Eribulin mesylate (Erib) plus capecitabine (X) for adjuvant treatment in post-menopausal estrogen receptor–positive (ER+) early-stage breast cancer: Phase II, multicenter, single-arm study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 563-563
Author(s):  
John W. Smith ◽  
Jessicca Rege ◽  
Hina Maniar ◽  
James Song ◽  
David Cox ◽  
...  
Keyword(s):  
Early Stage ◽  
Single Agent ◽  
Dose Intensity ◽  
Drug Discontinuation ◽  
Eribulin Mesylate ◽  
Estrogen Receptor Positive ◽  
Hand Foot Syndrome ◽  
Alternative Schedule ◽  
Post Menopausal ◽  
Dose Reductions

563 Background: Erib and X have both shown single agent activity in MBC; and X also has activity in ER+ adjuvant tx. This study was designed to evaluate the feasibility of the combination in the adjuvant setting. Methods: Female pts stage I-II, HER2 negative, ER+ BC received Erib at 1.4 mg/m2 iv D1 and D8 and X at 900 mg/m2 po bid on days 1-14 of 21 day cycle, for 4 cycles. The study was considered feasible if 80% of pts are able to achieve the target relative dose intensity (RDI) of at least 85% of the regimen and lower 95% confidence boundary (LCI) is above 70%. Results: Final results of 67pts enrolled are reported here. 88% pts completed 4 cycles of tx. Pt characteristics: Median age 62 yrs (range 28-80), ECOG 0(90%), stage 2(52%). 64/67 pts were evaluable for feasibility. The study met its primary endpoint demonstrating feasibility rate of 81%(95% LCI:71%) with average RDI of 91%. Results were mainly affected by X dose adjustments (Erib RDI-93%, X RDI-88%). X related dose reductions(24, (36%)), missed doses (57,(85%)) and discontinuations due to AE (11(16%)) were higher compared to that with Erib(14(21%), 5(8%) and 7(10%)), respectively. Most common AEs with dose reductions were gr 3/4 hand foot syndrome (HFS) (12%), neutropenia(8%), neuropathy(8%), and GI disorders(6%); and drug discontinuation were HFS(8%), neutropenia(3%), neuropathy(2%), and GI disorders(3%). Tx related AEs and SAE are reported in the Table. 14(21%) pts had an SAE with 12(18%) requiring hospitalization. Conclusions: Adjuvant tx with the Erib-X combination can be given safely with the majority of the patients able to achieve full dosing regimen. We plan to explore an alternative schedule of X(7wk on/off) with this regimen to see if it will further improve tolerability and the RDI. Clinical trial information: NCT01439282. [Table: see text]

scholarly journals Moist Exposed Burn Ointment Effectiveness for Capecitabine Associated Grade II and III Hand Foot Syndrome on Stage III Colonic

2021 ◽  
Vol 9 (B) ◽  
pp. 971-974
Author(s):  
Budhi Ida Bagus ◽  
Nunik Agustriani ◽  
Rieva Ermawan ◽  
Suwardi Suwardi ◽  
Amru Sungkar ◽  
...  
Keyword(s):  
Single Agent ◽  
Locally Advanced ◽  
Common Adverse Effect ◽  
Dose Intensity ◽  
Stage Iii ◽  
Advanced Stage ◽  
Chemotherapy Agent ◽  
Palmoplantar Erythrodysesthesia ◽  
Hand Foot Syndrome ◽  
Grade Ii

