Naxitamab, a new generation anti-GD2 monoclonal antibody (mAb) for treatment of relapsed/refractory high-risk neuroblastoma (HR-NB).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10543-10543
Author(s):  
Jaume Mora ◽  
Godfrey Chi-Fung Chan ◽  
Daniel A. Morgenstern ◽  
Karsten Nysom ◽  
Melissa K Bear ◽  
...  
Keyword(s):  
High Risk ◽  
Objective Response ◽  
High Risk Patient ◽  
Complete Response ◽  
Outpatient Setting ◽  
Response To Therapy ◽  
Gm Csf ◽  
Insufficient Response ◽  
Macrophage Colony ◽  
Relapsed Disease

10543 Background: NB is a rare cancer but represents the most common extracranial solid tumor of childhood. Most HR-NB patients present with or develop metastatic disease typically in bone or bone marrow (BM). Despite advances in frontline multimodal therapy ~50% of patients relapse. Refractory or relapsed disease represents an unmet medical need. GD2 is an adhesion molecule abundantly expressed in NB. Naxitamab is a humanized anti-GD2 mAb with high receptor affinity. Methods: We evaluated naxitamab in HR-NB patients with disease in bone and/or BM, who were refractory to initial treatment(s) or who had insufficient response to therapy for progressive/relapsed disease. Patients were treated in an outpatient setting with naxitamab as a planned 30-minute i.v. infusion and s.c. granulocyte-macrophage colony-stimulating factor (GM-CSF). Patients received 3 infusions of naxitamab 3 mg/kg/dose during the first week of a treatment cycle repeated initially every 4 weeks. Patients were evaluated for safety (CTCAE V4.0) and efficacy (INRC, Park et al. 2017). Results: We report on 24 patients recruited from April 2018 with a data cut off in June 2019. At diagnosis, 21 patients were stage 4, 1 was stage 3, 2 were unknown. At study entry, 11 patients had metastases in bone, 1 in BM and 12 in both bone and BM. Overall objective response was 75% (18/24), with complete response (CR) in 67% (16/24) and partial response in 8% (2/24). Of the 13 patients with BM involvement at enrollment, 12 achieved CR in BM during trial therapy. 6 treatment-related SAEs were reported in 5 patients (anaphylactic reaction, pyrexia, and respiratory depression). Conclusions: Naxitamab is an anti-GD2 mAb under development for HR-NB. In addition to a high CR rate of 67% and an overall objective response rate of 75% in a high-risk patient population, naxitamab offers an unique option for treatment of patients in the outpatient setting. These data and convenience to patients are strongly supportive of further drug development. Clinical trial information: NCT03363373.

Efficacy of naxitamab in patients with refractory/relapse (R/R) high-risk neuroblastoma (HR-NB) by bone/bone marrow (BM) evaluation, potential sites of residual disease.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10022-10022
Author(s):  
Brian H. Kushner ◽  
Daniel A. Morgenstern ◽  
Karsten Nysom ◽  
Melissa K. Bear ◽  
Karen Tornøe ◽  
...  
Keyword(s):  
High Risk ◽  
Residual Disease ◽  
Safety Data ◽  
The United States ◽  
Outpatient Setting ◽  
Minor Response ◽  
Overall Response ◽  
Gm Csf ◽  
Prior Therapy ◽  
Meaningful Activity

