Comparison of doxorubicin and cyclophosphamide (AC) versus single-agent paclitaxel (T) as adjuvant therapy for breast cancer in women with 0-3 positive axillary nodes: CALGB 40101.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1007-1007
Author(s):  
Lawrence N. Shulman ◽  
Donald A. Berry ◽  
Constance T. Cirrincione ◽  
Heather Becker ◽  
Edith A. Perez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Relative Effectiveness ◽  
Single Agent ◽  
Hazard Ratio ◽  
Hematologic Toxicity ◽  
Grade 3 ◽  
Reduced Toxicity ◽  
Absolute Advantage

1007 Background: Determining optimal adjuvant chemotherapy for early stage breast cancer depends on efficacy and toxicity. We sought to determine if T is equivalent to AC but with reduced toxicity. Methods: Pts with operable breast cancer with 0-3 positive nodes were enrolled on a 2x2 factorial design study which addressed (1) superiority of 6 vs. 4 cycles of therapy (previously reported, Shulman, JCO 2012) and (2) equivalence of single-agent T to standard AC, defined as upper bound of 95% confidence interval (CI) of hazard ratio (HR) of T vs. AC < 1.30 for the primary endpoint of relapse-free survival (RFS). A planned target of 567 RFS events required 4,646 pts with 4 yrs FU. At activation in 2002, T (80mg/m2) was q1wk for 12 or 18 wks and AC (60/600 mg/m2) was q3wk for 4 or 6 cycles. In 2003 (570 pts enrolled) schedules were revised to 4 or 6 cycles q2wk for both T (175 mg/m2) and AC. The 6-cycle arms were dropped in 2008 (3,171 pts enrolled) due to slow accrual. Relative effectiveness of T to AC is shown by hazard ratio (HR). Logrank p-values are measures of discordance but are not relevant for the equivalence question and are not adjusted for multiple comparisons. Results: After enrolling 3,871 pts, the study closed in 2010 due to slowing accrual. With a median follow-up of 6.1 yrs there are 437 RFS events. The HR of 1.26 (95% CI: 1.05-1.53; p = 0.02) does not allow a conclusion of equivalence of T with AC. With 266 deaths the HR for overall survival (OS) is 1.27 (95% CI=1.00-1.62; p = 0.05), favoring AC. The estimated absolute advantage of AC at 5 yrs is 3% (91 vs. 88%) for RFS and 1% (95 vs. 94%) for OS. All 9 treatment-related deaths were in pts receiving AC and are included in the survival analysis. The incidence of Grade 3+ toxicity for AC vs T was 33% vs. 4% for hematologic toxicity and 36% vs 22% for non-hematologic toxicity. Conclusions: This trial did not show equivalence of T to AC, a conclusion that is very unlikely to change with additional follow-up. T was less toxic than AC. Clinical trial information: CDR0000069444/NCT00041119.

scholarly journals Comparison of Doxorubicin and Cyclophosphamide Versus Single-Agent Paclitaxel As Adjuvant Therapy for Breast Cancer in Women With 0 to 3 Positive Axillary Nodes: CALGB 40101 (Alliance)

2014 ◽  
Vol 32 (22) ◽  
pp. 2311-2317 ◽  
Author(s):  
Lawrence N. Shulman ◽  
Donald A. Berry ◽  
Constance T. Cirrincione ◽  
Heather P. Becker ◽  
Edith A. Perez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Single Agent ◽  
Hematologic Toxicity ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Duration Of Therapy ◽  
The One ◽  
Absolute Advantage

Purpose Optimal adjuvant chemotherapy for early-stage breast cancer balances efficacy and toxicity. We sought to determine whether single-agent paclitaxel (T) was inferior to doxorubicin and cyclophosphamide (AC), when each was administered for four or six cycles of therapy, and whether it offered less toxicity. Patients and Methods Patients with operable breast cancer with 0 to 3 positive nodes were enrolled onto the study to address the noninferiority of single-agent T to AC, defined as the one-sided 95% upper-bound CI (UCB) of hazard ratio (HR) of T versus AC less than 1.30 for the primary end point of relapse-free survival (RFS). As a 2 × 2 factorial design, duration of therapy was also addressed and was previously reported. Results With 3,871 patients enrolled onto the trial, a median follow-up period of 6.1 years, and 437 RFS events, we achieved an HR of 1.26 (one sided 95% UCB, 1.48; favoring AC does not allow a conclusion of noninferiority of T with AC; UCB > 1.3). With 266 patient deaths, the HR for overall survival (OS) was 1.27 favoring AC (UCB, 1.56). The estimated absolute advantage of AC at 5 years is 3% for RFS (91 v 88%) and 1% for OS (95 v 94%). All nine treatment-related deaths were patients receiving AC and are included in the analyses of both RFS and OS. Hematologic toxicity was more common in patients treated with AC, and neuropathy was more common in patients treated with T. Conclusion This trial did not show noninferiority of T to AC, a conclusion that is unlikely to change with additional events and follow-up. T was less toxic than AC.

