scholarly journals Trimodality therapy for stage II-III carcinoma of the esophagus: A dose-ranging study of concurrent capecitabine, docetaxel, and thoracic radiotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14514-e14514
Author(s):  
Matthew D. Wood ◽  
Bassem I. Zaki ◽  
Stuart R. Gordon ◽  
John E. Sutton ◽  
Mikhail Lisovsky ◽  
...  
Keyword(s):  
Esophageal Carcinoma ◽  
Phase Ii ◽  
Locally Advanced ◽  
Stage Ii ◽  
Thoracic Radiotherapy ◽  
Trimodality Therapy ◽  
Weekly Docetaxel ◽  
Dose Ranging ◽  
Grade 3 ◽  
Recommended Phase Ii Dose

e14514 Background: This dose escalation study was performed to determine the recommended phase II dose of capecitabine to be delivered concurrently with thoracic radiation therapy and weekly docetaxel in patients with locally advanced esophageal carcinoma. Methods: Patients with operable stage II or III esophageal carcinoma were staged by endoscopic ultrasonography and CT. Two cycles of docetaxel (80 mg/m2) and carboplatin (target AUC of 6) were delivered over 6 weeks, followed by concurrent weekly docetaxel (15 mg/m2), thoracic radiotherapy (50.4 Gy in 28 fractions), and increasing doses of capecitabine (500-3500 mg) given prior to each fraction of radiotherapy. After re-staging, responding patients continued to esophagectomy. Results: Forty-four patients were enrolled and 40 were evaluable for the dose-ranging component of chemoradiotherapy. The median age was 63 (range 47-87), 32 patients (80%) were male, and 36 (90%) had adenocarcinoma while 4 (10%) had squamous cell carcinoma. EUS stages at enrollment were T3N1 (29), T3N0 (4), T2N1 (6), and T4N0 (1). The maximum tolerated dose of capecitabine was 3500 mg. Common non-hematologic grade 3 or 4 toxicities were dysphagia (n=6, 15%) and nausea/vomiting (n=3, 8%). Common grade 3 or 4 hematologic toxicities were ANC and WBC abnormalities (n=10, 25% and n=9, 23% respectively). Overall, 58% of patients had no stage 3 or 4 toxicity. Thirty-six patients had surgery; 83% had R0 (curative) resection and 14% had complete pathological response (pCR). With a median follow-up time of 18.9 months, the median overall survival was 23.5 months, with 34% and 27% alive at three and five years, respectively. The three- and five-year relapse-free survival was 37%. In patients who had pCR or microscopically residual disease, 5-year survival was 74% (n=8). Conclusions: The recommended phase II dose of capecitabine is 3500 mg when given concurrently with 50.4 Gy in 28 fractions of thoracic radiotherapy with weekly docetaxel. This trimodality therapy for locally advanced esophageal carcinoma was well-tolerated and remarkably active. This regimen holds promise for treatment of esophageal carcinoma and warrants further investigation.

Survival and toxicity with intensity modulated radiation therapy (IMRT) and chemotherapy for esophageal carcinoma, with or without surgery.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 125-125
Author(s):  
Kristin Kowalchik ◽  
Elizabeth Johnson ◽  
George P. Kim ◽  
C. Daniel Smith ◽  
Siyong Kim ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Acute Toxicity ◽  
Esophageal Carcinoma ◽  
Locally Advanced ◽  
Late Toxicity ◽  
Concurrent Chemotherapy ◽  
Conformal Radiation Therapy ◽  
Trimodality Therapy ◽  
Grade 3 ◽  
3D Crt

