Neoadjuvant chemotherapy with metronomic doxorubicin, cyclophosphamide, and capecitabine in patients with locally advanced (LA) triple-negative breast cancer (TNBC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12027-e12027
Author(s):  
Mona Frolova ◽  
Marina Skrypnikova ◽  
Ekaterina Ignatova ◽  
Alexander Petrovsky ◽  
Marina Stenina ◽  
...  

e12027 Background: TNBC is associated with aggressive behavior and poor prognosis. It has been shown that patients (pts) with TNBC with pathological complete regression (pCR) after neoadjuvant chemotherapy have a higher survival. Rates of pCR with standard antracycline- and taxanebased chemotherapy regimens don’t exceed 20-27%. Dose-dense and metronomic schedules may be more effective in these highly proliferative tumors. We performed a prospective pilot trial to evaluate efficacy of metronomic schedule of doxorubicin, cyclophosphamide and capecitabine in pts with LA TNBC. Methods: Pts with LA TNBC (cT2-4N1-3M0) were treated with doxorubicin 25 mg/m2 iv weekly, cyclophosphamide 50 mg po daily and capecitabine 1500 mg po daily for planned 16-19 weeks followed by surgery. Pathological response was evaluated according to the Chevallier classification. Results: Twenty pts was included in the study in 2009-2010. Median agewas 47 years (33-70), 63% of pts had tumor grade 3, Ki67 was >20% in all cases. Nineteen pts completed chemotherapy (median treatment duration 17.1 weeks) and underwent surgery. One pt had a disease progression during chemotherapy and was switched to 2nd-line chemotherapy. Seven pts (36,8%) achieved a pCR (6 pts class 1 and 1 pt class 2). With median follow-up of 33 months, 3-year DFS and OS were 60%. All but one pt with pCR, who developed brain mts shortly after surgery, are currently alive without relapse. In contrast 50% of pts with residual tumor relapsed. Pts with pCR had significantly higher median cumulative dose of doxorubicin (420 mg/m2) than pts with residual disease (300 mg/m2, p=0.046). The dose-limiting toxicities were hand-foot syndrome (26.3% grade 3), mucositis (31.6% grade 3), and neutropenia (31.6% grade 3-4), which resulted in permanent discontinuation of doxorubicin in 4 pts. Conclusions: Despiterelatively hightoxicity metronomic doxorubicin, cyclophosphamide and capecitabine regimen shows promising activity as neoadjuvant treatment of LA TNBC. Achievement of pCR and higher cumulative dose of doxorubicin were strongly associated with improvement of survival.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 96-96
Author(s):  
M. Ryu ◽  
Y. Choi ◽  
B. Kim ◽  
Y. Park ◽  
H. Kim ◽  
...  

96 Background: The aim of this study was to evaluate feasibility and safety of neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy in patients with potentially resectable adenocarcinoma of stomach or gastroesophageal junction. Methods: Forty-one patients with clinical stage T3-4N0M0 or T2-4N+M0 determined by CT, endoscopic ultrasonography, and laparoscopy were enrolled between DEC 2008 and MAR 2010. Gastrectomy with D2 lymph node dissection was conducted after 3 cycles of DOS chemotherapy. DOS chemotherapy consists of docetaxel 50 mg/m2 iv (day1), oxaliplatin 100 mg/m2 iv (day1), and S-1 40 mg/m2 po bid (days1-14) at 3 weeks interval. After curative gastrectomy, the patients were given 1 year of adjuvant chemotherapy with S-1 (40 mg/m2 D1-28, every 6 weeks). Results: All patients finished the planned neoadjuvant chemotherapy. Twenty-three (56%) patients achieved a partial response, and the remaining 18 patients had stable disease by CT scan after 3 cycles of DOS chemotherapy. No disease progression was observed during the neoadjuvant chemotherapy. A median 4.7 weeks (range, 4.0-7.6) after the start of the 3rd cycle of DOS chemotherapy, 39 (95%) patients underwent R0 resection with no pathologic residual disease in 4 (10%) patients. Hematologic toxicities were common including grade 4 neutropenia (32%), grade 3 thrombocytopenia (17%), and febrile neutropenia (10%). However, hematologic toxicities were generally transient and manageable. There were no grade 3 or 4 non-hematologic toxicities with frequency > 5% of patients. With all toxicities taken together, 21 (51%) patients experienced grade 3 or 4 toxicities (except grade 3 neutropenia). There was no treatment-related death, and surgical complications included only mild wound problem in 4 (10%) patients. Conclusions: In this study, neoadjuvant DOS chemotherapy could induce a sufficient down-staging and R0 resection of locally advanced gastric cancer with mild and manageable toxicities. A phase III randomized trial is planned for evaluating the benefit of neoadjuvant DOS chemotherapy in patients with locally advanced gastric cancer. [Table: see text]


