High Rate Of Febrile Neutropenia Research Articles

Chemo-Mobilization Provides Superior Mobilization and Collection in Autologous Stem Cell Transplants but with Less Predictability and At a Higher Cost,

Abstract 4048 Introduction:Chemotherapy + GCSF mobilization and GCSF alone are the most common mobilization regimens for autologous stem cell transplant (ASCT). We examined the benefits and limitations of both regimens in terms of mobilization success, predictability and costs. Methods:A retrospective, multi-center chart review was conducted of multiple myeloma (MM) and lymphoma patients mobilized between January 1, 2006 and December 31, 2007 for ASCT. Patients were excluded if they were mobilized with plerixafor (Mozobil®) or enrolled in a clinical trial of mobilization regimens. Data collected included demographics, disease and treatment history, mobilization regimen, blood counts, aphaeresis, remobilization, cells transplanted, time to engraftment and resource use. Stem cell collection practices and related clinical outcomes were analyzed separately for patients that were mobilized with chemotherapy + GCSF vs. GCSF alone. Resource use was evaluated using US unit cost data. Results:Data were collected for 227 consecutive patients from 11 centers (143 patients that received a chemotherapy + GCSF mobilization regimen and 84 patients who received GCSF alone). Total cells collected were significantly higher in the chemotherapy + GCSF mobilization group compared to GSF alone (18.6 × 106/kg vs.7.0 × 106/kg, p<0.001). While chemotherapy mobilization resulted in fewer days of aphaeresis (2.0 vs. 2.9; p<0.001), it was also associated with longer time to aphaeresis (12.5 days vs. 4.2 days; p<0.001), greater resource use and higher rates of febrile neutropenia. The chemotherapy + GCSF mobilization group had fewer re-mobilizations compared to GCSF alone (1.06 mobilizations vs. 1.2; p=0.016, 4.2% of chemotherapy + GCSF patients had more than one mobilization compared to 16.7% in GCSF alone).Even with fewer aphaeresis days and re-mobilizations, the cost total cost of mobilization, remobilization and aphaeresis with chemotherapy + GCSF was higher than GCSF alone ($19,614 vs. 16,852; p=0.003). Higher chemotherapy + GCSF costs were driven by the costs of chemotherapy, and extra days of GCSF. Chemotherapy + GCSF was also harder to predict in terms of timing the first day of aphaeresis. In patients receiving GCSF alone, the majority (95%) of first day aphaeresis occurred between Monday and Wednesday with the remaining 5% occurring on a Thursday or Friday. In contrast, chemotherapy + GCSF mobilizations resulted in 74.1% of first day aphaeresis occurring between Monday and Wednesday, 12.6% on Thursday and Friday and a further 13.3% occurring on a Saturday or Sunday. Discussion:Significant differences in mobilization success, costs and predictability were observed between patients that received chemotherapy + GCSF and those that received GCSF alone. While a chemotherapy + GCSF mobilization regimen may provide better mobilization and collection, there is a trade-off in terms of predictability, time to collection, costs and rate of febrile neutropenia. However, as chemotherapy + GCSF may be used for the treatment of the underlying malignancy; its use may not be completely comparable to GCSF mobilization alone. Disclosures:Grima:Cornerstone Research Group Inc.: Employment, Equity Ownership. Holmberg:Genzyme: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Research Funding; Otsuka: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Celgene: Research Funding. Fung:Genzyme: Consultancy, Honoraria, Speakers Bureau. Brown:Cornerstone Research: Employment. Horwitz:Genzyme: Honoraria, Research Funding. Bernard:Cornerstone Research: Employment, Equity Ownership. Shaughnessy:Genzyme: Consultancy, Honoraria, Research Funding, Speakers Bureau; Millenium: Honoraria, Speakers Bureau; Otsuka: Honoraria, Speakers Bureau.

