Incidence of febrile neutropenia and effectiveness of pegfilgrastim prophylaxis in patients with advanced-stage solid tumors receiving chemotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20564-e20564
Author(s):  
Jeffrey Crawford ◽  
Maureen Reiner ◽  
Phuong Khanh H. Morrow ◽  
Gary H. Lyman
Keyword(s):  
Febrile Neutropenia ◽  
Solid Tumors ◽  
Phase Iii ◽  
Disease Stage ◽  
Advanced Stage ◽  
Test Results ◽  
Advanced Disease Stage ◽  
Grade 3 ◽  
Advanced Stage Cancer ◽  
The Impact

e20564 Background: Advanced disease stage has been identified as an independent risk factor for the development of febrile neutropenia (FN), which continues to be associated with substantial morbidity. We report here results from two clinical trials on the impact of pegfilgrastim (PEG) in patients with advanced stage solid tumors. Methods: Patients were pooled from two placebo-controlled trials: a) a phase III trial of 928 patients with breast cancer, randomized to placebo or PEG 6 mg on day 2 of each 21-day cycle (Vogel CL, et al. JCO 23:1178-84, 2005); and b) a phase II trial of 241 patients with colorectal cancer (CRC), randomized to placebo or PEG 6 mg on day 4 of each 14-day cycle (Hecht JR et al. Clin CRC 9:95-101, 2010). Patients were grouped by disease stage at baseline: advanced (stage III, IIIA, IIIB, IV) or limited (stage I, II, IIA, IIB). Grade 3/4FN was defined as a temperature of ≥ 38.2°C and an ANC of <1.0 x 109/L. The Cochran-Mantel-Haenszel test was used to evaluate the association between PEG and grade 3/4 FN, odds ratio (OR) for FN was estimated by logistic regression, and a trend in the number of FN events per patient was estimated using a Cochran-Armitage test. Results: Characteristics of the 982 patients with advanced stage cancer are shown in the table. PEG was associated with significantly fewer grade 3/4 FN events (p < 0.001), with OR for PEG vs placebo of 0.12 (95% CI: 0.07, 0.22). The percentage of patients with 0, 1, and ≥ 2 FN events was 97%, 3%, and 0% with PEG and 81%, 18%, and 0.4% with placebo, and PEG significantly reduced the number of FN events (p< 0.001). Conclusions: Patients with advanced stage cancer are at considerable risk for developing FN, and PEG prophylaxis reduced that risk. Assessment of FN risk is essential in the advanced/metastatic treatment setting. [Table: see text]

Phase I trial of cabazitaxel plus cisplatin in patients with advanced solid tumors.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 162-162 ◽  
Author(s):  
Albert C. Lockhart ◽  
Shankar Sundaram ◽  
John Sarantopoulos ◽  
Monica M. Mita ◽  
Alex R. Lane ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Phase I ◽  
Solid Tumors ◽  
Dose Level ◽  
Combined Treatment ◽  
Primary Objective ◽  
Phase Iii ◽  
Clinical Activity ◽  
Primary Tumors ◽  
Grade 3