Background:Hand-foot syndrome (HFS), also known as palmoplantar erythrodysesthesia, is a common adverse effect of the fluoropyrimidine chemotherapy agent capecitabine. Hand-foot syndrome of any grade is reported to affect 43% to 71% of patients treated with single-agent capecitabine chemotherapy. Although not life-threatening, it can have adverse effects on the quality of life (QoL) and daily living activities of a patient.  Sometimes the dose interruptions and reductions required after observation of HFS can also impact on dose intensity and treatment outcomes.  As an option for the treatment of this case, we would reported our preliminary study of the effectiveness of moist exposed burn ointment (MEBO) for stage II and III HFS.   Methods:  We will evaluate the clinical sign and symptoms of hand foot syndrome grade II and III associated with capecitabine as adjuvant chemotherapy agent on advanced stage colorectal cancer.  All patients with HFS will treated with topical MEBO twice daily, the clinical improvement of the symptoms will be recorded.   Results: We reported 8 cases of grade II and III hand foot syndrome, 2 patients were grade III HFS and the others were grade II.  These symptoms occurred after 2 until 3 months after capecitabine administration for locally advanced (stage III) colonic adenocarsinoma.  Topical MEBO were used twice a day for 3 months, pain reduction was achieved with no capicetabine dose interruption and reduction during chemotherapy period.  Allergic reaction was not found during and after MEBO application in this case.   Conclusion:Moist exposed burn ointment was an effective treatment option in managing hand foot syndrome, better option in reducing the pain without interrupting the capecitabine doses.

Phase II trial of nab-paclitaxel (nanoparticle albumin-bound paclitaxel (ABX)) + capecitabine (XEL) in first-line treatment of metastatic breast cancer (MBC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1053-1053 ◽  
Author(s):  
B. G. Somer ◽  
L. S. Schwartzberg ◽  
F. Arena ◽  
A. Epperson ◽  
D. Fu ◽  
...  
Keyword(s):  
Dose Reduction ◽  
Phase Ii ◽  
Response Rate ◽  
Single Agent ◽  
Objective Response ◽  
Metastatic Breast ◽  
Safety And Efficacy ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
Dose Reductions

1053 Background: ABX and XEL both have substantial single agent activity in MBC. Taxane and anti-metabolite doublets improve response rate and TTP and longer survival. ABX administered weekly has an excellent safety and efficacy profile with maintenance of dose intensity. This study was designed to test the safety and efficacy of ABX + XEL given in a novel combination schedule. Methods: This phase II, multicenter open label study utilized ABX 125 mg/m2 IV on day 1, 8 and with no premeds and capecitabine 825 mg/m2 PO BID days 1–14 on a Q 3 week cycle. The primary endpoint is objective response rate, with evaluation performed after every 2 cycles. Entry criteria include measurable MBC by RECIST criteria, age >18, PS 0–2, no prior chemo for metastatic disease, > 6 months since adjuvant fluoropyrimidine and/or paclitaxel. Results: The full sample of 50 patients (pts) have been enrolled; data from 43 pts are available for analysis. Median age is 58 (range 23.7–90.6). 37% received prior adjuvant anthracycline and 33% prior adjuvant taxane. Median number of metastatic sites is 2 (range 1–7), with most common sites of disease liver, 53.5%; bone, 51.2%; and lung, 14%. 226 cycles of therapy have been delivered. 5 pts required a dose reduction in XEL (3 pts to 650 mg/m2; 2 to 550 mg/m2) and 4 pts had dose reduction in ABX to 100 mg/m2. XEL dose reductions occurred due to hand-foot syndrome (3), neutropenia (1), and fatigue (1). ABX dose reductions occurred due to mucositis, diarrhea, fatigue, and neuropathy (1 pt each). 10 pts had grade 3–4 non-hematologic AEs: 3 hand-foot syndrome, 4 fatigue, and 3 GI. Hematologic AEs included 4 with grade 3 and 1 with grade 4 neutropenia, and 2 with grade 4 febrile neutropenia. The most common AEs of any grade were GI (30), dermatological (23), fatigue (15), neuropathy (12), and hand-foot syndrome (11). The incidence of Grade 1–2 neuropathy was 25% (no grade 3–4). Of 38 pts available for analysis of response, the overall response rate is 47.5%: PR 39.5%, CR 8%. Total of 15 pts have stable disease, 20 pts have completed 6+ cycles. No significant financial relationships to disclose.