Incidence of febrile neutropenia in patients with early-stage breast cancer receiving adjuvant FEC-D treatment.

e11520 Background: Adjuvant chemotherapy is associated with serious toxicities such as febrile neutropenia (FN). FEC-D is currently the most common taxane-containing regimen used for early stage breast cancer (ESBC). In clinical practice, clinicians have noted a much higher rate of FN. The aim of the present study was to examine the incidence of FN in women receiving FEC-D for the treatment of ESBC. Secondary aims included reporting hospital admission and length of stay of patients with FN and the potential benefit of using granulocyte colony-stimulating factors (G-CSF) as primary prophylaxis with FEC-D. Methods: Retrospective chart reviews was conducted on all women with breast cancer referred to The Moncton Hospital, Canada between January 2005 and December 2009. The collected data was subsequently entered manually into Microsoft Access, which is used to build the Moncton Hospital Breast Cancer database. The data collected included: patient demographics, staging, hormone receptor status, number of patients treated with FEC-D, FN rate, admission to hospital, length of hospitalization and use of G-CSF. Results: A total of 127 patients were treated with FEC-D. Of these, 41 experienced FN, giving a total incidence of 32%. All of these patients required hospitalization with an average length of stay of 5.78 days. There was no toxic death. Patients who received primary prophylaxis had a lower incidence of FN (10%; 2/21) compared to those who did not receive primary prophylaxis (37%; 39/106). Further analysis of our data revealed that 44% of FN occurred during the FEC treatment while the remaining 56% occurred during the Docetaxel treatment. Conclusions: The incidence of FN in this retrospective analysis of ESBC patients receiving adjuvant FEC-D treatment without primary prophylaxis demonstrates a much higher rate(37%) than the rate initially reported in the PACS-01 study (11.4%). Our observations are consistent with those of other studies which also report high incidences of FN (24% and 29.4%). Patients who received primary prophylaxis in the present study had a lower incidence of FN (10%). Consistent with ASCO guidelines, prophylactic G-CSF should be considered for ESBC patients receiving an adjuvant FEC-D regimen.

The cost-effectiveness of primary prophylaxis with granulocyte colony-stimulating factor in docetaxel-containing adjuvant chemotherapy in early breast cancer: The impact of risk of febrile neutropenia and its mortality.

6086 Background: Studies have shown higher rates of febrile neutropenia (FN) with docetaxel (D) containing chemotherapy (C) in early breast cancer (BC) patients than those in clinical trials (CTs). Previous cost-effectiveness analyses (CEA) on FEC-D vs FEC and primary prophylaxis (PP) of granulocyte colony stimulating factor (GCSF) were based on FN risk from CTs that may not reflect the real world. These CEA lacked the complexity to model the risk of FN per cycle, address use of PP vs secondary prophylaxis (SP) & examine long term efficacy of FEC-D vs FEC jointly. Methods: A 2-stage Markov model was developed for a hypothetical cohort of patients age 50 with early BC. First stage modeled costs/outcomes of 6 cycles C (FEC or FEC-D), including events related to FN, complications and G-CSF use (either PP or SP). Second stage modeled costs/outcomes of local/distant relapse, and death from BC (10 year horizon). Efficacy data of C and G-CSF, and utility were obtained from published data. Model was based on 3rd party payer (2010 Canadian dollars - 3% discounting rate). 4 strategies were used: (S1) FEC x 6 with SP, (S2) FEC x 3 with SP → D x 3 with SP, (S3) FEC x 3 with SP → D x 3 with PP, (S4) FEC x 3 with PP → D x 3 with PP. Results: At a willingness-to-pay (WTP) threshold of $50,000/QALY, S2 is preferred to S1 when risk of FN with D per cycle without G-CSF is < 9%, 6% or 4% if risk of death from FN is 1%, 5% or 10% respectively. S3 may be preferred if the risk of death from FN is > 14%. At a WTP of $100,000/QALY, S3 is preferred to S2 when risk of FN with D per cycle is > 12%, 4% or 2% if the risk of death from FN is 1%, 5% or 10% respectively. S4 is preferred to S3 only if risk of death from FN is > 18%. S1 is preferred only if risk of FN with D per cycle is much > 40%. Conclusions: We developed an economic model to determine the cost-effectiveness of different C/GCSF strategies in early BC, calibrated to the efficacies reported in CTs. In the “real world”, the most cost-effective strategy will depend on accurate understanding of the risk of developing/dying from FN in the non CTs setting. Societal WTP threshold will have a significant impact on defining the optimal systemic approach.

Abstract P5-10-25: Docetaxel/Cyclophosphamide (TC) Chemotherapy for Early Breast Cancer: Is Primary g-csf Prophylaxis Necessary?

