Effect of paclitaxel-carboplatin (PC) consolidation chemotherapy after weekly PC concurrent chemo-radiotherapy (CCR) for patients with locally advanced non-small cell lung cancer (LA-NSCLC): 3-year definitive results of the B001-phase III GERCOR-study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7112-7112 ◽  
Author(s):  
P. Colin ◽  
N. Jovenin ◽  
G. Ganem ◽  
J. Duhamel ◽  
J. Oster ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Locally Advanced ◽  
Target Volume ◽  
Local Control Rate ◽  
Phase Iii ◽  
Rank Test ◽  
Eligibility Criteria ◽  
Additional Chemotherapy ◽  
Sequential Schedule

7112 Background: Local control rate of LA-NSCLC seems better after concurrent CCR than after sequential schedule; the role of additional chemotherapy is not clearly defined. A multi-institutional phase-III trial was conducted to evaluate the role of chemotherapy consolidation after CCR Methods: Eligibility criteria included mediastinoscopy-controlled unresectable NSCLC stage IIIA (27%) - IIIB (59%) and inoperable mediastinal recurrence after surgery (14%), PS < 3, clinical target volume compatible with a minimal 60 Gy dose radiation. After registration, patients (pts) were treated with combination of weekly P (45 mg/m2), C (AUC 2), and radiotherapy 60–66 Gy (5 × 2 Gy per week). The pts with response or stable disease were randomized either to receive 3 cycles of P (175 mg/m2) and C (AUC 5) consolidation on days 1–22–43 or observation. Primary endpoint was OS (log-rank test), planned sample was 122 pts. Results: Actually, 71 pts were enrolled. Thirty pts (42%) were not randomized because of progression (22%) and disease-related death (22%), toxicity (26%), refusal (9%), protocol violation (21%). Toxicity grade 3–4 per patient: for the PC-TRT sequence; neutropenia 5%, febrile neutropenia 5%, thrombopenia 5%, pneumonitis 5%, oesophagitis 19%. For the PC consolidation sequence; neutropenia 24%, febrile neutropenia 6%, thrombopenia 0% (no treatment-related death). After a minimal follow-up of 3 years, despite poor inclusion rate, OS and PFS were greater in the PC consolidation group with 3-year OS: 29.9% vs 10% (HR = 0.45; CI 0.95: 0.22–0.91) (p = 0.002) and 3-year PFS: 27.8% vs 10% (HR = 0.6; CI 0.95: 0.3–1.3) (p = 0.17). Nine pts developed metastasis in each treatment arm. Conclusions: The addition of PC consolidation to PC-CCR is not easily feasible for all LA-NSCLC. For selected pts (only 58% of pts in this trial), despite premature ending of the trial because of slow accrual, PC consolidation significantly improved the 3-year OS and probably PFS. Because no difference in the metastatic incidence was observed, the effect of chemotherapy dosage in the consolidation arm could be explained by delaying metastasis. No significant financial relationships to disclose.

scholarly journals The Prognosis and Feasibility of Extensive Clinical Target Volume in Postoperative Radiotherapy for Esophageal Squamous Cell Carcinoma: A Phase II Clinical Trial

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaofei Zhang ◽  
Dashan Ai ◽  
Juanqi Wang ◽  
Yun Chen ◽  
Qi Liu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Lymph Nodes ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Postoperative Radiotherapy ◽  
Locally Advanced ◽  
Target Volume ◽  
Local Control Rate

