Folinic acid, 5-fluorouracil, irinotecan (FOLFIRI) plus chemoradiation (CRT) with 5-fluorouracil (5FU) as adjuvant treatment for patients with operable gastric cancer (OGC): A feasibility study with pharmacogenetic analysis.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 44-44
Author(s):  
A. Athanasiadis ◽  
I. Boukovinas ◽  
M. Sfakianaki ◽  
Z. Saridaki ◽  
C. Papadaki ◽  
...  
Keyword(s):  
Adjuvant Treatment ◽  
Drug Exposure ◽  
Free Probability ◽  
Disease Free Survival ◽  
Free Survival ◽  
Probability Of Survival ◽  
Common Grade ◽  
Grade 3 ◽  
Median Rate

44 Background: To evaluate the efficacy and safety of FOLFIRI plus CRT with 5FU as adjuvant treatment for patients with OGC. Methods: Patients received treatment with FOLFIRI (irinotrecan 150 mg/m2, d1, LV 200 mg/m2, d1+2 and 5FU [400 mg/m2/d bolus and 600 mg/m2/d, 22 h infusion, d1+2]) for 2 15-day cycles followed by RT (45Gy) with 5FU continuous infusion (325 mg/m2/d in the 1st and 5th week) administration. Eight additional cycles of FOLFIRI were administered after the completion of CRT. BRCA1, ERCC1, XPD, TOPO-I, TOPO-IIA and B and TS mRNA expression was determined in the primary tumor where available. Results: The median age of the 171 enrolled patients was 62 years, 114 (66%) were males, 136 (79%) had R0 resections and 152 (89%) had at least a D1 resection. Treatment was completed as per protocol in 107 (63%) of the patients. CRT was completed in all but 5 (3%) patients. The median rate of drug exposure was 93% for irinotecan, 87% for 5FU and 91% for LV. The most common grade 3/4 adverse events were neutropenia (32%), febrile neutropenia (3.5%) and diarrhea (7%). After a median follow-up of 45.7 months 84 had relapsed and 70 were deceased. The median disease-free survival (DFS) was 30 months (95% CI: 18-41 months), while the projected median overall survival (mOS) was 53.7 months (95% CI: 30-77 months). The recurrence free probability at 5 years was 44% while the probability of survival at 5 years was 46%. From the studied pharmacogenetic markers only TS low expression was correlated with a trend towards improved DFS and OS in patients with R0 resections. Conclusions: These results show that the administration of FOLFIRI plus CRT with 5FU as adjuvant treatment in OGC is a feasible approach with acceptable toxicity and challenging efficacy which merits further evaluation in a randomized trial. No significant financial relationships to disclose.

Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon Cancer

2017 ◽  
Author(s):  
Kelly McLeon
Keyword(s):  
Colon Cancer ◽  
Adjuvant Treatment ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Reference Standard ◽  
Free Survival ◽  
Stage Iii Colon Cancer ◽  
Study Intervention ◽  
Disease Free

The landmark MOSAIC trial examined whether the addition of oxaliplatin to a postoperative adjuvant treatment regimen of fluorouracil and leucovorin affected disease-free survival from colon cancer. The MOSAIC trial established the efficacy of FOLFOX over 5-FU/LV as adjuvant treatment for stage III colon cancer and established FOLFOX4 as the reference standard for adjuvant treatment for stage III disease. This chapter describes the basics of the study, including funding, year study began, year study was published, study location, who was studied, who was excluded, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, gives a summary and discusses implications, and concludes with a relevant clinical case.