Abstract Introduction Febrile neutropenia (FN) is a recognised complication of adjuvant systemic chemotherapy which leads to hospitalisation, treatment delays and dose reductions which ultimately may compromises treatment efficacy and patient (pt) outcomes. The use of granulocyte-colony stimulating factor (G-CSF) is recommended within clinical guidelines as routine prophylaxis if the chemotherapy regimen is likely to cause FN rates of &amp;gt;20%.For regimens associated with FN rates of 10-20%, pt may increase the risk.(Aapro et al, 2006). Following the publication of Jones et al (2006), the Beatson West of Scotland Cancer Centre (BWOSCC) adopted TC chemotherapy as an option for patients with intermediate/high risk breast cancer as an alternative to anthracyline based regimens. This was primarily for patients who had major co-morbidities precluding anthracycline use, had prior exposure to anthracylines or who were deemed unable to tolerate a protracted course of treatment for clinical reasons. The study by Jones et al (2006) described an overall FN rate of 5% with an increased rate of FN (8%) in patients &amp;gt; 65 yrs, with a 4% rate in those &amp;lt;65yrs. Recently Soong et al (2009) reported a higher rate of FN of 50% within the first cohort of patients (6/12 pts) treated within their centre, which resulted in subsequent prophylactic G-CSF usage. A recent paper by Chan et al (2010) concluded that Asian patients who have a recognised higher incidence of Docetaxel induced myelosuppresion warranted G-CSF propylaxis. Their experience of using TC resulted in FN rates of 25% in those patients who didn't receive G-CSF, 6.3% FN rates in those who did with an absolute risk reduction of FN events by 18.7%. With this in mind, an audit of our local practice and usage of TC chemotherapy was conducted. Methods A retrospective/prospective case note review of patients treated using (neo) adjuvant TC within the BWOSCC and satellite units between October 2007 and October 2010 is being undertaken. Data in respect to the first 51 consecutive pts identified from pharmacy records, treated between October 2007 and October 2009 is available. The median age was 58 (range 27 — 81): female 50, male 1: adjuvant 50, neo-adjuvant 1. All patients received Docetaxel 75mg/m2 and Cyclophosphamide 600mg/m2 at first cycle. Results 5/51 pts (9.8%) had an episode of FN, 2 pts at cycle 1, with 1 pt at cycles 2, 3 and 4. No pt had more than 1 episode of FN.22 pts (43%) received primary G-CSF prophylaxis whilst 29pts (57%) did not. The rate of FN in the primary prophylactic group was 9% (2/22 pts) and 10% (3/29pts) in those who didn't receive G-CSF. In the G-CSF group, 1 patient required a dose reduction and 5 patients had dose delays whilst 5 patients had a dose reduction and 3 required dose delays in the non G-CSF group. Conclusion The overall rate of FN observed was approximately 10% and for a substantial proportion of patients, primary prophylaxis with G-CSF is not required. Results of ongoing data collection will be presented with regard to patient characteristics, outcomes, and indications for G-CSF primary prophylaxis in this group of patients. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-25.

Hematologic toxicity with adjuvant docetaxel and cyclophosphamide in early breast cancer.

e11081 Background: After the results of docetaxel and cyclophosphamide (TC) superiority over doxorubicin and cyclophosphamide (AC) scheme, TC has been adopted at the A. C. Camargo Cancer Hospital as an option for adjuvant chemotherapy to early-breast cancer patients. However we have noticed a high rate of febrile neutropenia with this schedule. Methods: We conducted a retropective analysis of all patients with early breast cancer submitted to adjuvant chemotherapy with docetaxel 75 mg/m2 plus cyclophosphide 600 mg/m2, between January 2008 and July 2009, at A. C. Camargo Hospital in São Paulo-SP, Brazil. Primary end-point was to evaluate the rate of febrile neutropenia. Results: We have treated 30 women with TC. Median age was 55.7 years (33 to 76 years old). With regards to histologic caracteristics 58.6% were T1, 37.9% were T2, with a median tumor size of 16 mm; 6.9% had macroscopic positive axilar node; 65.5% patients were hormone receptor positive, 13.8% were HER2/neu positive. There was a total of 118 cycles of TC and we had 41.9% (n = 12) of patients with grade 3 or 4 neutropenia, and 31% (n = 9) needed hospitalization for febrile neutropenia (FN). Two patients initated TC with primary prophylaxis with growth factor. When we analysed only the first cycle, we found that 20.9% (n = 6) of patients had FN. After the first event, the use of secundary prophylaxis was initiated in all patients (n = 7) and there was still two further hospitalization for NF. One of them had dose reduction. Mean time of filgrastim 300 mcg/d administration was 5 days. We had no death related to FN. Ninety-three percent of all patients completed the treatment programmed. Conclusions: We have found a higher rate of FN with hospitalization (31%), in contrast with the hematologic toxicity reported preveously by US Oncology Group. The use of growth factor was able to prevent most of further hospitalization and mantain dose-intensity. G-CSF prophylaxis should be used in patients receiving adjuvant TC. No significant financial relationships to disclose.