2004 ◽  
Vol 22 (12) ◽  
pp. 2303-2312 ◽  
Author(s):  
Allen M. Chen ◽  
Funda Meric-Bernstam ◽  
Kelly K. Hunt ◽  
Howard D. Thames ◽  
Mary Jane Oswald ◽  
...  

Purpose To determine patterns of local-regional recurrence (LRR) and ipsilateral breast tumor recurrence (IBTR) among patients treated with breast conservation therapy after neoadjuvant chemotherapy. Patients and Methods Between 1987 and 2000, 340 cases of breast cancer were treated with neoadjuvant chemotherapy followed by conservative surgery and radiation therapy. Clinical stage at diagnosis (according to the 2003 American Joint Committee on Cancer system) was I in 4%, II in 58%, and III in 38% of patients. Only 4% had positive surgical margins. Results At a median follow-up period of 60 months (range, 10 to 180 months), 29 patients had developed LRR, 16 of which were IBTRs. Five-year actuarial rates of IBTR-free and LRR-free survival were 95% and 91%, respectively. Variables that positively correlated with IBTR and LRR were clinical N2 or N3 disease, pathologic residual tumor larger than 2 cm, a multifocal pattern of residual disease, and lymphovascular space invasion in the specimen. The presence of any one of these factors was associated with 5-year actuarial IBTR-free and LRR-free survival rates of 87% to 91% and 77% to 84%, respectively. Initial T category (T1–2 v T3–4) correlated with LRR but did not correlate with IBTR (5-year IBTR-free rates of 96% v 92%, respectively, P = .19). Conclusion Breast conservation therapy after neoadjuvant chemotherapy results in acceptably low rates of LRR and IBTR in appropriately selected patients, even those with T3 or T4 disease. Advanced nodal involvement at diagnosis, residual tumor larger than 2 cm, multifocal residual disease, and lymphovascular space invasion predict higher rates of LRR and IBTR.


2018 ◽  
Vol 11 (2) ◽  
pp. 450-460 ◽  
Author(s):  
Satoko Arai ◽  
Tomohiko Hara ◽  
Yoshiyuki Matsui ◽  
Keiichi Koido ◽  
Hironobu Hashimoto ◽  
...  

Objective: Compared with standard treatment, a modified tri-weekly MVAC (methotrexate, doxorubicin, vinblastine, and cisplatin) treatment regimen with a high cisplatin dose intensity shows good efficacy and lower toxicity. Thus, we retrospectively investigated the tolerability and efficacy of a modified tri-weekly MVAC neoadjuvant regimen. Methods: We analyzed 25 patients with locally advanced bladder cancer medicated by a modified tri-weekly MVAC neoadjuvant regimen that omits treatment on days 15 and 22. The efficacy and tolerability were assessed retrospectively. Results: The numbers of patients in clinical stages 2, 3, and 4 were 13 (52.0%), 1 (4.0%), and 11 (44.0%), respectively. Surgery could be performed on all patients. Five patients (20.0%) had no cancer remaining in their surgical specimens. Remaining non-muscle-invasive cancer without metastasis was observed in 7 patients (28.0%), and the total downstaging rate was 44.0%. The 5-year overall and relapse-free survival rates were 79.0 and 75.0%, respectively. The overall relative dose intensity was 0.90. Serious hematologic toxicities rated grade 3 or greater were leukopenia in 6 patients (24.0%) and anemia in 1 patient (4.0%). Conclusions: Sufficient efficacy and tolerability of a modified tri-weekly MVAC neoadjuvant regimen were suggested. Thus, tri-weekly modified MVAC may be an option for neoadjuvant chemotherapy of advanced bladder cancer.


