scholarly journals Phase II randomized trial of capecitabine with bevacizumab and external beam radiation therapy as preoperative treatment for patients with resectable locally advanced rectal adenocarcinoma: long term results

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ramón Salazar ◽  
◽  
Jaume Capdevila ◽  
Jose Luis Manzano ◽  
Carles Pericay ◽  
...  

Abstract Background Preoperative chemoradiotherapy with capecitabine is considered as a standard of care for locally advanced rectal cancer. The “Tratamiento de Tumores Digestivos” group (TTD) previously reported in a randomized Ph II study that the addition of Bevacizumab to capecitabine-RT conferred no differences in the pre-defined efficacy endpoint (pathological complete response). We present the follow-up results of progression-free survival, distant relapse-free survival, and overall survival data at 3 and 5 years. Methods Patients (pts) were randomized to receive 5 weeks of radiotherapy (45 Gy/25 fractions) with concurrent Capecitabine 825 mg/m2 twice daily, 5 days per week with (arm A) or without (arm b) bevacizumab (5 mg/kg once every 2 weeks). Results In our study, the addition of bevacizumab to capecitabine and radiotherapy in the neoadjuvant setting shows no differences in pathological complete response (15.9% vs 10.9%), distant relapse-free survival (81.0 vs 80.4 and 76.2% vs 78.2% at 3 and 5 years respectively), disease-free survival (75% vs 71.7 and 68.1% vs 69.57% at 3 and 5 years respectively) nor overall survival at 5-years of follow-up (81.8% vs 86.9%). Conclusions the addition of bevacizumab to capecitabine plus radiotherapy does not confer statistically significant advantages neither in distant relapse-free survival nor in disease-free survival nor in Overall Survival in the short or long term. Trial registration EudraCT number: 2009–010192-24. Clinicaltrials.gov number: NCT01043484.

1999 ◽  
Vol 17 (4) ◽  
pp. 1118-1118 ◽  
Author(s):  
C. Hudis ◽  
M. Fornier ◽  
L. Riccio ◽  
D. Lebwohl ◽  
J. Crown ◽  
...  

PURPOSE: We conducted a phase II pilot study of dose-intensive adjuvant chemotherapy with doxorubicin followed sequentially by high-dose cyclophosphamide to determine the safety and feasibility of this dose-dense treatment and to estimate the disease-free and overall survival in breast cancer patients with four or more involved axillary lymph nodes. PATIENTS AND METHODS: Seventy-three patients received adjuvant treatment with four cycles of doxorubicin 75 mg/m2 as an intravenous bolus every 21 days, followed by three cycles of cyclophosphamide 3,000 mg/m2 every 14 days with granulocyte colony-stimulating factor support. RESULTS: Seventy-one patients were assessable, and all but two completed all planned chemotherapy. There was no treatment-related mortality. The most common toxicity was neutropenic fever, which occurred in 39% of patients. Median disease-free survival is 66 months (95% confidence interval, 34 to 98 months), and median overall survival has not yet been reached. At 5 years of follow-up, the disease-free survival is 51.7%, and overall survival is 60.0%. There is no long-term treatment-related toxicity, and no cases of acute myelogenous leukemia or myelodysplastic syndrome have been observed. CONCLUSION: Our pilot study of doxorubicin followed by cyclophosphamide demonstrates the safety and feasibility of the sequential dose-dense plan. Long-term follow-up, although noncomparative, is promising. However, this regimen is associated with a higher incidence of toxicity (and also higher costs) than the standard dose and schedule of doxorubicin and cyclophosphamide, and therefore it should not be used as conventional therapy in the absence of demonstrated improvement of outcome. Randomized trials testing the dose-dense approach have been completed but not yet reported. Because the sequential plan can decrease overlapping toxicities, it is an appropriate platform for the addition of newer active agents, such as taxanes or monoclonal antibodies.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 144-144
Author(s):  
Boo Gyeong Kim ◽  
Byung-Wook Kim ◽  
Joon Sung Kim ◽  
Sung Min Park ◽  
Keun Joon Lim ◽  
...  