Open-label, multicenter, phase Ib, dose-escalation study of oral lapatinib (L) in combination with docetaxel (D) and trastuzumab (T) in untreated HER2-overexpressing (HER+) metastatic breast cancer (MBC).

1049 Background: While most patients with HER+ MBC respond to treatment with D+T, the majority ultimately develop and die from progressive MBC. L produces responses in patients with T-pretreated HER+ MBC, and the combination of T+L is synergistic in vitro and superior to L in a trial in T-failed MBC. There is thus a rationale for the study of D+L+T in HER+ MBC. We performed a phase Ib study to determine the recommended optimally-tolerated, first-line regimen for phase II trials (ROTR) of these drugs in patients with untreated HER+ MBC. Methods: Eligibility criteria included HER+ MBC (3+ immunochemistry and/or FISH positive). T was given weekly at a fixed dose of 2mg/kg IV following a loading dose of 4mg/kg. D was given IV every 3 weeks at increasing doses (60, 75, and 100mg/m2). L was given orally once daily at increasing fixed doses (500, 750, 1,000, 1,250, and 1,500mg). Dose escalation followed a classical 3+3 design. Dose-limiting toxicities (DLT) were assessed during the first treatment cycle. The ROTR was defined as the dose level that produced a rate of DLT <33%. The protocol was amended to include growth-stimulating factor (GSF) support because of a high rate of febrile neutropenia at the first 2 dose levels. Results: Fifty patients with locally advanced or metastatic breast cancers were enrolled. Median age was 51 years (range: 22-67). Most patients had an ECOG performance status of 0 or 1. Sites of metastatic disease included bone (52%), lung (36%), liver (34%), and brain (4%). Twenty-six (52%) patients received prior adjuvant chemotherapy, including T in 23 (46%) patients. DLTs consisted mainly of myelosuppression, rash, diarrhea, and peripheral neuropathy. Two ROTR have been determined, including T in combination with L 1,250 mg daily and D with GSF support 75 mg/m2; IV every 3 weeks, or L 1,000 mg and D 100 mg/m2;. Efficacy data will be presented. Conclusions: L in combination with D and T is tolerable with 2 ROTR: either L 1,250 mg-D 75 mg/m2; or L 1,000 mg-D 100 mg/m2; with T. The first regimen is 1 of the study arms of the adjuvant ALTTO trial. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline Celgene, Debiopharm, GlaxoSmithKline, Pierre Fabre Oncologie, sanofi-aventis

Impact of colony-stimulating factors to reduce febrile neutropenic events in breast cancer patients receiving docetaxel plus cyclophosphamide chemotherapy

Data from US Oncology Adjuvant Trial 9735 has shown that four cycles of docetaxel plus cyclophosphamide (TC) improved disease-free and overall survival when compared against doxorubicin and cyclophosphamide (AC) in early-stage breast cancer. The febrile neutropenia (FN) rate was 4% in this study without primary granulocyte colony-stimulating factors (G-CSF) prophylaxis. However, the incidence of docetaxel-induced myelosuppression is recognized to be higher among Asian population. Hence, this study was designed to evaluate the impact of G-CSF to reduce FN-related events in Asian cancer patients treated with TC. This retrospective cohort study was conducted on Asian breast cancer patients who have received intravenous docetaxel 75 mg/m(2) and cyclophosphamide 600 mg/m(2) between 2006 to 2008. Patients did not receive oral antibiotic prophylaxis, and prophylactic G-CSF after chemotherapy was prescribed under the discretion of the primary oncologist. During cycle 1 of chemotherapy, 6.3% patients received G-CSF manifested FN, while 25% patients who did not receive G-CSF manifested FN (RR = 0.252, 95% CI 0.102 to 0.622). Introduction of G-CSF as primary prophylaxis provided an absolute risk reduction of FN events by 18.7%. Chemotherapy doses were maintained throughout all cycles. Patients with pretreatment white blood cell counts (WBC) below 6.0 × 10(3)/mm(3) and absolute neutrophil counts (ANC) below 3.1 × 10(3)/mm(3) were associated with higher rates of FN during Cycle 1 (p = 0.009, p = 0.007). Our findings indicate that TC was associated with higher rates of FN than reported in the clinical trial. The 25% incidence fulfills the requirement of primary prophylaxis with G-CSF. Routine administration of G-CSF is highly recommended to reduce the rates of FN in breast cancer patients receiving TC.