Frontline Combined Chemoimmunotherapy with Fludarabine, Cyclophosphamide, Alemtuzumab and Rituximab (CFAR) in High-Risk Chronic Lymphocytic Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 208-208 ◽  
Author(s):  
Sameer A Parikh ◽  
Michael Keating ◽  
Susan O'Brien ◽  
Alessandra Ferrajoli ◽  
Stefan Faderl ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Single Agent ◽  
Lymphocytic Leukemia ◽  
Hematologic Toxicity ◽  
Frontline Therapy ◽  
Grade 3 ◽  
Tract Infections ◽  
Cmv Reactivation

Abstract Abstract 208 Background: Combined chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab (FCR) has excellent clinical activity as frontline therapy for patients (pts) with chronic lymphocytic leukemia (CLL). In a subset of pts who exhibited high-risk features, such as serum beta-2 microglobulin (B2M) ≥4 mg/L; the complete remission (CR) was lower and time to progression (TTP) and overall survival (OS) were shorter; therefore characterizing these pts as high-risk. Alemtuzumab (A) has activity as a single-agent and in combination with F in pts with relapsed/refractory CLL. To improve the CR and OS for pts with high-risk CLL, we added A to the FCR regimen (CFAR) as frontline therapy in a Phase II clinical trial. Methods: All pts who met NCI-WG criteria to initiate therapy, were < 70 years and had a B2M ≥4 mg/L were eligible for the study. Frontline CFAR consisted of C-200 mg/m2 D3-5, F-20mg/m2 D3-5, A-30mg IV D1,3,5, and R-375–500 mg/m2 D2. Courses were repeated every 28 days for a total of 6 courses. All pts received pegylated filgrastim 6mg SC with each course of therapy. All pts received allopurinol for tumor lysis prophylaxis. Antibiotic prophylaxis with TMP/SMX DS and valacyclovir or valganciclovir was also given to all pts. CMV antigenemia was monitored before each course. Results: A total of 60 pts were enrolled from July 2005 through August 2008 (Table). One pt was lost to follow-up. The median age was 59 yrs (range 42–69) and 44 (75%) were male. Median B2M was 5.1 mg/L (4–11.6); HGB was 11.5gm/dL (5.5–15.1); PLT was 139 k/μL(41–446); WBC was 100k/μL (5–665); ALC was 92k/μL (4–619); and 30 pts (51%) were Rai stage III-IV. The median number of courses administered was 4 (2–6); reasons for not completing 6 courses included delayed recovery of counts (18), infection (8), AIHA (4), treatment failure (3) and pt. choice (2). CR was achieved in 70%, nPR in 3%, PR in 18%, and 7% pts did not respond, leading to an ORR of 92% (Table). There was no significant correlation between CR or OR with Rai Stage, IgVH mutation status, FISH status, ZAP70 and CD38 expression. After a median follow-up of 24 months (3–49), 19(32%) pts have progressive disease. Patients with 17p deletion and unmutated IgVH had significantly shorter TTP as shown in the >Table. Eleven (19%) pts have died: 4 with disease progression after achieving CR; 2 who did not respond; 2 with Richter's transformation; 1 transformed into AML; 1 due to metastatic lung cancer; and 1 due to severe pneumonia 8 months after achieving CR. Grade 3/4 neutropenia and thrombocytopenia occurred in 31% and 13% courses. Major infections, including pneumonia and sepsis, were reported for 10(17%) pts. Minor infectious such as bronchitis, urinary tract infections and herpes zoster were reported for 15(25%) pts. In a historic cohort of high-risk pts treated with FCR, grade 3/4 neutropenia and thrombocytopenia occurred in 31% and 10% courses; and major and minor infections were seen in 15% and 23% pts respectively, all comparable to that seen with frontline CFAR. A-associated infusion reactions occurred in 42 (71%) pts. CMV reactivation occurred in 7 (12%) pts, all of whom were on valacyclovir prophylaxis. There was 1 death due to CMV pneumonia; all other episodes of CMV reactivation were promptly treated with valaganciclovir leading to resolution of fever and/or antigenemia. The median OS for all pts has not been reached (49+mo) and the median TTP is 38 months. Conclusion: CFAR is an active frontline regimen in high-risk pts with CLL. Although CR rates in pts with other high-risk features such as 17p deletion and unmutated IgVH were >50%, TTP was significantly shorter for these pts than for pts without these features. With current follow-up, OS, TTP, infectious complications and grade 3/4 hematologic toxicity are comparable to historic high-risk pts treated with FCR. Disclosures: Keating: Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wierda:Genentech: Consultancy, Honoraria; Genzyme: Research Funding.

