Neoadjuvant dose-dense (DD) concurrent doxorubicin (A) and docetaxel (T) for stage III breast cancer (BC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10721-10721
Author(s):  
M. Abu-Khalaf ◽  
R. Kim ◽  
M. Cohenuram ◽  
G. Chung ◽  
M. Digiovanna ◽  
...  

10721 Background: The addition of taxanes to anthracycline therapy results in improved disease-free survival (DFS) in the adjuvant setting, and increased pathologic complete response rates (pCR) in the neoadjuvant setting. DD chemotherapy improves DFS and overall survival (OS). We evaluated neoadjuvant DD concurrent AT. Methods: Eligible patients (pts) with stage III BC were treated with AT q 14 days at 1 of 3 dose levels; L1 = 60 mg/m2 for both drugs (4 pts), L2 = A 75 mg/m2 and T 60 mg/m2 (6 pts) or L3 = 75 mg/m2 for both drugs (7 pts) × 6 cycles with G-CSF. Dexrazoxane was given after a cumulative dose of 300 mg/m2 of A. Pts were stratified to post-operative moderate risk (ModR) (≥ partial response, ≤ 3 lymph nodes (LN)) and received adjuvant IV cyclophosphamide (C) 600 mg/m2, methotrexate 40 mg/m2, 5FU 600 mg/m2 IV q 21 d × 6 (CMF), or high risk (HiR) (≤ minor response +/or ≥ 4 LN) and received C 3 gm/m2 q 14 d x 3. Primary endpoints were clinical and pathologic response rates of neoadjuvant AT. Sample size was 42 pts to estimate pCR and provide 90% confidence the true incidence of severe toxicity is <10%. Results: 17 pts with stage III BC were enrolled between 2/1999 and 7/2001; accrual was halted after data on pre-operative trastuzumab were presented. Median age was 50 yrs [range: 34–69]. 3/17 pts (17.6%) had a pCR, and 3 pts had near pCR (residual foci ≤ 1mm), 4/17 (23.5%) had path (-) LN, 7/17 (41%) had a lumpectomy, 7/17 (41%) required dose reductions of AT due to grade 4 neutropenia (5 pts) and grade 3 neuropathy (2 pts). 3 pts required treatment cessation; 1 pt (L2) for prolonged neutropenic fever and 2 pts (L3) for decreased ejection fraction and for acute renal failure. 15 pts were ModR and received adjuvant CMF, 1/2 pts stratified to high dose C declined it and received CMF. Median follow-up is 63 months [range: 28–80] with 13/17 (76.5%) pts surviving, and 12/17 (70.5%) pts surviving and free of disease. Conclusion: Neoadjuvant DD AT every 2 weeks is well-tolerated, with promising activity and survival in locally advanced BC. [Table: see text]

2021 ◽  
Author(s):  
Yongjune Lee ◽  
Young Seok Kim ◽  
Bumsik Hong ◽  
Yong Mee Cho ◽  
Jae-Lyun Lee

Abstract PurposeTo compare the efficacy and safety of high dose-intensity combination of methotrexate, vinblastine, adriamycin and cisplatin (HD MVAC) with gemcitabine plus cisplatin (GC) as a neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) or locally advanced upper tract urothelial cancer (UTUC). Patients and MethodsA retrospective analysis was conducted for patients with UC (cT2-4aN0-1M0) who received NAC from January 2011 and December 2017 at Asan Medical Center. Pathologic complete response (pCR), down-staging (<ypT2 and no N upstaging), disease-free survival (DFS), OS and safety were compared for each regimen. ResultsOut of a total of 277 patients, 176 patients received GC and 41 patients received HD MVAC. With the exception of age (patients receiving GC were younger; p=0.002), other baseline characteristics were well balanced between groups. pCR rates were 27.0% for GC and 22.6% for HD MVAC (p=0.62), and down-staging rate was 50.8% for GC and 58.1% for HD MVAC (p=0.47). There were no differences in OS (72.1% vs 73.1% for GC vs HD MVAC; p=0.58) and DFS (54.9% vs 63.3% for GC vs HD MVAC; p=0.21) at 3 years. HD MVAC with prophylactic G-CSF was associated with a higher incidence of febrile neutropenia (p<0.001) than GC. The NAC regimen was not an independent prognostic factor for OS. ConclusionsOncologic outcomes were not significantly different between the GC and HD MVAC when used as NAC in MIBC/UTUC.