Incidence of Febrile Neutropenia with Taxane-Based Systemic Therapy in Women with Early Stage Breast Cancer.

Abstract Background: Febrile neutropenia (FN) is one of the most significant toxicities experienced by patients treated with systemic therapy. Taxanes now play an integral role in the systemic therapy for women with early stage breast cancer. The most common taxane-containing regimen utilized in Ontario, Canada is 5-Fluorouracil/Epirubicin/Cyclophosphamide x 3 followed by Docetaxel x 3 (FEC-D). PACS 01 reported a febrile neutropenia (FN) rate of 11.2% in the FEC-D arm. In our clinical practice, clinicians have noted a much higher rate of FN. We report the FN rate with the use of FEC-D in women with early stage breast cancer treated at tertiary care centers in Ontario.Methods: All women with early stage breast cancer who were treated with FEC-D from three tertiary care cancer centers in Ontario, Canada (London, Sudbury, Ottawa) between June 2006 and December 2008 were included in this retrospective analysis. Data included: demographics, staging, hormone receptor status, primary prophylaxis use with growth factors, FN rate, admission to hospital and duration of hospital admission.Results: Median age of 630 women is 52 years (r: 24-77). Staging was: I (88), IIA (243), IIB (159), IIIA (94), IIIB (23), IIIC (14) and 9 unknown. A total of 474 (75.2%) were ER positive. Primary prophylaxis with growth factor support was given to 222 patients (35%) and 408 patients (65%) did not have upfront prophylaxis. Of the 222 patients who were given primary prophylaxis, 14 patients (6.3%) were diagnosed with FN. Of the 408 patients who did not receive primary prophylaxis, 120 patients (29.4%) were diagnosed with FN. All patients (n=120) diagnosed with FN received secondary prophylaxis with growth factor support. A total of 126 patients (20%) were admitted to hospital for FN. The median duration of hospital admission was 3.9 days (r: 1-65 days). The impact of risk factors, the use of filgastrim versus pegylated filgastrim on FN rates and the clinical ramifications of febrile neutropenia (ICU admissions/deaths) will be reported.Conclusions: The results of this retrospective analysis demonstrate a much higher risk of FN (29.4%) with FEC-D than has been previously reported. More complete reporting of primary prophylaxis is required. This rate of FN would warrant use of primary prophylaxis for patients prescribed FEC-D, particularly in high risk subgroups. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2087.

High Rate of Febrile Neutropenia in Patients With Operable Breast Cancer Receiving Docetaxel and Cyclophosphamide

High Rate of Febrile Neutropenia in Patients With Operable Breast Cancer Receiving Docetaxel and Cyclophosphamide

A phase I study of sorafenib in association with docetaxel-prednisone in chemonaive metastatic castration-resistant prostate cancer

5153 Background: Docetaxel (D)-prednisone (P) is the standard regimen for metastatic castrate-resistant prostate cancer (mCRPC). Sorafenib (S) is a dual-action kinase inhibitor that blocks cell proliferation and angiogenesis with antitumor activity in CRPC. The objectives were dose limiting toxicities (DLTs)/recommended dose (RD) of S in combination with D-P, pharmacokinetics (PK), and safety at the RD in an expanded cohort. Methods: 6 pts were enrolled per dose level (DL). All pts received D 75 mg/m2/3 wks in 6 chemotherapy cycles and P 10 mg/d. S dose escalation included 4 DL. DL 1: S 200 mg bid from day 3 to 19 of each chemotherapy cycle. DL 2: S 200 mg bid started at day 3 of the 1st cycle and continued without interruption through the cycles. DL 3: S 400 mg bid from day 3 to 19 of each cycle. DL 4: S 400 mg bid started at day 3 of the 1st cycle without interruption through the cycles. DLTs were determined during the first cycle. Results: 24 chemo-naive mCRPC pts (median age 68) were included in the dose-escalation study. PK analysis showed that mean Cmax and AUC of D were increased at cycle 2 in cohort 2, 3, and 4 indicating a PK interaction dependent on the exposure to S. For the 24 pts, the main Gr 3–4 toxicities (N pts) were febrile neutropenia (8), uncomplicated neutropenia (5), and hand-foot syndrome (4). No DLT was found. PSA response (&gt; 50% in PSA decrease) was recorded in 15 out of 20 pts. Conclusions: The RD of S in combination with D is 400 mg bid continuously. PK analysis revealed an interaction between D and S that may explain the high rate of febrile neutropenia and Gr4 neutropenia. 14 pts were included in an expanded cohort to further explore the safety of this regimen. Updated data will be presented. [Table: see text] No significant financial relationships to disclose.