A phase II trial of voreloxin in women with platinum-resistant ovarian cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5559-5559
Author(s):  
H. W. Hirte ◽  
W. McGuire ◽  
R. Edwards ◽  
A. Husain ◽  
P. Hoskins ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Topoisomerase Ii ◽  
Single Agent ◽  
Safety Data ◽  
Dose Intensity ◽  
Clinical Activity ◽  
Platinum Resistant ◽  
Dose Levels ◽  
Dose Reductions

5559 Background: Voreloxin is a naphthyridine analog that intercalates DNA and inhibits topoisomerase II, inducing apoptosis. Clinical activity has been observed in ovarian cancer and AML. Results are reported from a fully enrolled phase II study of 3 dose levels of single agent voreloxin in patients (pts) with 1° or 2° platinum-resistant or refractory ovarian cancer. Methods: Pts may have received ≤ 3 prior platinum regimens plus one additional non-platinum regimen. PS of 0–1 was required. Voreloxin regimens: Cohort A 48 mg/m2q3weeks (wk) (N = 65), Cohort B 60 mg/m2q4wk (N = 35), and Cohort C 75 mg/m2q4wk (N = 35) by short IV infusion. BRCA status is reported by pt consent. Results: Cohort A: 2CRs, 5PRs; ORR 11%; median PFS 82 days (52–98 days 95%CI); Cohort B: 1CR, 3PRs; ORR 11%, median PFS too early to evaluate (TETE); Cohort C - TETE. Cohort A: Febrile neutropenia (FN) incidence was low (8%). Other common G3 or G4 AEs reported (≥ 5%) were fatigue (14%) and nausea (5%). Dose delays or reductions (40%) occurred typically at Cycle 1, largely due to neutropenia. Cohort B: Dose was increased to 60 mg/m2 and dosing interval was lengthened to 4 wk, maintaining dose intensity (DI) and allowing adequate time for marrow recovery. ANC dosing criterion was changed from ANC ≥ 1,500 to ≥ 1,000. There was a marked decrease in dose delays and reductions (14%) with only 3% incidence of FN. Common G3 or 4 AEs reported (≥ 5%) were fatigue (11%) and nausea (5%). The safety profile supported further dose escalation to 75 mg/m2q4wk (Cohort C- DI increased by 25%). Data are TETE. Conclusions: Preliminary data suggest Cohorts A and B have similar safety and efficacy profiles as anticipated based on comparable DI. Fewer dose reductions and delays occurred in Cohort B, due to revised dosing criteria and increased cycle length to 4 wk. Accrual to Cohort C is complete. Efficacy and safety data for all cohorts will be reported. [Table: see text]

Current patterns of chemotherapy and supportive care for early-stage breast cancer (ESBC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1062-1062
Author(s):  
Gary H. Lyman ◽  
David C. Dale ◽  
Dianne Tomita ◽  
Sadie Whittaker ◽  
Jeffrey Crawford
Keyword(s):  
Antimicrobial Therapy ◽  
Early Stage ◽  
Dose Intensity ◽  
Myelosuppressive Chemotherapy ◽  
Prophylactic Use ◽  
Grade 3 ◽  
Dose Dense ◽  
Stimulating Factor ◽  
Schedule Dose ◽  
Dose Reductions