162 Background: Cabazitaxel (Cbz) is a novel taxane with broad in vivo efficacy in taxane-sensitive and -resistant tumors. Clinical activity of Cbz was confirmed in the Phase III TROPIC trial ( NCT00417079 ); Cbz significantly improved overall survival compared with mitoxantrone in patients (pts) with metastatic castration-resistant prostate cancer whose disease had progressed during or after a prior docetaxel-containing regimen. Therapeutic synergism of Cbz/cisplatin (Cis) has been demonstrated in tumor-bearing mice. Methods: The primary objective in part 1 of this Phase I study ( NCT00925743 ) was to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of Cbz/Cis. Secondary objectives were safety, pharmacokinetics (PK) and efficacy. The primary objective of part 2 was to determine the antitumor activity at the MTD. Eligible pts were ≥ 18 yrs, ECOG PS ≤ 1, with confirmed metastatic or unresectable solid tumors for which Cis therapy was considered appropriate. A 3 + 3 dose escalation with a starting dose (level 0) of 20/75 mg/m2 (Cbz/Cis), administered IV Q3W, was used. The MTD was the highest dose at which 0/3 or ≤ 1/6 pts experienced a DLT in Cycle 1. Results: Pts (N = 25; 10 in part 1; 15 in part 2) with a median age of 56 yrs were enrolled. The most frequent primary tumors were lung (n = 4), prostate, ovary and pancreas (each n = 2). 2 of 6 evaluable pts experienced a DLT at dose level 0 (Grade 3 acute renal failure; febrile neutropenia). The MTD was 15/75 mg/m2 as no DLTs were observed. Eighteen pts were treated at the MTD and 60 cycles were administered (median = 3; range 1–8). The most frequent non-hematologic treatment-related adverse events (all Grade/Grade 3–4) were nausea (78%/22%), vomiting (72%/11%), fatigue (61%/17%), anorexia (67%/11%) and diarrhea (44%/0%). Incidence of Grade 3–4 neutropenia was 78% and 1 pt had febrile neutropenia. No PK interactions between Cbz and Cis were observed. Stable disease was seen in 11 pts. No objective responses were reported. Conclusions: The MTD of Cbz/Cis was 15/75 mg/m2. The combination had a manageable safety profile consistent with that of a platinum/taxane combination. No PK interactions were seen. Further investigations into the combined treatment combination are planned.

scholarly journals The Impact of Age on the Outcome of Primary Treatment for Classical Hodgkin's Lymphoma: 70 Years of Age Is a Clinical Relevant Cutpoint and the Most Important Predictor of Overall Survival

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1559-1559
Author(s):  
Lourdes Calvente ◽  
Manjula Maganti ◽  
Mary Gospodarowicz ◽  
David C. Hodgson ◽  
Danielle Rodin ◽  
...  
Keyword(s):  
High Risk ◽  
Febrile Neutropenia ◽  
Treatment Outcomes ◽  
Older Patients ◽  
Research Funding ◽  
Multivariable Analysis ◽  
Advanced Stage ◽  
Age Group ◽  
Grade 3 ◽  
The Impact