Gemcitabine plus docetaxel versus docetaxel in patients (pts) with HER2-negative locally advanced or metastatic breast cancer (MBC): A randomized phase III study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1015-1015
Author(s):  
D. L. Nielsen ◽  
S. T. Langkjer ◽  
K. Bjerre ◽  
S. Cold ◽  
L. Stenbygaard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Rank Test ◽  
Hematologic Toxicity ◽  
Phase Iii Study ◽  
Her 2 ◽  
Grade 3

1015 Background: Gemcitabine (G), either as a single agent or in combination with taxanes, has demonstrated efficacy in MBC in phase II and III studies. We conducted a phase III study to compare time to progression (TTP) of G plus docetaxel (T) versus (vs.) T alone. The secondary endpoints included overall survival (OS), overall response rate (ORR), and toxicity. Methods: Females with HER-2-negative locally advanced or MBC and a WHO performance status ≤ 2 were randomized to GT (G 1,000mg/m2 day 1 + 8; T 75mg/m2 day 1) or T (100mg/m2 day 1) every 21 days. Pts were previously untreated, had prior anthracycline-based (neo)adjuvant chemotherapy or had received a single prior anthracycline-bsed chemotherapy regimen for MBC. Time-to-event endpoints were estimated using the Kaplan-Meier method, and the log-rank test was applied for comparisons between regimens. The planned sample size was 254 evaluable pts with α I and β of 0.05 and 0.90, respectively. Results: A total of 336 pts were randomized (170 GT; 166 T), data from one centre are yet missing and the present evaluation is based on data from 306 pts (155 GT; 151 T). The pts had a median age of 58 years in both regimens; range 36–73 years and 30–74 years, respectively. The median TTP was 7.5 months for the GT regimen vs. 6.5 months for the T regimen. The GT arm demonstrated an ORR of 44% vs. 38% in the T arm with 4 and 3 % complete responses, respectively. The OS was 13.4 vs. 13.2 months in the GT and T arm, respectively. Hematologic toxicity was common, especially grade 3–4 neutropenia (GT = 69%; T = 61%); infection was reported in 22 and 20% of the pts, respectively (none of the pts received G-CSF). The most commonly reported non-hematologic toxicities of grade 3–4 included mucositis (GT = 2%; T = 5%), diarrhea (GT = 4%; T = 7 %), fatigue (GT = 6%; T = 11%), oedema (GT = 10%; T = 3%), and peripheral neuropathy (GT = 9%; T = 28%). Conclusions: Preliminary data of GT as first- or second-line chemotherapy demonstrates a TTP advantage among HER-2-negative pts with advanced breast cancer. Updated results and proper statistical analyses will be presented. No significant financial relationships to disclose.

Toxicity and outcome data in a phase II study of weekly docetaxel in combination with erlotinib in recurrent and/or metastatic breast cancer (MBC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10623-10623 ◽  
Author(s):  
H. Kaur ◽  
P. Silverman ◽  
D. Singh ◽  
B. W. Cooper ◽  
P. Fu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Treatment Plan ◽  
Single Agent ◽  
Active Agent ◽  
Metastatic Breast ◽  
Hematologic Toxicity ◽  
Egfr Inhibition ◽  
Weekly Docetaxel ◽  
Grade 3