144 Background: The aim of this study is to evaluate the long-term clinical and oncologic outcome of ESD for differentiated EGC of an expanded indication compared to surgical resection. Methods: Retrospective analyses were performed in patients who underwent ESD or surgical resection for EGC of an expanded indication from 2006 and 2008 in Incheon St. Mary’s Hospital, Seoul St. Mary’s Hospital, Yeouido St. Mary’s Hospital, and St. Paul’s Hospital. First arm study was performed according to pre-ESD diagnosis including pathologic diagnosis and endoscopic findings. Second arm study was obtained from post-ESD final pathologic result. All the patients were checked with endoscopy and stomach CT regularly at least 5 years. Clinical outcomes, disease free survival and overall survival were compared between the ESD group and surgical resection group in each arm. Results: In first arm study, 41 patients who received ESD and 106 patients who received surgical resection were enrolled. Metachronous recur was found in 4 patients among ESD group and in 2 patients among surgical resection group during the follow up period. There was no local recurrence in both groups. The disease free survival was not different between the two groups (ESD vs surgical resection; 87.8 vs 95.3%, p=0.291). The 5-year overall survival rate was 100% in both groups. In second arm study, 74 patients who received ESD and 165 patients who received surgical resection were enrolled. Metachronous recur was found in 5 patients among ESD group and in 2 patients among surgical resection group during the follow up period. Local recurrence did not occur in both groups. Surgical resection group was superior to ESD group in disease free survival (97.6% vs 87.6%, p=0.002). The 5-year overall survival rate was 100% in both groups. Conclusions: ESD for EGC might be acceptable considering the overall survival rates. However, intensive surveillance should be performed to find the metachronous recur after ESD.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5574-5574
Author(s):  
P. M. Specenier ◽  
D. Van Den Weyngaert ◽  
C. Van Laer ◽  
J. Van Den Brande ◽  
M. Huizing ◽  
...  

5574 Background: RT with concurrent chemotherapy is superior to RT alone as treatment for locally advanced SCCHN. Gem is a potent radiosensitizer in vitro and in vivo and in addition has a good activity in SCCHN. Exploitation of these properties was the rationale for a single institution phase II study which evaluates the efficacy and toxicities of standard RT + weekly low dose Gem. Methods: Eligible were patients with primary inoperable or locally advanced stage III and IV SCCHN. Treatment: Planned RT was 70 Gy over 7 weeks with weekly Gem 100 mg/m2 within 2 hours prior to RT (Eisbrüch et al., ASCO, 1997, 1998). Presented endpoints are response rate (according to WHO), acute and late toxicity (according to NCICTC), disease free survival (DFS), local relapse free survival (LRFS) and overall survival (OS). Results: 26 patients (21 male, 5 female; performance status 0–2; no prior treatment) entered the study between November 1998 and September 2003. Median age was 56 years (range 48–78). Tumor sites were oropharynx (6), hypopharynx (17), glottis (1), paranasal sinus (1), unknown (1). Clinical stage was III (2) or IV (24). 7 Patients had T4N2 disease and 2 had T4N3 disease. Patients received a median of 7 Gem cycles (range 2–8) and a median of 70 Gy (66–84.75). 7 patients underwent radical neck dissection. Grade 3–4 acute toxicities included mucositis (22/26), dermatitis (18/26), pharyngitis and/or oesophagitis (21/26), pain (7/25), xerostomia (1/24), neutropenia (1/26) and anemia (1/26). 21/26 patients needed tube feeding and 21/26 needed to be hospitalized. After recovery from acute toxicity 6/23 could feed normally, 5/23 needed soft food, 5/23 were able to swallow liquid food and 2/23 required permanent tube feeding. Response was evaluable in 22 patients (11 CR, 11 PR). Intial relapse was at distant sites in 9/26 and local in 8/26. Median follow up of the patients still alive is 46 months. Median OS is 576 days, median DFS is 401 days, median LRFS is not reached. 7/26 remain free of disease more than 3 years after end of treatment. Conclusions: RT + Gem (100 mg/m2/week) is feasible but toxic. The combination is highly active in SCCHN and provides a good long term local control. [Table: see text]


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11065-11065 ◽  
Author(s):  
Anna Maria Frezza ◽  
Naofumi Asano ◽  
Robin Jones ◽  
Ravin Ratan ◽  
Pawel Teterycz ◽  
...  