Introduction: Classical Hodgkin lymphoma (cHL) typically affects younger patients but 15-35% are &gt;60 years. The age used to define an elderly population has varied but age 60 is frequently used. A clinically relevant definition of older age could be based on the use of alternate treatments due to different efficacy and/or toxicity. Treatment outcomes may also be influenced by tumor biology and patient comorbidity that vary with age. We evaluated the effect of age on treatment outcomes in cHL. Methods: All cHL patients treated at our centre between Jan 1999 and Dec 2015 were retrospectively analyzed. Clinical data were obtained from prospectively collected Lymphoma database and additional data was manually retrieved. Treatment for localized disease was combined modality (2-4 cycles of ABVD and potentially 6 cycles for bulk disease &gt; 10 cm; radiation doses 20-35 Gy) with advanced disease typically receiving chemotherapy alone (ABVD 6-8 cycles). Older patients received individualized treatment. We used the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI), (Sorror Blood 2005) as the elements can be abstracted retrospectively. Results: 607 patients were identified; 14% were &gt;60 years and 6% were age &gt;70. Baseline characteristics are outlined in table 1. Patients &gt;70 presented more frequently with high-risk HCT-CI and worse ECOG PS. Patients &gt; 60 presented more frequently with advanced stage (61-70 age group: 40%; &gt;70 years: 46%). 65% of the patients age &gt;70 presented with an IPS of &gt;3. Chemotherapy alone approaches were used more commonly in older patients (age 61-70: 40%; age 70+: 51%) than in those &lt;60 years (25%). Within the whole cohort 12 patients received non-anthracycline based treatment (&lt;60: n=4; 61-70: n=1; and &gt;70: n=7).For patients &lt;60 and &gt;70 this decision was made due to prior comorbidities that precluded the use of standard treatment, and for the patient in the 61-70 was because of acute toxicity with ABVD-based chemotherapy. Treatment was discontinued in 33% of the patients &gt; 70 (77% due to toxicity), 21% in the 61-70 years group (30% toxicity) and 6% in patients &lt;60 (29% toxicity). Patients &gt; 70 had higher rates of grade 3-5 febrile neutropenia (28% versus 15% [age 61-70] and 7% [age &lt;60]). Bleomycin toxicity was more common in older patients (age &gt;70: grade 3-4 events 12% of the patients with discontinuation in 66%; age 61-70: 13% with discontinuation rate of 20%) compared to a 1% rate of grade 3-5 events in age &lt;60. There was a grade 5 episode of febrile neutropenia in &gt;70 group and 1 death related to bleomycin in age &lt;60. With a median follow up of 8.6 years, the 10-year OS and PFS were 80.5% and 71.2%, respectively. By age-group, the 10-year OS was 88% (&lt;60 years), 57% (61-70 years) and 15% (age &gt;70 years); (p&lt;0.001) (Figure 1a-b). In multivariable analysis for OS, age 61-70 (HR 2.44, p=0.002) and age &gt;70 (HR 5.72, p=0.001), non-anthracycline based chemotherapy (HR 3.69, p&lt;0.001), high-risk HCT-CI (HR 3.03, p=0.001) and ECOG 2-4 (HR 1.8, p=0.017), were significant. Age &gt;70, type of chemotherapy, high-risk HCT-CI, and advanced stage were significant for PFS in the multivariable analysis (Table 2a-b). Death due to disease or toxicity at 10 years was 13.6% (age &lt;60: 9.7%, 61-70 years: 23.2%; and for age &gt; 70: 50.7%; [p=&lt;0.001]) (Figure 2a-b). Multivariable analysis for cause-specific survival identified age &gt;70 years (HR 4.04, p=&lt;0.001), extranodal disease (HR 2.57, p=0.001) and ECOG 2-4 (HR 2.10, p=0.010) as significant predictors(Table 3). Conclusions: Age &gt;70 years is a clinically relevant age cutoff as it has additional prognostic significance and greater rates of treatment discontinuation and toxicity compared to age 60. The HCT-CI is a useful predictor of outcome in cHL and should be validated prospectively. In multivariable analysis, age, type of treatment, comorbidity and ECOG performance status are independent predictors of OS. Further studies are ongoing to validate these findings and assess biologic differences in older versus younger cHL patients. Disclosures Tsang: Nordic Nanovector: Research Funding. Kridel:Gilead Sciences: Research Funding. Kukreti:Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Prica:Celgene: Honoraria; Janssen: Honoraria. Kuruvilla:Janssen: Research Funding; Roche: Honoraria; Novartis: Honoraria; Merck: Honoraria; Gilead: Honoraria; Seattle Genetics: Consultancy; Roche: Consultancy; Merck: Consultancy; Karyopharm: Consultancy; Celgene: Honoraria; BMS: Honoraria; BMS: Consultancy; Abbvie: Consultancy; Gilead: Consultancy; Astra Zeneca: Honoraria; Janssen: Honoraria; Roche: Research Funding; Amgen: Honoraria; Seattle Genetics: Honoraria; Karyopharm: Honoraria.

Exposure-response (E-R) efficacy and safety (E-S) analyses of tremelimumab as monotherapy or in combination with durvalumab in patients (pts) with unresectable hepatocellular carcinoma (uHCC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 313-313
Author(s):  
Xuyang Song ◽  
Robin Kate Kelley ◽  
Anis Khan ◽  
Nathan Standifer ◽  
Rajesh Krishna ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Objective Response ◽  
Small Sample ◽  
Phase Iii ◽  
Combination Regimen ◽  
Cell Counts ◽  
Size Limitation ◽  
Population Pk ◽  
Grade 3 ◽  
The Impact

