Tolerability of neoadjuvant chemotherapy with gemcitabine plus cisplatin in elderly (older than age 65) patients (pts) with muscle-invasive urothelial cancer.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 296-296
Author(s):  
D. Niedersuess-Beke ◽  
B. Gruenberger ◽  
T. Puntus ◽  
W. Bauer ◽  
M. Lamche ◽  
...  

296 Background: Urothelial cancer (UC) is a common tumor with a peak in the seventh decade. Locally advanced disease has a significant risk for developing metastases. Neoadjuvant, platinum-containing, combination chemotherapy improves survival over radical cystectomy (RC). Chemotherapy with gemcitabine plus cisplatin (GC) shows equivalent efficacy with less toxicity to methotrexate-vinblastine-doxorubicin- cisplatin (MVAC) in metastatic setting. Methods: We prospectively evaluated 23 elderly pts (8 female, 15 male) with a median age of 72 years, WHO performance status 0/1, with muscle invasive UC who received neoadjuvant GC (gemcitabine 1,000 mg/m2 days 1, 8, 15 and cisplatin 70 mg/m2, day 2 q28) for 3 cycles between 2006 and 2010 prior to RC. Assessments included toxicity of GC, pathologic response, progression free survival (PFS) and overall survival (OS). Results: 21 (91.3%) out of 23 pts finished intended chemotherapy. Two refused chemotherapy due to personal reasons. According to CTCAE guidelines 43.5% developed grade 3 hematologic toxicities; 13% developed grade 4 thrombopenia. Grade 3 non-hematologic toxicities included nausea in 2 patients. In 2 (8.7%) pts grade 4 thromboembolic events occurred. There was no treatment related febrile neutropenia or death. 15 (71.4%) of the pts underwent RC. 5 (23.8%) pts refused RC due to personal reasons. 1 of them agreed second look TURB. 1 patient underwent palliative radiotherapy due to progression of disease. Out of the 16 pts 43.75% achieved pathological response (18.75% pT0 stage and 25% pT1 stage). 56.25% had muscle invasive UC. 18.75% of them nodal positive disease. All 7 pts achieving < pT2 pathologic stage remained progression-free at a median follow up of 16 months. Pts > pT2 stage had a median PFS of 14 months. Median OS was not reached yet. Conclusions: Neoadjuvant GC is a well tolerated regiment in elderly pts and it seems to be less toxic than MVAC. Prophylactic anticoagulation during treatment should be considered. Although pathologic response is lower than in previously published retrospective data we recommend neoadjuvant treatment with GC in elderly pts. [Table: see text]

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 160-160 ◽  
Author(s):  
Shaun P. Tolan ◽  
Peter Mbanu ◽  
Richard C. Walshaw ◽  
Peter Robson ◽  
Chinnamani Eswarvee ◽  
...  

160 Background: In the current era of PSA screening and advances in image guided intensity modulated radiotherapy, not all patients with carcinoma of the prostate (CaP) are suitable for radical radiotherapy (RT). Some patients have locally advanced disease and are unfit for radical RT or have significant local symptoms with coexisting metastatic disease. The outcomes of a weekly palliative RT schedule of 6 x 5 or 6Gy fractions are reported. Methods: This retrospective analysis identified 80 patients with CaP who received palliative prostate RT between 2003 and 2007. 62 patients received six, weekly fractions of 3D conformal RT and are included in this study. Clinico-pathological data of the cases are presented along with the clinical outcomes and survival data. Median follow up was 16.5 months. Results: 62 patients (median age 70 yrs), received 30Gy (87%) or 36Gy (10%) in 6 fractions over 6 weeks. Two patients received 27Gy. Gleason score at diagnosis was ≤6, 7, or 8–10 in 21%, 16% and 45% of cases respectively and was associated with a median PSA of 53ng/ml, and T3/4 stage in 59%. The median time from diagnosis to RT was 15.9 months and prior to RT, treatment included hormone therapy (100%), TURP (60%) and chemotherapy (13%). Disease was metastatic in 68% and castrate resistant in 77% of cases. ECOG performance status was 0–1 in 44% and 2–3 in 24%. No patients with PS 4 were treated over 6 weeks. Indications for RT were obstructive urinary symptoms (69%), pain (44%), haematuria (35%), obstructive bowel symptoms (23%), and rectal bleeding (2%). At 3–6 months post-RT the frequency of these symptoms was 27%, 13%, 4%, 17% and 2% respectively. RTOG grade 3 or 4 bladder toxicity was 18% and grade 3 or 4 bowel toxicity was 6%. Median overall survival after RT was 16.0 months and on multivariate analysis lower pre-RT PSA and prior use of chemotherapy were predictive of improved survival. Conclusions: A weekly fractionation schedule of 5 or 6Gy over 6 weeks provides effective palliation, particularly for the symptoms of urinary obstruction, pain and haematuria, and is associated with acceptable toxicity. The prognosis of this group of patients remains poor, but can be improved by the use of chemotherapy if clinically appropriate.