10623 Background: Single agent weekly docetaxel (D) is an active agent in the treatment of MBC with response rates of 29% - 53%. Erlotinib (OSI-774, Tarceva) is a tyrosine kinase inhibitor directed against the epidermal growth factor receptor (EGFR), and is overexpressed in 30–40% of breast cancers. EGFR inhibition by erlotinib (E) and its possible modulation of growth factor synthesis by breast cancer (BC) cells is an attractive treatment target. This study was designed to assess the combination of D and E in previously untreated recurrent &/or MBC. Methods: Adult patients (pts) with histologically confirmed BC without prior chemotherapy for recurrence or metastases were eligible. Treatment plan was: D [35 mg/m2 iv infusion weekly x 3 q4wks] and E 150 mg/d uninterrupted (D+E). E was to be continued in 4 week cycles after maximum tumor response or disease stabilization [following a minimum of 6 cycles of D+E]. The overall survival (OS) was estimated by Kaplan-Meier method. Results: 31of 40 planned female pts were enrolled between 12/02 and 9/05. Median age 52 years, range: 29–79. The median number of cycles of D +E received was 4, (range 1–9) and of E following D+E was 4 (range 1–29). The first 26 pts received planned D dose of 35mg/m2. Because of non-hematologic toxicity, trial was subsequently modified to start D at 30mg/m2.11/31 (36%) were not evaluable due to toxicity. Hematologic grade 3 or 4 toxicity was seen in 45% cases. Principal non-hematologic grade 3–4 toxicities included nausea, diarrhea, and constitutional symptoms seen in 30% of the pts. 4/9 pts receiving E after D+E experienced hematologic, hepatic, constitiutional, and eye (1 each) grade 3 toxicity only. Best clinical response in the 20 evaluable pts included; PR 11(55%), SD 7 (35%), PD 2 (10%). OS (n = 31) was 71% at 12mos, 42% at 24 mos with median OS 23 mos. Conclusions: Combination therapy of advanced breast cancer with Docetaxel and Erlotinib showed promising activity with favorable response compared to other studies. The combination is associated with moderate to severe hematological and non-hematological toxicities. Randomized trials are warranted to further investivate the efficacy of this combination compared to single agent Docetaxel. (Support: Sanofi-Aventis & Genentech.) [Table: see text]

scholarly journals Effect of Pretreatment Renal Function on Treatment and Clinical Outcomes in the Adjuvant Treatment of Older Women With Breast Cancer: Alliance A171201, an Ancillary Study of CALGB/CTSU 49907

2016 ◽  
Vol 34 (7) ◽  
pp. 699-705 ◽  
Author(s):  
Stuart M. Lichtman ◽  
Constance T. Cirrincione ◽  
Arti Hurria ◽  
Aminah Jatoi ◽  
Maria Theodoulou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Renal Function ◽  
Renal Insufficiency ◽  
Early Stage ◽  
Single Agent ◽  
Hematologic Toxicity ◽  
End Points ◽  
Increased Risk ◽  
The Relationship

Purpose CALGB 49907 showed the superiority of standard therapy, which included either cyclophosphamide/doxorubicin (AC) or cyclophosphamide/methotrexate/fluorouracil over single-agent capecitabine in the treatment of patients age ≥ 65 with early-stage breast cancer. The treatment allowed dosing adjustments of methotrexate and capecitabine for pretreatment renal function. The purpose of the current analysis was to assess the relationship between pretreatment renal function and five end points: toxicity, dose modification, therapy completion, relapse-free survival, and overall survival. Methods Pretreatment renal function was defined as creatinine clearance (CrCl) using the Cockcroft-Gault equation. Multivariable logistic and proportional hazards regression were used to model separately for each regimen the relationship between CrCl and the first three binary end points and the last two time-to-event end points, respectively, after adjusting for variables of prognostic importance. Results Six hundred nineteen assessable patients were analyzed. The incidence of stage III (moderate) or stage IV (severe) renal dysfunction was 72%, 64%, and 75% for treatment with cyclophosphamide/methotrexate/fluorouracil, AC, and capecitabine, respectively. There was no relationship for any regimen between pretreatment renal function and the five end points. For AC, as CrCl increased, the odds of nonhematologic toxicity decreased (P = .008), whereas for capecitabine, as CrCl increased, the odds of experiencing toxicity of any type also increased (P = .035). Patients with renal insufficiency who received dose modifications were not at increased risk for complications compared with those who did not have renal insufficiency and received a full dose. Conclusion Excluding from clinical trials patients with renal insufficiency but good performance status on the basis of concern of excessive hematologic toxicity or poor outcomes may not be justified with appropriate dosing modifications. Results should be considered in the design of clinical trials for older patients.