BackgroundThis trial aims to explore the feasibility and safety of postoperative radiotherapy covering all regional lymph node areas for locally advanced thoracic esophageal squamous cell carcinoma patients treated with intensity-modulated radiation therapy (IMRT).MethodsThis was a single-center single-arm, phase II clinical trial initiated in 2014. Patients who were treated with radical transthoracic resection and had negative margins within 3 months and histologically confirmed esophageal squamous cell carcinoma (pT3-4 or N+, M0 determined by the 7th edition of the AJCC guidelines) were recruited in this trial. Postoperative radiotherapy was performed with a total dose of 40 Gy in 20 fractions using IMRT. Clinical target volumes (CTVs) included the tumor bed, anastomosis, bilateral supraclavicular region, mediastinal lymph nodes, left gastric lymph nodes and celiac trunk lymph nodes. The primary endpoint was the 2-year local control rate, and the secondary endpoints were overall survival (OS) and adverse events (AEs).ResultsA total of 70 eligible patients were recruited from 2014 to 2016. The 2-year local control rate, as the primary endpoint, was 67.3%. In addition, the median OS was 57.0 months, with 1-year and 3-year OS rates of 92.8% and 60.9%, respectively. Among the patients, 28/40 (40%) developed locoregional recurrence, with 25.7% involving hematogenous recurrences. All reported AEs occurred during the course of IMRT or within 6 months thereafter. None of them suffered grade 4 hematological or nonhematological AEs. Nearly all patients completed the entire course of postoperative radiotherapy, with a completion rate of 97.1%.ConclusionFor an extensive target volume, 40 Gy is feasible and shows acceptable toxicity in patients with locally advanced thoracic esophageal squamous cell carcinoma, although the local recurrence rate is relatively high. Our findings provide a basis for further exploration of high-dose radiation with extensive CTV combined with chemotherapy.Clinical Trial Registration[http://www.clinicaltrials.gov/ct2/results?cond=&amp;term=NCT02384811&amp;cntry=&amp;state=&amp;city=&amp;dist=], identifier [NCT02384811].

scholarly journals Prognostic role of primary tumor, nodal neck, and retropharyngeal GTVs for unresectable sinonasal cancers treated with IMRT and chemotherapy

2019 ◽  
Vol 106 (1) ◽  
pp. 39-46
Author(s):  
Letizia Ferella ◽  
Anna Cavallo ◽  
Rosalba Miceli ◽  
Nicola Alessandro Iacovelli ◽  
Tommaso Giandini ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Locally Advanced ◽  
Treatment Strategies ◽  
Intensity Modulated Radiotherapy ◽  
Progression Free Survival ◽  
Nodal Metastasis ◽  
Rank Test ◽  
Prognostic Role ◽  
Sinonasal Cancer

Background: We evaluated the prognostic role of gross tumor volumes (GTVs) of primary tumor and positive lymph nodes on overall survival (OS) and progression-free survival (PFS) in locally advanced unresectable sinonasal cancer (SNC) treated with definitive intensity-modulated radiotherapy (IMRT) with or without chemotherapy. Methods: Primary tumor GTV (GTV-T), pathologic neck nodes GTV (GTV-N), and positive retropharyngeal nodes GTV (GTV-RPN) of 34 patients with epithelial nonglandular SNC receiving IMRT with or without chemotherapy were retrospectively measured. The GTV variables were analyzed in relation with OS and PFS. Survival curves were estimated using the Kaplan-Meier method and compared with the log-rank test. We also estimated the crude cumulative incidence of locoregional relapses only. The optimal volume cutoff value was determined using an outcome-oriented method among the observed values. Results: GTV-T was significantly associated with decreased OS ( P=0.003) and PFS ( P=0.003). Moreover, patients with disease total volumes (GTV) smaller than 149.44 cm³ had better OS and PFS than patients with higher volumes ( P<0.0001 for both). Neck nodal metastasis impacted on OS and PFS ( P=0.030 and P=0.033, respectively), but GTV-N did not ( P=0.961; P=0.958). Retropharyngeal nodes metastasis was not associated with prognosis (OS: P=0.400; PFS: P=0.104). When GTV-RPN was added to GTV-N (GTV-TN), a relation with PFS ( P=0.041) and a trend toward significance for OS ( P=0.075) were found. Conclusions: Our results show that tumor volume is a powerful predictor of outcome in SNC. This could be useful to identify patients with worse prognosis deserving different treatment strategies.

scholarly journals The Role of Platinum Based Chemotherapy in Neoadjuvant Treatment of Locally Advanced Triple Negative Breast cancer

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
H M Abdelaziz ◽  
D R Diab ◽  
A M Adel ◽  
M Y Mostafa ◽  
M M Gaddalla
Keyword(s):  
Breast Cancer ◽  
Clinical Oncology ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Phase Iii ◽  
End Point ◽  
Platinum Based Chemotherapy