125 Background: Treatment for locally advanced esophageal carcinoma is radiation and chemotherapy, with or without surgery. Radiation has traditionally been delivered with 3D conformal radiation therapy (3D CRT). This study evaluates late toxicity in patients treated with IMRT as well as early outcomes and acute toxicity. Methods: This is a retrospective review of 32 patients with esophageal carcinoma treated with IMRT at Mayo Clinic Florida from 2008 -2012. Pathology includes squamous cell and adenocarcinomas. Tumor sites include middle and lower thoracic and GE junction. Clinical stages are TX-T3, N0-3, M0-1. All patients received at least one cycle of concurrent chemotherapy. IMRT dose was 50.4 Gy in 28 fractions prescribed to a target volume including the tumor and regional lymphatics. IMRT plans utilized coplaner beams in a 7-9 beam arrangement or volumetric modulated arc therapy. Results: Median follow-up is 8.9 months (range 2.4-23.0) for all patients and 13.1 months (range 2.8-23.0 months) in surviving patients. Median patient age is 69 (range 46-87). Trimodality treatment was completed in 20 patients (62.5%). Surgery was either an open or minimally invasive esophagogastrectomy. The incidence of grade 3 or greater late toxicity at 1 year was 48% in surgery patients and 26% in non-surgery patients. The most common grade 3 or higher toxicity was esophageal strictures in 25%. The incidence of any grade 3 or greater acute toxicity was 65% in the surgery patients and 75% in the non-surgery patients. Overall survival (OS) for all patients at 18 months is 57% (CI 37-86%) and progression-free survival (PFS) is 60% (36-99%). OS and PFS for trimodality therapy at 12 months is 83% (66-100%) and 81% (63-100%) respectively and for bimodality therapy is 34% (12-93%) and 70% (33-100%) respectively. Conclusions: Increased late toxicity occurs in surgery patients, and increased acute toxicity in non-surgery patients. Lower survival in non-surgery patients may be due to early progression, morbidities which preclude surgery or improved survival with surgery. Overall, IMRT is a feasible treatment modality, which may be equally efficacious to 3D CRT for the treatment of esophageal carcinoma.

scholarly journals Trimodality Therapy for Stage II–III Carcinoma of the Esophagus: A Dose-Ranging Study of Concurrent Capecitabine, Docetaxel, and Thoracic Radiotherapy

2013 ◽  
Vol 8 (4) ◽  
pp. 487-494 ◽  
Author(s):  
Matthew D. Wood ◽  
Bassem I. Zaki ◽  
Stuart R. Gordon ◽  
John E. Sutton ◽  
Mikhail Lisovsky ◽  
...  
Keyword(s):  
Stage Ii ◽  
Thoracic Radiotherapy ◽  
Trimodality Therapy ◽  
Carcinoma Of The Esophagus ◽  
Dose Ranging

Phase II study of postoperative chemoradiotherapy for esophageal carcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15606-e15606
Author(s):  
S. Wu ◽  
X. Deng ◽  
P. Zhang ◽  
C. Xie ◽  
X. Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Esophageal Carcinoma ◽  
Distant Metastasis ◽  
Postoperative Radiotherapy ◽  
Locally Advanced ◽  
Multimodality Treatment ◽  
Preoperative Chemoradiotherapy ◽  
Stage Ii ◽  
Free Survival ◽  
Grade 3