11065 Background: To report on a multi-institution retrospective study on the activity of anthracycline-based (Ab) and gemcitabine-based (Gb) regimens as well as pazopanib (P) in patients with advanced epithelioid sarcoma (ES) treated within 16 sarcoma reference centres in Europe, US and Japan. Methods: Patients with a histologically confirmed diagnosis of locally advanced/metastatic ES were selected. Classic and distal subtypes were defined based on morphology (WHO 2014). INI1 expression is under evaluation.Response was evaluated by RECIST.Progression-free survival (PFS) and overall survival (OS) were computed by Kaplan-Meier method. Results: Ninety ES patients were identified (Table 1). They were treated with Ab (72), Gb (30) and P (20); 25 pts received more than one treatment. The median follow-up for Ab, Gb and P groups was 32, 24 and 22 months, respectively. The response rate (RR) for Ab was 25% (95% CI 16%-37%), with a median PFS and OS of 6 and 17 months. The RR for Gb was 23% (95% CI 10% - 42%), with 1 complete response and a median PFS and OS of 5 and 20 months. In the P group, no objective responses were reported, and median PFS and OS were 3 and 9 months. A non-statistically significant trend towards a greater RR in proximal than classic subtype was seen in both Ab (27% vs 22%) and Gb (30% vs 13%) groups. Conclusions: This retrospective series, the largest currently available, confirms the activity of Ab and Gb in ES, with a similar RR and PFS in both groups. In this population, the value of P seems limited. These data may serve as a benchmark for trials of novel agents in ES. [Table: see text]


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17569-e17569
Author(s):  
Ayush Garg ◽  
Piyush Kumar ◽  
Arvind Kumar Chauhan ◽  
Pavan Kumar

e17569 Background: Concurrent Cisplatin with radiotherapy improves outcomes in locally advanced squamous cell carcinomas of the head neck.Cisplatin at 35mg/m2(weekly) raise compliance & hospitalization. There are only few reports on efficacy and toxicity of low dose Cisplatin (6mg/m2). Hence the purpose of this study was to evaluate the compliance and clinical outcomes between two concurrent cisplatin chemotherapy regimens & to see long term effects. Methods: Total 50 patients were included in study from Nov 2015 to Mar 2017 with 25 in each group. Radiotherapy given 70Gy/35# in 7weeks & Cisplatin at 35mg/m2 weekly (Group I) and 6mg/m2 daily (Group II). Assessment of toxicity was done by RTOG scoring criteria. WHO Response criterion was used to assess clinical response. Median follow up was 6 months. Results: Group I(80%) and Group II(84%)patients completed Radiotherapy. In Group I 48% patients received less than 6 cycles and Group II 40% received ≤25 cycles chemotherapy. Median OTT in Group I & II in was 51 & 52days. Neutropenia & Mucositis statistically insignificant between both groups.There was no statistical difference in complete response between the two groups. In Group I 40% patients developed Progressive disease on follow up as compared to 12% in Group II(p-0.02). After 1.5 years of follow up, Group I vs Group II 4 patients had complete response, 6 had recurrence & 11 vs 4 patients expired (p-0.03). At a median follow up of 6 months overall survival in Group I and II was 56% and 44%(p-0.39). While as median disease free survival in Group I & II was 6.6 & 11.9 months(p-0.14). Conclusions: Low dose daily Cisplatin offers ease of administration in the outpatient clinic, better tolerability and better quality of life.Group II patients were more compliant in terms of patients receiving chemotherapy or completing radiotherapy. At median follow up of 6 months there was no statistical difference in terms of overall and disease-free survival. The statistical difference was seen in terms of patients expired in Group I (44%) as compared to Group II (16%). Therefore, we need a larger number of patients for the use of low dose Cisplatin to be evaluated in future clinical trials.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2299-2299
Author(s):  
Mary-Elizabeth Percival ◽  
Lloyd E. Damon ◽  
Thomas Martin ◽  
Lawrence Kaplan ◽  
Weiyun Ai ◽  
...  