Long-Term Disease-Free Survival of Patients with AML Relapse After T-Cell-Depleted Allogeneic Stem Cell Transplantation by Re-Induction Therapy and Subsequent Interferon-Boosted Donor Lymphocyte Infusion

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3064-3064
Author(s):  
M. Eefting ◽  
C.J.M. Halkes ◽  
S. Kersting ◽  
W.A.F. Marijt ◽  
P.A. von dem Borne ◽  
...  
Keyword(s):  
Immune Response ◽  
Induction Therapy ◽  
Acute Gvhd ◽  
Disease Free Survival ◽  
Remission Induction ◽  
Free Survival ◽  
Grade 3 ◽  
Disease Free

Abstract Abstract 3064 Relapse of AML after allogeneic stem cell transplantation (alloSCT) has a very poor prognosis. Salvage re-induction chemotherapy leads to clinical remissions in a substantial number of patients, but these remissions tend to be of short duration. In contrast, donor lymphocyte infusions (DLI) have the potential to effect long-lasting remissions, but the interval of several weeks to months that is required to develop a DLI-induced anti-leukemia response may prevent efficient control of a highly proliferative leukemia. In addition, a high tumor burden may suppress the immune response. In contrast, the combination of efficient cytoreduction by chemotherapy with DLI administered in rapid succession under circumstances favoring the development of an early and profound immune response might have the potential to eradicate otherwise resistant leukemia cells. We therefore adopted an institutional therapeutic strategy for relapsed myeloid leukemia post-allogeneic SCT based on administration of DLI at the anticipated end of the neutropenic phase after salvage re-induction chemotherapy. At this time point, the high prevalence of a pro-inflammatory milieu should favor the induction of the immune response, and an expected state of lymphopenia should promote the expansion of infused T cells by homeostatic proliferation. If 3 weeks after DLI no graft versus host disease (GvHD) was observed, the potential anti-leukemia immune response was further amplified by treatment with interferon- α (IFN- α) until GvHD occurred. Between January 2000 and December 2009 44 patients with relapsed myeloid malignancy after alloSCT were treated at our hospital. Pre-transplant diagnoses were AML n=40, CMML n=1 and MDS n=3. Median time from SCT to relapse was 187 days. Median follow-up after relapse was 3.1 years. 5 patients had a smouldering relapse (<10% bone marrow blasts) and 39 patients had an overt relapse. Of 39 patients with overt relapse, 7 patients (18%) did not receive re-induction therapy due to poor performance status (n=5) or patient choice (n=2). 32 patients received remission-induction therapy consisting of gemtuzumab ozogamycin (n=9), cytosine arabinoside-containing chemotherapy (n=17), or both (n=6). Following this treatment, 7 of 32 patients had rapidly progressive disease during induction therapy (n=6) or died due to toxicity (n=1) and did not receive DLI. The remaining 25 patients received DLI at a dose of 5.0×10 ^6 CD3+ cells/kg for related and 2.5×10 ^6 CD3+ cells/kg for unrelated donors 3 weeks after the start of remission-induction therapy. In 16 of these patients DLI was boosted with IFN- α 3.0×10 ^6 IE once daily. This strategy resulted in acute GvHD in 17 of 25 patients (n=8 grade 1–2, n=9 grade 3–4). At 6 weeks after DLI, 16 patients had reached CR, 5 patients had failed to reach CR (2 with GvHD) and 4 suffered treatment-related mortality (3 with GvHD). Of the 16 patients in CR, 4 had no signs of GvHD and developed a second relapse during the follow-up period. Only 3 of 12 patients in CR with signs of acute GvHD at 6 weeks after DLI developed a second relapse. In total, 9 of 17 patients (53%) with acute GvHD after DLI had long term survival versus none without acute GvHD. During follow-up, 8 patients developed chronic GvHD (n=4 limited, n=4 extensive). Finally, 5 patients with an early detected smouldering relapse received DLI, which was boosted with IFN- α in 2 patients, without salvage re-induction therapy. All 5 patients developed GvHD (n=2 grade 1–2, n=3 grade 3–4) and 3 patients achieved a CR of whom 1 patient died from GvHD. Our results indicate that treatment of relapsed AML after alloSCT with salvage re-induction therapy followed by DLI at the end of the neutropenic phase during minimal residual disease, with additional boosting of the immune response with IFN- α, can result in long-term disease-free survival. Disclosures: Off Label Use: Interferon: DLI-boosting.