313 Background: In a phase II study in uHCC (Study 22, NCT02519348), a novel, priming combination regimen of tremelimumab (T; anti-CTLA-4) and durvalumab (D; anti-PD-L1) (T300+D) has shown favorable clinical activity vs each agent as monotherapy or vs another combination (T75+D). The analyses presented here assess the pharmacokinetics (PK) and relationships between tremelimumab exposure, as monotherapy or in combination, and safety, efficacy, and pharmacodynamics (PD) in this study. Methods: Overall, 216 pts were included in these analyses (T, n=65; T300+D, n=72; T75+D, n=79). Safety, antitumor activity, PK, PD, and immunogenicity were analyzed using standard pharmacometrics methods. A previously developed population PK model for T across solid tumors was validated using T monotherapy and combination therapy data from Study 22, including a post-hoc covariate analysis to assess the impact of covariates on individual PK parameters. Population PK and PD models related individual T exposures to safety parameters, PD, and efficacy (overall survival, OS; progression-free survival, PFS; and objective response rate, ORR). The E-R relationships for time-to-event variables OS and PFS were explored by Kaplan-Meier estimates and analyzed by Cox proportional-hazards models (CPHM). Results: For T monotherapy and T+D combinations, no significant E-S relationships were observed for grade 3/4 treatment-related adverse events (TRAEs), grade 3/4 TRAEs of special interest, and AEs leading to treatment discontinuation. Analyses of each quartile of T exposure suggest pts with higher exposure (3rd and 4th quartile) may have longer OS vs lower quartiles. The CPHManalysis showed that after accounting for prognostic factors (baseline albumin and neutrophil-to-lymphocyte ratio), neither AUC nor Cmin appeared to be a significant factor for OS hazard. There was no significant relationship between response and ORR, PFS and any T PK exposure metric in T-treated pts. Saturable relationships (described by Emax) were observed for maximum change from baseline for proliferating T-cell counts as functions of exposure. Conclusions: The observed PK data are generally consistent with predictions based on a historical population PK model, suggesting the PK of T in uHCC pts is consistent with pts with other solid tumors. No significant relationships were observed between E-S and E-R; therefore, PK is not a significant predictor to evaluate for T efficacy or safety. Considering the small sample size limitation, still the saturable relationships observed in proliferating T-cells appear to support a dose of T300. Future studies of pooled data from Study 22 and the larger phase III HIMALAYA study (NCT03298451) will be conducted to further the characterization of E-R relationships and the development of the T300+D regimen. Clinical trial information: NCT02519348.

scholarly journals Health disparities and impact on outcomes in children with primary central nervous system solid tumors

2016 ◽  
Vol 18 (5) ◽  
pp. 585-593 ◽  
Author(s):  
Mary T. Austin ◽  
Emma Hamilton ◽  
Denna Zebda ◽  
Hoang Nguyen ◽  
Jan M. Eberth ◽  
...  
Keyword(s):  
Health Disparities ◽  
Solid Tumors ◽  
Survival Probability ◽  
Cox Regression ◽  
Disease Stage ◽  
Advanced Stage ◽  
Stage Disease ◽  
Hispanic Patients ◽  
The Impact ◽  
Racial Ethnic

OBJECTIVE Health disparities in access to care, early detection, and survival exist among adult patients with cancer. However, there have been few reports assessing how health disparities impact pediatric patients with malignancies. The objective in this study was to examine the impact of racial/ethnic and social factors on disease presentation and outcome for children with primary CNS solid tumors. METHODS The authors examined all children (age ≤ 18 years) in whom CNS solid tumors were diagnosed and who were enrolled in the Texas Cancer Registry between 1995 and 2009 (n = 2421). Geocoded information was used to calculate the driving distance between a patient's home and the nearest pediatric cancer treatment center. Socioeconomic status (SES) was determined using the Agency for Healthcare Research and Quality formula and 2007–2011 US Census block group data. Logistic regression was used to determine factors associated with advanced-stage disease. Survival probability and hazard ratios were calculated using life table methods and Cox regression. RESULTS Children with advanced-stage CNS solid tumors were more likely to be < 1 year old, Hispanic, and in the lowest SES quartile (all p < 0.05). The adjusted odds ratios of presenting with advanced-stage disease were higher in children < 1 year old compared with children > 10 years old (OR 1.71, 95% CI 1.06–2.75), and in Hispanic patients compared with non-Hispanic white patients (OR 1.56, 95% CI 1.19–2.04). Distance to treatment and SES did not impact disease stage at presentation in the adjusted analysis. Furthermore, 1- and 5-year survival probability were worst in children 1–10 years old, Hispanic patients, non-Hispanic black patients, and those in the lowest SES quartile (p < 0.05). In the adjusted survival model, only advanced disease and malignant behavior were predictive of mortality. CONCLUSIONS Racial/ethnic disparities are associated with advanced-stage disease presentation for children with CNS solid tumors. Disease stage at presentation and tumor behavior are the most important predictors of survival.