10022 Background: NB is the most common extracranial solid tumor in children and half of patients present with high-risk disease. Bone and BM are frequent sites of metastatic disease and can serve as a reservoir for residual disease driving relapse. Naxitamab, a GD2-binding monoclonal antibody, was recently approved in the United States in combination with GM-CSF for the treatment of pediatric patients ≥1 year of age and adult patients with R/R HR-NB in the bone/BM who have demonstrated a partial response (PR), minor response (MR), or stable disease (SD) to prior therapy. Here we describe outcomes from the registrational Trial 201 (NCT03363373) detailed by bone/BM involvement. Methods: HR-NB patients with primary refractory disease or incomplete response to salvage treatment following relapse or progressive disease (PD) (in both cases including SD, MR and PR) with disease limited to bone and/or BM were eligible. Naxitamab was administered over ≥30 min in the outpatient setting on Days 1, 3 and 5 at 3 mg/kg/infusion (9 mg/kg/cycle) in combination with GM-CSF at 250 µg/m2/day on Days -4 to 0 and at 500 µg/m2/day on days 1 to 5. Treatment cycles were repeated every 4 weeks. Response was assessed after Cycle 2 and then every 2-3 months by revised International Neuroblastoma Response Criteria (INRC) using BM biopsies/aspirates and 123I-MIBG scintigraphy or FDG-PET. Effectiveness was concluded if the lower limit of the Clopper-Pearson exact 95% confidence interval (CI) of overall response rate (ORR) was >20%. We report efficacy data on 22 patients and safety data on the first 25 patients enrolled. Results: 13 (59%) patients had NB in bone, 2 (9%) had NB in BM, and 7 (32%) had NB in both bone and BM. Summary of overall response and response by compartment. Conclusions: Naxitamab provided clinically meaningful activity in both bone and BM with ORR of 68% and had a manageable AE profile. Clinical trial information: NCT03363373. [Table: see text]

scholarly journals Intensive chemotherapy with mitoxantrone and high-dose cytosine arabinoside followed by granulocyte-macrophage colony-stimulating factor in the treatment of patients with acute lymphocytic leukemia

Blood ◽  
1992 ◽  
Vol 79 (4) ◽  
pp. 876-881 ◽  
Author(s):  
HM Kantarjian ◽  
EH Estey ◽  
S O'Brien ◽  
E Anaissie ◽  
M Beran ◽  
...  
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Remission Induction ◽  
Intensive Chemotherapy ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Thirty-four adults with refractory acute lymphocytic leukemia received salvage therapy with mitoxantrone 5 mg/m2 intravenously over 1 hour daily for 5 days and cytosine arabinoside (ara-C) 3 g/m2 intravenously over 2 hours every 12 hours for six doses, followed by granulocyte- macrophage colony-stimulating factor (GM-CSF) 125 microgram/m2 intravenously over 4 hours daily until recovery of granulocytes above 2.0 x 10(3)/microL. Their outcome was compared with 29 prognostically similar historical control patients treated with the identical chemotherapy without GM-CSF. Overall, the complete response rates were similar in the treatment and control groups (13 of 34 [38%] v 11 of 29 [38%]). There was a trend for less remission induction mortality in the GM-CSF-treated patients (2 of 34 [6%] v 6 of 29 [21%]; P = .08), but, conversely, a higher rate of resistant disease (19 of 34 [56%] v 10 of 29 [34%]; P = .09). Recovery of granulocyte counts above 500/microL was significantly faster in the GM-CSF-treated group (25 days v 33 days; P less than .01), but there was no reduction in the incidence of febrile episodes (91% v 93%) or of documented infections (59% v 59%). Survival was prolonged in the GM-CSF-treated patients but was not of clinical relevance (31 v 20 weeks; P = .05). In summary, the addition of GM-CSF to intensive chemotherapy in refractory adult ALL was associated with a reduction in the remission induction mortality, probably secondary to a shorter duration of granulocytopenia, but not with an improvement in complete response rates.

Increasing 4'-epidoxorubicin and fixed ifosfamide doses plus granulocyte-macrophage colony-stimulating factor in advanced soft tissue sarcomas: a pilot study.