Phase III study of doxorubicin-cyclophosphamide followed by paclitaxel or docetaxel given every 3 weeks or weekly in operable breast cancer: Results of Intergroup Trial E1199

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 516-516 ◽  
Author(s):  
J. A. Sparano ◽  
M. Wang ◽  
S. Martino ◽  
V. Jones ◽  
E. Perez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Axillary Lymph ◽  
Free Survival ◽  
Significant Difference ◽  
Phase Iii Study ◽  
Grade 3

516 Background: Evidence suggests that docetaxel is more effective than paclitaxel, and paclitaxel is more effective when given weekly than every 3 weeks in metastatic breast cancer (BC). Methods: Eligibility included axillary lymph node positive or high-risk (tumor at least 2 cm) node-negative BC. All patients received 4 cycles of AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) every 3 weeks, followed by either: (1) paclitaxel 175 mg/m2 every 3 weeks × 4 (P3), (2) paclitaxel 80 mg/m2 weekly × 12 (P1), (3) docetaxel 100 mg/m2 every 3 weeks × 4 (D3), or (4) docetaxel 35 mg/m2 weekly × 12 (D1). The primary comparisons included taxane (P vs. D) and schedule (every 3 weeks vs. weekly), and secondary comparisons included P3 vs. other arms. The trial had 86% power to detect a 17.5% decrease in disease-free survival (DFS) for either primary comparison, and 80% power to detect a 22% decrease for the secondary comparisons (2-sided nomimal 5% level tests corrected for multiple comparisons). Results: A total of 4,950 eligible patients were accrued. There was no difference in the primary comparisons afer 856 DFS events and 483 deaths after a median follow-up of 46.5 months at the 4th interim analysis ( www.sabcs.org , abstract 48). This is the final pre-specified analysis for the primary comparisons after 1,042 DFS events and 650 deaths (with 1,020 DFS events at this time, to be updated at the meeting). After a median followup of 60.2 months, there remains no significant difference in the hazard ratio (HR) for the taxane (1.02; p=0.73) or schedule (1.07; p=0.30) (as in the first analysis). In secondary comparisons of the standard arm (P3) with the other arms (HR > 1 favoring the experimental arms), the HRs were 1.30 (p = 0.003) for arm P1, 1.24 (p=0.02) for arm D3, and 1.09 (p=0.33) for arm D1. Analysis of interaction by hormone-receptor status will be presented. The incidence of worst grade toxicity (grade 3/4) was 24%/6% for arm P3, 24%/3% for arm P1, 21%/50% for arm D3, and 38%/6% for arm D1. Conclusions: There were no differences in DFS when comparing taxane or schedule overall. DFS was significantly improved in the weekly paclitaxel and every 3-week docetaxel arms compared with the every 3-week paclitaxel arm. [Table: see text]

125I Brachytherapy for Localized Prostate Cancer: A Single Institution Experience

2013 ◽  
Vol 99 (1) ◽  
pp. 83-87 ◽  
Author(s):  
Alessia Guarneri ◽  
Angela Botticella ◽  
Andrea Riccardo Filippi ◽  
Fernando Munoz ◽  
Giancarlo Beltramo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Multivariate Analysis ◽  
Early Stage ◽  
Disease Free Survival ◽  
Localized Prostate Cancer ◽  
Free Survival ◽  
Genitourinary Toxicity ◽  
Grade 3 ◽  
Disease Free

