The Impact of Relative Dose Intensity on Response and Survival in a Series of 180 Newly Diagnosed Patients with Hodgkin’s Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2671-2671
Author(s):  
Filippo Russo ◽  
Gino Svanera ◽  
Paola Della Cioppa ◽  
Gaetano Corazzelli ◽  
Ferdinando Frigeri ◽  
...  
Keyword(s):  
Survival Rates ◽  
Dose Intensity ◽  
Complete Response ◽  
Relative Dose Intensity ◽  
Rank Statistic ◽  
Cycle Period ◽  
Newly Diagnosed ◽  
Exact Test ◽  
Dose Dense ◽  
The Impact

Abstract To improve ABVD results we first developed a protocol which adds G-CSF to the standard ABVD treatment. From March 1997 to May 2004 69 patients with HL were treated with ABVD+G-CSF and 22 with a standard ABVD. Recently we designed a new dose-dense and dose-intensity ABVD scheme (escABVD-21) for advanced HL; in this new schedule the adriamycin was escalated from 25 to 35 mg/m2 (cycles 1,2,3,4) and the inter-cycle period was shortened from 28 to 21 days (for all 6 cycles); primary G-CSF was administered from d3 to d8 and drugs were delivered at d10 and d21 of every cycle. From June 2004, 19 patients were treated with this protocol. Relative dose-intensity (RDI) was calculated for any of these 110 newly diagnosed HL patients treated with ABVD. The results were also compared with a historical group of 70 patients who had undergone hybrid MOPP/ABVD. HL patients received from 4 to 8 cycles of CT +/− IF-RT. Patients were divided in 4 groups according to the RDI. The first group included 20 (11%) pts with RDI less than 0.80; the 2nd group, 64 (36%) pts with RDI values between 0.80 and 0.95, the 3rd group, 74 (42%) pts with RDI values between 0.96 and 1.10 and, finally, the 4th group included pts with RDI values of more than 1.10. In Tab 2 we report the CR, EFS and OS rates according to the 4 levels of RDI. Figures 1 shows EFS curve according to Kaplan-Meyer. Response and survival rates of groups 1,2,3 and 4 were: 50%vs91%vs97% vs 100%, for CR (p<0.0001); 20%vs78%vs92%vs100% for EFS (p< 0.0001); and 25%vs91%vs99%vs100% for OS (p< 0.0001). The best progression rates of CR, EFS and OS were seen in patients with RDI >1.10. In particular, the new dose-dense and dose-intensity escABVD-21 protocol seems very promising in terms of complete response and toxicity profile: 19/19 pts (100%) obtained an early CR; (PET negative at the end of the 2nd cycle), and, as on 8th August 2005, all these19 patients were disease-free. The dose-escalation of adriamycin and the dose-density of the schedule were well-tolerated; toxicity was mild. These results show that subptimal RDI may compromise outcomes proportionally to the level of RDI reduction. On the contrary, Primary G-CSF permits to deliver dose-dense and dose intense schedules such as escABVD-21 maintaining the same profile of toxicity of standard ABVD, higher RDI levels, and consequently, a significant impact on complete response and survival rates. tab1 Presentation features n. of pts male sex age>45 yrs advanced stage E sites>1 bulky B symptoms IPI score ≥ 3 180 92 43 148 23 80 83 56 % 51% 24% 82% 13% 44% 46% 31% tab.2 Response and Survival according to 4 RDI levels RDI level (range 0.5–1.5) N. of pts. (%) CR rate Fisher’s Exact test (2-sided) EFS rate log-rank statistic 0S rate log-rank statistic overall 180(100%) 90% 80% 88% <0.80 20 (11%) 50% 20% 25% 0.80–0.95 64 (36%) 91% 28.391 78% 74.99 91% 96.76 0.96–1.10 76 (42%) 97% 92% 99% >1.10 20 (11%) 100% 100% 100% significance <0.0001 <0.0001 <0.0001 Figure Figure

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]

scholarly journals Pathologic Complete Response Following Neoadjuvant Therapy for Gastric Adenocarcinoma: A National Cancer Database Analysis on Incidence, Predictors, and Outcomes

2020 ◽  
pp. 000313482097208
Author(s):  
Christof Kaltenmeier ◽  
Alison Althans ◽  
Maria Mascara ◽  
Ibrahim Nassour ◽  
Sidrah Khan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Therapy ◽  
Gastric Adenocarcinoma ◽  
Survival Rates ◽  
Pathologic Complete Response ◽  
Tumor Grade ◽  
Complete Response ◽  
Neoadjuvant Chemoradiation ◽  
National Cancer Database ◽  
The Impact