2017 ◽  
Vol 3 (5) ◽  
pp. 455-458
Author(s):  
Reyad Dada ◽  
Mohamed El Sayed ◽  
Jamal Zekri

Purpose Capecitabine, an oral fluorouracil (5-FU) derivative, has replaced 5-FU in many chemotherapy regimens used in various GI tract cancers. The experience with capecitabine in nasopharyngeal carcinoma (NPC) is limited. Patients and Methods We report on eight patients with locally advanced NPC treated with neoadjuvant chemotherapy with capecitabine and cisplatin. Results All eight patients responded well to the chemotherapy combination and achieved complete remission after definitive chemoradiotherapy. No grade 3/4 toxicities were observed. Five patients experienced a relapse after 6, 8, 9, 12, and 17 months. Conclusion In the patients studied, capecitabine (in combination with cisplatin) was a safe and effective substitution for 5-FU for the neoadjuvant treatment of locally advanced NPC. Larger prospective clinical studies are required to confirm these results.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6055-6055
Author(s):  
S. Hameed ◽  
A. Jamshed ◽  
R. Hussain ◽  
M. Ali ◽  
H. Iqbal ◽  
...  

6055 Background: The treatment of locally advanced nasal and paranasal sinus tumors is controversial. The disease is chemosensitive and there is increasing interest in the use of chemotherapy with radiation in this group of patients. Our aim was to determine survival in patients with locally advanced nasal and paranasal sinus tumors treated with neoadjuvant chemotherapy followed by radiotherapy or chemoradiation (RT/CRT). Methods: Between August 2005 and August 2008, 21 patients with AJCC stage III or IV nasal and paranasal sinus tumors were treated with neoadjuvant chemotherapy followed by RT/CRT in our institution. There were 15 males and 6 females (M 71%:F 29%) with a median age of 49 years (range 19 - 70 years). Site of disease was nasal cavity 33% (7), ethamoid sinus 43% (9), maxillary antrum 19% (4), and frontal sinus in 5% (1) of patients. Histopathological diagnosis was squamous cell carcinoma 43% (9), undifferentiated carcinoma 29% (6), adenocarcinoma 19% (4), esthesioneuroblastoma in 9% (2) of patients. Induction chemotherapy consisted of cisplatin 75 mg / metre2 day 1 and gemcitabine 1 gm / metre2 day 1 and 8 every three weeks. Eighty-five percent (18/21) received 2 cycles of neoadjuvant chemotherapy (range 1–4 cycles) prior to radiotherapy. Radiotherapy dose was 54 Gy - 70 Gy (median radiation dose 66 Gy). Fifty-seven percent (12/21) received concomitant cisplatin with radiotherapy. Results: Response to neoadjuvant chemotherapy; complete in 19% (4), partial in 67% (14), no response/progression 14% (3). Following RT/CRT 86% (18/21) had complete regression of disease. Thirty-three percent (7/21) have failed treatment (local 3, regional 2, and distant metastasis in 2 patients). Among treatment failures 2 patients were successfully salvaged; surgery for local recurrence in one patient and in the other case radiation was given for regional recurrence. Disease free and overall survival at 40 months was 52% and 63%, respectively. Conclusions: Gemcitabine cisplatin chemotherapy has good activity in nasal and paranasal sinus tumors. In combination with RT/CRT survival rates are encouraging and the approach merits further investigations in clinical trials. No significant financial relationships to disclose.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 91-91
Author(s):  
Daxuan Hao ◽  
Xue Li ◽  
Yuanyuan Yang ◽  
Yougai Zhang ◽  
Xiaoyuan Wu ◽  
...  