Aims and background To evaluate the clinical outcome of a cohort of localized prostate cancer patients treated with 125I permanent brachytherapy at the University of Turin. Methods and study design A retrospective analysis was carried out on 167 consecutive patients with early stage prostate adenocarcinoma who underwent 125I brachytherapy between January 2003 and December 2010. A minimum follow-up of ≥12 months was mandatory for inclusion. Biochemical disease-free survival (defined on the basis of the ASTRO definition and the ASTRO-Phoenix definition) was chosen as the primary end point. Secondary end points were gastrointestinal and genitourinary toxicity (acute and late, defined according to the RTOG scale). Results With a median follow-up of 42 months (range, 13.5–90.7), biochemical disease-free survival at 3 and 5 years was respectively 91.1% and 85.7%, according to the ASTRO definition and 94.5% and 85.1% according to ASTRO-Phoenix definition (for statistical purposes, only the ASTRO definition was used). Hormone treatment and nadir PSA (cutoff of 0.35 ng/ml) were the only factors affecting biochemical disease-free survival both on univariate ( P = 0.02 and P = 0.001, respectively) and multivariate analysis (HR 0.024; P = 0.021 and HR 21.6; P = 0.006, respectively). Only 3.6% of patients experienced ≥grade 3 acute urinary toxicity and 5% ≥grade 3 late urinary toxicity. Prior transurethral prostate resection was the only independent predictor of grade 3 late urinary toxicity on multivariate analysis (HR 0.13; P = 0.009). Conclusions This mono-institutional series confirmed that brachytherapy is an effective and safe treatment modality for localized prostate cancer, with acceptable short- and long-term morbidity rates.

Postoperative LV5FU2 combination chemotherapy in patients with curative resected advanced gastric cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15660-e15660
Author(s):  
H. Lee ◽  
K. Lee ◽  
E. Park ◽  
I. Hwang ◽  
J. Jang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Continuous Infusion ◽  
Advanced Gastric Cancer ◽  
Cancer Progression ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Postoperative Chemotherapy ◽  
Free Survival ◽  
Grade 3

e15660 Background: To illuminate the effect and toxicity of fortnightly low-dose leucovorin(LV) and fluorouracil(5FU) bolus plus continuous infusion(LV5FU2) postoperative chemotherapy(adjuvant) in patients with curative resected, advanced gastric cancer. Methods: Total 40 patients were enrolled in this study. All patients received LV 20mg/m2(bolus), 5FU 400mg/m2(bolus), 5FU 600mg/m2(24-hour continuous infusion) on day 1, 2, 15, and 16, every 4 weeks(LV5FU2), total 6 cycles. Results: Postoperative chemotherapy was initiated median 19 days after surgery. Total of 238 cycles were administered and median follow-up was 602 days. The median disease-free survival time was 728 days (95% CI, 411∼1045) and 2-year overall survival was 77%. Relapses were reported in 18 (45%) of the patients : Two of 9 patients relapsed in stage IIIA (22.2%), seven of 12 patients relapsed in stage IIIB (58.3%) and nine of 17 patients relapsed in stage IV (52.9%). They were all distant relapsed. Eight patients died. 7 patients died as a result of cancer progression and 1 patient suicided while receiving palliative chemotheraphy for cancer relapse. The grade 3∼4 toxicity of neutropenia 8.4% and anemia 0.4%, neutropenic fever 0.4% were observed. Conclusions: Postoperative LV5FU2 adjuvant chemotherapy is effective and tolerable for the patients with curative resected, advanced gastric cancer. No significant financial relationships to disclose.

A phase II study of cetuximab-based neoadjuvant and adjuvant treatment strategies, with or without surgery, in patients with locally very advanced squamous cell carcinoma of the oral cavity.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16050-e16050
Author(s):  
Pei-Jen Lou ◽  
Chun-Ta Liao ◽  
Cheng-Ping Wang ◽  
Shiang-Fu Huang ◽  
Shin-June Cheng ◽  
...  
Keyword(s):  
Radical Surgery ◽  
Treatment Strategies ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Free Survival ◽  
Common Grade ◽  
Sequential Regimen ◽  
Grade 3 ◽  
Neo Adjuvant Chemotherapy ◽  
Weekly Cycles