Adjuvant treatment of early-stage HER2+ elderly breast cancer patients: A retrospective, multicenter French study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 636-636
Author(s):  
Philippe Barthelemy ◽  
Karine Bassot ◽  
Florence Joly ◽  
Isabelle Ray Coquard ◽  
Gilles Freyer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Adjuvant Treatment ◽  
Early Stage ◽  
Single Agent ◽  
Her2 Status ◽  
Routine Practice ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer

636 Background: Trastuzumab (T) is the standard of care for the adjuvant treatment of early stage, HER2+ breast cancer (BC). However, few data are available for elderly HER2+ breast cancer patients in this setting. In this current study, the patterns of care for elderly HER2+ early stage BC in 7 French cancer centres was evaluated. Methods: Medical records of all consecutive early stage HER2+ BC patients over 70 years old treated between 2006 and 2011 among participating centres were retrospectively reviewed. Specific factors such as age, comorbidities, tumor stage, grade, ER/PR and HER2 status, treatment characteristics, follow-up and cardiotoxicity data were analysed. Results: One hundred and two patients were identified, median age 75.4 (range 70-95). Elderly patients presented mostly (57%) large tumors (pT ≥2), and positive lymph node involvement (n=61). Trastuzumab-based adjuvant treatment was administered in 62% of patients (n=63). 54% of patients (n=55) received adjuvant chemotherapy whereas five patients received neoadjuvant chemotherapy. Chemotherapy without T was administered in 2 additional patients. Anthracyclines (A)-Taxanes (Ta) combination-based chemotherapy was given in 27% of patients (n=16), whereas 38% received a Ta-based chemotherapy (n=23), 35% (n=19) an A-based chemotherapy. Five patients received single-agent T. Treatment delays for T were required in 37% of patients (n=23) among whom 15 and 8 permanently or temporarily stopped T, respectively. The most frequent reason for interrupting or delaying therapy was cardiotoxicity (n=12) as well as patients refusal (n=7). A ≥ 10% decrease in LVEF was observed in 18/63 (29%) of patients, among whom T was stopped in 12. After a median 33 months follow-up, the median progression-free survival was not reached in patients receiving T-based therapy. The 2 and 3-year PFS rate were 94 and 89.5%, respectively. Conclusions: In routine practice only 62% of elderly early stage HER2+ BC patients are treated with a neoadjuvant or adjuvant T-based regimen. However, less than 50% of all patients completed their therapy. A-based chemotherapy was administered in around 60% of treated patients, and could explain cardiotoxicity in this setting.

Early Experience with Clofarabine Pre-Conditioning Prior to Full Intensity or Reduced Toxicity Allogeneic Stem Cell Transplantation: A Promising New Therapy for the Treatment of Refractory Acute Leukaemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4511-4511
Author(s):  
Deborah S. Richardson ◽  
Amy Publicover ◽  
Kate Hill ◽  
Carol Hurlock ◽  
Joan Newman ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Acute Leukaemia ◽  
Single Agent ◽  
Allogeneic Transplantation ◽  
Grade 3 ◽  
Reduced Toxicity ◽  
Full Intensity ◽  
Disease Present