91 Background: Neoadjuvant chemoradiotherapy (nCRT) combined with surgery has been recommended as the standard treatment for locally advanced esophageal cancer in western countries. However, in clinical practice, neoadjuvant chemotherapy (nCT), rather than nCRT, is preferred for a large cohort of patients with locally advanced esophageal squamous cell carcinoma (ESCC) for fear of increasing the odds of postoperative morbidity in China. The aim of this study is to compare the clinical efficacy of nCRT and nCT in terms of postoperative morbidity, tumor pathology and survival in patients with locally advanced ESCC. Methods: A total of 111 patients with locally advanced ESCC (T2-4N0-1M0) received neoadjuvant treatment at our institution from January 2009 through January 2014.Among these patients, 53 cases received one cycle of neoadjuvant chemotherapy with concurrent radiotherapy while the remaining 58 cases received two cycles of neoadjuvant chemotherapy only before surgery. Results: pCR was observed in 15 patients in nCRT group (28.3%) and 8 patients in nCT group (13.8%, P= 0.060). Postoperative morbidity was 32.1% in nCRT group and 37.9% in nCT group (P= 0.660). Disease-free survival rates at 1, 2, 3 years were 73.1%, 66.7%, 53.6% in nCRT group and 73.7%, 60.4%, 52.2% in nCT group (P= 0.848). Overall survival rates at 1, 2, 3 years were 88.5%, 78.0%, 59.5% in nCRT group and 89.5%,72.9% and 56.2% in nCT group(P= 0.749). No significant differences were found in recurrence rate between two groups (P= 0.836). Conclusions: Neoadjuvant CRT may achieve higher pCR rate than neoadjuvant CT without increasing the odds of postoperative morbidity. Both neoadjuvant CRT and CT can prolong survival in patients with locally advanced ESCC. Further study is needed to prove which one is better.


2019 ◽  
Vol 65 (5) ◽  
pp. 721-725
Author(s):  
Elmira Shakirova ◽  
Andrey Panov ◽  
Alevtina Akhmetzyanova ◽  
Aliya Gafiullina ◽  
L. Ibragimova ◽  
...  

Aims: Chemoradiation (CRT) is the standard treatment for locally advanced cervical cancer (LACC). However part of the patients develop recurrence during the first year after treatment despite good visible effect at the first follow-up. The role of completion surgery after radiotherapy (RT) is still debated. A number of papers have showed that up to 60% of patients have residual tumor after CRT and RT. But such a surgery is not widely recommended because of increased morbidity of the treatment. The aim of this study was to assess the results of surgery after radiotherapy of LACC. Method: We retrospectively evaluated data on 86 patients with cervical cancer IB - IIIB stages (mostly stage IIB) who underwent surgery in different modalities after CRT and RT with good clinical response in our department in 2015-2018. Results: When small asymptomatic residual disease was detected early after radiotherapy radical hysterectomy was feasible in most of the cases. Patients with clinical manifestation of recurrence had very poor prognosis. Surgery of recurrent cervical cancer sufficiently deteriorates quality of life, even if possible. Conclusion: Thorough examination with adding MRI imaging after initial treatment of cervical cancer needed to identify patients who may benefit from adjuvant hysterectomy.


2016 ◽  
Author(s):  
Ashish Bhange ◽  
Abhishek Gulia ◽  
Anirudh Punnakal ◽  
Anil Kumar Anand ◽  
Anil Kumar Bansal ◽  
...  