e16050 Background: The purpose is to evaluate the efficacy of sequential regimen using cetuximab-based doublet neoadjuvant chemotherapy, followed by surgery, if tumors resectable, and adjuvant cetuximab-based chemoradiotherapy in locally very advanced OSCC patients. Methods: Patients with T4a/b or N2b/c or N3 OSCC were enrolled to determine the response rate of cetuximab, cisplatin, and 5-FU neo-adjuvant chemotherapy. Cetuximab (400 mg/m2 loading, followed by 250 mg/m2 weekly x 6 weeks) was combined with 2 3-weekly cycles of cisplatin (100 mg/m2) and 5-FU (1000 mg/m2 x 3 days) as neo-adjuvant. Patients whose tumors became operable after neoadjuvant underwent radical surgery followed by adjuvant weekly cetuximab (250 mg/m2), cisplatin (30 mg/m2) and XRT (up to 70 Gy). Patients whose tumors remained inoperable after neoadjuvant received weekly cetuximab (250 mg/m2), cisplatin (30 mg/m2) and XRT (up to 70 Gy). Results: 33 patients were enrolled from Dec. 2009 to Jan. 2011. Average age was 47.3 years. 51.5% had primary lesion in buccal mucosa and 21.2% on tongue. 66.7% and 27.2% had T4b or T4a disease respectively, while 72.7% had N2b/N2c/N3 disease. 28/33 completed treatment course. On ITT analysis, 39.4% (13/33) had partial response and 48.5% (16/33) had stable disease after neoadjuvant. 42.4% (14/33) underwent radical surgery after neoadjuvant, while another 9% (3/33) underwent surgery after bio-chemoradiation. The 1 year disease free survival (resected group), progression free survival (ITT group), and overall survival (ITT group) were 48.8%, 73.2%, and 51.7% respectively. The most common grade 3/ 4 adverse event in neo-adjuvant phase was vomiting (16.1%), while mucositis (75%) and dermatitis (42.8%) accounted for major grade 3/ 4 adverse events during bio-chemoradiation. Conclusions: Cetuximab based sequential regimen was efficacious and well tolerated in improving treatment outcomes in locally very advanced OSCC patients with manageable side effects.

Gemcitabine and cisplatin (GP) induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) versus CCRT alone in locoregionally advanced nasopharyngeal carcinoma (NPC): A phase 3, multicenter, randomized controlled trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6003-6003 ◽  
Author(s):  
Jun Ma ◽  
Yuan Zhang ◽  
Ying Sun ◽  
Fangyun Xie ◽  
Weihan Hu ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Intensity Modulated Radiotherapy ◽  
Free Survival ◽  
Intention To Treat ◽  
Multicenter Randomized Controlled Trial ◽  
Common Grade ◽  
Grade 3 ◽  
To Receive ◽  
Treat Population

6003 Background: GP regimen has been established as the standard first-line treatment option for patients with recurrent/metastatic NPC. However, its efficacy in locoregionally advanced disease remains unclear. Methods: Patients with previously untreated, non-metastatic stage III-IVB (except T3-4N0M0, AJCC 7th) NPC, aged 18–64 years without severe comorbidities were eligible. They were randomly assigned (1:1) to receive GP IC (gemcitabine 1 g/m2on days 1 & 8, cisplatin 80 mg/m2 on day 1, q3w for 3 cycles) plus CCRT (cisplatin 100 mg/m2, q3w for 3 cycles, concurrently with intensity-modulated radiotherapy) or CCRT alone. The primary endpoint was failure-free survival (FFS). The calculated sample size was 238 per group, with an 80% power (two-sided α 0.05) to detect a treatment failure hazard ratio (HR) of 0.52. Results: From Dec 2013 to Sep 2016, 480 patients from 12 centers were randomly assigned to IC+CCRT (n = 242) or CCRT alone (n = 238) group. Baseline characteristics were well balanced. After a median follow-up of 39 months, 3-year FFS was 85.8% in the IC+CCRT group and 77.2% in the CCRT alone group (intention-to-treat population; HR 0.53, 95% confidence interval 0.34–0.81; P = 0.003). In GP+CCRT group, 239 patients started GP IC and 231 (96.7%) completed all three cycles. The most common ≥grade 3 adverse events (AE) in IC+CCRT and CCRT group were mucositis (28.9% vs. 32.1%), neutropenia (28.0% vs. 10.5%) and leukopenia (26.4% vs. 20.3%). Conclusions: Adding GP IC to CCRT significantly improved FFS in locoregionally advanced NPC and is well tolerated with favorable toxicity profile. Clinical trial information: NCT01872962. [Table: see text]