scholarly journals Clinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tereza Vaclova ◽  
Ursula Grazini ◽  
Lewis Ward ◽  
Daniel O’Neill ◽  
Aleksandra Markovets ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Advanced Stage ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
The Impact ◽  
Egfr T790m

AbstractAdvanced non-small-cell lung cancer (NSCLC) patients with EGFR T790M-positive tumours benefit from osimertinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Here we show that the size of the EGFR T790M-positive clone impacts response to osimertinib. T790M subclonality, as assessed by a retrospective NGS analysis of 289 baseline plasma ctDNA samples from T790M‐positive advanced NSCLC patients from the AURA3 phase III trial, is associated with shorter progression-free survival (PFS), both in the osimertinib and the chemotherapy-treated patients. Both baseline and longitudinal ctDNA profiling indicate that the T790M subclonal tumours are enriched for PIK3CA alterations, which we demonstrate to confer resistance to osimertinib in vitro that can be partially reversed by PI3K pathway inhibitors. Overall, our results elucidate the impact of tumour heterogeneity on response to osimertinib in advanced stage NSCLC patients and could help define appropriate combination therapies in these patients.

Phase I and Pharmacokinetic Study of Docetaxel and Irinotecan in Patients With Advanced Solid Tumors

2000 ◽  
Vol 18 (20) ◽  
pp. 3545-3552 ◽  
Author(s):  
Corinne Couteau ◽  
Marie-Laure Risse ◽  
Michel Ducreux ◽  
Florence Lefresne-Soulas ◽  
Alessandro Riva ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Phase I ◽  
Solid Tumors ◽  
Pharmacokinetic Study ◽  
Topoisomerase I ◽  
Maximum Tolerated Dose ◽  
Hematologic Toxicity ◽  
Advanced Solid Tumors ◽  
Phase Ii Studies ◽  
Grade 3

PURPOSE: We conducted a phase I and pharmacokinetic study of docetaxel in combination with irinotecan to determine the dose-limiting toxicity (DLT), the maximum-tolerated dose (MTD), and the dose at which at least 50% of the patients experienced a DLT during the first cycle, and to evaluate the safety and pharmacokinetic profiles in patients with advanced solid tumors. PATIENTS AND METHODS: Patients with only one prior chemotherapy treatment (without taxanes or topoisomerase I inhibitors) for advanced disease were included in the study. Docetaxel was administered as a 1-hour IV infusion after premedication with corticosteroids followed immediately by irinotecan as a 90-minute IV infusion, every 3 weeks. No hematologic growth factors were allowed. RESULTS: Forty patients were entered through the following seven dose levels (docetaxel/irinotecan): 40/140 mg/m2, 50/175 mg/m2, 60/210 mg/m2, 60/250 mg/m2, 60/275 mg/m2, 60/300 mg/m2, and 70/250 mg/m2. Two hundred cycles were administered. Two MTDs were determined, 70/250 mg/m2 and 60/300 mg/m2; the DLTs were febrile neutropenia and diarrhea. Neutropenia was the main hematologic toxicity, with 85% of patients experiencing grade 4 neutropenia. Grade 3/4 nonhematologic toxicities in patients included late diarrhea (7.5%), asthenia (15.0%), febrile neutropenia (22.5%), infection (7.5%), and nausea (5.0%). Pharmacokinetics of both docetaxel and irinotecan were not modified with the administration schedule of this study. CONCLUSION: The recommended dose of docetaxel in combination with irinotecan is 60/275 mg/m2, respectively. At this dose level, the safety profile is manageable. The activity of this combination should be evaluated in phase II studies in different tumor types.