1997 ◽  
Vol 15 (4) ◽  
pp. 1418-1426 ◽  
Author(s):  
S Frustaci ◽  
A Buonadonna ◽  
E Galligioni ◽  
D Favaro ◽  
A De Paoli ◽  
...  
Keyword(s):  
Dose Level ◽  
Response Rate ◽  
Objective Response ◽  
Colony Stimulating Factor ◽  
Hematopoietic Progenitors ◽  
Gm Csf ◽  
The Third ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

PURPOSE To determine the maximum-tolerated dose (MTD) of 4'-epidoxorubicin (EPI) in combination with full dose of ifosfamide (IFO) when granulocyte-macrophage colony-stimulating factor (GM-CSF) was used, to estimate its clinical efficacy, and to evaluate the mobilization of hematopoietic progenitors. PATIENTS AND METHODS Previously untreated advanced patients were treated with fixed doses of IFO at 1.8 g/m2/d for 5 days and escalating doses of EPI. The starting dose level of EPI was 50 mg/m2 bolus on days 1 and 2; subsequent levels were 60 mg/m2 and 70 mg/ m2 given on days 1 and 2. GM-CSF (5 micrograms/kg/d) was administered from days +6 to +19. Clinical evaluation of response was performed after three consecutive cycles. Mobilization of hematopoietic progenitors was evaluated as day 14 CFU-GM after the first cycle only. RESULTS Overall, six, 18, and 13 assessable patients were entered onto each EPI dose level, respectively. The first and the second EPI level were considered feasible. Conversely, at the third level, only six of 13 patients [46%] tolerated full EPI doses at the scheduled time. Therefore, the dose-intensity of the three levels was 100%, 99.7%, and 86.1%, respectively. Overall, 20 of 37 patients (54%) obtained an objective response. The response rates for the three EPI dose levels were significantly different [17%, 33%, and 100%, respectively; test for trend, P < .001]. Considering only lung metastases, the overall response rate was 72% (20%, 66%, and 100% for the three EPI levels, respectively). The most relevant mobilization effect was obtained at the third EPI level, when both GM-CSF and IL-3 were used as in vitro-stimulating factors. CONCLUSION The third EPI level (70 mg/m2 on days 1 and 2) is the MTD of this program, since it was administered, without dose reduction or treatment delay, for three consecutive cycles in less than half of the patients. Nevertheless, this level proved to be interesting with regard to response rate (13 of 13 objective responses) and in mobilization of the hematopoietic progenitors.

Therapeutic CSF Primed Donor Lymphocyte Infusion Using Cells Reserved at the Time of Transplantation for Patients with Relapsed Hematologic Malignancies after allo-PBSCT.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5285-5285
Author(s):  
Sang Kyun Sohn ◽  
YoonYoung Cho ◽  
JongGwang Kim ◽  
YeeSoo Chae
Keyword(s):  
High Risk ◽  
Complete Response ◽  
Hematologic Malignancies ◽  
Donor Lymphocyte Infusion ◽  
Cd34 Cells ◽  
New Development ◽  
Risk Patients ◽  
Unrelated Donors ◽  
Intent To Treat ◽  
Relapsed Disease

Abstract Background Reharvesting leukocytes from donors for a donor lymphocyte infusion (DLI) is inconvenient and occasionally impossible in case of unrelated donors. The effect of a growth factor-primed DLI is known to be comparable to that of nonprimed DLI for patients with relapsed disease. We reserved some portion of PBSCs harvested at the time of transplantation for the purpose of future DLI for relaping disease. Method In total, ninety nine patients (43 high risk, 46 standard disease) with hematologic malignancies who were treated by allo-PBSCT were allocated on an intent-to-treat basis. The dose of CD34+ cells with a range of 2–6*106/kg was transplanted, and additional PBSCs were cryopreserved. Result PBSC harvest for transplantation allowed to reserve extra cells in 35 (67.3%) high risk patients and in low risk 25 (55.6%) patients. Among 29 patients (29.9%) who relapsed after allogeneic PBSCT, 19 (65.5%) patients were treated with mainly cytarabine-based chemotherapy followed by cryopreserved PBSC infusion. The median dose of CD3+ and CD34+ cells for the primed DLI was 1.43*108/kg and 4.75*106/kg, respectively. Six (24.9%) out of 19 relapsed patients exhibited a complete response after the primed DLI, and their 1-year survival rate was 36%. The new development or progression of graft-versus-host disease after the primed DLI was observed in 16 (82%) patients. Overall, the survival at 1 year after the primed DLI was 21%. Conclusion The induction of a graft-versus-leukemia effect through a primed DLI, using additional PBSCs reserved at the time of transplantation, would appear to be feasible for patients with relapsed hematologic malignancies. Furthermore, this approach seem to be more convenient for donors.