2006 ◽  
Vol 24 (21) ◽  
pp. 3451-3457 ◽  
Author(s):  
Christopher J. Sweeney ◽  
Bruce J. Roth ◽  
Fairooz F. Kabbinavar ◽  
David J. Vaughn ◽  
Michael Arning ◽  
...  

Purpose To assess the antitumor activity and toxicity of pemetrexed as second-line chemotherapy in patients with locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium. Patients and Methods Eligible patients had a performance status of 0 or 1, adequate organ function, previous treatment with one prior chemotherapy regimen for locally advanced or metastatic TCC of the urothelium or relapsed within 1 year of adjuvant or neoadjuvant treatment. Patients received pemetrexed 500 mg/m2 intravenously on day 1 every 21 days, with vitamin B12, folic acid, and dexamethasone prophylaxis. Results Forty-seven patients were enrolled and included in the intent-to-treat efficacy analysis. Responses: 3 (6.4%) complete responses and 10 (21.3%) partial responses produced an overall response rate of 27.7%. Ten patients (21.3%) had stable disease and 22 patients (46.8%) progressed. The median time to progressive disease was 2.9 months (95% CI, 1.7 months to 4.6 months) and median overall survival was 9.6 months (95% CI, 5.1 months to 14.6 months). Median duration of response was 5.0 months (95% CI, 3.9 months to 13.8 months). Of the 47 patients assessable for safety, grade 3 or 4 hematologic events were thrombocytopenia (8.5%; 0.0%), neutropenia (4.3%; 4.3%) and anemia (2.1%; 2.1%), respectively. Nonlaboratory toxicities included grade 4 stomatitis/pharyngitis, sepsis syndrome (one patient each), and grade 3 fatigue (three patients) and diarrhea (two patients). Conclusion Single-agent pemetrexed is safe and active as second-line treatment of patients with advanced TCC of the urothelium. Additional evaluation in the first- or second-line setting in TCC of the urothelium is warranted.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 421-421 ◽  
Author(s):  
Mathias Alline ◽  
Pierre Emmanuel Colombo ◽  
François Quenet ◽  
Marta Jarlier ◽  
Fabienne Portales ◽  
...  

421 Background: FOLFIRINOX has already demonstrated its efficiency in metastatic pancreatic cancer (PC). This combination need to be assessed in a neoadjuvant situation for locally advanced non metastatic PC. Methods: From 2009 to 2013, 31 patients with borderline or locally advanced PC received a neoadjuvant treatment with FOLFIRINOX so as to get them to a resectable situation. According to the tumoral response, chemoradiotherapy with gemcitabine was done. The primary analysis endpoint was the resecability rate. Pathologic response, chemotherapy’s toxicity and surgical morbidity were also evaluated. Results: Among the 31 PC, 17 were borderline resectable and 14 locally advanced according to NCCN classification. 16 (52%) received complete chemotherapy with a median of 4 cycles. Toxicity lead to treatment modification or interruption for 9 patients (29%). Grade 3-4 toxicity occurred in 7 patients (24%). 22 patients (71%) underwent chemoradiotherapy after FOLFIRINOX chemotherapy. 13 patients (42%) had disease progression under treatment whereas 18 patients with objective radiologic response or at least stable disease were surgically explored with a resection completed in 13 cases (42%). Surgical morbidity was controlled with grade 1-2 complications for 9 patients (69%) and no mortality. 11 patients (35%) demonstrated a significant pathologic response. Resected patients had a global survival median of 36 months. Conclusions: FOLFIRINOX in a neoadjuvant setting seems feasible with limited morbidity in locally advanced PC with encouraging resecability and pathologic response rates. Resected patients’ survival is promising but need to be confirmed in larger series.