1062 Background: ESBC is commonly treated with myelosuppressive chemotherapy, and high relative dose intensity (RDI) correlates with improved overall survival. A retrospective analysis of patients with ESBC treated from 1997–2000 showed that 56% received an RDI < 85% (Lyman et al. JCO. 2003;21:4524-4531). To determine current practice, we evaluated ESBC treatment patterns at 24 US community- and hospital-based oncology practices. Methods: Data were abstracted from medical records of 532 patients with ESBC treated from January 2007–December 2009. Inclusion criteria included surgically resected ESBC (stage I-IIIA); ≥ 18 years old; and completion of at least 1 standard chemotherapy cycle on an every 2 or 3 week schedule. The primary endpoint was RDI over planned cycles. Other endpoints were incidence of dose delays ≥ 7 days, dose reductions ≥ 15% from standard, grade 3/4 neutropenia (SN), febrile neutropenia (FN), FN-related hospitalization, granulocyte-colony stimulating factor (G-CSF) use, and antimicrobial therapy. Descriptive statistics were generated for all endpoints. Results: In this study, mean (range) age was 55 (29–85) years. Relative to previously published results, chemotherapy regimens have shifted from mainly doxorubicin + cyclophosphamide (AC) (previously 35%) to docetaxel + cyclophosphamide (TC; n = 221; 42%) and AC followed by paclitaxel (AC-T; n = 163; 31%). Mean RDI is now higher (93% for both TC and the most common AC-T schedule [dose dense AC-T; n = 84] vs 79% previously); the incidence of dose delays (16% vs 25% previously) and dose reductions (21% vs 37% previously) have decreased; and primary prophylactic use of G-CSF has increased (76% vs 3% previously). In this study, 40% of patients had SN, 3% had FN, 2% had an FN-related hospitalization, and 30% received antimicrobial therapy. These measures were not available in the previously published results. Conclusions: The observed changes between the two studies are noteworthy though inferential comparisons are limited by changes in treatments and other factors. RDI has improved over time, but 16% of patients in this study received an RDI < 85%. Further evaluation is needed to identify factors associated with lower RDI and determine outcomes for these patients.

scholarly journals Chemotherapy Relative Dose Intensity and Therapy Efficacy in Hodgkin and Non-Hodgkin Lymphoma: The Effect of Dose Reductions and Delays on Cure

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5092-5092
Author(s):  
Elizabeth Bowhay-Carnes ◽  
Christos Fountzilas ◽  
Michelle Janania Martinez ◽  
Brandon Konkel ◽  
Brandon Stormes ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Univariate Analysis ◽  
Dose Intensity ◽  
B Cell Lymphoma ◽  
Hematologic Malignancies ◽  
Relative Dose Intensity ◽  
Non Hodgkin Lymphoma ◽  
Dose Reductions

Abstract Introduction: The fundamental design behind combination chemotherapeutic regimens for hematologic malignancies is based on mathematical modeling that attempts to achieve rapid tumor reduction with appropriate cytotoxic doses given at predetermined intervals designed to minimize the chance of regrowth during treatment. The current standard primary treatment for Hodgkin lymphoma includes combination chemotherapy with Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine given at 14 day intervals (ABVD). For high-grade Non-Hodgkin lymphoma, the most common first line combination chemotherapy regimen includes Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone given at 21 day intervals (RCHOP-21). In clinical practice, it is common for patients to experience chemotherapy dose reductions or treatment delays due to various factors leading to a decrease in relative dose intensity (RDI). The relationship between chemotherapy relative dose intensity (RDI) and treatment efficacy was investigated. Methods: Patients with Hodgkin lymphoma (HL) who received ABVD and patients with diffuse large B cell lymphoma (DLBCL) who received RCHOP-21 at our institution between 2004-2014 were retrospectively studied in 2 different cohorts. The following data was collected: age, sex, ethnicity, stage, Charleston Comorbidity Index (CCI), duration of follow-up, chemotherapy RDI, treatment outcome (remission vs primary refractory/relapse). The HL cohort consisted of 46 patients with the following characteristics: average age 36 years (range 18-74 years), 50% male/50% female, 50% Hispanic/50% Non-Hispanic, 44% early stage/56% late stage, 75% CCI 2/29% CCI >2, average follow-up 34 months (range 2-118 mo). The DLBCL cohort consisted of 104 patients with the following characteristics: average age 53 years (range 19-82 years), 50% male/50% female, 59% Hispanic/41% Non-Hispanic, 49% early stage/51% late stage, 60% CCI 2/40% CCI >2, average follow-up 34 months (range 2-163 mo). Results: The HL cohort treated with ABVD had a mean RDI of 83% (range 50-100%) with outcomes as follows: remission 38 (82%), primary refractory 4 (9%), relapsed 4 (9%). Univariate analysis showed no difference in outcome between patients who received ABVD RDI >90% vs 80-89% vs <80% (p=0.6). The DLBCL cohort treated with RCHOP-21 had a mean RDI of 86% (range 32-100%) with outcomes as follows: remission 81 (79%), primary refractory 16 (15%), relapse 7 (6%). Univariate analysis showed no difference in outcome between patients who received RCHOP-21 RDI >90% vs 80-89% vs <80% (p=0.6). For both cohorts, there was no difference between outcomes based on stage (early vs advanced) or ethnicity (Hispanic vs Non-Hispanic). In the Hodgkin lymphoma cohort, there was a correlation between comorbidity index and RDI. Patients with higher CCI scores has a significantly lower average ABVD RDI compared to patients with lower CCI scores (77% vs 86%, p = 0.04). Conclusions: There was no correlation between chemotherapy relative dose intensity and treatment efficacy in two cohorts of patients with Hodgkin lymphoma and diffuse large B cell lymphoma. These findings may suggest that for patients with these potentially curative hematologic malignancies, small dose reductions or short delays between chemotherapy cycles that result in decreased chemotherapy relative dose intensity may not affect overall outcomes. However, further studies are needed to determine the level at which a decreased relative dose intensity becomes significant. Disclosures No relevant conflicts of interest to declare.

