Incidence Of FN Research Articles

Delivered relative dose intensity and febrile neutropenia rate with common adjuvant chemotherapy regimens: A review

11505 Background: Adjuvant chemotherapy for early-stage breast cancer decreases the risk of recurrence and improves survival. Prior work has pointed out that <85% of relative dose intensity (RDI) could result in compromised outcome. Methods: Among consecutively treated patients, one hundred patients treated with (AC-T) doxorubicin, cyclophosphamide (4 cycles) followed by paclitaxel (4 cycles), one hundred patients treated with (FEC-D) 5FU, epirubicin and cyclophosphamide (3 cycles) followed by docetaxel (3 cycles) and 75 patients treated with (FEC100) 5FU, epirubicin and cyclophosphamide (6 cycles) were retrospectively analyzed. Summation dose intensity (SDI) is used as a reference for RDI. To calculate SDI of each regimen, a unit dose intensity (UDI) of each drug in the combination regimen is calculated, defined as the dose of the drug required to produce 30% complete plus partial response when used as a first-line single agent in metastatic breast cancer. The dose intensity of each drug in a combination is expressed as a fraction of that drug’s UDI and fractions for all the drugs are added together. The incidence of FN was recorded as well. Results: Almost 30% of patients receiving FEC-100, 4% with AC-T and 10% with FEC-D were over 65 years. Only 4% with AC-T, 5% with FEC-D but 21% patients receiving FEC-100 had <85% RDI. About 1/3rd of FEC-100 patients but 63% of AC-T and 77% patients of FEC-D had 100% of RDI delivered. FN rates were 7% for AC-T and 23% for FEC-D. Almost all FN cases were seen with the dose of Docetaxel (19/23) in patients receiving FEC-D. Conclusions: To our knowledge, delivered RDI and/SDI for these regimens have not been reported previously and the results show the experience of an academic cancer centre. The delivered RDI for AC-T and FEC-D is excellent but for FEC-100 is sub-optimal. This variability could be due to a smaller sample, relatively elderly population and various other factors. Although the FN rate for AC-T appears to be similar as previously reported, the FN rate for FEC-D is higher. This higher rate combined with the fact that the most FN cases occurred with docetaxel appears to reflect the experience for the patients outside the clinical trial. No significant financial relationships to disclose.

Colony stimulating factor use and outcomes for breast, lung, and colorectal cancer patients in Washington State

6616 Background: Guidelines recommend colony stimulating factor (CSF) primary prophylaxis (PP) with chemotherapy if febrile neutropenia risk (FN) is =20%. Use of and outcomes for persons receiving CSF in clinical practice are relatively unknown. Methods: Using claims for Medicare and Medicaid enrollees linked to the Puget Sound SEER registry, breast (BCa), lung (LCa) and colorectal cancer (CRCa) patients diagnosed 2002–04 who received chemotherapy were categorized as: CSF at the start of chemotherapy (PP); other CSF; no CSF. Logistic regression was used to determine predictors of CSF PP and hospitalization for FN, controlling for cancer stage, age, sex, race, chemotherapy FN risk (from the National Comprehensive Cancer Network), radiation therapy, CSF use, health insurance, surgery =30 days of chemotherapy. Results: 364 BCa, 908 LCa, and 452 CRCa patients received chemotherapy. 43% of BCa, 30% of LCa, and 15% of CRCa patients received CSF. Only 9%, 6%, and 0.6% of patients initiated CSF as PP in the first cycle of chemotherapy. CSF use increased for all cancers, but most for BCa, (36% in 2002 to 70% in 2004); PP increased from 5% to 26%. Significant predictors (p&lt;0.05) of PP were: BCa–local vs distant stage (OR 0.2), regional vs distant (OR 0.6), chemotherapy FN risk high vs low (OR 6.7); LCa–chemotherapy FN risk high vs low (OR 8.9), intermediate vs low (OR 6.3). FN incidence was 11%, 18% and 32% for BCa, CRCa, LCa, respectively. Significant predictors of FN were: BCa–nonwhite race (OR 2.7); LCa–surgery within 30 days (OR 1.7); CRCa–regional vs. distant (OR 0.4) and chemotherapy FN risk intermediate vs. low (OR 4.2). Conclusions: CSF use has increased significantly, but often in settings where efficacy is uncertain. Cancer type, stage and chemotherapy risk of FN influenced use of primary prophylaxis. Non-chemotherapy factors also appear to influence risk for FN. No significant financial relationships to disclose.