2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Yan Zheng ◽  
Jiangong Zhang ◽  
Wenqun Xing

Abstract   In recent years, immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of ESCC. More than 20 phase II clinical trials have been launched to explore combinations of ICIs in the neoadjuvant setting for ESCC. Based on our phase II clinical trial, a two-arm phase III trial was launched in our Hospital. Methods A two-arm phase III trial was launched in April 2020 in our Hospital. Patient recruitment will be completed within 18 months. The primary endpoint is event-free survival (EFS). The secondary endpoints include pathologic complete response (pCR), disease-free survival (DFS) rate, overall response rate (ORR), R0 resection rate, major pathologic response (MPR), adverse events (AEs), complication rate and quality of life (QOL). A biobank of pretreatment, resected tumor tissue and paired blood samples will be built for translational research in the future. Results Until Dec. 2021, one hundred and twenty ESCC patients recruited in the trial. The trial is ongoing. Conclusion This RCT directly compares NAC with neoadjuvant toripalimab plus chemotherapy in terms of EFS for locally advanced ESCC. The results may usher in a new era of resectable ESCC treatment.


2021 ◽  
Vol 11 (2) ◽  
pp. 19-28
Author(s):  
Z. Z. Mamedli ◽  
A. V. Polynovskiy ◽  
D. V. Kuzmichev ◽  
S. I. Tkachev ◽  
A. A. Aniskin

The aim of the study: to increase the frequency of achieving pathologic complete response and increase disease-free survival in the investigational group of patients with locally advanced rectal cancer T3(MRF+)–4N0–2M0 by developing a new strategy for neoadjuvant therapy.Materials and methods. In total, 414 patients were assigned to treatment. Control group I included 89 patients who underwent radiotherapy (RT) 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week. Control group II included 160 patients who underwent RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and oxaliplatin once a week, during the course of RT. Study group III consisted of 165 patients. This group combined RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and additional consecutive CapOx cycles. This group was divided into 2 subgroups: subgroup IIIa included 106 patients with consolidating chemotherapy (after CRT); subgroup IIIb included 59 patients who underwent “sandwich” treatment. Therapy consisted of conducting from 1 to 2 cycles of induction CapOx (up to CRT) and from 1 to 2 cycles of consolidating CapOx with an interval of 7 days. In the interval between the courses of drug therapy, RT 52–56 Gy/26–28 fractions was performed. According to the results of the control examination, further treatment tactics were determined. The primary end points were 5-year disease-free survival and the achievement of a pathologic complete response.Results. Pathologic complete response was significantly more often recorded in patients in the investigational group III (17.48 %; p = 0.021) compared with control groups (7.95 % in the I group and 8.28 % in the II group). 5-year disease-free survival in patients in the study groups was: 71.5 % in the III group, 65.6 % in the II group and 56.9 % in the I group.Conclusion. The shift in emphasis on strengthening the neoadjuvant effect on the tumor and improving approaches to drug therapy regimens have significantly improved disease-free survival of patients with locally advanced rectal cancer.


1988 ◽  
Vol 6 (4) ◽  
pp. 576-582 ◽  
Author(s):  
S Riddell ◽  
F R Appelbaum ◽  
C D Buckner ◽  
P Stewart ◽  
R Clift ◽  
...  