scholarly journals A Phase IV Clinical Trial of Patients with Solid Tumors Receiving Lenograstim as Primary Prophylaxis for Chemotherapy-Induced Neutropenia, in a Docetaxel-Based Regimen

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Samuel J. Fourie ◽  
Alicia McMaster ◽  
Rashem Mothilal ◽  
Keith I. Maart
Keyword(s):  
Febrile Neutropenia ◽  
Solid Tumors ◽  
Primary Prophylaxis ◽  
Duration Of Treatment ◽  
Open Label ◽  
Recurrence Rates ◽  
Optimal Dosing ◽  
Grade 3 ◽  
African Patients ◽  
Phase Iv

Docetaxel-based chemotherapy regimens have substantially improved survival and recurrence rates for cancer patients. Safety profile of docetaxel regimens includes toxicities, particularly a high risk of neutropenia and febrile neutropenia. Granotax was a prospective, open label, multicentre, national phase IV study that evaluated the incidence and severity of neutropenia in adult patients with solid tumors being treated with a docetaxel-based regimen while receiving the GCSF lenograstim. Among the 394 enrolled patients the incidence of grade 3-4 neutropenia was 16.2% and of febrile neutropenia was 1.5%, far lower than the reported 85–100% and 30–40% incidence without G-CSFs. A total of 68 patients (17.3%) were reported to have experienced at least one grade 3-4 adverse event during the study. Two (0.5%) patients and 32 (8.1%) patients had dose delayed due to febrile neutropenia and neutropenia, respectively. Four (1.0%) patients and 32 (8.1%) patients had a dose changed due to febrile neutropenia and neutropenia, respectively. The low incidence of adverse effects and chemotherapy dose changes, delays, and withdrawals supports the use of lenograstim as effective primary prophylaxis in South African patients being treated with a docetaxel-based regimen. Furthermore, lenograstim may increase the patient’s exposure to chemotherapy allowing patients to receive optimal dosing and duration of treatment, benefitting survival.

Granulocyte-Colony Stimulating Factor Use in Young Fit CLL Patients Receiving Fludarabine-Cyclophosphamide-Rituximab Frontline: Impact on Outcomes, Relative Dose Intensity and Toxicities

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1798-1798
Author(s):  
Emmanuelle Bouvet ◽  
Lucie Oberic ◽  
Christian Recher ◽  
Françoise Huguet ◽  
Xavier Carles ◽  
...  
Keyword(s):  
Creatinine Clearance ◽  
Residual Disease ◽  
Dose Intensity ◽  
Phase Iii ◽  
Relative Dose Intensity ◽  
Color Flow ◽  
Group 2 ◽  
Grade 3 ◽  
The Impact ◽  
Group 1