Abstract Abstract 2299 Poster Board II-276 Introduction: Patients with low- and intermediate-risk AML have several options for consolidation therapy, including chemotherapy alone and ACST or AlloSCT. Since randomized studies comparing these approaches show no option to be clearly superior to the others, several centers focus on sequencing of therapies in terms of patient tolerance and toxicity. Since 1986 our preferred consolidation regimen at UCSF for these patients consists of high-dose chemotherapy with ASCT. Consequently, at the time of relapse, we are often presented with the need for a second transplant (usually AlloSCT), in the setting of prior ASCT. As there is a paucity of data describing the toxicity and efficacy of AlloSCT in this setting, we designed this study to evaluate these parameters. Patients and Methods: This is a retrospective-cohort, single-institution study of patients with AML treated at UCSF between 1986 and 2008 and who received a second transplant at the time of relapse. Patients were identified through our prospective database, and data were collected from electronic medical records and primary clinical charts when available. Dates of death were corroborated with the social security database. Statistical analysis was performed using STATA (v9). Censoring date for all analyses was July 31st, 2009. This study was approved by the UCSF institutional review board. Results: Thirty-one patients with AML were identified who underwent an AlloSCT in the setting of relapse following a prior ASCT, with a median follow up of 54 months. The median time from the first to the second transplant was 17 months (range: 6 – 48). The median age at the time of the AlloSCT was 43 years (range: 20 – 64). Response status at the time of transplant was: 17 patients (55%) in complete remission (CR), 12 patients (39%) with less than CR, and 2 patients (6%) with response status unknown. The transplant was myeloablative in 14 patients (45%), non-myeloablative in 13 patients (42%), and cord-blood-based in 4 patients (13%). The donor was unrelated in 17 patients (55%). There were 7 (18%) treatment-related deaths in the first 6 months and 10 (32%) treatment-related deaths overall (pulmonary toxicity: 4, graft-versus-host-disease: 3, and infection: 3). Twelve patients (39%) died due to progressive disease. The median overall survival was 7 months, with 48% and 31% of patients being alive at 12 and 24 months respectively. Remission status prior to transplant was the most significant predictor of survival; the median survival among complete responders vs. all others was 19 months vs. 3.5 months respectively (p=0.006). Following transplantation, the median relapse-free survival among responders was 38 months, with 31% of patients being relapse-free at last follow-up. The time between transplants, as well as age, sex, and intensity of conditioning regimen had no effect on overall and relapse-free survival in our cohort. However, peripheral stem cell transplant was associated with improved overall survival (compared to bone marrow, p=0.02), though this likely reflects different eras of supportive therapy. Conclusions: Our results suggest that AlloSCT is an effective approach for patients with AML with relapsed or refractory disease after a prior ASCT. In this cohort spanning 22 years, treatment-related mortality from AlloSCT was 32%, and 31% of responders remain free of relapse with long-term follow-up. Disclosures: No relevant conflicts of interest to declare.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 686-686
Author(s):  
Madiha Naseem ◽  
Joshua Murray ◽  
Christine E. Simmons ◽  
Nancy Baxter ◽  
Marcus J. Burnstein ◽  
...  

686 Background: Pathologic complete response (pCR) is associated with lower rates of recurrences and longer disease-free survival rates in locally advanced rectal cancer (LARC) patients. The purpose of this study was to evaluate clinical outcomes of neoadjuvant chemoradiation and pCR among these patients. Methods: A retrospective chart review was performed for all patients treated for LARC between August 2005 and May 2011 at St. Michael's Hospital, Toronto. Patients were stratified into pCR and no-pCR groups and compared with respect to tumor size, nodal status, and treatment characteristics. Descriptive statistics were calculated for all variables of interest. Chi-square and t-tests were conducted to test for associations between categorical and continuous variables respectively. Disease free survival was calculated as the time between diagnosis and recurrence date, censored at last follow up. Results: A total of 92 patient charts were reviewed; 21 patients had metastatic carcinoma and were excluded from analysis. 63.4% (45/71) were male, with a mean age of 61.2 years and median follow up of 15 months. 12.7% (9/71) of patients achieved a pCR, while the remaining 87.35% (62/71) were no-pCR. All pCR patients received and completed standard pre-operative chemotherapy-radiotherapy. 73.4% (52/71) of the patients had complications from chemoradiotherapy. Furthermore, there was a significant association between having a significant response to treatment and achieving a pCR; where 78% (7/9) of pCR patients had a significant response to treatment. Overall, 4/71 patients had a local recurrence, 22.2% (2/9) pCR and 3.2% (2/62) no-pCR. Those with no-pCR had a recurrence at 1 and 2.2 years post diagnosis, while those with pCR had a recurrence at 3.7 years. Conclusions: This study suggests that patients undergoing standard pre-operative chemoradiotherapy are likely to have a significant response and achieve a pCR. Based on this study, although a pCR does not prevent the risk of recurrence, it delays the onset of local recurrence. Longer follow-up is required to determine if these results are robust and to develop future studies to improve efficacy of treatment delivery in LARC patients.