Idiotype Vaccination in Human Myeloma: Generation of Tumor-Specific Immune Responses After High-Dose Chemotherapy

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 673-683 ◽  
Author(s):  
Massimo Massaia ◽  
Paolo Borrione ◽  
Silvano Battaglio ◽  
Sara Mariani ◽  
Eloise Beggiato ◽  
...  
Keyword(s):  
Immune Responses ◽  
Residual Disease ◽  
Interleukin 2 ◽  
Keyhole Limpet Hemocyanin ◽  
High Dose Chemotherapy ◽  
Outpatient Setting ◽  
Delayed Type Hypersensitivity ◽  
High Dose ◽  
Gm Csf ◽  
Macrophage Colony

Abstract Igs contain unique portions, collectively termed idiotypes (Id), that can be recognized by the immune system. Id expressed by tumor cells in B-cell malignancies can be regarded as tumor-specific antigens and a target for vaccine immunotherapy. We have started a vaccination trial in multiple myeloma (MM) using Id-specific proteins conjugated to keyhole limpet hemocyanin (KLH) as immunogens and low doses of subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-2 (IL-2) as immunoadjuvants. Twelve patients who had previously been treated with high-dose chemotherapy followed by peripheral blood progenitor cell (PBPC) transplantation entered this study from August 1995 to January 1998. All patients were in first remission at the time of vaccination. They received subcutaneous injections of Id vaccines and immunoadjuvants in an outpatient setting. The generation of Id-specific T-cell proliferative responses was documented in 2 patients, whereas a positive Id-specific delayed-type hypersensitivity (DTH) reaction was observed in 8 of the 10 patients studied. DTH specificity was confirmed in 1 patient by investigating the reactivity to synthetic peptides derived from the VDJ sequence of the tumor-specific Ig heavy chain. None of the patients generated soluble immune responses to Id, whereas the generation of soluble and cellular immune responses to KLH was observed in 100% and 80%, respectively. Eleven patients completed the treatment, whereas 1 patient failed to finish owing to progression of disease. Freedom from disease progression (FFDP), measured from the date of first Id/KLH injection to the date of first treatment after vaccination or last follow-up, ranged from 9 to 36 months. These data indicate that the immune competence status of MM patients is still susceptible to specific immunization after high-dose chemotherapy and PBPC transplantation. It remains to be determined whether generation of Id-specific immune responses can reduce the relapse rate of patients with minimal residual disease.

Immunological effects and clinical outcomes in patients with high-risk melanoma given adjuvant therapy with granulocyte-macrophage colony stimulating factor (GM-CSF, sargramostim)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20004-e20004
Author(s):  
L. E. Spitler ◽  
R. W. Weber ◽  
S. Cruickshank ◽  
T. L. Whiteside
Keyword(s):  
T Cells ◽  
High Risk ◽  
Clinical Outcomes ◽  
Peripheral Circulation ◽  
Activated T Cells ◽  
Gm Csf ◽  
High Risk Melanoma ◽  
Risk Melanoma ◽  
Immunological Effects ◽  
Macrophage Colony