Introduction: Locally advanced carcinoma cervix includes stages IIB, IIIA, IIIB and IVA. Interstitial brachytherapy has the potential to deliver adequate dose to lateral parametrium and to vagina. Hence, it is preferable in cases with distorted anatomy, extensive (lower) vaginal wall involvement, bulky residual disease post EBRT and parametrium involvement upto lateral pelvic wall. Aim and Objective: To determine clinical outcome and complications (acute and chronic) in locally advanced carcinoma cervix, treated with interstitial brachytherapy using template (MUPIT - Martinez universal perineal interstitial template). Materials and Methods: This study is a retrospective analysis of 37 cases of locally advanced carcinoma cervix (stage IIB-2, IIIB-30, IVA-5), treated with EBRT (dose-median 45Gy/25#) ± concurrent chemotherapy (CCT) - Inj. Cisplatin/Inj Carboplatin, followed by interstitial brachytherapy using MUPIT from December 2009 to June 2015. Initial treatment with EBRT ± CCT was followed by intertstitial brachytherapy. Under spinal anaesthesia and epidural analgesia, MUPIT application was done. Straight and divergent needles (median 26, range 19-29) were inserted to cover parametrium adequately. Needle position was verified with planning CT scan and Brachytherapy planning was done. Dose was normalized to 5 mm box surface from outermost needle with optimization of dose to OAR (Bladder, Rectum and Sigmoid colon). Prescription dose –25Gy in 5#. Treatment was delivered by Microselectron HDR using Ir192 source. Treatment fractions were delivered twice daily with min 6 Hrs. gap in-between fractions. Results: The median duration of follow-up was 25 months. Local control was achieved in 28 patients with residual disease in 7 patients and local recurrence in 2 patients. 10 patients had acute lower GI toxicity {Grade1 (n=6), Grade 2 (n=4)}, 2 patients had acute Grade 1 bladder toxicity. 1 patient had grade 3 and 1 patient had grade 4 chronic bladder toxicity. Chronic rectal toxicity was seen in 10 patients {Grade 2 (n=4), Grade 3 (n=4), Grade 4 (n=2)}. Conclusion: Local control was achieved in 28/37 patients (75.6%) and overall survival rate of 81.1% at median follow up of 25 months in patients with locally advanced carcinoma cervix and unfavorable prognostic factors.


2020 ◽  
Vol 8 (B) ◽  
pp. 1077-1082
Author(s):  
Ainura Maratovna Zhumakayeva ◽  
K. D. Rakhimov ◽  
I. M. Omarova ◽  
S. M. Adekenov ◽  
S. S. Zhumakayeva

BACKGROUND: Activated forms of RAS increase both in breast cancer and in cell lines in the presence of estimated glomerular filtration rate (EGFR) or HER2 expression. HRAS oncoproteins play an important role in enhancing the proliferation and resistance of breast cancer tumor cells to apoptosis. A number of studies have shown a significant decrease in EGFR expression after neoadjuvant chemotherapy, which has been clinical, manifested by an improvement in immediate efficacy and an increase in overall and relapse-free breast cancer survival rates. AIM: The aim of the study was to study relapse-free survival depending on the expression of the H-RAS oncoprotein in patients with breast cancer who received different treatment regimens for the farnesyltransferase inhibitor. METHODS: H-RAS status was assessed by immunohistochemistry. RESULTS: A comparative analysis of patients with negative expression of H-RAS oncoproteins showed a statistically significant increase in relapse-free survival in the subgroups who received neoadjuvant chemotherapy according to the AC regimen (adriablastin + cyclophosphamide) and AC + arglabin, compared with monotherapy by arglabin: Kruskal–Wallis= 12.56, where p = 0.001. A comparative analysis of patients with positive expression of H-RAS showed that in the subgroups treated with arglabin and AC+arglabin, there was a statistically significant increase in relapse-free survival compared with the AC subgroup: Kruskal–Wallis = 10.96, where p = 0.004. It was established that the positive expression of H-RAS negatively affects not only the direct effectiveness of neoadjuvant therapy but also worsens the rates of relapse-free survival. However, in patients with positive H-RAS expression who received arglabin in monotherapy, there was a statistically significant increase in relapse-free survival up to 16.5 ± 1.1 months compared with the standard AC regimen (13.5 ± 1.1 months) (р ˂ 0.05), the addition of arglabin to the standard AC regime also increased this indicator to 16.4 ± 1.2 months (р ˂ 0.05). CONCLUSION: These results may indicate the clinical applicability of determining H-RAS as a prognostic factor for relapse-free survival in breast cancer.


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