Introduction With advances in multimodal therapy, survival rates in gastric cancer have significantly improved over the last two decades. Neoadjuvant therapy increases the likelihood of achieving negative margins and may even lead to pathologic complete response (pCR). However, the impact of pCR on survival in gastric cancer has been poorly described. We analyzed the rate and predictors of pCR in patients receiving neoadjuvant therapy as well as impact of pCR on survival. Methods We conducted a National Cancer Database (NCDB) analysis (2004-2016) of patients with gastric adenocarcinoma who received neoadjuvant chemotherapy followed by surgical resection. Results The pCR rate was 2.2%. Following adjustment, only neoadjuvant chemoradiation, non-signet histology, and tumor grade remained as significant factors predicting pCR. pCR was a statistically significant predictor of survival. Conclusion In this NCDB study, pCR was a predictor of survival. Though chemoradiation rather than chemotherapy alone was a predictor of pCR, it was not a predictor of survival. Further studies are needed to elucidate the role of radiation in the neoadjuvant setting and to discern the impact of pCR on survival.

scholarly journals Prognostic Impact of Stromal Immune Infiltration before and after Neoadjuvant Chemotherapy (NAC) in Triple Negative Inflammatory Breast Cancers (TNIBC) Treated with Dose-Dense Dose-Intense NAC

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2657
Author(s):  
Luca Campedel ◽  
Paul Blanc-Durand ◽  
Asker Bin Asker ◽  
Jacqueline Lehmann-Che ◽  
Caroline Cuvier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Univariate Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Complete Response ◽  
Prognostic Impact ◽  
Breast Cancers ◽  
Dose Dense ◽  
The Impact

Inflammatory breast cancers are very aggressive, and among them, triple negative breast cancer (TNBC) has the worst prognosis. While many studies have investigated the association between tumor-infiltrating lymphocytes (TIL) before neoadjuvant chemotherapy (NAC) and outcome in TNBC, the impact of post-NAC TIL and TIL variation in triple negative inflammatory breast cancer (TNIBC) outcome is unknown. Between January 2010 to December 2018, all patients with TNIBC seen at the breast disease unit (Saint-Louis Hospital) were treated with dose-dense dose-intense NAC. The main objective of the study was to determine factors associated with event-free survival (EFS), particularly pathological complete response (pCR), pre- and post-NAC TIL, delta TIL and post-NAC lymphovascular invasion (LVI). After univariate analysis, post-NAC LVI (HR 2.06; CI 1.13–3.74; p = 0.02), high post-NAC TIL (HR 1.81; CI 1.07–3.06; p = 0.03) and positive delta TIL (HR 2.20; CI 1.36–3.52; p = 0.001) were significantly associated with impaired EFS. After multivariate analysis, only a positive TIL variation remained negatively associated with EFS (HR 1.88; CI 1.05–3.35; p = 0.01). TNIBC patients treated with intensive NAC who present TIL enrichment after NAC have a high risk of relapse, which could be used as a prognostic marker in TNIBC and could help to choose adjuvant post-NAC treatment.

scholarly journals Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance)

2015 ◽  
Vol 33 (1) ◽  
pp. 13-21 ◽  
Author(s):  
William M. Sikov ◽  
Donald A. Berry ◽  
Charles M. Perou ◽  
Baljit Singh ◽  
Constance T. Cirrincione ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Stage Ii ◽  
Open Label ◽  
Grade 3 ◽  
Dose Dense ◽  
The Impact

