 2010 (Abstract no.0877)
(ii) Pettengell, R. Ann Hematol 2008; 87:429-430.
(iii) Macmillan Cancer Support. CHOP Chemotherapy. http://www.mac millan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Chemot herapy/Combinationregimen/CHOP.aspx
(iv) Common Toxicity Criteria [electronic document]. Version 2.0. Bethesda, Md: National Cancer Institute, National Institutes of Health, Department of Health and Human Services; 2003. Available at http://ctep.cancer.gov/forms/docs/zwiebel_memo.doc. Accessed May 28, 2003.
(v) Macmillan Cancer Support. G-CSF http://www.macmillan.org.uk/C ancerinformation/Cancertreatment/Treatmenttypes/Supportivetherapies/H aematopoieticGrowthFactors.aspx
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