Abstract Background The treatment of patients with TNBC is the biggest challenge in the breast cancer (BC) scenario. TNBC remains the poorest prognosis breast cancer (BC) subtype, usually high-grade tumors with higher incidence of visceral and cerebral metastases. Cytotoxic chemotherapy is the backbone of triple-negative breast cancer treatment. Objective A phase III prospective study designed to investigate the role of addition the platinum based chemotherapy to the neoadjuvant setting in treatment of locally advanced triple negative breast cancer, Considering pathological response, complete (pCR) and partial (pPR) as a primary end point, and toxicity, disease free survival as a secondary end point. Patients and Methods This study was a phase III prospective one. 51 female patients Included with locally advanced triple negative Breast Cancer referred to Clinical Oncology& Radiotherapy Department, AIN SHAMS University Hospitals. Results A total of 51 female patients between ages 23-73 years with median age was 45 years old and with locally advanced features of breast cancer, (stage IIIa-IIIb-IIIc) were enrolled in the study during a recruiting period from October 2013 till October 2017 at Ain Shams University, clinical oncology department. Six patients (11.8%) were excluded from the analysis after enrollment, they didn’t receive neoadjuvant treatment because they underwent surgery or they developed metastasis So, only 45 patients received the neoadjuvant treatment. The median follow-up duration was 19 months after surgery. Conclusion Clearly, there were no statistical significance neither survival benefit in addition of the platinum to the NST comparison with the classic anthracyclines + taxens treatment. Even there was more clinical regression with platinum, but more recurrence and relapse occurred. There for, there is a major need to better understand the characteristics and the clinical behavior of TNBCs with an aim to develop effective treatments for this BC subtype.

Radiotherapy (RT) dose escalation study with concurrent cisplatin and S-1 in patients with inoperable stage III non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7542-7542
Author(s):  
H. Harada ◽  
M. Nishio ◽  
H. Murakami ◽  
F. Ohyanagi ◽  
T. Kozuka ◽  
...  
Keyword(s):  
Radiation Dose ◽  
Febrile Neutropenia ◽  
Organs At Risk ◽  
Performance Status ◽  
Target Volume ◽  
Stage Iii ◽  
Eligibility Criteria ◽  
Metastatic Node ◽  
Dose Escalation Study ◽  
Grade 3

7542 Background: Standard treatment for inoperable stage III NSCLC is concurrent chemoradiotherapy using 3-D conformal RT to a total dose of 60 Gy, but the outcome is still dismal with median survival time (MST) of 16 months and 5-year survival of 15%. We conducted a phase II trial using cisplatin, S-1 and concurrent RT of 60 Gy (J Clin Oncol 2008;26:a7556). MST (33months) was encouraging, however, local failure rate with this trial remained still high. The purpose of this study was to establish the recommended dose (RD) of RT with concurrent cisplatin and S-1. Methods: The eligibility criteria were: histologically or cytologically proven NSCLC, 20–75 years old, performance status 0–1, without any prior chemotherapy or RT. Patients were treated with cisplatin (60 mg/m2 on day 1) and S-1 (orally at 40 mg/m2/dose b.i.d., on days 1–14) repeated every 4 weeks for 4 cycles and RT was started on day 1. Radiation dose was escalated from 66 Gy in 33 fractions (Arm 1) to 70 Gy in 35 fractions (Arm 2), then 74 Gy in 37 fractions (Arm 3). The dose was to be escalated if DLTs were observed in 2 or less patients. The target volume of RT included primary tumor and metastatic node only and elective nodal irradiation was not performed. Dose constraints to the organs at risk were: the lung, V20 < 30%; the esophagus, mean dose < 34 Gy and V55 < 30%; the spinal cord, max dose < 50 Gy. Results: Six patients in each arm were enrolled. Two patients in Arm 1 experienced DLTs: one patient developed grade 3 febrile neutropenia, grade 3 mucositis in oral cavity and grade 3 diarrhea and one patient developed grade 3 febrile neutropenia. One patient in Arm 3 has not been completed evaluation yet. Otherwise no DLT was observed. Conclusions: The radiation dose of 74 Gy in 37 fractions with concurrent cisplatin and S-1 seemed to be tolerable and was judged to be the RD. This study is still open to accrue another six patients to confirm the safety of the RD. No significant financial relationships to disclose.