Purpose One third of patients with triple-negative breast cancer (TNBC) achieve pathologic complete response (pCR) with standard neoadjuvant chemotherapy (NACT). CALGB 40603 (Alliance), a 2 × 2 factorial, open-label, randomized phase II trial, evaluated the impact of adding carboplatin and/or bevacizumab. Patients and Methods Patients (N = 443) with stage II to III TNBC received paclitaxel 80 mg/m2 once per week (wP) for 12 weeks, followed by doxorubicin plus cyclophosphamide once every 2 weeks (ddAC) for four cycles, and were randomly assigned to concurrent carboplatin (area under curve 6) once every 3 weeks for four cycles and/or bevacizumab 10 mg/kg once every 2 weeks for nine cycles. Effects of adding these agents on pCR breast (ypT0/is), pCR breast/axilla (ypT0/isN0), treatment delivery, and toxicities were analyzed. Results Patients assigned to either carboplatin or bevacizumab were less likely to complete wP and ddAC without skipped doses, dose modification, or early discontinuation resulting from toxicity. Grade ≥ 3 neutropenia and thrombocytopenia were more common with carboplatin, as were hypertension, infection, thromboembolic events, bleeding, and postoperative complications with bevacizumab. Employing one-sided P values, addition of either carboplatin (60% v 44%; P = .0018) or bevacizumab (59% v 48%; P = .0089) significantly increased pCR breast, whereas only carboplatin (54% v 41%; P = .0029) significantly raised pCR breast/axilla. More-than-additive interactions between the two agents could not be demonstrated. Conclusion In stage II to III TNBC, addition of either carboplatin or bevacizumab to NACT increased pCR rates, but whether this will improve relapse-free or overall survival is unknown. Given results from recently reported adjuvant trials, further investigation of bevacizumab in this setting is unlikely, but the role of carboplatin could be evaluated in definitive studies, ideally limited to biologically defined patient subsets most likely to benefit from this agent.

The Impact of Relative Dose Intensity (RDI) of CHOP on Outcome of Diffuse Large B-Cell Lymphoma: Results of a Single Center Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4456-4456
Author(s):  
Yoshiki Terada ◽  
Hirohisa Nakamae ◽  
Takahiko Nakane ◽  
Hideo Koh ◽  
Yasunobu Takeoka ◽  
...  
Keyword(s):  
B Cell ◽  
Clinical Outcomes ◽  
Cell Lymphoma ◽  
Dose Intensity ◽  
B Cell Lymphoma ◽  
Relative Dose Intensity ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Abstract Introduction: The achievement of a clinical response to the first induction chemotherapy has been considered for predicting survival in patients (pts) with aggressive non-Hodgkin lymphoma (NHL). Reduced dose intensity of chemotherapy has been likely to compromise long-term outcome of the patients with aggressive NHL treated with a standard chemotherapy of cyclophosphamide (CY), doxorubicin (ADR), vincristine and prednisone (CHOP). In particular, recent studies have revealed the relevance of relative dose intensity (RDI) to clinical outcomes, with reduced RDI leading to a poor survival, as well as the impact of RDI<85% for aggressive NHL with detailed analysis of risk factors influencing reduce RDI<85% (Gary H. Lyman, J. Clin Oncol22: 4302, 2004). This study was conducted to investigate the impact of RDI<85% of CHOP on outcomes of the pts with diffuse large B-Cell lymphoma (DLCL). Methods: Data were retrospectively collected on 100 pts with DLCL who had been initially treated with more than 3 courses of CHOP (n=70) or CHOP plus rituximab (CHOP-R, n=30) at our institution between 1995 and 2006. We evaluated whether RDI might affect clinical outcomes, including complete response (CR) and event free survival (EFS). The average RDI derived from CY and ADR (referred to as RDI-CY/ADR) was determined for each patient, with classified into 2 populations according to the differences from the value of 85%, including RDI-CY/ADR<85% (n=60), and RDI-CY/ADR≥85% (n=40). Results: The median age of the study population was 54 years (range, 17 to 76), with 36 pts older than 60 years (yrs) of age. According to International Prognostic Index (IPI) score, pts were classified into 2 groups of low/ low-intermediate (n=46) and high/ high-intermediate (n=54). The overall CR rate reached 62%, and the probability of overall survival (OS) or EFS at 5 years estimated 77% or 43%, respectively with a median follow-up of 13.3 months. Multivariate analysis identified RDI-CY/ADR<85%, as well as IPI score to be associated with CR rate and EFS. Thus, RDI-CY/ADR<85% and IPI score of high/ high-intermediate were significant factors for lower CR rate (as RDI-CY/ADR≥85%, HR=0.3, 95% CI 0.1 to 0.7, p=0.009, and HR=5.5, 95% CI 2.2 to 14, p<0.001, respectively), and for reduced EFS (HR=1.9, 95% CI 1.0 to 3.7, p=0.048, and as IPI score of low/ low-intermediate HR=0.3, 95% CI 0.2 to 0.6, p<0.001, respectively). Furthermore, logrank analysis revealed that CY/ADR-RDI<85% was the significant factor for reduced EFS in non elderly pts (≤60 yrs of age), or in pts with IPI score of low/ low-intermediate (p=0.01, p=0.02, respectively). Conclusion: These data thus suggested the impact of RDI-CY/ADR<85% in influencing outcomes of the pts with DLCL, in terms of CR rate and EFS. Further investigation is currently planned to confirm this promising results with longer follow-up in larger numbers of pts with NHL.