Patterns of Growth Factor (GF) Usage and Febrile Neutropenia (FN) among Older Patients (pts) with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with CHOP or R-CHOP: An Intergroup Experience (CALGB 9793, ECOG-SWOG 4494).

The use of anthracycline-based combination chemotherapy to treat DLBCL in older pts is complicated by the more common occurrence of therapy-related myelosuppression, which may lead to dose reductions that might impair efficacy. The preliminary results of initial therapy with cyclophosphamide, doxorubicin, vincristine, prednisone alone (CHOP) or with rituximab (R-CHOP) as induction therapy in patients age 60 years (yrs) or greater with DLBCL have been reported (Blood 2003; 102:6a, Abstr 8). Pts were randomized at induction to receive 6–8 cycles of CHOP or R-CHOP. Responding patients were then randomized to receive either no treatment or maintenance rituximab. Per protocol, GF was not to be given with the 1st cycle of therapy, and thereafter ASCO guidelines were to be followed regarding use of GF. The objectives of this study were to determine the frequency of and indications for GF usage and the incidence of FN. GF usage was defined as the use of either GCSF or GMCSF for the purpose of preventing dose reduction/dose delay or as prophylaxis in pts with a prior hospitalization for FN. Of the 546 eligible pts, adequate data was available to report on 528 patients. Among these pts, 75% were >=65 yrs, 41% hemoglobin <12 g/dl, 50% male, 59% elevated LDH and 59% HI/High IPI. 264 of 528 pts (50%) used GF in at least 1 cycle of therapy (GF used in 307 cycles to treat neutropenia). 181 of the 528 pts (34%) used GF per our definition with the 93% using GCSF only in at least 1 cycle of therapy. For these 181 pts, the median number of cycles of GF use was 5 (range 1–8) and the median duration of GF use was 9 d (SD=3). GF was used in 552 of 3256 cycles (17%). Significantly more patients used GF at later cycles of therapy (65/513,13% at cycle 2 vs 98/429, 23% at cycle 6, p<0.001). The use of GF was evaluated by study entry characteristics (age, sex, performance status, IPI score). The only significant difference was that pts age 60–64 yrs were less likely to have received GF than pts >=65 yrs (25% vs 37%,p=0.01). 217 pts (41%, 95% CI [37,45%]) had at least one FN event. FN occurred in 267/3247 (8%) cycles of therapy with 103 (39%, 95% CI [33,45%]) FN events occurring in cycle 1. The median time to FN was d 11 (SD=3) of the cycle. In this older pt population treated with CHOP+/− R therapy for DLBCL, GF was used in 17% of the cycles, with usage more common in later cycles of therapy. FN was most common in the first cycle of therapy occurring mostly within the first two weeks. This early occurrence of FN supports consideration of GF use to prevent FN from the 1st cycle of CHOP-based therapy in older pts (>=60 yrs), in addition to any other usage per ASCO guidelines. Results will be presented on the impact of delivered dose intensity on GF usage and FN.

Fever in neutropenia in children and adolescents: Evolution over time of main characteristics in a single center, 1993?2001

To assess the evolution over time of main characteristics of episodes of fever in severe chemotherapy-induced neutropenia (FN) in children and adolescents with cancer treated for FN following nonmyeloablative chemotherapy, to compare the results with the experiences of other centers, and to assess the impact of the changes found on management of FN and on risk prediction rules. Retrospective cohort study of all children and adolescents up to 18 years presenting with FN in a single pediatric oncology unit between 1993 and 2001. In 132 patients, 364 episodes of FN were reported. The relative incidence of FN increased significantly over time in patients with precursor B-cell acute lymphoblastic leukemia (PBC-ALL), reflecting the increased intensity of chemotherapy. At presentation with FN, the proportions of patients (1) with PBC-ALL versus other malignancies, (2) with other malignancies being in complete remission, (3) with a central venous catheter, and (4) with shaking chills all significantly increased over time (overall proportions, 64%, 60%, 50%, and 5%, respectively; p <0.001 for all). In 337 (93%) episodes, ceftriaxone plus amikacin was used as empirical broad spectrum antimicrobial therapy. This study demonstrates that some characteristics of FN, though not necessarily its management, change over time, implying regular update of risk prediction rules. In contrast to other centers, the first-line antimicrobial therapy did not need modification because of changing resistance patterns.