Long-term survivors and gilteritinib safety beyond one year in FLT3-mutated R/R AML: ADMIRAL trial follow-up.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 7514-7514 ◽  
Author(s):  
Alexander E. Perl ◽  
Giovanni Martinelli ◽  
Andreas Neubauer ◽  
Ellin Berman ◽  
Maria R. Baer ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Salvage Chemotherapy ◽  
Average Dose ◽  
Primary Analysis ◽  
Day Range ◽  
Common Grade ◽  
Grade 3 ◽  
One Year

7514 Background: The phase 3 ADMIRAL trial showed that gilteritinib was superior to salvage chemotherapy (SC; median overall survival [OS]: 9.3 vs 5.6 mo, respectively) in FLT3mut+ R/R AML patients (pts; Perl, et al. N Engl J Med. 2019). This follow up (FU) of the ADMIRAL trial assessed long-term (LT) survivors and gilteritinib safety beyond 1 year. Methods: A data cut was performed 1 year after the primary analysis. Response outcomes in LT survivors (OS ≥18 mo) in the gilteritinib arm, and safety during and after 12 mo of gilteritinib therapy were assessed. Results: At 1 year after the primary analysis, median FU for OS was 29.2 mo. Median OS remained longer with gilteritinib (9.3 mo) than with SC (5.6 mo; HR=0.679 [95% CI: 0.527, 0.875], nominal P=0.0026); 18-mo OS rates were 27% and 15%, respectively (Table). Of 49 censored pts in the gilteritinib arm, 20 continued treatment; 13 of these 20 pts underwent transplantation (HSCT) and received gilteritinib post-HSCT. Median gilteritinib exposure was 4.1 mo (IQR, 2.1-8.2) and median average dose was 120 mg/day (range, 43.8-192.3); 12% (n=30/246) of pts had ≥18 mo and 7% (n=17/246) had ≥24 mo of drug exposure. A total of 63 gilteritinib-treated pts had OS ≥18 mo (median exposure, 17.6 mo [IQR, 3.1-25.7 mo]). A high proportion of these LT survivors achieved remission pre-HSCT (Table); median durations of complete remission (CR) or CR with partial hematologic recovery (CRh) have not been reached. After a median of 3.5 mo, 35 of 63 (56%) LT survivors underwent HSCT; 25 of these 35 pts (71%) received post-HSCT gilteritinib therapy. Of 28 pts who did not undergo HSCT, 15 (54%) received gilteritinib for ≥18 mo. Most common grade ≥3 adverse events (AEs) during the first 12 mo of gilteritinib therapy were febrile neutropenia (45%), anemia (40%), and thrombocytopenia (23%); rates of these grade ≥3 AEs decreased to 8%, 10%, and 0, respectively, after 12 mo of treatment. Most common fatal AEs during the first 12 mo of gilteritinib therapy were AML (11%), infections (11%), and cardiac disorders (3%); after 12 mo of treatment, rates of these fatal AEs were 6%, 8%, and 2%, respectively. Conclusions: Results from this ADMIRAL trial FU suggest LT survival in pts receiving gilteritinib is related to ongoing remission, subsequent HSCT, or post-HSCT gilteritinib therapy. The safety profile of gilteritinib beyond 1 year was stable. Clinical trial information: NCT02421939 . [Table: see text]

scholarly journals Clofarabine Plus Cytarabine Compared With Cytarabine Alone in Older Patients With Relapsed or Refractory Acute Myelogenous Leukemia: Results From the CLASSIC I Trial