e20004 Background: Our previous study suggested that administration of GM-CSF to high-risk melanoma patients may prolong survival (JCO 18(8):1614–1621, 2000) and led to a prospective randomized trial (E4697). This study has completed accrual and follow-up is now ongoing. Simultaneously, we conducted a follow-on study to gain further information about the immunological effects and clinical outcomes of adjuvant GM-CSF therapy of melanoma. Methods: GM-CSF, 125 μg/m2, was administered subcutaneously in 28-day cycles of 14 days on/14 days off for 1 year. Blood draws were keyed to GM-CSF administration: Days 0 (before), 15 (after 14 days on GM-CSF), 29 (after 14 days off GM-CSF), 155 and 351 (after 14 days on GM-CSF in the 6th and 13th cycle). Forty- nine patients were evaluable for immunologic responses on Day 15. Immunophenotyping of the white cell population was done on a subset consisting of 6 patients. Results: In 42 patients, there was an increase in the WBC counts to above normal after 14 days of GM-CSF therapy in the first cycle. This increase did not occur in 7 patients and these patients had a significantly shorter survival. There was a similar increase in neopterin levels following 14 days of GM-CSF administration, which returned to baseline after 14 days off therapy and did not correlate with clinical outcome. Immunophenotypic analysis showed an increase in activated and regulatory T cells and a decrease in the percent of CD11c+DC (myeloid) cells in the 6 patients evaluated, all returning to baseline on Day 29. Conclusions: GM-CSF therapy was associated an increase in the WBC counts in the majority of patients after 14 days of treatment and patients who did not experience this increase had a significantly shorter life expectancy. The observed increase in neopterin levels is consistent with macrophage activation as the potential mechanism of action of adjuvant GM-CSF administration. Additional immunologic effects which may play a role during GM-CSF therapy include the increase in activated T-cells and decrease in CD11c+DC, which may be moving from the peripheral circulation into the tissues. [Table: see text]

Evaluation of early response by anatomic imaging to predict survival among patients with group III rhabdomyosarcoma: A report from the Children’s Oncology Group.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10012-10012
Author(s):  
Douglas S. Hawkins ◽  
Abby R. Rosenberg ◽  
Elizabeth Lyden ◽  
James Robert Anderson ◽  
David A. Rodeberg ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Objective Response ◽  
Prognostic Significance ◽  
Complete Response ◽  
Early Response ◽  
Response To Therapy ◽  
Rank Test ◽  
Oncology Group ◽  
Group Iii ◽  
Kaplan Meier

10012 Background: The prognostic significance of response to induction therapy for rhabdomyosarcoma (RMS) by anatomic imaging (computerized tomographic [CT] or magnetic resonance imaging [MRI] scan) is controversial. We previously reported no relationship between early response and failure-free survival (FFS) for patients on IRS-IV. We repeated the same analysis using an independent cohort of patients with non-metastatic, initially unresected RMS treated on a more recent clinical trial. Methods: A total of 338 patients enrolled in Children’s Oncology Group study D9803 met the following inclusion criteria for this analysis: 1) non-metastatic, initially unresected (Group III); 2) embryonal (ERMS) or alveolar (ARMS) histology; 3) documented response to induction chemotherapy (excluding progressive disease) based on anatomic imaging; and 4) documented therapy beyond week 12. Response at week 12 was determined by the treating institution as complete response (CR, complete resolution), partial response (PR, decrease of >= 50% of the sum of the products of maximum perpendicular diameters), or no response (NR, between 50% reduction and 25% increase in the sum of the products of maximum perpendicular diameters). FFS was estimated using the Kaplan-Meier method, and comparisons between groups were made using the log-rank test. Results: Overall objective response rate (CR+PR) at week 12 of therapy was 85%, with similar responses for ERMS and ARMS. FFS was similar among all patients with CR, PR, or NR (p=0.49). Restricting the analysis to either ERMS or ARMS, there was no difference in FFS by histology (p=0.20 and p=0.45, respectively). Conclusions: These findings provide additional evidence that anatomic imaging assessment of early response to therapy among RMS patients does not predict outcome and should not be used to tailor subsequent therapy. Clinical trial information: NCT00003958. [Table: see text]