Gemcitabine plus docetaxel versus docetaxel in patients (pts) with HER2-negative locally advanced or metastatic breast cancer (MBC): A randomized phase III study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1015-1015
Author(s):  
D. L. Nielsen ◽  
S. T. Langkjer ◽  
K. Bjerre ◽  
S. Cold ◽  
L. Stenbygaard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Rank Test ◽  
Hematologic Toxicity ◽  
Phase Iii Study ◽  
Her 2 ◽  
Grade 3

1015 Background: Gemcitabine (G), either as a single agent or in combination with taxanes, has demonstrated efficacy in MBC in phase II and III studies. We conducted a phase III study to compare time to progression (TTP) of G plus docetaxel (T) versus (vs.) T alone. The secondary endpoints included overall survival (OS), overall response rate (ORR), and toxicity. Methods: Females with HER-2-negative locally advanced or MBC and a WHO performance status ≤ 2 were randomized to GT (G 1,000mg/m2 day 1 + 8; T 75mg/m2 day 1) or T (100mg/m2 day 1) every 21 days. Pts were previously untreated, had prior anthracycline-based (neo)adjuvant chemotherapy or had received a single prior anthracycline-bsed chemotherapy regimen for MBC. Time-to-event endpoints were estimated using the Kaplan-Meier method, and the log-rank test was applied for comparisons between regimens. The planned sample size was 254 evaluable pts with α I and β of 0.05 and 0.90, respectively. Results: A total of 336 pts were randomized (170 GT; 166 T), data from one centre are yet missing and the present evaluation is based on data from 306 pts (155 GT; 151 T). The pts had a median age of 58 years in both regimens; range 36–73 years and 30–74 years, respectively. The median TTP was 7.5 months for the GT regimen vs. 6.5 months for the T regimen. The GT arm demonstrated an ORR of 44% vs. 38% in the T arm with 4 and 3 % complete responses, respectively. The OS was 13.4 vs. 13.2 months in the GT and T arm, respectively. Hematologic toxicity was common, especially grade 3–4 neutropenia (GT = 69%; T = 61%); infection was reported in 22 and 20% of the pts, respectively (none of the pts received G-CSF). The most commonly reported non-hematologic toxicities of grade 3–4 included mucositis (GT = 2%; T = 5%), diarrhea (GT = 4%; T = 7 %), fatigue (GT = 6%; T = 11%), oedema (GT = 10%; T = 3%), and peripheral neuropathy (GT = 9%; T = 28%). Conclusions: Preliminary data of GT as first- or second-line chemotherapy demonstrates a TTP advantage among HER-2-negative pts with advanced breast cancer. Updated results and proper statistical analyses will be presented. No significant financial relationships to disclose.

A phase III trial comparing atezolizumab with enzalutamide vs enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS5090-TPS5090 ◽  
Author(s):  
Thomas Powles ◽  
Karim Fizazi ◽  
Silke Gillessen ◽  
Charles G. Drake ◽  
Dana E. Rathkopf ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Locally Advanced ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Effective Treatment Option ◽  
Synthesis Inhibitor ◽  
Eligibility Criteria ◽  
Androgen Synthesis ◽  
Ecog Ps

TPS5090 Background: In the past decade, several therapies have been approved for patients (pts) with mCRPC, including the androgen receptor (AR) antagonist enzalutamide (enza) and the androgen synthesis inhibitor abiraterone acetate (abi). Despite these advances, most pts experience disease progression and there are inadequate data to guide the sequencing of agents to optimize outcomes. Pts with mCRPC who progress on enza have increased circulating PD-L1/PD-L2–positive dendritic cells compared with enza-naive pts or pts who are still responding to treatment (Bishop et al. Oncotarget. 2014). In two recent studies, PSA and radiographic responses were observed in mCRPC pts treated with a PD-L1/PD-1 pathway inhibitor with or without enza (Graff et al. Oncotarget. 2016; Hansen et al. Ann Oncol. 2016). Atezolizumab (atezo) is an anti–PD-L1 monoclonal antibody that inhibits the interaction between PD-L1 and its receptors, PD-1 and B7.1, enhancing T-cell responses and improving anti-tumor activity. Taken together, this suggests that the combination of atezo and enza may provide an effective treatment option for mCRPC pts. Methods: A Phase III randomized, multicenter, clinical trial (NCT03016312) is being conducted to evaluate the efficacy and safety of atezo with enza compared with enza alone in mCRPC pts who have received prior abi treatment and have progressed on, are ineligible for, or have refused a taxane regimen. Eligibility criteria include mCRPC or locally advanced, incurable CRPC and ECOG PS 0-1. Exclusion criteria include CNS metastasis, autoimmune disease, history of seizures, prior immunotherapy and prior treatment with enza or any other newer AR antagonists. Pts will be randomized 1:1 to receive atezo 1200 mg q3w and enza 160 mg qd or enza alone. The primary endpoint is OS, and secondary endpoints include PSA response rate, rPFS, ORR and safety. Exploratory biomarkers associated with responses to atezo and enza will be evaluated in tumor tissue collected at baseline and progression. Approximately 550 pts will be enrolled at 150 sites globally. Clinical trial information: NCT03016312.