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS596-TPS596
Author(s):  
Roberto Iacovelli ◽  
Sebastiano Buti ◽  
Consuelo Buttigliero ◽  
Rocco De Vivo ◽  
Claudia Caserta ◽  
...  

TPS596 Background: Urothelial cancer (UC) is the ninth most common cancer worldwide, this tumour has a poor prognosis when in advanced stage. Cisplatin-based chemotherapy is considered the most effective treatment but more than 50% of patients are considered not eligible ( cis-unfit) for this regimen and have a median survival of only 6-9 months. In the past years, the most used chemotherapy regimen for cis-unfit patients was the combination of carboplatin and gemcitabine. Two single arm studies tested the anti-PD-L1/PD1 monoclonal antibodies atezolizumab and pembrolizumab and reported a response rate of 25% with good safety profile in an unselected population for PD-L1 expression. Recently, atezolizumab alone showed longer OS compared to carboplatin-gemcitabine regimen. Avelumab is another fully human anti-PD-L1 IgG1 antibody already tested in urothelial and in other cancers with a promising safety and efficacy profile. Methods: The single arm, phase II ARIES trial (NCT03891238), aims to evaluate the activity and efficacy of avelumab in patients with metastatic or locally advanced UC considered cis-unfit with PD-L1 expression ≥5%. Overall survival is the primary endpoint. Cis-unfit definition includes at least one of the following characteristics (i) ECOG-Performance status=2; (ii) creatinine clearance <60 ml/min; (iii) grade ≥2 peripheral neuropathy or hearing loss; (iv) disease progression within six months after a previous adjuvant/neoadjuvant treatment with cisplatin-based therapy. Avelumab will be administered at standard dose of 10 mg/kg in 1-hour intravenous infusion every 2 weeks (Q2W). Sixty-seven patients will be enrolled, and supportive care is allowed during the study. Avelumab may be continued after radiological progression of disease at physician’s discretion if an improvement of symptoms or not new symptoms will be reported. The study is currently ongoing in twenty centres in Italy. Clinical trial information: NCT03891238.


2012 ◽  
Vol 30 (28) ◽  
pp. 3545-3551 ◽  
Author(s):  
Yu-Ning Wong ◽  
Samuel Litwin ◽  
David Vaughn ◽  
Seth Cohen ◽  
Elizabeth R. Plimack ◽  
...  

Purpose The benefit of salvage chemotherapy is modest in metastatic urothelial cancer. We conducted a randomized, noncomparative phase II study to measure the efficacy of cetuximab with or without paclitaxel in patients with previously treated urothelial cancer. Patients and Methods Patients with metastatic urothelial cancer who received one line of chemotherapy in the perioperative or metastatic setting were randomly assigned to 4-week cycles of cetuximab 250 mg/m2 with or without paclitaxel 80 mg/m2 per week. We used early progression as an indicator of futility. Either arm would close if seven of the initial 15 patients in that arm progressed at the first disease evaluation at 8 weeks. Results We enrolled 39 evaluable patients. The single-agent cetuximab arm closed after nine of the first 11 patients progressed by 8 weeks. The combination arm completed the full accrual of 28 patients, of whom 22 patients (78.5%) had visceral disease. Twelve of 28 patients had progression-free survival greater than 16 weeks. The overall response rate was 25% (95% CI, 11% to 45%; three complete responses and four partial responses). The median progression-free survival was 16.4 weeks (95% CI, 12 to 25.1 weeks), and the median overall survival was 42 weeks (95% CI, 30.4 to 78 weeks). Treatment-related grade 3 and 4 adverse events that occurred in at least two patients were rash (six cases), fatigue (five cases), and low magnesium (three cases). Conclusion Although it had limited activity as a single agent, cetuximab appears to augment the antitumor activity of paclitaxel in previously treated urothelial cancers. The cetuximab and paclitaxel combination merits additional study to establish its role in the treatment of urothelial cancers.