Twenty-nine patients were conditioned for allogeneic marrow transplant with cytarabine (ara-C) (3 g/m2 every 12 hours for 12 doses) and total body irradiation (TBI) (200 cGy daily for six days) with or without cyclophosphamide (CY) (60 mg/kg) to determine toxicity and efficacy. Four patients had chronic myelogenous leukemia (CML) in accelerated phase or blast crisis, and 25 patients had acute leukemia, 24 at stages later than first remission. Three patients (10%) had fatal regimen-related toxicity and another 10% experienced severe toxicity in at least one organ system. The addition of CY to the ara-C and TBI regimen was not associated with an increase in the frequency of severe toxicity. Twenty-five of 29 patients engrafted eight to 33 days posttransplant: three died early before engraftment, and one patient failed to engraft. Ten of 29 patients are alive without disease, and the actuarial probability of disease-free survival for the entire group at 3 years is 33%. Three of ten patients with acute nonlymphocytic leukemia (ANL), six of 15 with acute lymphocytic leukemia (ALL), and one of four with CML are alive and disease free 25 to 42 months (median, 30 months) after transplant. High-dose ara-C (HDara-C) and TBI with or without CY can be administered with approximately the same toxicity as CY plus TBI. Phase III studies appear warranted to determine if these newer regimens provide improved results compared with currently used regimens.


2020 ◽  
pp. 030089162096798
Author(s):  
Yirui Zhai ◽  
Dazhi Chen ◽  
Yushun Gao ◽  
Zhouguang Hui ◽  
Liyan Xue ◽  
...  

Purpose: To improve resectability in patients with stage III–IVA thymic epithelial neoplasms, neoadjuvant chemotherapy and radiotherapy are considered. This retrospective study aimed to investigate the efficacy and safety of neoadjuvant therapies using modern techniques in thymic epithelial neoplasms. Methods: We included 32 patients with Masaoka stage III–IV disease treated at our institution from January 2010 to December 2017. Data regarding clinicopathologic characteristics, treatment protocols, toxicities, and survival were collected. Response was evaluated according to the Response Evaluation Criteria in Solid Tumours 1.1. Survival was assessed using the Kaplan-Meier method. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Results: Neoadjuvant radiotherapy alone, chemotherapy alone, sequence chemoradiotherapy, and concurrent chemoradiotherapy were administered to 10 (31.3%), 9 (28.1%), 3 (9.4%), and 10 (31.3%) patients, respectively. Twenty-nine patients (90.6%) underwent R0 resection. The median follow-up time was 38.0 months (3.3–109.5 months). After neoadjuvant therapy, 18 patients (56.3%) achieved partial response and 14 (43.8%) had stable disease. Pathologic complete response was achieved in 6 patients (18.8%), all of whom had thymic carcinoma. The 5-year overall and progression-free survival rates were 90.9% and 67.5%, respectively. For patients with thymic carcinoma, the 5-year overall and progression-free survival rates were 80.0% and 66.2%, respectively. Grade 3 toxicities were observed in only 1 patient (leukopenia). Conclusions: For patients with primary unresectable thymic neoplasms, neoadjuvant chemoradiotherapy is an efficient and safe choice, with favorable response and survival and moderate toxicities. Patients with thymic carcinoma might benefit more from neoadjuvant therapies.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11090-11090
Author(s):  
S. Altintas ◽  
M. T. Huizing ◽  
I. Spoormans ◽  
J. Van den Brande ◽  
P. Wilmes ◽  
...  