Phase I/II study of avadomide (CC-122) in combination with R-CHOP for newly diagnosed DLBCL.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3501-3501
Author(s):  
Neha Mehta-Shah ◽  
Julio C. Chavez ◽  
Pau Abrisqueta ◽  
Nathalie Johnson ◽  
Juan Miguel Bergua Burgues ◽  
...  
Keyword(s):  
High Risk ◽  
Phase 1 ◽  
Prognostic Score ◽  
Objective Response ◽  
Survival Rates ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Newly Diagnosed

3501 Background: In certain subsets of patients (pts) with diffuse large B-cell lymphoma (DLBCL), the failure rate of standard R-CHOP treatment is high. Pts with high-risk disease (International Prognostic score [IPI] 3-5) have a particularly poor prognosis, with 3-y survival rates of ~62% with R-CHOP alone. The cereblon E3 ligase modulator avadomide (CC-122) showed activity in pts with relapsed or refractory DLBCL. We report results of avadomide plus R-CHOP in previously untreated pts with high-risk DLBCL. Methods: CC-122-DLBCL-002 (NCT03283202) is a phase 1/2 study of avadomide plus R-CHOP-21 in pts newly diagnosed with DLBCL not otherwise specified with IPI scores 3-5 who were aged ≥18 y. Pts received standard R-CHOP and escalating doses (1-3 mg) of oral avadomide for up to six 21-d cycles (Table). All pts received pegfilgrastim support. Primary objectives were to assess safety, tolerability, and complete response (CR) rate. Secondary objectives include evaluation of additional efficacy parameters (objective response rate [ORR], progression-free survival [PFS], and overall survival) and biomarkers. Results: As of July 30, 2019, 35 pts were enrolled in the phase 1 part of the study. Median age was 66 y (range, 20-75), 23 pts (66%) were aged > 60 y, 18 (51%) had an IPI score of 3, and 17 (49%) had an IPI score of 4-5. Thirty-two pts (91%) completed 6 cycles of treatment. Median relative total dose intensity of avadomide was 99% and the average relative dose intensity of R-CHOP was 95%. Six pts had dose-limiting toxicities: 1 pt had neutropenia and bacterial hepatic infection; 1 had pneumonia; 1 had febrile neutropenia (FN); 1 had FN and hypotension; 1 had FN due to skin infections; and 1 had sepsis. The recommended phase 2 dose was 3 mg 2/3 wk. Grade 3/4 adverse events in ≥10% of pts were neutropenia (54%), anemia (20%), leukopenia (20%), lymphopenia (14%), hypophosphatemia (14%), and FN (11%). Among 34 efficacy-evaluable pts, the ORR was 88% (n = 30/34), including a CR rate of 79% (n = 27/34) at the end of treatment. With a median follow-up of 10 mo, the 1-y PFS rate was 80% (95% CI, 58-92). Correlative analyses will be presented at the meeting. Conclusions: Avadomide plus R-CHOP was well-tolerated with no significant additive toxicities. The promising efficacy in this high-risk pt population warrants further evaluation of immunomodulatory drugs combined with immunochemotherapy for pts with previously untreated DLBCL. Clinical trial information: NCT03283202 . [Table: see text]

Randomized, placebo-controlled, multicenter trial of granulocyte-macrophage colony-stimulating factor as infection prophylaxis in oncologic surgery. Leukine Surgical Prophylaxis Research Group.