2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Feng Wang ◽  
Yu Qi ◽  
Xiangrui Meng ◽  
Qingxia Fan

Abstract   At present, ESCC has a dismal prognosis with huge unmet clinical needs. With the potential benefit of combining PD-1 inhibitor with nCT, we conducted a phase II trial to assess the efficacy and safety of Camrelizumab plus nCT for locally advanced ESCC. Methods 45 patients (pts) with histologically confirmed stage II/III/IVa(cT2-4aN0-3 M0) ESCC were enrolled from February 2020 to March 2021.The study was divided into two stages, stage1: we administered 1 cycle of Camrelizumab for induction therapy (200 mg q2 weeks); stage2: pts received 2 cycle of Camrelizumab (200 mg every 3 weeks) plus docetaxel and nedaplatin, followed by surgery within 4 ~ 6 weeks after neoadjuvant therapy completion. Primary endpoint was major pathologic response (MPR). Secondary endpoints included pathologic complete response (pCR), R0 resection rate, disease-free survival (DFS) and overall survival (OS). Results At the cutoff date of Mar 9, 2021, 45 eligible pts were enrolled, neoadjuvant treatment was completed in 39 pts. Thus far 32 pts were resected, all patients underwent an R0 resection. Postoperative pathology showed that TNM stage decreased in 28 pts with 87.5% reduction rate. 19 pts (59.38%) reached major pathologic response, 9 pts (28.13%) reached pathologic complete response (no surgery related mortality). A total of 75.56% had AEs with 13.33% of grade ≥ 3 AEs. Date for median DFS and OS were not matured. Conclusion Camrelizumab in combination with preoperative chemotherapy followed by surgery for locally advanced ESCC showed promising downstaging effect and MPR with good tolerance, and its efficacy and safety could be further studied in later trials. Clinical trial information: NCT03917966.


2010 ◽  
Vol 28 (6) ◽  
pp. 976-983 ◽  
Author(s):  
Andrew M. Wardley ◽  
Xavier Pivot ◽  
Flavia Morales-Vasquez ◽  
Luis M. Zetina ◽  
Maria de Fátima Dias Gaui ◽  
...  

PurposeTo evaluate trastuzumab (H) and docetaxel (T) with or without capecitabine (X) as first-line combination therapy for human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer.Patients and MethodsPatients with HER2-positive locally advanced or metastatic breast cancer were randomly assigned to H (8 mg/kg loading; 6 mg/kg every 3 weeks) plus T (75 mg/m2in HTX arm, 100 mg/m2in HT arm, every 3 weeks) with or without X (950 mg/m2twice per day on days 1 to 14 every 3 weeks). The primary end point was overall response rate (ORR).ResultsIn 222 patients, median follow-up was approximately 24 months. ORR was high with both regimens (70.5% with HTX; 72.7% with HT; P = .717); complete response rate was 23.2% with HTX compared with 16.4% with HT. HTX demonstrated significantly longer progression-free survival: median 17.9 months compared with 12.8 months with HT (hazard ratio, 0.72; P = .045), which translates to a gain of around 5 months. Two-year survival probability was 75% with HTX compared with 66% with HT. Febrile neutropenia (27% v 15%) and grade 3/4 neutropenia (77% v 54%) incidences were higher with HT than HTX. Treatment-related grade 3 hand-foot syndrome (17% v < 1%) and grade 3/4 diarrhea (11% v 4%) occurred more commonly with HTX than HT. One case of congestive heart failure occurred in each arm.ConclusionHTX is an effective and feasible first-line therapy for HER2-positive locally advanced or metastatic breast cancer, although it should be reserved for patients with good performance status who are not receiving long-term steroids.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16029-e16029
Author(s):  
Delin Liu ◽  
Qin Zhang ◽  
Jinghua Zhu ◽  
Ting Qian ◽  
Rong Yin ◽  
...  