Abstract Abstract 1798 INTRODUCTION: fludarabine-cyclophosphamide-rituximab (FCR) is the standard upfront immunochemotherapy for young fit CLL patients. The clinical benefit of growth factors support is yet unclear, despite recently published possible impact on outcomes in a series of 32 patients [Grüber M, 2011]. The use of G-CSF is not recommended in the CLL8 trial, outside febrile neutropenia, but often applied outside clinical trials to prevent toxicities and achieve good relative dose-intensity (RDI). We retrospectively assessed, in an Hematology healthcare network, the impact of G-CSF on survivals (PFS, TTNT, OS), outcomes (RDI, minimal residual disease (MRD), overall response rates (CR/CRi), and toxicities (grade 3–4 neutropenia, fever, hospitalizations). PATIENTS AND METHODS: among 101 patients treated with FCR frontline, three groups of patients are considered: group 1 (no G-CSF), group 2 (primary prophylaxis with pegfilgrastim after each course of FCR), and group 3 (patients of group 1 initially, but who were treated with G-CSF due to at least one episode of grade 4 neutropenia (at the discretion of the physician)). Respectively, toxicities have been assessed in 24/28/13 patients, and outcomes in 45/23/23 patients. Pretreatment characteristics were well balanced between G-CSF-naïve and -treated patients (IgVH, Binet stage, del11q). No del17p patient was included in this series. Planned RDI for F and C were calculated before 1st cycle of FCR according to age (-20% if >65y), and creatinine clearance (-25% if <60ml/mn). Average RDI (ARDI) actually prescribed to patients were assessed at the last cycle, in mg/m2/week (6xFCR=24 wks) to include dose delays in the calculation of RDI. RESULTS: median age in the cohort of 101 FCR treated pts was 60y (21–83y), 68% were males. 20% had >65y, 13% had creatinine clearance <60ml/mn, CIRS-G comorbidity scores were: 0 (25.5%), 1 (26.5%), 2 (19%), 3 (10%), 4 (8%), 5 (5%), 6 (2%), ≥7 (4%). Planned RDI was ≤75% standard FCR doses (due to age, CrCL, or physician's choice) in 12% of cases, and ARDI was further decreased ≥20% of initial planned RDI in 25% of patients. Peripheral blood 4-color flow MRD wad undetectable in 49% of patients. Impact of G-CSF use on outcomes: results are summarized in Table 1. The use of G-CSF on curative intent for grade 4 neutropenia induced an increase in rates of CRi and prolonged neutropenia at the end of therapy. When used at the time of neutropenia (d15-d21 after FCR cycle), stimulation with G-CSF may be deleterious due to the prescription of the next FCR at d28. Median PFS, TTNT, OS were not significantly improved by the use of G-CSF (prophylactic or curative). G-CSF did not impact on MRD levels neither. MRD eradication was the strongest parameter linked to PFS/TTNT. Impact of G-CSF use on toxicities and RDI: results are summarized in Table 2. The use of prophylactic G-CSF (group 2) significantly reduced the rate of neutropenia grade 3–4, and tended to decrease the need for antibiotics given for fever. A dose modification (>10%) was observed in 26% vs 33.3% in patients receiving prophylactic G-CSF or not, respectively. A planned RDI <75% standard FCR doses was linked to reduced PFS and TTNT, but not OS. Prophylactic G-CSF did not prevent a decrease >20% of planned RDI at the end of therapy. CONCLUSIONS: Our data suggest that prophylactic G-CSF use after FCR decreases toxicities but does not impact on outcomes. We plan to study G-CSF impact on FCR results in an older, less fit population (FORTIS phase III trial). Disclosures: Ysebaert: Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Final results from a phase I trial of ixabepilone in patients with advanced malignancies and lymphoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2039-2039
Author(s):  
C. Aghajanian ◽  
O. O’Connor ◽  
M. Cohen ◽  
R. Peck ◽  
H. Burris
Keyword(s):  
Febrile Neutropenia ◽  
Phase I ◽  
Solid Tumors ◽  
Phase I Trial ◽  
Objective Response ◽  
Maximum Tolerated Dose ◽  
Clinical Activity ◽  
Hematologic Toxicity ◽  
Phase Ii Studies ◽  
Grade 3

2039 Background: Ixabepilone is the first analog in a new class of antineoplastic agents, the epothilones, which stabilizes microtubules and induces apoptosis. Ixabepilone has shown clinical activity in a broad range of tumors. Methods: This Phase I trial was designed to establish the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), efficacy, safety, pharmacokinetics and pharmacodynamics of ixabepilone when administered as a 1-hour infusion every 3 weeks to patients with advanced solid tumors or lymphoma. Eligible patients were aged ≥18 years with histologically/cytologically confirmed non-hematologic cancer, or a pathologic diagnosis of relapsed/primary refractory non-Hodgkin’s lymphoma (NHL) or relapsed/primary refractory mantle cell lymphoma, with ≤CTC Grade 1 neuropathy. Ixabepilone doses ranged from 7.5–65 mg/m2. Response was assessed every 6 weeks using RECIST. DLT was defined as Grade 4 neutropenia and/or febrile neutropenia, thrombocytopenia, ≥Grade 3 nausea/vomiting and non-hematologic toxicity, or treatment delay of >2 weeks due to delayed recovery. Results: Of 61 patients (median age 58, range 18–81), 75% had solid tumors; 25% had lymphoma. 98% and 67% of patients had received one or ≥ two prior chemotherapy regimens, respectively. The MTD of ixabepilone as a 1-hour infusion every 3 weeks was established as 50 mg/m2. The most common DLTs were neutropenia, myalgia, arthralgia and stomatitis/pharyngitis. A total of eight patients (13%) achieved a durable objective response. Complete responses were achieved in two patients with primary peritoneal cancer and NHL. A partial response was seen in six patients. The most common Grade 3/4 treatment-related adverse events (only observed at doses ≥40 mg/m2) were sensory neuropathy (13%), fatigue (13%), myalgia (10%), arthralgia (7%), nausea (5%), febrile neutropenia (5%) and neutropenia (5%). Recovery to baseline or ≤Grade 1 neuropathy occurred in some patients. Conclusions: The recommended dose of ixabepilone for the initiation of Phase II studies based on this study is 50 mg/m2 over 1 hour every 3 weeks. Ixabepilone demonstrates promising safety in patients with solid tumors or lymphoma who have failed standard therapy. Encouraging activity was reported in several tumor types. [Table: see text]