e15606 Background: Esophageal squamous cell carcinoma is still a virulent disease diagnosed at late stage and remains a major cause of carcinoma mortality in China. The preoperative chemoradiotherapy had been applied to patients with esophageal carcinoma in an effort to reduce the relapse and improve survival. However, randomized controlled trails have shown conflicting results. Intergroup study 0116 demonstrated that postoperative chemoradiotherapy significantly improved overall survival in gastric carcinoma patients. The question remains whether postoperative chemoradiotherapy can improve overall survival in patients with esophageal carcinoma. Our planning study was to investigate the role of postoperative chemoradiotherapy in the multimodality treatment for locally advanced esophageal carcinoma. Methods: From October 2000 to October 2007, Fifty-two patients who underwent esophagectomy with stage II-III esophageal carcinoma were enrolled. All patients received 50Gy of postoperative radiotherapy over 25 fractions in 5 weeks. Two cycles of chemotherapy (Paclitaxel 135mg/m2 d1,cisplatin 20mg/m2d1–3) were administered concurrently on days 1–3 and days 29–31 of radiotherapy. Results: Of the total 52 patients, 28 (54%) developed grade 3 or 4 toxicity.At the time of analysis, 23 patients died. The median follow-up for surviving patients was 23.5 months. The median survival time was 37.2 months. Incidences of tumor recurrence were 53.8 % (28/52) of patients. As expected, distant metastasis was predominant. The 2-year local-regional control survival, distant metastasis-free survival and relapse-free survival were 60.01%, 71.38% and 42.01%, respectively. 1-year and 3-year overall survival were 82.19% and 47.13%, respectively. Conclusions: This novel postoperative chemoradiation regimen for treatment of patients with stage II-III esophageal cancer has a tolerable toxicity and promising 3-year overall survival. No significant financial relationships to disclose.

Carboplatin, S-1 and concurrent thoracic radiotherapy for elderly patients with locally advanced non-small cell lung cancer: a multicenter Phase I/II study

2019 ◽  
Vol 49 (7) ◽  
pp. 614-619 ◽  
Author(s):  
Seiji Niho ◽  
Yukio Hosomi ◽  
Hiroaki Okamoto ◽  
Keiji Nihei ◽  
Hiroshi Tanaka ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Elderly Patients ◽  
Phase I ◽  
Phase Ii ◽  
Radiation Pneumonitis ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Small Cell ◽  
Thoracic Radiotherapy ◽  
Small Cell Lung

Abstract Objectives We conducted a Phase I/II study of carboplatin, S-1 and concurrent thoracic radiotherapy (TRT) for elderly patients (71 years or older) with unresectable stage III non-small cell lung cancer (NSCLC). Materials and methods Patients received carboplatin (AUC 3-5) on Day 1 and S-1 (30–40 mg/m2 two times daily) on Days 1–14, every 2 weeks, for up to four cycles, plus concurrent TRT at a total dose of 60 Gy. The primary endpoint for the Phase II study was the 1-year progression-free survival (PFS) rate. Results Eighteen patients were enrolled in the Phase I study. Febrile neutropenia, a decreased platelet count and esophagitis were dose-limiting toxicities. The recommended doses for the Phase II study were determined to be an AUC of 3 for carboplatin, 40 mg/m2 twice daily for S-1. Twenty-eight patients were evaluated in the Phase II study. The 1-year PFS rate was 57.1% (90% CI 41.6–71.4%), and the median PFS was 16.8 months (95% CI 7.8–not assessable [NA]). The lower limit of the 90% CI for 1-year PFS exceeded the prespecified threshold value of 30%; therefore, the primary endpoint was met. Grades 3–4 toxicities included thrombocytopenia (21%) and hyponatremia (11%). Grade 3 radiation pneumonitis was observed in 18% of patients. No treatment-related deaths were observed. Conclusion Combination chemotherapy consisting of carboplatin plus S-1 and concurrent TRT had a promising efficacy in elderly patients with locally advanced NSCLC; however, radiation pneumonitis was frequently observed.

Phase I Trial of Escalating-Dose Irinotecan Given Weekly With Cisplatin and Concurrent Radiotherapy in Locally Advanced Esophageal Cancer

2003 ◽  
Vol 21 (15) ◽  
pp. 2926-2932 ◽  
Author(s):  
David H. Ilson ◽  
Manjit Bains ◽  
David P. Kelsen ◽  
Eileen O’Reilly ◽  
Martin Karpeh ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Phase I ◽  
Induction Chemotherapy ◽  
Phase Ii ◽  
Phase I Trial ◽  
Locally Advanced ◽  
Phase Iii ◽  
Concurrent Radiotherapy ◽  
Minimal Toxicity ◽  
Grade 3