Retrospective study of efficacy and toxicity on patients older than 70 years within a randomized clinical trial of two cisplatin-based combinations in patients with small-cell lung cancer

A retrospective analysis based on the Spanish Lung Cancer Group (SLCG) clinical trial of high-dose epirubicin/cisplatin in patients with small-cell lung cancer (SCLC) was performed. Patients younger than 70 years vs. older than 70 years old were analyzed to evaluate the influence of age on response to treatment, toxicity, time to progression (TTP) and overall survival (OS) of the chemotherapy schedule. Three hundred and thirty eight patients <70 years and sixty-four >70 years, were analyzed. Objective responses were similar in both groups. In patients less than 70 years higher TTP (36 weeks vs. 32 weeks) and OS (47 weeks vs. 42 weeks) were seen, attributable to the improved results observed in the subgroup of patients with limited disease (LD). No significant differences were observed when toxicity profile of both groups was compared, except for a higher rate of febrile neutropenia observed in the elderly group with extensive disease (4.6% vs. 8.8%, p=0.01). In the subgroup of patients with LD, elderly patients received less total cisplatin dose (401 vs. 508 mg/m(2), p=0.01) although less treatment delays were reported (10 days vs. 15 days, p=0.05). Age was likely to be a negative prognostic factor for OS of elderly patients with LD. It also seemed to be related to a greater dose reduction, which may explain that toxic episodes and delays occurred more frequently in the younger patients receiving the full scheduled dose. However, the definitive reason to explain this could not be established due to the characteristics of our analysis.

Erlotinib and vinorelbine in advanced malignant solid tumors: a phase I study

Erlotinib is an oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI). Vinorelbine, a vinca alkaloid, interferes with microtubule assembly inhibiting mitosis during metaphase. Both drugs are commonly used as single agents in the treatment of advanced non small cell lung cancer (NSCLC). Given their efficacy in NSCLC and their non-overlapping toxicity profile, we conducted a phase I study of erlotinib and vinorelbine to establish the feasibility and safety of the combination and to determine the maximum tolerated dose (MTD). Patients with advanced solid tumors were treated with vinorelbine intravenously on day 1 and 8 and erlotinib orally daily on a 21 day schedule. The dose levels of vinorelbine/erlotinib were 25 mg/m(2)/100 mg, 25/150 and 30/150. Sixteen patients were enrolled. Five patients were chemo-naïve; 11 had one prior therapy. The majority of patients had NSCLC (n = 7). Dose limiting toxicities included febrile neutropenia (4 patients) and grade 5 infection (1 patient). Non-hematologic grade 3/4 toxicities included diarrhea, hypokalemia, infection, dyspnea and mucositis. Of 12 patients assessable for radiologic response, there were no objective responses; eight had stable disease. (1) The MTD was vinorelbine 25 mg/m2 day 1 and 8 with erlotinib 100 mg/day every 21 days. (2) The combination was associated with high rate of febrile neutropenia (25%). (3) Due to subsequent data demonstrating a lack of efficacy of erlotinib in combination with platinum doublets in advanced NSCLC, this combination has not been explored further.

Final Results of a Placebo-Controlled Study of Filgrastim in Small-Cell Lung Cancer: Exploration of Risk Factors for Febrile Neutropenia

BackgroundA phase III study of filgrastim as an adjunct to combination chemotherapy in previously untreated patients with limited- or extensive-stage small-cell lung cancer was conducted. This final analysis explores baseline factors that might predict febrile neutropenia and also reports the results of 463 open-label filgrastim cycles that were delivered after patients' initial episode of the primary endpoint, ie, febrile neutropenia. Patients and MethodsA total of 244 patients were randomized to receive placebo or filgrastim in ≤ 6 cycles of chemotherapy (cyclophosphamide/doxorubicin/etoposide). ResultsThe cumulative percent of patients receiving filgrastim who experienced febrile neutropenia was approximately 50% lower than those given placebo (38% vs. 74%, respectively; P < 0.0001). Significant treatment-related reductions were also seen in the incidence and duration of grade 4 neutropenia. Cycle 1 displayed the highest incidence of neutropenia with or without fever and the longest duration of neutropenia relative to later cycles. Patients crossing over to open-label filgrastim from their blinded treatment assignment displayed event rates similar to those in the blinded filgrastim group. Patients who experienced febrile neutropenia in cycle 1 were at a significantly higher risk for subsequent events compared with those who were event-free in cycle 1. Women displayed a higher risk for febrile neutropenia than men, but no other baseline risk factors were detected. ConclusionGiven the high rate of febrile neutropenia in cycle 1 and the higher risk for subsequent events in patients with a cycle 1 event, we conclude that growth factor administration starting in cycle 1 should be considered for patients receiving moderately to highly myelosuppressive chemotherapy regimens.