e16029 Background: Compared with neoadjuvant chemotherapy alone,Neoadjuvant radiochemotherapy can significantly increase pCR rate in esophageal squamous cell carcinoma and improve patient overall survival. However, the addition of radiotherapy increases the risk of adverse reactions and surgery. Neoadjuvant radiochemotherapy is currently used in < 5% of Chinese patients.The purpose of this phase II study is to assess the efficacy and safety of toripalimab combined with paclitaxel and cisplatin as neoadjuvant treatment for resectable locally advanced esophageal squamous cell carcinoma(clinical trial registration number: ChiCTR1900025318). Methods: Patients 18–75 years old with esophageal squamous cell carcinoma confirmed by endoscopic biopsy, assessed to be locally advanced esophageal squamous cell carcinoma (cT1–cT2, N+; cT3–cT4 a, any N), and expected to be resectable were given toripalimab (240 mg d1 + PTX 175 mg/m2 + PDD 75 mg/m2 q3w) before surgery for two treatment cycles, followed by efficacy assessment. A consultation meeting with thoracic surgeons was held to assess radical surgery for patients with resectable lesions 4–6 weeks after neoadjuvant therapy was completed. pCR and postoperative-stage statistical analysis were conducted based on postoperative pathology test results. These results were used to determine the efficacy and safety of PD-1 monoclonal antibody combined with chemotherapy as neoadjuvant therapy for locally advanced esophageal cancer. Results: By December 2020, 23 subjects were enrolled. Of the subjects, five withdrew without undergoing surgery (three subjects refused surgery and switched to radical radiochemotherapy, one subject progressed to PD after two cycles of neoadjuvant therapy and switched to palliative treatment, and one subject could not undergo surgery after neoadjuvant treatment and gave up the treatment) and 18 evaluable patients underwent surgery. The R0 resection rate was 100%, and T0–Tis 33.3% (6/18) achieved pCR. Among these patients, 61.1% (11/18) achieved T0–T1 after surgery, and 72.2% (13/18) achieved N0. Moreover, stage reduction effects were significant compared with preoperative TN staging. Common side-effects include nausea, vomiting, neutropenia, thrombocytopenia, rash, asthenia, constipation, and muscle soreness. Most adverse events were grades 1–2, and grades 3/4 adverse events include one case of grade 3 neutropenia and one case of grade 3 diarrhea (suspected immune-related colitis), which improved after symptomatic treatment. Conclusions: Toripalimab combined with the TP scheme showed preliminary efficacy and controllable safety in the treatment of resectable locally advanced esophageal squamous cell carcinoma and is worthy of further exploration. Clinical trial information: ChiCTR1900025318.


Chemotherapy ◽  
2020 ◽  
Vol 65 (1-2) ◽  
pp. 29-34
Author(s):  
Noriko Takahashi ◽  
Tomiko Sunaga ◽  
Tatsuhiro Fujimiya ◽  
Tatsuya Kurihara ◽  
Akiko Nagatani ◽  
...  

Introduction: Combination chemotherapy of gemcitabine and cisplatin (GC) is the standard treatment for patients with urothelial cancer (UC). However, hematological toxicity is a major side effect of GC therapy in patients with UC. In particular, discontinuation of the GC therapy is associated to adverse events such as hematological toxicity. Some studies have reported general risk factors of hematological toxicity such as age. However, little is known about risk factors for GC therapy-associated hematological toxicity in patients with UC. Objective: We aimed to identify risk factors for hematological toxicity in patients with UC receiving GC therapy. Methods: We performed a retrospective evaluation of the data of 128 patients with UC who received GC therapy. The study end point was defined as the occurrence of grade 4 neutropenia and grade ≥3 thrombocytopenia. Logistic regression analysis was used to determine risk factors that were significantly associated with neutropenia and thrombocytopenia. Results: In total, 62 (48.4%) patients experienced grade 4 neutropenia, and 27 (21.1%) patients experienced grade ≥3 thrombocytopenia. In the multivariate analysis, performance status (PS) ≥1 (odds ratio [OR] 3.764, 95% confidence interval [CI] 1.410–10.047, p = 0.008) and neutrophil count (OR 0.648, 95% CI 0.468–0.898, p = 0.009) were significantly associated with grade 4 neutropenia. Platelet count (PLT) (OR 0.896, 95% CI 0.832–0.966, p = 0.004) and potassium (K) level (OR 6.966, 95% CI 1.313–36.989, p = 0.023) were also significantly associated with grade ≥3 thrombocytopenia. Conclusions: PS ≥ 1, neutrophil count, PLT, and K level were important risk factors for GC therapy-induced hematological toxicity in patients with UC. To continue GC therapy, further management systems by hematological toxicity risk factors for patients with UC will be required.


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