Achievement of Complete Response Is a Strong Prognostic Factor In Elderly Newly Diagnosed Myeloma: Retrospective Analysis of 1175 Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1949-1949
Author(s):  
Francesca Gay ◽  
Alessandra Larocca ◽  
P.W. Wijermans ◽  
Sara Bringhen ◽  
Tommasina Guglielmelli ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Complete Response ◽  
New Drugs ◽  
Response To Treatment ◽  
Maximal Response ◽  
High Dose ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Best Response ◽  
The Impact

Abstract Abstract 1949 Introduction: There is extensive evidence from numerous studies in the transplant setting that achievement of complete response (CR) or at least very good partial response (VGPR) is significantly associated with prolonged progression-free survival (PFS) and overall survival (OS). In elderly myeloma patients CR was a rare event since new drugs has been added to standard melphalan-prednisone (MP). After the introduction of novel agents, CR represents an achievable goal, also outside of the transplant setting. Aims: to assess the impact of response to treatment on time-to-event parameters (PFS and OS) in elderly myeloma patients. Methods: We retrospectively analysed newly diagnosed myeloma patients, older than 65 years old, or younger but not eligible for high-dose chemotherapy and transplant. Patients were enrolled in 3 multicentre randomized European trials of the GIMEMA and Hovon groups, and were treated with MP (n=332), MP plus thalidomide (MPT, n=332), MP plus bortezomib (VMP, n=257) or MP plus bortezomib-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT, n=254). PFS, OS and duration of CR were analysed by the Cox proportional hazards model, comparing the two arms by the Wald test and calculating 95% confidence interval (CI). Univariate and multivariate analyses were performed for the following variables: age at diagnosis (>75 vs. ≤75 yrs), International Staging System (ISS) stages, type of chemotherapy and best response achieved. Best response was treated as a time-dependent variable. Results: A total of 1,175 patients, enrolled from November, 2001 to January, 2009, were retrospectively analysed. The best response to treatment was available in 1,136 patients: CR was reported in 195, VGPR in 212, PR in 397. Baseline characteristics according to best response achieved in patients who obtained CR, VGPR or PR were similar. Since response rates vary according to treatment regimens the proportion of patients who received MP, MPT, VMP, and VMPT-VT was different in the different response categories. After a median follow-up of 29 months, PFS was significantly higher in patients who achieved CR compared to those who obtained VGPR (HR 0.16; 95% CI 0.10–0.24; p<0.001) or PR (HR 0.07; 95% CI 0.04–0.13; p<0.001). The advantage in PFS translated into an advantage in OS: patients obtaining CR have a significantly prolonged OS than patients who achieved VGPR (HR 0.15; 95% CI 0.08–0.28; p<0.001) or PR (HR 0.08; 95% CI 0.04–0.16, p<0.001), (table). In multivariate analysis CR achievement was as an independent predictor of longer PFS and OS, regardless of age, ISS stage, and treatment administered. In patients > 75 years, both PFS and OS were shorter as compared to younger patients. Despite these differences, the impact of CR on outcome was identical. In the subgroup of patients > 75 years, PFS was significantly prolonged in patients who achieved CR, compared with those who obtained VGPR (HR 0.26; 95% CI 0.12–0.58, p = 0.001) or PR (HR 0.20; 95% CI 0.10–0.41, p < 0.001). Accordingly, OS was significantly higher in patients who achieved CR, compared with those who obtained VGPR (HR 0.13; 95% IC 0.03–0.58; p = 0.007), or PR (HR 0.12; 95% IC 0.03–0.51, p = 0.004), (table). No significant PFS differences between patients obtaining CR during the first 6 months of treatment or later were seen (HR 1.06; 95% IC 0.49–2.27; p=0.878). Similarly, no OS differences between these two groups were detected (p = 0.676). Duration of CR was comparable in patients who obtained CR during or after the first 6 months of treatment (HR 0.66; 95% CI 0.30–1.45; p = 0.305). Patients whose CR lasted more than 18 months have a significant OS benefit compared to patients who did not (p=0.006). Conclusions: These finding highlight the importance of CR, also outside of the transplant setting, regardless of age, ISS and treatment administered, and support the use of new drugs, also in patients older than 75 years, to achieve and maintain maximal response. Disclosures: Gay: Celgene: Honoraria. Bringhen:Calgene: Honoraria; Janssen-Cilag: Honoraria. Guglielmelli:Celgene: Honoraria; Janssen Cilag: Honoraria. Boccadoro:Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees. Sonneveld:Celgene: Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson : Membership on an entity's Board of Directors or advisory committees. Palumbo:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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.