Purpose: To identify the maximum-tolerated dose and dose-limiting toxicity (DLT) of weekly irinotecan combined with cisplatin and radiation in esophageal cancer. Patients and Methods: Nineteen patients with clinical stage II to III esophageal squamous cell or adenocarcinoma were treated on this phase I trial. Induction chemotherapy with weekly cisplatin 30 mg/m2 and irinotecan 65 mg/m2 was administered for four treatments during weeks 1 to 5. Radiotherapy was delivered weeks 8 to 13 in 1.8-Gy daily fractions to a dose of 50.4 Gy. Cisplatin 30 mg/m2 and escalating-dose irinotecan (40, 50, 65, and 80 mg/m2) were administered on days 1, 8, 22, and 29 of radiotherapy. DLT was defined as a 2-week delay in radiotherapy for grade 3 to 4 toxicity. Results: Minimal toxicity was observed during chemoradiotherapy, with no grade 3 or 4 esophagitis, diarrhea, or stomatitis. DLT caused by myelosuppression was seen in two of six patients treated at the 80-mg/m2 dose level, thus irinotecan 65 mg/m2 was defined as the recommended phase II dose. Dysphagia improved or resolved after induction chemotherapy in 13 (81%) of 16 patients who reported dysphagia before therapy. Only one patient (5%) required a feeding tube. Six complete responses (32%) were observed, including four pathologic complete responses in 15 patients selected to undergo surgery (27%). Conclusion: Cisplatin, irinotecan, and concurrent radiotherapy can be administered on a convenient schedule with relatively minimal toxicity and an acceptable rate of complete response in esophageal cancer. Further phase II evaluation of this regimen is ongoing. A phase III comparison to fluorouracil or taxane-containing chemoradiotherapy should be considered.

scholarly journals A Phase II Trial of Adjuvant Durvalumab Following Trimodality Therapy for Locally Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma: A Big Ten Cancer Research Consortium Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Hirva Mamdani ◽  
Bryan Schneider ◽  
Susan M. Perkins ◽  
Heather N. Burney ◽  
Pashtoon Murtaza Kasi ◽  
...  
Keyword(s):  
T Cells ◽  
Adverse Events ◽  
Phase Ii ◽  
Residual Disease ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
M2 Macrophages ◽  
Activated T Cells ◽  
Trimodality Therapy ◽  
Surgical Specimen

BackgroundMost patients with resectable locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma (AC) receive concurrent chemoradiation (CRT) followed by esophagectomy. The majority of patients do not achieve pathologic complete response (pCR) with neoadjuvant CRT, and the relapse rate is high among these patients.MethodsWe conducted a phase II study (ClinicalTrials.gov Identifier: NCT02639065) evaluating the efficacy and safety of PD-L1 inhibitor durvalumab in patients with locally advanced esophageal and GEJ AC who have undergone neoadjuvant CRT followed by R0 resection with evidence of persistent residual disease in the surgical specimen. Patients received durvalumab 1500 mg IV every 4 weeks for up to 1 year. The primary endpoint was 1-year relapse free survival (RFS). Secondary endpoint was safety and tolerability of durvalumab following trimodality therapy. Exploratory endpoints included correlation of RFS with PD-L1 expression, HER-2 expression, and tumor immune cell population.ResultsThirty-seven patients were enrolled. The majority (64.9%) had pathologically positive lymph nodes. The most common treatment related adverse events were fatigue (27%), diarrhea (18.9%), arthralgia (16.2%), nausea (16.2%), pruritus (16.2%), cough (10.8%), and increase in AST/ALT/bilirubin (10.8%). Three (8.1%) patients developed grade 3 immune mediated adverse events. One-year RFS was 73% (95% CI, 56–84%) with median RFS of 21 months (95% CI, 14–40.4 months). Patients with GEJ AC had a trend toward superior 1-year RFS compared to those with esophageal AC (83% vs. 63%, p = 0.1534). There was a numerical trend toward superior 1-year RFS among patients with PD-L1 positive disease compared to those with PD-L1 negative disease, using CPS of ≥10 (100% vs. 66.7%, p = 0.1551) and ≥1 (84.2% vs. 61.1%, p = 0.1510) cutoffs. A higher relative proportion of M2 macrophages and CD4 memory activated T cells was associated with improved RFS (HR = 0.16; 95% CI, 0.05–0.59; p = 0.0053; and HR = 0.37; 95% CI, 0.15–0.93, p = 0.0351, respectively).ConclusionsAdjuvant durvalumab in patients with residual disease in the surgical specimen following trimodality therapy for locally advanced esophageal and GEJ AC led to clinically meaningful improvement in 1-year RFS compared to historical control rate. Higher PD-L1 expression may have a correlation with the efficacy of durvalumab in this setting. Higher proportion of M2 macrophages and CD4 memory activated T cells was associated with superior RFS.