scholarly journals Real-World Outcomes of Patients Treated with Single-Agent Ibrutinib for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): A Systematic Review and Meta-Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-14
Author(s):  
Matthew C. Cheung ◽  
Irina Amitai
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trials ◽  
Adverse Events ◽  
Real World ◽  
Meta Analysis ◽  
Single Agent ◽  
Lymphocytic Leukemia ◽  
Drug Discontinuation ◽  
Small Lymphocytic Lymphoma ◽  
Dose Reductions

BACKGROUND: Ibrutinib improves progression-free survival (PFS) compared to chemo-immunotherapy in both previously untreated and relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; hereafter, CLL) patients. Adverse events, such as atrial fibrillation, bleeding and fungal infections, are the leading cause of drug discontinuation. Observational studies of real-world patients suggest that the rate of ibrutinib-related adverse events is higher in practice than in clinical trials. Dose reductions and drug discontinuations are more common, which may affect outcomes, although evidence has been conflicting. OBJECTIVES: The objective of this study is to systematically review and synthesize real-world toxicity and tolerability of CLL patients on ibrutinib. METHODS: Prospective and retrospective cohort studies and case series of patients with CLL treated with single agent ibrutinib as first or subsequent line treatment outside of clinical trials were retrieved from the Pubmed, Embase, and CENTRAL databases. Studies were critically appraised using Joanna-Briggs Institute checklists. Meta-analyses of studies deemed of moderate to high quality were done if the risk of heterogeneity was low. RESULTS: We screened 4458 titles and abstracts and moved 251 records to full-text review. 25 full-text studies were included in the qualitative analysis. Most studies were of low to moderate quality. Rates of any bleeding ranged from 5.4 to 54.1 events/100 persons-year. Rates of severe bleeding ranged from 0 to 6.4 events/100 persons-year. Rate of infection was 9.2 to 49.8 infections/100 persons-year. Rate of atrial fibrillation varied from 2.5 to 26.0 events/100 persons-year. Pooled estimate of risk of atrial fibrillation per 100 person-years was 7.0 (95% CI 5.8, 8.2) by meta-analysis of moderate quality studies. Rate of dose reductions varied from 15.1 to 26.8 events/100 person-years, and dose reductions did not affect outcomes. The rate of drug discontinuation varied from 6.4 to 55.2 events/100 person-years. The most common cause for drug discontinuation was adverse events. CONCLUSION: The risk of atrial fibrillation is higher in the real-world than reported from clinical trials. There was a large range of prevalence of other bleeding and infection. These adverse events were the leading cause of dose reduction and drug discontinuation. This study has many limitations arising from heterogeneity of patient characteristics and outcomes ascertainment. This highlights the need for standardized post-marketing studies of new drugs and for inclusive criteria for inclusion into randomized controlled trials. Disclosures No relevant conflicts of interest to declare.

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