scholarly journals Stereotactic Body Radiotherapy for Small Lung Tumors in the University of Tokyo Hospital

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Hideomi Yamashita ◽  
Wataru Takahashi ◽  
Akihiro Haga ◽  
Satoshi Kida ◽  
Naoya Saotome ◽  
...  
Keyword(s):  
Treatment Time ◽  
Volumetric Modulated Arc Therapy ◽  
Dose Calculation ◽  
Target Volume ◽  
Lung Tumors ◽  
Local Control Rate ◽  
Internal Target Volume ◽  
Eligibility Criteria ◽  
Flattening Filter Free ◽  
Heterogeneity Correction

Our work on stereotactic body radiation therapy (SBRT) for primary and metastatic lung tumors will be described. The eligibility criteria for SBRT, our previous SBRT method, the definition of target volume, heterogeneity correction, the position adjustment using four-dimensional cone-beam computed tomography (4D CBCT) immediately before SBRT, volumetric modulated arc therapy (VMAT) method for SBRT, verifying of tumor position within internal target volume (ITV) using in-treatment 4D-CBCT during VMAT-SBRT, shortening of treatment time using flattening-filter-free (FFF) techniques, delivery of 4D dose calculation for lung-VMAT patients using in-treatment CBCT and LINAC log data with agility multileaf collimator, and SBRT method for centrally located lung tumors in our institution will be shown. In our institution, these efforts have been made with the goal of raising the local control rate and decreasing adverse effects after SBRT.

Chemoradiotherapy in the Management of Locally Advanced Pancreatic Carcinoma: A Qualitative Systematic Review

2009 ◽  
Vol 27 (13) ◽  
pp. 2269-2277 ◽  
Author(s):  
Florence Huguet ◽  
Nicolas Girard ◽  
Clotilde Séblain-El Guerche ◽  
Christophe Hennequin ◽  
Françoise Mornex ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pancreatic Carcinoma ◽  
Induction Chemotherapy ◽  
Randomized Trials ◽  
Locally Advanced ◽  
Phase Iii ◽  
Level Of Evidence ◽  
Qualitative Systematic Review ◽  
Survival Level

PurposePancreatic carcinoma is one of the leading causes of cancer-related mortality. At time of diagnosis, 30% of patients present with a locally advanced unresectable but nonmetastatic pancreatic carcinoma (LAPC). The French program Standards, Options, and Recommendations was promoted to conduct a qualitative systematic review to evaluate the role of radiotherapy in patients with LAPC.MethodsA search to identify eligible studies was undertaken using the MEDLINE database. All phase III randomized trials and systematic reviews evaluating the role of radiotherapy in LAPC were included, together with some noncontrolled studies if no phase III trials were retrieved. The quality and clinical relevance of the studies were evaluated using validated checklists, which allowed associating each result with a level of evidence.ResultsTwenty-one studies were included, as follows: two meta-analyses, 13 randomized trials, and six nonrandomized trials. Chemoradiotherapy increases overall survival when compared with best supportive care (level of evidence C) or with exclusive radiotherapy (level B1), but is more toxic (level B1). Chemoradiotherapy is not superior to chemotherapy in terms of survival (level B1) and increases toxicity (level A). Recent data favor limited irradiation to the tumor volume (level C). Fluorouracil is still the reference chemotherapy in association with radiotherapy (level B1). Induction chemotherapy before chemoradiotherapy improves survival (level C).ConclusionNo standard treatment exists, but there are two options for treatment of LAPC; these are gemcitabine-based chemotherapy and chemoradiotherapy. Induction chemotherapy followed by a chemoradiotherapy is a promising strategy for selection of patients without early metastatic/progressing disease.

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