Toxicity and health-related quality of life (HRQoL) in node-negative breast cancer (BC) patients (pts) receiving adjuvant treatment with TAC (docetaxel, doxorubicin, cyclophosphamide) or FAC (5-fluorouracil, doxorubicin, cyclophosphamide): Impact of adding prophylactic growth factors (GF) to TAC. GEICAM Study 9805

604 Background: Node-positive BC pts treated with TAC have a longer disease-free and overall survival but a higher rate of febrile neutropenia (FN) compared with pts treated with FAC. We evaluated the toxicity and HRQoL of both regimens and assessed the impact of adding prophylactic granulocyte GF to TAC.Methods: 1059 pts with operable, high-risk (St Gallen, 1998), node-negative BC, 18–70 yrs old, were randomized to FAC (F 500 mg/m2, A 50 mg/m2, C 500 mg/m2) or TAC (T 75 mg/m2, A 50 mg/m2, C 500 mg/m2) day 1 every 3wks for 6 cycles. After enrolling 224 pts, the study was amended to require prophylactic GF for pts subsequently treated with TAC, but not FAC. The EORTC QLQ-C30 was administered at baseline, after each chemotherapy cycle and 6, 12 and 24 months after completion of chemotherapy. Rates of FN (fever ≥gr 2 with gr 4 neutropenia), severe asthenia, gr 3–4 diarrhea, and gr 2–4 mucositis were analyzed. Results: 530 pts received TAC, 114 without GF [TAC] and 416 with GF [TAC+G]; 520 received FAC. During chemotherapy, HRQoL was worse with TAC than with FAC (p=0.008), with a maximum difference of 8.0 points during cycle 4. However, no statistically significant differences in HRQoL were observed between TAC+G and FAC, with 6.1 points as the highest difference during cycle 3. During the follow-up period, no statistically significant differences in HRQoL were observed among TAC alone, TAC+G and FAC. The incidence[95%CI] of: FN was 2.3%[1.0–3.6%] for FAC, 24.6%[16.7–32.5%] for TAC, and 5.8%[3.53–8.01%] for TAC+G; gr 3–4 diarrhea 0.8% FAC, 7.0% TAC, and 2.6% TAC+G (p=0.0415); severe asthenia 1.8% FAC, 20.2% TAC, and 5.5% TAC+G (p<0.0001); gr 2–4 mucositis 24.4% FAC, 35.1% TAC, and 23.3% TAC+G (p=0.011). Conclusions: TAC transiently worsens HRQoL compared with FAC during chemotherapy. However, BC pts treated with TAC plus GF support experience the same HRQoL as pts treated with FAC. The addition of GF to TAC significantly reduces the incidence of FN, gr 3–4 diarrhea, severe asthenia, and gr 2–4 mucositis compared with TAC alone. No significant financial relationships to disclose.

Predicting Risk of Febrile Neutropenia after CHOP Chemotherapy.