2020 ◽  
Vol 33 (Supplement_2) ◽  
Author(s):  
Eline M de Groot ◽  
Sylvia van der Horst ◽  
B Feike Kingma ◽  
Lucas Goense ◽  
Pieter C van der Sluis ◽  
...  

ABSTRACT Initial results of the ROBOT, which randomized between robot-assisted minimally invasive esophagectomy (RAMIE) and open transthoracic esophagectomy (OTE), showed significantly better short-term postoperative outcomes in favor of RAMIE. However, it is not yet clarified if RAMIE is equivalent to OTE regarding long-term outcomes. The aim of this study was to report the long-term oncological results of the ROBOT trial in terms of survival and disease-free survival. This study is a follow-up study of the ROBOT trial, which was a randomized controlled trial comparing RAMIE to OTE in 112 patients with intrathoracic esophageal cancer. Both the trial protocol and short-term results were previously published. The primary outcome of the current study was 5-year overall survival. Secondary outcomes were disease-free survival and recurrence patterns. Analysis was by intention to treat. During the recruitment period, 109 patients were included in the survival analysis (RAMIE n = 54, OTE n = 55). Majority of patients had clinical stage III or IV (RAMIE 63%, OTE 55%) and received neoadjuvant chemoradiotherapy (80%). Median follow-up was 60 months (range 31–60). The combined 5-year overall survival rates for RAMIE and OTE were 41% (95% CI 27–55) and 40% (95% CI 26–53), respectively (log rank test P = 0.827). The 5-year disease-free survival rate was 42% (95% CI 28–55) in the RAMIE group and 43% (95% CI 29–57) in the OTE group (log rank test P = 0.749). Out of 104 patients, 57 (55%) developed recurrent disease detected at a median of 10 months (range 0–56) after surgery. No statistically difference in recurrence rate nor recurrence pattern was observed between both groups. Overall survival and disease-free survival of RAMIE are comparable to OTE. These results continue to support the use of robotic surgery for esophageal cancer.


2016 ◽  
Author(s):  
S. Singh ◽  
V. Goel ◽  
V. Talwar ◽  
S. Raina ◽  
S. Mitra ◽  
...  

Background: Cervical cancer is ranked as the most common cancer in Indian women, second most common cancer worldwide and the leading cause of death in the developing countries. In the developing countries majority of the patients are diagnosed at locally advanced stages. The standard treatment of locally advanced cervical cancer is concomitant chemoradiation (CTRT) using platinum based chemotherapy. However, some randomized studies have shown improved results for patients receiving neoadjuvant chemotherapy (NACT) followed by surgical resection in comparison to patient receiving radiation alone. The present study was designed to compare response to the treatment and survival of and NACT followed by radical surgery (RS) with CTRT in the patients of uterine cervix of a tertiary cancer care centre. Patients and Methods: Retrospective study was performed in locally advanced/advance stage patients of cervix UTERI registered in the institute between years 2009 to 2013. Patients were included in the two groups, group A consists of 89 patients who have received NACT + RS and 67 patients in group B who have received CTRT. Clinical records were reviewed with particular reference to presenting complaint, clinical stage, response to the therapy, disease free survival and overall survival. Statistical analysis was done using SPSS version 22. Results: In the neoadjuvant group (group A) (n=89) the median age of patients was 53 years (range 31-80 years), most of the patients (70%) were presented with complaint of postmenopausal bleeding. Of the total patients, 69 (77.5%) underwent to radical surgery and 5 (8.5%) received radiotherapy after NACT. From 69 patients, who had undergone to surgery, 54 (78.3%) had also received radiation. The overall response to induction chemotherapy was 84%. In the chemo radiation group (group B) (n=65) median age was 56 years (33-75 years). Vaginal bleeding (34%) followed by postmenopausal bleeding (32%) was major presenting complaint in this group. Overall response to the complete treatment was 91%. The median follow up time was 14.3 months in group A and 12.2 months in group B. The disease free survival for NACT group was 32 months (95% CI 26.8-36.5) whereas for CTRT group it was 28 months (95% CI 23.5-33) with 12 and 13 recurrences per group (p = .226). In NACT group overall survival was 46.2 months (95% CI 44-48.3) and for CTRT group it was 38.3 months (95%CI 36.6-40) with 3 and 2 deaths per group (p=.883). Conclusion: Present study shows comparable results, with no difference in survival between both the groups. However, NACT + RS group had showed better disease free and overall survival than another group. Further studies should be performed with larger number of patients and longer duration of follow up.


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