Safety and effectiveness of dose dense neoadjuvant chemotherapy in patients with stage II/III breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10622-10622
Author(s):  
S. A. McDaniel ◽  
H. Krontiras ◽  
J. T. Carpenter ◽  
L. M. Nabell ◽  
K. I. Bland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Grade 3 ◽  
Dose Dense ◽  
To Receive

10622 Background: NSABP B-18 randomized women with operable breast cancer to receive chemotherapy either pre- or postoperatively; OS and DSF rates at 9 years were identical. Importantly, pathologic complete response (pCR) was directly proportional to DFS and OS. Recently, dose dense adjuvant chemotherapy has shown a statistically significant improvement in DFS and OS. However, no data is available for the use of dose dense preoperative chemotherapy at this time. Methods: Women enrolled in the I-SPY correlative trial with newly diagnosed breast cancer, T ≥ 3cm, any N, M0 were evaluated to assess response rates and safety to dose dense neoadjuvant chemotherapy (doxorubicin 60 mg/m2 IV Q2 wks × 4, paclitaxel 175 mg/m2 IV Q2 wks × 4, and cyclophosphamide 600 mg/m2 IV Q2 wks × 4). Results: Since 02/2003, 43 pts have been treated with dose dense neoadjuvant chemotherapy on the I-SPY trial at UAB (mean age 47.9). 47% of the pts were ER+, 37% were PR+ and 5% were Her2+ by FISH. 2 pts dropped out for personal reasons and 9 pts are actively undergoing treatment. Overall, 32 pts received dose dense chemotherapy and proceeded to surgery. Of those, 31 received dose dense sequential ATC and 1 received dose dense concurrent AC followed by T. 34% had a pCR (breast & nodes) while an additional 10% had a pCR in the breast but residual disease in lymph nodes; 41% had a PR; 9% had SD; and 6% had PD. Hematologic toxicity consisted of grade 3 anemia in 2 pts, febrile neutropenia in 2 pts and no grade 4 thrombocytopenia. Non-hematologic grade 3–4 toxicity consisted of mediport-associated thrombosis in 2 pts, hyperglycemia in 2 pts, syncope in 1 pt, neuropathy in 1 pt, and disseminated varicella in 1 pt. Conclusion: Our results show that dose dense neoadjuvant chemotherapy achieves a pCR (breast & nodes) in about 1/3 of patients (34%) with tolerable toxicity. No significant financial relationships to disclose.

Impact of obesity upon the survival of cholangiocarcinoma patients.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 288-288
Author(s):  
Phani Keerthi Surapaneni ◽  
Zhuo Li ◽  
Lalitha Padmanabha Vemireddy ◽  
Pashtoon Murtaza Kasi ◽  
Jason Scott Starr ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
Survival Rates ◽  
Tumor Location ◽  
Normal Weight ◽  
Categorical Variables ◽  
Overall Survival Rate ◽  
Exact Test ◽  
Significant Difference ◽  
The Impact