11090 Background: NACT improves survival in LABC. The optimal regimen, dose and duration is still under study Objective: To determine the efficacy and safety of prolonged preoperative HD-AC plus G-CSF. Methods: LABC patients (pts) were treated with AC for 6 cycles (Cy): Cy 1: A 90 mg/m2, C 1000 mg/m2; Cy 2–3: A 82.5 mg/m2, C 875 mg/m2; Cy 4–6: A 75mg/m2, C 750 mg/m2) with prophylactic (peg)filgastrim q3wks. In case of cardiotoxicity or poor tumor response (TR) pts switched to Docetaxel (D) 100mg/m2 q3wks. Within 5 weeks after NACT, pts underwent mastectomy with axillary lymph node dissection followed by radiotherapy. In case of positive estrogen (ER) or progesteron receptor (PgR), hormonal treatment was given for 5 yrs. Toxicity was scored weekly (NCI-CTC 2), response every 3 wks (WHO). Kaplan-Meier analysis was performed to calculate disease free survival (DFS) and overall survival (OS). Results: Between 8/1997 and 10/2003 21 pts (median age 55 years, range 22–74) were enrolled. One pt had stage IIB, 6 stage IIIA, 14 stage IIIB disease (10 T4d). 10 tumors were ER+, 5 PgR+, none overexpressed Her-2/Neu. A total of 130 NACT Cy was given. 15 pts completed all 6 AC Cy, 6 switched to D because of a decrease in left ventricular ejection fraction (LVEF? >10%, n=2) or insufficient TR (n=4). Dose reduction of AC was needed in 1 pt (last Cy), dose delays in 4 pts. Nausea and vomiting were generally mild; grade 4 anorexia occured in one pt. Grade 4 leucopenia and neutropenia in 14 and 18 pts, respectively. Neutropenic fever requiring hospitalization occurred in 5 pts, thrombocytopenia grade 4 in 7 pts and grade 3 anemia in 3 pts. Two pts developed cardiomyopathy (9.5%) < 2 years after NACT. The overall TR rate (PR and CR) was 81%, clinical CR rate 14%, pathologic CR rate 10% and 14% had minimal residual disease. Three pts showed SD and only 1 pt had PD. The median follow up of all pts was 51 months (range 9–110), 5 yrs DFS 47%, OS 56%. 5 yrs DFS and OS for pT4d pts was 50% and 56%, respectively. Conclusions: NACT with HD-AC plus G-CSF for 6 Cy in this poor risk population is active and further supports the use of prolonged preoperative CT. The routine use of D after a restricted number of AC Cy may further improve results and decrease (cardio)toxicity. No significant financial relationships to disclose.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14531-14531
Author(s):  
F. Bertolini ◽  
S. Zironi ◽  
N. Malavasi ◽  
C. Dealis ◽  
F. Bertoni ◽  
...  

14531 Background: Pre-operative chemo-radiotherapy in locally advanced RC has been used to improve local control and to facilitate sphincter-sparing surgery for distal tumors. Cetuximab, an anti EGFR monoclonal antibody, has proved efficacy in advanced colorectal cancer. Methods: Study design provided: 1) tumor biopsy to confirm diagnosis and to measure tumor biomarkers (EGFR, TS, p53, MAP kinase, Ki 67, p21, bcl-2; immunological cell profile at the tumor level: CD45RO, CD68, CD56 CD4+/CD25+, CD31, HLA-A, -B and -C), 2) Cetuximab single agent (400 mg/sqm loading dose, then 250 mg/sqm weekly) for 3 doses, 3) a second biopsy to evaluate tumor biomarkers, 4) Cetuximab 250 mg/sqm weekly plus 5FU (225 mg/sqm in continuous infusion) concomitantly with RT (50 Gy), 5) surgery. Tumor biomarkers are measured again on tumor specimen in non pCR patients (pts). 66 pts with resectable uT3/uT4 N0/+ RC will enter the study. Primary aim is: toxicity and activity (pathologic complete response). Secondary aim is: evaluation of biological parameters, rates of sphincter sparing surgery and disease free survival. Results: Up to now 29 pts are valuable for toxicity (M/F= 22/5; median age: 61; range: 35–74). Ultrasound staging at diagnosis is: uT3N0: 7; uT3N1: 20; uT4N1: 2. Four pts (14%) withdrew neo-adjuvant treatment after 1 administration of Cetuximab: 2 for hypersensitivity reactions (1 G3; 1 G4), 1 for progression and 1 for purulent arthritis. Twenty-two pts (75%) presented acne-like rash; treatment with Cetuximab was interrupted or reduced in 4 pts (14%): in 2 for acne-like rash grade 3 (NCI-CTC) and in 2 pts for refuse. Grade 1–2 gastro-intestinal toxicity (unrelated to Cetuximab) was observed in 13 pts (proctitis: 4; diarrhoea: 9); in 1 case: diarrhoea G4. Twenty pts are valuable for surgery: 18 pts (90%) underwent conservative surgery. Two pts (10%) experienced post-surgical complications: 1 anastomotic fistula and 1 colonic necrosis. Conclusions: Pre-operative treatment with 5FU, Cetuximab and pelvic RT is well tolerated and does not increase surgical complication rate. An update on efficacy data and biological markers evaluation will be presented at the meeting. No significant financial relationships to disclose.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6059-6059
Author(s):  
M. S. Kandil ◽  
H. S. Alnasser ◽  
S. A. Bandey ◽  
A. S. Almutairy ◽  
F. A. Ammar ◽  
...  