The pathology of facial and vestibular neuronitis

Objective: To measure disease of idiopathic nature in the ganglia of the human facial (FN) and vestibular nerves (VN). Method: One hundred horizontally sectioned human temporal bones (TB) were examined under light microscopy. The TB were sectioned at 20 μm, and every 10th section was stained with hematoxylin and eosin and mounted. The volume fractions (VF) of degenerated cells in the FN ganglion and focal axonal degeneration in the VN were measured with stereologic techniques. Results: Twenty-five TB were excluded because of artifact or poor staining of the FN and VN. Fifty-one TB contained degenerated cells in the FN meatal ganglion (MG) and/or focal axonal degeneration in the VN. Thirty-one FN had degenerated cells in the MG (VF = 1 % to 55%) and none in the geniculate ganglion. In 45 TB, focal axonal degeneration was found in the VN (VF = 1 % to 50%; the VF was less than 15% in all but one TB). MG and VN degeneration occurred together in 25 TB. None of the cases had a history of FN paralysis, but 20 had a history of vertigo. Twenty-four TB from patients of similar ages with similar otopathologies did not reveal degeneration in the FN or VN. Conclusion: The FN and VN lesions in these 51 TB may be virus-induced and reflect a higher incidence of idiopathic FN and VN neuronitis than previously thought.

Early lymphopenia after cytotoxic chemotherapy as a risk factor for febrile neutropenia.

Febrile grade four (ie, < or = 500/microL) neutropenia (FN) is a frequent life-threatening complication of cancer chemotherapy. Although its incidence correlates to the dose of chemotherapy, FN may occur after almost any cytotoxic regimen. At present, there is no predictive method to identify patients who will experience FN. Univariate and multivariate analyses of risk factors for FN were performed on a retrospective cohort of 112 consecutive patients treated with various chemotherapy regimens. Two independent risk factors were identified by the logistic regression and used to create a risk model for FN. The validity of the model was tested in three distinct groups of patients: two prospective groups of patients treated in two institutions (Centre Léon Berard [CLB] and Institut G. Roussy [IGR]) and the group of patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) treated with the doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) regimen between 1988 and 1992 at CLB. Within the retrospective group, 23 of 47 (49%) patients with lymphocyte counts < or = 700/microL at day 5 after chemotherapy experienced FN compared with seven of 65 (11%) of other patients (P = .00002). The type of chemotherapy (high dose v others) was also significantly correlated to FN (48% v 11%, P = .0003). Age, performance status, the number of previous chemotherapy cycles, or polymorphonuclear leukocyte (PMN) counts, were not significantly correlated to the incidence of FN in univariate analyses. Two independent risk factors were identified in the logistic regression: day 5 lymphocyte counts (beta = 1.97 +/- 0.53) and the type of chemotherapy regimen (beta = 1.91 +/- 0.53). The calculated probability to experience FN in patients with none, one, and both of these risk factors was 4.3%, 24.0%, and 68.8%, respectively. The validity of this model was tested in the three groups of patients used as validation samples. The observed incidences of FN in the above defined risk subgroups were 3%, 19%, and 67%, respectively, within the CLB prospective series and 6%, 19%, and 75% within the IGR prospective series. In the ACVBP group, the incidence of FN was 33% and 72%, respectively, in patients from the intermediate- and high-risk groups. In the two prospective groups and in the ACVBP series, the observed numbers of FN in the different risk groups did not differ significantly from those calculated by the model (P = .89, P = .86, and P = .72 for these three groups, respectively). Day 5 lymphocyte counts < or = 700/microL and the type of chemotherapy regimen enable oncologists to define subgroups of patients treated with chemotherapy as those with a high intermediate, and low risk of FN. These criteria could be used to select subjects in whom prophylactic measures for FN, in particular hematopoietic growth factors, should be proposed.