Introduction: Febrile neutropenia (FN) is a major cause of morbidity following chemotherapy for lymphoma and results in increased hospitalization, antibiotic use and cost. Predicting who is at highest risk of FN allows preventive measures such as GCSF to be used for those who will benefit the most. This study was performed to determine the incidence of FN and to identify which prognostic factors may predict for increased risk for FNMethods: Retrospective chart review of patients who received CHOP or CHOP plus Rituximab chemotherapy between 2001– 2003 at our centre. The following prognostic factors were used- IPI score, LDH, age, stage, number of extranodal sites, performance status, B symptoms, bone marrow involvement, albumin (ALB), hemoglobin (HGB), platelet count and neutrophil count prior to first chemotherapy. Outcome measured was FN after any cycle of chemotherapy.Results: Seventy patients receiving a total of 232 cycles (median 6, 1–8) were included. Twenty-one patients were male and 39 were female. Median age was 60 (29 – 85). LDH was elevated in 56%, 21% had bone marrow involvement, 25% had ECOG > 1, 21% had >1 extranodal site involved and 32% had B symptoms. 30% of patients had IPI score 0–1, 64% IPI 2–3, and 6% IPI 4–5. CHOP alone was given to 51(73%) of patients and 19 (27%) patients received CHOP plus Rituximab. FN occurred in 50 out of 232 cycles (22%). 42% of patients developed FN, 21% with their 1st cycle. Thirteen (19%) patients had more than 1 episode of FN. Two patients received primary prophylaxis with G-CSF prior to 1st cycle of chemotherapy and neither developed febrile neutropenia. 29 patients started secondary prophylaxis with G-CSF after developing FN, or for other reasons, and 13 of these (45%) had least one more episode of FN. These 29 patients received a total of 95 cycles of chemotherapy after starting secondary prophylaxis, and FN developed in 20 of these cycles (21%). By univariate analysis, only hemoglobin (p=.044) and albumin (p=0.01) were statistically significant predictors of FN. Using logistic regression analysis neither was an independent predictor due to high correlation between the two (r= 0.49, p<0.01). Using the mean values for HGB (110g/L) and ALB (30g/L), we found that rate of FN was 61% (19/31) if ALB, HGB, or both were below these thresholds, compared to 33% (13/39) if neither was low.Conclusion: The incidence of FN was almost twice as high in patients with low hemoglobin or albumin. Other factors were not statistically significant. These two factors may be indicative of poor underlying health and diminished bone marrow reserve, both of which could predispose to FN. Interestingly, disease specific factors such as IPI, LDH, etc were not predictive. On multivariate analysis, none of these prognostic factors appeared to be an independent predictor of febrile neutropenia. This was mainly due to the high correlation seen between the two, but may also be affected by the small sample size studied, and the overall unexpectedly high rate of FN in this group.

Chimiothérapie en pratique de routine des cancers bronchiques non à petites cellules (CBNPC) localement avancés ou métastasés: Évaluation des pratiques et analyse médico-économique

Patients in ANCCLC chemotherapy-trials are not representative of the general lung cancer population. The purpose of this study was to describe the ANCCLC population routinely treated by chemotherapy in a general hospital, and to assess the results of chemotherapy in this population.All newly diagnosed IIIB/IV ANCCLC chemotherapy-treated patients over a three-year period were prospectively assessed for response rate, toxicity and survival.Seventy seven patients (70% stage IV, 69% PS 1/0, 30% with cerebral metastases, 60% ineligible for major lung trials) received first-line chemotherapy (cisplatine or paraplatine with vinorelbine) with tumor control in 31 (40%) and symptom improvement in 20 (26%) patients. 17 (22%) patients experienced febrile neutropenia. 33 (43%) patients received second line chemotherapy (gemcitabine) with tumor control in 12 (36%) and symptom improvement in 9 (27%) patients. Overall median survival was 7 months and 30% patients were alive at 1 year.Routinely ANCCLC chemotherapy-treated patients in our center have poor prognostic factors and many comorbidities. Chemotherapy results in tumor control in 43% patients, - of whom two thirds have symptom improvement -, with a high rate of febrile neutropenia.

Prophylactic growth factor (GF) support with adjuvant docetaxel, doxorubicin, and cyclophosphamide (TAC) for node-negative breast cancer (BC): An interim safety analysis of the GEICAM 9805 study

620 Background: For patients (pts) with node-positive BC, TAC confers signficant disease-free and overall survival benefits vs FAC (5-fluorouracil, doxorubicin, cyclophosphamide), but with a higher rate of febrile neutropenia (Martin, SABCS 2003 ab 43). In our study of TAC vs FAC for node-negative BC, we performed an interim safety analysis to assess the impact of GF support on the incidence of TAC-related adverse events. Methods: Following surgery, patients (pts) with operable, high-risk (St Gallen, 1998), node-negative BC, 18–70 yr old, KPS ≥ 80%, and adequate hematologic and organ function were randomized to FAC (F 500 mg/m2, A 50 mg/m2, C 500 mg/m2) or TAC (T 75 mg/m2, A 50 mg/m2, C 500 mg/m2) day 1 every 3 wk for 6 cycles. After enrollment of 224 pts, the study was amended to require prophylactic G-CSF for pts subsequently treated with TAC, but not FAC. The present analysis assessed the impact of G-CSF on the incidence of febrile neutropenia (FN; fever ≥ grade 2 with gr 4 neutropenia) and other gr 3/...