Abstract Abstract 4511 Introduction: The outcome for patients with primary refractory or refractory relapse of acute leukaemia, particularly those with disease present at the time of transplant, remains very poor even using full intensity conditioning schedules. With the aim of improving outcome, we have employed the use of pre-conditioning chemotherapy prior to the delivery of both reduced toxicity (RTC) and full intensity transplants during the subsequent period of cytopenia. Initial results indicate feasibility and efficacy in this poor risk disease. The bi-halogen purine analogue Clofarabine has significant activity as a single agent for the treatment of ALL and AML and is well tolerated, characteristics suggesting Clofarabine is an ideal agent to use in pre-conditioning. Patients and methods: We have treated 11 patients with high-risk, refractory acute leukaemia or advanced myelodysplasia (MDS) using Clofarabine pre-conditioning to reduce disease burden before full intensity or RTC allogeneic transplantation. Patient characteristics for the two groups are shown below (Table 1). Clofarabine was administered as a single agent (40mg/m2/day for 5 days), five received RTC using Busulphan or Melphalan-containing transplant schedules; six full intensity total body irradiation (TBI) based conditioning. Indications for using Clofarabine included severe allergy to Cytarabine, heavy prior exposure to anthracycline or lack of response to other salvage agents. 10 of 11 patients had significant marrow involvement prior to administration of Clofarabine. Results: In this cohort we have not seen additional unexpected complications. One patient who received a RTC regimen, was treated for VOD on clinical suspicion but liver biopsy indicated grade 3–4 haemosiderosis only. Two patients who received TBI-based transplants suffered grade 3–4 mucositis. The extended period of pancytopenia compared with conventional transplant schedules was manageable, with no unexpected infectious complications. The median time to a neutrophil count of > 0.5 × 109/l was 18 days post stem cell infusion (range 12–33 days) and to a platelet count > 20 × 109/l was 13 days (range 11–32 days). All patients achieved ≥ 98% donor chimerism by day +30. 2 of 11 patients (18%) experienced grade 3–4 acute GvHD (1 cutaneous, 1 gut) which responded to additional immunosuppression. 9 of 10 patients with disease present at the time of Clofarabine achieved substantial bulk reduction or eradication of marrow leukaemic blasts following the Clofarabine. 5 of 11 patients died from disease relapse post allograft at 2–13 months post transplant, including the patient with Clofarabine-refractory disease. 6 patients are currently in CR at 1–77 months follow up. Overall survival for the 11 patients, using Kaplan-Meier analysis, is 48% with a median follow up of survivors of 26 months (range 1–77), shown below in figure 1: Conclusions: The use of Clofarabine as a pre-conditioning agent prior to the administration of the transplant conditioning schedule is well tolerated with both full intensity and reduced toxicity protocols. This approach to allogeneic transplantation shows promise for the therapy of patients with high risk refractory acute leukaemia. Disclosures: Richardson: Genzyme: Advisory board Other, Research Funding. Off Label Use: Clofarabine is licensed for the treatment of relapsed/refractory ALL in paediatric and young adult patients. This paper includes discussion of use in the treatment of AML/high risk MDS for which the drug has orphan drug status in the EU.

Dose-dense (DD) cyclophosphamide, methotrexate, and fluorouracil (CMF) at 14-day intervals: A pilot study of every 14- and 10–11-day dosing intervals for women with early-stage breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 590-590
Author(s):  
P. Drullinsky ◽  
M. N. Fornier ◽  
S. Sugarman ◽  
G. D'Andrea ◽  
T. Troso-Sandoval ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Hematologic Toxicity ◽  
Type I ◽  
Initial Cohort ◽  
Grade 3 ◽  
Dose Dense ◽  
Q 14 ◽  
Dosing Intervals

590 Background: CMF (C 600 mg/m2, M 40 mg/m2, F 600 mg/m2) is an option for adjuvant therapy for patients with low risk early stage breast cancer. DD regimens as predicted by mathematical models of cancer growth and treatment response are superior. We previously demonstrated the safety of DD EC (epirubicin/cyclophosphamide) followed by paclitaxel at 10–11 day (d) intervals. We investigated the feasibility of administering DD adjuvant CMF every 14 d and then every 10–11 d in a 2-stage phase II trial. Methods: An initial cohort (A) was treated q 14 d with PEG-filgrastim (Neulasta) support. A second cohort (B) was treated every 10–11 d with filgrastim/Neupogen x 5 d and then, based on feasibility, modified (cohort C) to use 7 d filgrastim. The primary end point was feasibility defined as having ANC > 1.5 x 103/uL on day 1 of planned treatment for all 8 cycles with no grade 3 or higher non-hematologic toxicity. All three cohorts were tested using a Simon's two-stage optimal design with type I and type II errors set at 10%. This design would effectively discriminate between true tolerability (as protocol-defined) rates of< 60% and> 80%. Cohort A: 38 pts with early stage breast cancer were accrued from 3/2008 though 6/2008. Cohort B: 7 pts were accrued from June 2008 through August 2008. Cohort C: Is still open with 16 pts accrued from August 2008 through December 5, 2008. Results: Median age 51: range 38 to 78. Cohort A: 29/38 pts completed 8 cycles of CMF. The regimen was considered feasible. 2 other pts completed 7 cycles and were withdrawn for depression and grade 2 transaminitis. The 7 other pts completed between 1 and 6 cycles of CMF were withdrawn as follows: 3 personal, 1 (grade 3) bone pain, 2 allergy unrelated to CMF, and 1 seizure. Cohort B: 7 pts were accrued. 6 out of 7 pts could not complete 8 cycles of chemotherapy secondary to neutropenia and 1 secondary to grade 3 ALT elevation. Cohort C: Accrual has not been completed. 16 pts are currently enrolled. Conclusions: Dose dense adjuvant CMF is feasible at 14 d intervals with PEG-filgrastim support. Adjuvant CMF every 10–11 days with filgrastim given for 5 days beginning day 2 is not feasible. Accrual is ongoing for CMF at 10–11 days with filgrastim x 7 days. Updated results will be available for Cohort C. [Table: see text]

