Updated analysis of SWOG 0023: A randomized phase III trial of gefitinib versus placebo maintenance after definitive chemoradiation followed by docetaxel in patients with locally advanced stage III non-small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7513-7513 ◽  
Author(s):  
K. Kelly ◽  
K. Chansky ◽  
L. E. Gaspar ◽  
J. R. Jett ◽  
Y. Ung ◽  
...  
Keyword(s):  
Median Survival ◽  
Alternative Hypothesis ◽  
Locally Advanced ◽  
Phase Iii ◽  
Stage Iii ◽  
Definitive Treatment ◽  
Logrank Test ◽  
Ideal Agent ◽  
Thoracic Radiation ◽  
Grade 3

7513 Background: Early clinical studies with gefitinib (G) showed promising efficacy and mild toxicity in patients (pts) with advanced NSCLC. Thus, G was an ideal agent to evaluate in a maintenance setting in stage III disease following definitive treatment. Methods: Untreated pts with stage III NSCLC, a PS of 0–1 and adequate organ function were eligible. Patients received the SWOG 9504 core regimen (cisplatin 50 mg/m2, d1 & 8 plus etoposide 50 mg/m2 day 1–5, every 28 days for 2 cycles with concurrent thoracic radiation, 1.8–2 Gy fractions/day, total dose 61 Gy, followed by 3 cycles of docetaxel 75 mg/m2). Non- progressing pts were randomized to G 250 mg per day or placebo (P) until disease progression, intolerable toxicity or 5 years. The planned sample size was 672, to confer power of 0.89 to detect a 33% increase over the expected median survival of 21 months (one-sided 0.025 level logrank test). Randomization was stratified by stage and histology. Results: Enrollment began in July 2001. An unplanned interim analysis prompted by outside data was conducted in April 2005 and the alternative hypothesis of improved survival was rejected at the 0.0015 level for 243 randomized patients. The study closed and preliminary results were reported (ASCO 2005). Now with a median follow up of 27 months, median survival for the G arm (n=118) was 23 months and was 35 months for the P arm (n=125) (two sided p=0.013). Overall survival for the 571eligible patients was 19 months. ≥ Grade 3 toxicities in the G arm were rash (7%), diarrhea (7%) and pneumonitis (3%). Conclusion: In this unselected population G did not improve survival. Decreased survival was due to cancer not G toxicity. Three year survival estimates will be presented. Molecular studies of the EGFR pathway are underway and will be correlated with outcomes. No significant financial relationships to disclose.

scholarly journals Randomized Phase III Study of Thoracic Radiation in Combination With Paclitaxel and Carboplatin With or Without Thalidomide in Patients With Stage III Non–Small-Cell Lung Cancer: The ECOG 3598 Study

2012 ◽  
Vol 30 (6) ◽  
pp. 616-622 ◽  
Author(s):  
Tien Hoang ◽  
Suzanne E. Dahlberg ◽  
Joan H. Schiller ◽  
Minesh P. Mehta ◽  
Thomas J. Fitzgerald ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Locally Advanced ◽  
Small Cell ◽  
Phase Iii ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Thoracic Radiation ◽  
Grade 3

Purpose The primary objective of this study was to compare the survival of patients with unresectable stage III non–small-cell lung cancer (NSCLC) treated with combined chemoradiotherapy with or without thalidomide. Patients and Methods Patients were randomly assigned to the control arm (PC) involving two cycles of induction paclitaxel 225 mg/m2 and carboplatin area under the curve (AUC) 6 followed by 60 Gy thoracic radiation administered concurrently with weekly paclitaxel 45 mg/m2 and carboplatin AUC 2, or to the experimental arm (TPC), receiving the same treatment in combination with thalidomide at a starting dose of 200 mg daily. The protocol allowed an increase in thalidomide dose up to 1,000 mg daily based on patient tolerability. Results A total of 546 patients were eligible, including 275 in the PC arm and 271 in the TPC arm. Median overall survival, progression-free survival, and overall response rate were 15.3 months, 7.4 months, and 35.0%, respectively, for patients in the PC arm, in comparison with 16.0 months (P = .99), 7.8 months (P = .96), and 38.2% (P = .47), respectively, for patients in the TPC arm. Overall, there was higher incidence of grade 3 toxicities in patients treated with thalidomide. Several grade 3 or higher events were observed more often in the TPC arm, including thromboembolism, fatigue, depressed consciousness, dizziness, sensory neuropathy, tremor, constipation, dyspnea, hypoxia, hypokalemia, rash, and edema. Low-dose aspirin did not reduce the thromboembolic rate. Conclusion The addition of thalidomide to chemoradiotherapy increased toxicities but did not improve survival in patients with locally advanced NSCLC.