A phase I study of brostallicin (B) combined with either bevacizumab (BV) or irinotecan (I) in patients (pts) with advanced solid malignancies

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13531-e13531
Author(s):  
R. B. MacArthur ◽  
J. Singer ◽  
C. Becerra ◽  
S. Weitman ◽  
D. Von Hoff
Keyword(s):  
Febrile Neutropenia ◽  
Phase I ◽  
Solid Tumors ◽  
Performance Status ◽  
Single Agent ◽  
Primary Objective ◽  
Additional Patient ◽  
Dna Minor Groove ◽  
Grade 3 ◽  
Group Grade

e13531 Background: B is a DNA minor groove binding (MGB) agent with single agent cytotoxic activity. B has shown synergy with BV and I. The combinations were studied using a “complete” phase I design. Methods: The primary objective was to determine the maximally tolerated dose (MTD) and dose limiting toxicities (DLT) of B+BV and B+I. For B+BV cohort 1 both drugs were infused on day 1 of a 21 day cycle. BV was dosed at 15mg/kg, B was dosed at 6 mg/m2. For cohort 2, the BV dose was unchanged, and B dose reduced to 4 mg/m2. For B+I cohort 1 both drugs were also infused on cycle day 1. I was dosed at 200 mg/m2 with B at 4 mg/m2. For cohort 2, I was reduced to 125 mg/m2 and B reduced to 2 mg/m2. Cycle 1 DLT was defined: grade 4 neutropenia lasting ≥ 5 days, grade 3 or higher febrile neutropenia, grade 4 thrombocytopenia or grade 3 or 4 thrombocytopenia with bleeding, grade 3 or higher diarrhea, nausea or vomiting despite optimal management, grade 3 or higher for all other non-hematologic toxicities. For pts receiving BV, grade 2 or higher proteinuria. Eligible pts had treatment refractory metastatic/unresectable solid tumors, acceptable performance status, and adequate hematologic parameters and organ function. Results: 19 pts were enrolled. 11 pts received B+BV and 8 received B+I. Median age was 58 years. For B+BV 5 patients were treated in cohort 1, 6 in cohort 2. For B+I, 2 patients were treated in cohort 1, 6 in cohort 2. The MTD has not been defined for either treatment combination. In the current preliminary dataset 18/19 pts (93.3%) experienced one or more adverse events (AEs). In the B+BV group, grade 4 neutropenia was reported in 2/11 patients, both in cohort 1, and grade 3 neutropenia in one additional patient, also in cohort 1. In the B+I group, grade 4 AEs included neutropenia (DLT), febrile neutropenia (DLT), severe abdominal pain, and thrombocytopenia. Of the evaluable pts, no complete or partial responses were seen. For B+BV 5/11 pts have received 4 or more cycles, and for B+I 2/8. Conclusions: The combination of B+BV and B+I show manageable toxicity in advanced solid tumors at the doses reached in cohort 2. Additional data will be provided at the time of presentation. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document