288 Background: Obesity is a risk factor for developing cholangiocarcinoma (CCA). However, the effect of obesity on survival of CCA is unclear. The primary aim of this study was to analyze the impact of obesity upon overall survival of CCA patients. Secondary aims were to analyze impact of obesity upon other disease characteristics such as tumor site, stage, age, sex, BMI and Ca 19-9. Methods: A total of 411 unique pts diagnosed with CCA at Mayo Clinic Florida between 2000 and 2018 were retrieved from our collective SDMS database. Variables evaluated included:demographics, Body Mass Index (BMI), AJCC stage, tumor location and Ca 19-9.A total of 185 pts had all data available pertaining to these variables. We further restricted the analysis to pts with intrahepatic CCA classified BMI as per CDC criteria normal (18.5-25kg/m2), overweight (25-29.9kg/m2) and obese (≥30 kg/m2), thus leaving a total of 152 pts. Continuous and categorical variables were compared across BMI groups using Chi-squared or Fisher’s exact test. Overall survival rates after diagnosis at 1, 2 and 3 years were estimated using Kaplan-Meier method. Results: Among 152 pts included in the study, 28% were normal weight, 40% were overweight and 32% were obese. The overall survival rate at 1, 2 and 3 years for normal weight pts with all stages combined was 54.1%, 35%, and 30.7%, respectively. The overall survival rate at 1, 2 and 3 years for overweight pts with all stages combined was 59.7 %, 32.6%, and 25.4%, respectively. The overall survival rate at 1, 2 and 3 years for obese pts with all stages combined was 63.9%, 37.6%, and 26.7%, respectively(p = 0.8766). Multivariate analysis demonstrated is no significant difference in overall survival for obese pts compared to normal or overweight pts.(Table to be shown) However it showed, gender and Ca19-9 were statistically significant predictors of overall survival, with males and pts with Ca19-9≥100 doing worse (HR1.65 (CI = 1.05, 2.61, p = 0.031) and HR 2.31 (CI = 1.49, 3.59, p = < 0.01), respectively). Conclusions: BMI did not make a significant impact on the overall survival, though there may be a trend toward worse OS for ptswith higher BMI. A larger, stage focused evaluation is warranted for further exploration of this trend.

Analysis of the impact of growth factor on the haematological safety of dose-dense regimen in the randomized phase II adjuvant trial BO3

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 605-605
Author(s):  
C. Delbaldo ◽  
D. Serin ◽  
F. Priou ◽  
P. Laplaige ◽  
S. Greget ◽  
...  
Keyword(s):  
Phase Ii ◽  
Cox Model ◽  
Haematological Toxicity ◽  
Safety Data ◽  
Dose Intensity ◽  
Breast Adenocarcinoma ◽  
Sequence Versus ◽  
Randomized Phase Ii ◽  
Dose Dense ◽  
The Impact

605 Background: In a randomized phase II study, P. Piedbois et al. explored a dose-dense docetaxel (T) followed by epirubicin/cyclophosphamide (EC) every two weeks versus the reverse sequence, versus standard-dose docetaxel, epiribucin and cyclophosphamide (TEC) every 3 weeks. The main purpose of this second analysis was to further explore the haematological safety of each regimen in patients receiving primary prophylactic pegfilgrastim. Methods: One hundred patients with node-positive invasive breast adenocarcinoma were randomized between (arm A) docetaxel 75 mg/m2, epiribucin 75 mg/m2 and cyclophosphamide 500 mg/m2 (TEC) every 3 weeks for 6 cycles (35 patients) or (arm B) epiribucin 100 mg/m2 and cyclophosphamide 600 mg/m2 every 2 weeks for 4 cycles, followed by T 100 mg/m2 (EC→T) every 2 weeks for 4 cycles (31 patients) or (arm C) T→ EC (34 patients). Among the 99 patients who received chemotherapy, 79 received pegfilgrastim 6 mg subcutaneous day 1 from the first cycle (27 in arm A, 23 in arm B and 29 in arm C). The safety data of these 79 patients were reported here. Results: Our results showed grade 3/4: neutropenia (arm A 30 %, arm B 39 %, arm C 31 %) and febrile neutropenia (FN) (arm A 11 %, arm B 13 %, arm C 3 %), grade 2–4: anaemia (arm A 26 %, arm B 61 %, arm C 55 %) and thrombocytopenia (arm A 15 %, arm B 9 %, arm C 3 %), respectively. Crude proportion and time to toxicity summaries showed that in dose-dense arms, patients allocated to the EC→ T sequence were more exposed to FN than patients allocated to the T→ EC. In the Cox model taking into account all allocated treatment and age, treatment was a predictor of grade 2–4 anaemia, whereas age was significantly correlated to grade 2–4 thrombocytopenia. There was no clear relationship between haematological toxicity and dose intensity across all treatment arms. Except for nausea (17 % versus 3 %) and neurological toxicity (13 % versus 3 %), non-haematological toxicities were similar in arm B and C. Conclusions: These analyzes confirmed that dose-dense regimens EC→ T or T→ EC are feasible with pegfilgrastim primary prophylaxis. The T→ EC sequence seems to be associated with a better haematological tolerance, and should be the preferred dose-dense regimen providing similar efficacy. The trial was supported by Amgen. No significant financial relationships to disclose.

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