1998 ◽  
Vol 16 (3) ◽  
pp. 1167-1173 ◽  
Author(s):  
N J Meropol ◽  
D E Wood ◽  
J Nemunaitis ◽  
N J Petrelli ◽  
B J Lipman ◽  
...  
Keyword(s):  
High Risk ◽  
Cancer Patients ◽  
Infection Prophylaxis ◽  
Colony Stimulating Factor ◽  
Postoperative Infections ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
To Receive ◽  
Stimulating Factor

PURPOSE Postoperative infections are a frequent source of preventable morbidity and mortality in the oncologic population. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent modulator of immune effector cells in vitro and in vivo. This study was conducted to determine whether GM-CSF, when administered perioperatively, could reduce the incidence of surgical infections in cancer patients. METHODS This was a prospective, randomized, placebo-controlled, multicenter study. Cancer patients at high risk of infectious surgical morbidity were randomized to receive GM-CSF 125 microg/m2 per day or placebo subcutaneously for 8 days beginning 3 days preoperatively. Routine antibiotic prophylaxis was administered to all patients. RESULTS Three hundred ninety-nine patients were enrolled, with 198 randomized to receive GM-CSF. Twenty-one percent of patients experienced infections during the first 2 weeks postoperatively, and there was no difference in infection rate between the study groups. The most common sites of infection were respiratory tract (53%) and surgical wound (25%). The duration of operation and American Society of Anesthesiology (ASA) physical status classification were the most significant predictors of infection in multivariate analysis. GM-CSF was well tolerated and was not associated with fever. CONCLUSION The eligibility criteria for this study were successful at defining a patient subgroup at high risk for postoperative infections. At an immunomodulatory dose of 125 microg/m2 per day, GM-CSF was safe and well tolerated, but did not reduce the incidence of postoperative infections in this high-risk oncologic population. Infectious morbidity in surgical oncology remains an important subject for continued clinical investigation.

Granulocyte-macrophage colony-stimulating factor in patients with neutropenic fever is potent after low-risk but not after high-risk neutropenic chemotherapy regimens: results of a randomized phase III trial.

1998 ◽  
Vol 16 (9) ◽  
pp. 2930-2936 ◽  
Author(s):  
A Ravaud ◽  
C Chevreau ◽  
L Cany ◽  
P Houyau ◽  
N Dohollou ◽  
...  
Keyword(s):  
High Risk ◽  
Febrile Neutropenia ◽  
Low Risk ◽  
Phase Iii ◽  
Colony Stimulating Factor ◽  
Phase Iii Trial ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

PURPOSE A randomized unblinded phase III trial was designed to determine the ability of granulocyte-macrophage colony-stimulating factor (GM-CSF) to accelerate recovery from febrile neutropenia induced by chemotherapy. PATIENTS AND METHODS A total of 68 patients with febrile neutropenia following chemotherapy defined as axillary temperature greater than 38 degrees C and absolute neutrophil count (ANC) less than 1 x 10(9)/L were included. After stratification for high- and low-risk chemotherapy to induce febrile neutropenia, treatment was randomized between GM-CSF at 5 microg/kg/d or control, both being associated with antibiotics. RESULTS GM-CSF significantly reduced the median duration of neutropenia from 6 to 3 days for ANC less than 1 x 10(9)/L(P < .001) and from 4 to 3 days for ANC less than 0.5 x 10(9)/L (P=.024), days of hospitalization required for febrile neutropenia, and duration of antibiotics during hospitalization. The greatest benefit with GM-CSF appeared for patients who had received low-risk chemotherapy, for which the median duration of ANC less than 1 x 10(9)/L was reduced from 7 to 2.5 days (P < .001) and from 4 to 2 days for ANC less than 0.5 x 10(9)/L (P=.0011), the duration of hospitalization during the study from 7 to 4 days (P=.003), and the duration on antibiotics during hospitalization from 7 to 3.5 days (P < .001). A multivariate analysis, using Cox regression, showed that variables predictive for recovery from neutropenia were GM-CSF (P=.0010) and time interval between the first day of chemotherapy and randomization (P=.030). There was no benefit for GM-CSF when high-risk chemotherapy was considered. CONCLUSION GM-CSF significantly shortened duration of neutropenia, duration of neutropenic fever-related hospitalization, and duration on antibiotics during hospitalization when febrile neutropenia occurred after low-risk chemotherapy, but not high-risk chemotherapy.

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