6059 Background: Neoadjuvant cisplatin/docetaxel are active agents for locally advanced nasopharyngeal cancer (LANPXCA). The efficacy and tolerability of neoadjuvant cisplatin/docetaxel followed by concurrent cisplatin with radiotherapy are explored in a phase II trial. Methods: From Jan 2003 to Jan 2005; 23 patients with LANPXCA stage III, IVA, IVB, (AJCC 2002), were treated with 3 cycles of neoadjuvant docetaxel 60mg/m2, 1 hour IV infusion D1 and cisplatin 60 mg/m2, 2 hours IV infusion D1 with prophylactic GSCF as 5μg/kg sc D3–7,(recycle D22). This was followed by 2 cycles of cisplatin 100 mg/m2, 2 hours IV infusion D1 , (recycle D22), concurrently with radiotherapy aiming at 70Gy / 35 fractions / 7 weeks. The median follow up was 27.9 months (18.3–47.3). Results: The median age was 38 years (16–68) and male to female ratio was 7.66:1. Neck mass 95.7%, neck pain 73.9%, nasal obstruction 65.2%, , headache 56.5%, impaired hearing 52.2%, and epistaxis 52.2% were the commonest symptoms. All patients had G3 squamous cell carcinoma. The majority of patients were stage IV 52.2% while 47.8 % were stage III. Grade one ECOG performance status was the commonest 52.2% while 47.8% were G2. The treatment was tolerable with commonest G3 acute toxicities were dysphagia 43.4% , and oral mucositis 8.7%. The commonest G3 late toxicities were dry mouth 17.4% and impaired hearing 13%. Complete remission was achieved in 22/23 patients 95.7% while 1/23 patients 4.3% was partial responder. Failure sites include; Distant; liver and/or bone 8.7%, local; skull base 4.3% or local and distant 4.3%.The Kaplan Meyer 47 month disease free survival was 82.61% while the 47 month overall survival was 91.3%. Conclusion: Neoadjuvant docetaxel / cisplatin followed by concurrent Cisplatin with radiotherapy is an effective and tolerable outpatient treatment for LANPXCA. No significant financial relationships to disclose.


2015 ◽  
Vol 2015 ◽  
pp. 1-10
Author(s):  
Shahab Hajibandeh ◽  
Shahin Hajibandeh

Background. Recent meta-analysis of 21 randomised controlled trials (RCTs) supports the use of adjuvant chemotherapy for nonmetastatic rectal carcinoma. In order to define a subgroup of patients who can potentially benefit from postoperative adjuvant chemotherapy, this study aims to review trials investigating adjuvant chemotherapy with respect to stage of disease in patients with locally advanced rectal cancer who had undergone surgery for cure (stage II and stage III). Methods. We searched electronic information sources to identify randomised trials evaluating adjuvant chemotherapy in patients with stages II and III rectal cancer with overall survival or disease-free survival as outcomes. Scottish Intercollegiate Guidelines Network notes on methodology were used to assess the methodological quality of the selected studies. Random-effects models were applied to calculate pooled outcome data. Results. Eight studies reporting total of 5527 patients were selected for analysis. Adjuvant chemotherapy was associated with statistically significant improvement in disease-free survival and overall survival compared to surgery alone in both stage II and stage III cancer. Conclusions. This study indicates that both stage II and stage III rectal cancer patients may benefit from postoperative adjuvant chemotherapy. However, the benefits of adjuvant chemotherapy for patients who already had neoadjuvant chemoradiation still remain unknown.


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