scholarly journals Belinostat in combination with standard cyclophosphamide, doxorubicin, vincristine and prednisone as first-line treatment for patients with newly diagnosed peripheral T-cell lymphoma

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Patrick B. Johnston ◽  
Amanda F. Cashen ◽  
Petros G. Nikolinakos ◽  
Anne W. Beaven ◽  
Stefan Klaus Barta ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Dose Intensity ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
T Cell Lymphoma ◽  
Hematologic Toxicity ◽  
Peripheral T Cell Lymphoma ◽  
Grade 3

Abstract Background Belinostat is a histone deacetylase inhibitor approved for relapsed refractory peripheral T-cell lymphoma (PTCL). The primary objective of this study was to determine the maximum tolerated dose (MTD) of belinostat combined with CHOP (Bel-CHOP). Secondary objectives included safety/tolerability, overall response rate (ORR), and belinostat pharmacokinetics (PK). Methods Patients were ≥ 18 years with histologically confirmed, previously untreated PTCL. Patients received belinostat (1000 mg/m2 once daily) + standard CHOP for 6 cycles with varying schedules using a 3 + 3 design in Part A. Part B enrolled patients at MTD dose. Results Twenty-three patients were treated. One patient experienced DLT (Grade 3 non-hematologic toxicity) on Day 1–3 schedule, resulting in escalation to Day 1–5 schedule (n = 3). No DLTs were observed and Day 1–5 schedule with 1000 mg/m2 was declared as MTD. Twelve additional patients were enrolled in Part B using MTD. Median relative dose intensity was 98%. All patients experienced adverse events (AEs), including nausea (78%), fatigue (61%), and vomiting (57%). Serious AEs occurred in 43%, with febrile neutropenia (17%) and pyrexia (13%). Overall ORR was 86% with 71% reported CR at MTD. Belinostat PK parameters were similar to single-agent. Conclusions Bel-CHOP was well tolerated and MTD in CHOP combination was the same dose and schedule as single agent dosing. Trial Registration: ClinicalTrials.gov Identifier: NCT01839097.

scholarly journals Lenalidomide and prednisone for myelofibrosis: Eastern Cooperative Oncology Group (ECOG) phase 2 trial E4903

Blood ◽  
2010 ◽  
Vol 116 (22) ◽  
pp. 4436-4438 ◽  
Author(s):  
Ruben A. Mesa ◽  
Xiaopan Yao ◽  
Larry D. Cripe ◽  
Chin Yang Li ◽  
Mark Litzow ◽  
...  
Keyword(s):  
Eastern Cooperative Oncology Group ◽  
Hematologic Toxicity ◽  
Cooperative Group ◽  
Phase 2 ◽  
Phase 2 Trial ◽  
Nonhematologic Toxicity ◽  
Grade 3 ◽  
Bone Marrow Analysis ◽  
Dose Prednisone

A multicenter Eastern Cooperative Group (ECOG) phase 2 trial assessed whether adding prednisone to lenalidomide would improve previously reported responses in persons with myelofibrosis (MF). Forty-eight subjects with anemia (42 evaluable) received lenalidomide, 10 mg/d, with a 3-month low-dose prednisone taper. Ten subjects received 3 months, and 25 received 6 months of therapy. Myelosuppression was the main toxicity with 88% with ≥ grade 3 hematologic toxicity and 45% ≥ grade 3 nonhematologic toxicity. There were responses in 10 subjects (23%) using the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT)–defined clinical improvement of anemia in 8 (19%) and/or decreased spleen size in 4 (10%). Serial bone marrow analysis showed no resolution of disease-related fibrosis or angiogenesis. With a median follow-up of 2.3 years, 23 subjects are alive. Lenali-domide and prednisone for myelofibro-sis evaluated through a multicentered-cooperative group mechanism is only modestly active and myelosuppre-sive. This study was registered at http://clinicaltrials.gov as NCT00227591.

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