Preliminary analysis of a U.S. phase II study of the safety and tolerability of proxalutamide (GT0918) in subjects with mCRPC who had progressed on either abiraterone (Abi) or enzalutamide (Enza).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 99-99
Author(s):  
Nicholas J. Vogelzang ◽  
Richard Levin ◽  
Arash Rezazadeh ◽  
Chandler H. Park ◽  
Britt Haley Bolemon ◽  
...  
Keyword(s):  
Phase Ii ◽  
Lipid Lowering ◽  
Early Discontinuation ◽  
Once Daily ◽  
Experimental Therapies ◽  
Daily Dose ◽  
Grade 3 ◽  
Good Treatment Option ◽  
Recommended Phase Ii Dose ◽  
Clinical Trial Information

99 Background: GT0918, an androgen receptor (AR) antagonist, is a new chemical entity with reduced drug accumulation in the CNS. In a phase I dose escalation trial (NCT02826772), GT0918 was well tolerated with some durable responses in mCRPC patients (pts) who had progressed on ≥2 lines of standard and experimental therapies. This Phase 2 was designed to study the safety and efficacy of GT0918 400 mg vs. 500 mg oral daily in mCRPC pts who had progressed on either Abi or Enza with or without prior docetaxel. Methods: Pts with histologically confirmed mCRPC who had progressed on either Abi or Enza with or without prior docetaxel were eligible and randomized to 400 mg or 500 mg of GT0918 administered once daily orally. Pts continued treatment with GT0918 at their assigned dose until disease progression, intolerable toxicities or withdrawal of consent. PSA and labs were checked monthly. Imaging scans (CT/MRI and bone scan), circulating tumor cells and cf-DNA/RNA were performed every 3 months. Results: 61 pts were enrolled at 9 US sites and randomized 1:1 to 400 mg (n = 31) or 500 mg (n = 30) daily dose. All pts had progressed on either Abi (n = 34) or Enza (n = 27). Most of the reported AEs related to GT0918 were grade 1 or 2 as per CTCAE v4.03, but 22 AEs (5.3%) were reported as grade ≥ 3, such as fatigue, increase ALT/AST, rhabdomyolysis, or muscle weakness. Some AEs were due to drug-drug interaction with lipid-lowering medications leading to early discontinuation (26.2%). As of 5 October 2020, twelve pts finished 6 cycles. Among them, three finished 12 cycles and remained on the treatment. Treatment duration showed more pts in the 400 mg cohort with stable disease (SD) on imaging (9/31 finished 6 cycles) compared to the 500 mg cohort (3/30 finished 6 cycles). Further, all three pts who finished 12 cycles had progressed on Abi indicating that GT0918 might be a good treatment option for pts who had progressed on Abi. Conclusions: Proxalutamide (GT0918) administrated orally once a day is well tolerated and resulted in SD in pts who had progressed on either Abi or Enza. The 400 mg/day will be considered as the recommended phase II dose for further clinical trials. GT0918 is warranted for pts failed either Abi or Enza. Clinical trial information: NCT03899467.

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