2012 ◽  
Vol 30 (20) ◽  
pp. 2492-2499 ◽  
Author(s):  
Stefan Faderl ◽  
Meir Wetzler ◽  
David Rizzieri ◽  
Gary Schiller ◽  
Madan Jagasia ◽  
...  
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Remission Rate ◽  
Disease Free Survival ◽  
Myelogenous Leukemia ◽  
Free Survival ◽  
End Point ◽  
Common Grade ◽  
Acute Myelogenous ◽  
Grade 3

Purpose To compare the receipt of clofarabine plus cytarabine (Clo+Ara-C arm) with cytarabine (Ara-C arm) in patients ≥ 55 years old with refractory or relapsed acute myelogenous leukemia (AML). Patients and Methods Patients were randomly assigned to receive either clofarabine (Clo) 40 mg/m2 or a placebo followed by Ara-C 1 g/m2 for five consecutive days. The primary end point was overall survival (OS). Secondary end points included event-free survival (EFS), 4-month EFS, overall remission rate (ORR; complete remission [CR] plus CR with incomplete peripheral blood count recovery), disease-free survival (DFS), duration of remission (DOR), and safety. Results Among 320 patients with confirmed AML (median age, 67 years), the median OS was 6.6 months in the Clo+Ara-C arm and 6.3 months in the Ara-C arm (hazard ratio [HR], 1.00; 95% CI, 0.78 to 1.28; P = 1.00). The ORR was 46.9% in the Clo+Ara-C arm (35.2% CR) versus 22.9% in the Ara-C arm (17.8% CR; P < .01). EFS (HR: 0.63; 95% CI, 0.49 to 0.80; P < .01) and 4-month EFS (37.7% v 16.6%; P < .01) favored the Clo+Ara-C arm compared with Ara-C arm, respectively. DFS and DOR were similar in both arms. Overall 30-day mortality was 16% and 5% for CLO+Ara-C and Ara-C arms, respectively. In the Clo+Ara-C and Ara-C arms, the most common grade 3 to 4 toxicities were febrile neutropenia (47% v 35%, respectively), hypokalemia (18% v 11%, respectively), thrombocytopenia (16% v 17%, respectively), pneumonia (14% v 10%, respectively), anemia (13% v 0%, respectively), neutropenia (11% v 9%, respectively), increased AST (11% v 2%, respectively), and increased ALT (10% v 3%, respectively). Conclusion Although the primary end point of OS did not differ between arms, Clo+Ara-C significantly improved response rates and EFS. Study follow-up continues, and the role of clofarabine in the treatment of adult patients with AML continues to be investigated.

Arsenic trioxide dose capping to decrease toxicity in the treatment of acute promyelocytic leukemia

2021 ◽  
pp. 107815522110247
Author(s):  
Kyle Zacholski ◽  
Bryan Hambley ◽  
Erin Hickey ◽  
Sarah Kashanian ◽  
Andrew Li ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Promyelocytic Leukemia ◽  
Free Survival ◽  
All Trans Retinoic Acid ◽  
Grade 3 ◽  
Disease Free

Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) combination therapy yields high complete remission and disease-free survival rates in acute promyelocytic leukemia (APL). ATO is dosed on actual body weight and high ATO doses in overweight patients may contribute to increased toxicity. We performed a retrospective, two-center study comparing toxicities in patients who received the Lo-Coco et al ATRA/ATO regimen with capped ATO, ≤10 mg/dose, and non-capped ATO, >10 mg/dose. A total of 44 patients were included; 15 received doses ≤10 mg and 29 received >10 mg. During induction, there was no difference in the incidence of grade ≥3 hepatotoxicity, grade ≥3 QTc prolongation, neurotoxicity, and cardiac toxicity between groups. In consolidation, patients receiving >10 mg/dose experienced a greater incidence of neurotoxicity (66.7% vs 22.2%; p = 0.046). Capping doses saved $24634.37/patient and reduced waste of partially-used vials. At a median follow-up of 27 months, no disease relapses occurred in either group. This represents an opportunity to improve the safety profile of this highly effective regimen.

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