Results of semimonthly 5-florouracil/leucovorin combined with paclitaxel and oxaliplatin in treatment of advanced gastric cancer (AGC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15045-15045
Author(s):  
R. Lin ◽  
N. Fan ◽  
Z. Guo ◽  
X. Wang ◽  
Q. Chen ◽  
...  
Keyword(s):  
Median Survival ◽  
Chemotherapy Regimen ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Patient Choice ◽  
Phase Iii ◽  
Standard Chemotherapy Regimen ◽  
Ambulatory Pump ◽  
Grade 3

15045 Background: At present there is still no standard chemotherapy regimen for AGC, the progress of AGC exhibits a pessimistic result with a median survival of less than 9 months. The purpose of this trial was designed to enhance the treatment efficacy for AGC by using semimonthly FU/LV combined with paclitaxel and oxaliplatin. Methods: Patients chosen with histologically proven diagnosis of adenocarcinoma of the stomach or gastroesophageal junction, locally advanced (i.e., unresectable) or metastatic and measurable disease. The chemotherapy regimen was comprised of a 3-hour infusion of 135 mg/m2 of paclitaxel followed by oxaliplatin 85 mg/m2 and LV 400 mg/m2, administered simultaneously as a 2-hour infusion, then continued a 46-hour infusion of FU 2.4 g/m2 using an ambulatory pump. Treatment was continued until disease progressed, unacceptable toxicity, or patient choice. The primary endpoint was response rate. Results: Twenty-seven patients were enrolled onto this study in our center between September 19, 2005 and December 25, 2006. The median patient age was 51 years (range, 28 to 66 years), 21 were males and 6 were females. All patients received the chemotherapy between at least two cycles and maximum eight cycles with a median of three. Four CRs of 27 enrolled patients, fifteen PRs and eight SDs were observed. Nineteen patients were chemonaive within enrolled patients: Four CRs, eleven PRs. At a median follow-up of 8.7 months, the median survival was 6.8 months. Frequent grade 3 to 4 toxicities were: neutropenia (37.0%), stomatitis (7.4%), nausea (7.4%), vomiting (7.4%), hepatic dysfunction (3.7%), paresthesia (18.5%). No treatment-related death occurred. Conclusion: Semimonthly FU/LV combined with paclitaxel and oxaliplatin appears to be of well efficacy and is well tolerated in patients with AGC. Currently, this regimen is being tested in the phase III trial involving patients with AGC on the basis of well result. No significant financial relationships to disclose.

A phase III trial of carboplatin, paclitaxel, and thoracic radiation therapy with or without thalidomide in patients with stage III non-small cell carcinoma of the lung (NSCLC): E3598

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7503-7503 ◽  
Author(s):  
J. H. Schiller ◽  
S. E. Dahlberg ◽  
M. Mehta ◽  
D. H. Johnson
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Angiogenesis Inhibitor ◽  
Data Monitoring Committee ◽  
Phase Iii ◽  
Stage Iii ◽  
Thoracic Radiation ◽  
Stage Iii Nsclc ◽  
Clinically Significant ◽  
Grade 3

7503 Background: Thalidomide (T) is an oral angiogenesis inhibitor with anti-tumor activity in hematological malignancies. Given that antiangiogenic drugs such as bevacizumab have proven activity in advanced NSCLC, ECOG conducted a phase III study to compare the effects of the addition of thalidomide to paclitaxel/carboplatin/radiation therapy (PC/RT) on overall survival (OS) in pts with newly diagnosed stage III NSCLC. Secondary endpoints included time to progression (PFS) and toxicity. Methods: Pts were required to have inoperable stage IIIA or IIIB (no pleural effusion) NSCLC and a PS of 0 or 1. Pts were randomized to receive 2 cycles of P (225 mg/m2)+ C (AUC=6) every 3 wks or PC + thalidomide starting at 200 mg daily with the possibility of dose escalation. This was followed by weekly C (AUC=2), P (45 mg/m2) and concurrent RT (60 Gy) ± T. Pts on PC/RT + T continued thalidomide for 24 mo. or until disease progression. Results: 277 eligible pts were randomized to PC/RT and 272 pts to PC/RT + T. Median age was 63; 61% of pts had stage IIIB disease, 35% had squamous histology, and 46% were PS 0. The third planned interim analysis was conducted with 403 of 506 planned deaths (73.9%) for full analysis and the trial was stopped early by the ECOG Data Monitoring Committee for futility. The median overall survival for the no T arm was 15.3 mo. (12.4–20.2 mo.) compared to 16.0 mo for the T arm (14.4–18.3 mo.); hazard ratio = 0.985 (0.81–1.19); p = 0.88. Median PFS for the no T arm was 7.6 mo. (6.6–8.7 mo.) compared to 8.0 mo. for the T arm (7.1–9.1 mo.), p>0.05. The most common toxicity on both arms was myelosuppression. 11% of pts on the T arm had a grade 3–5 thrombosis/embolism, compared to <3% on the no T arm. Conclusions: The addition of thalidomide to PC/RT in pts with stage III NSCLC does not provide a clinically significant benefit. [Table: see text]

The progress of small cell lung cancer management using irinotecan plus cisplatin chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7721-7721 ◽  
Author(s):  
J. S. Lee ◽  
J. Han ◽  
S. Yu ◽  
S. Yoon ◽  
E. Lim ◽  
...  
Keyword(s):  
Median Survival ◽  
Response Rate ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Cancer Management ◽  
Phase Ii Studies ◽  
Thoracic Radiation ◽  
Grade 3 ◽  
Ecog Ps

7721 Background: Etoposide/cisplatin (EP) is the most widely used regimen resulting in a median survival of 8–10 mos and 17–20 mos respectively for patients (pts) with extensive-disease (ED) and limited-disease (LD). Encouraged by a phase III trial result that showed better survival outcome after Irinotecan/cisplatin (IP) combination as compared with EP, we previously reported promising activity of IP regimen for LD-SCLC and also for ED-SCLC. To further evaluate the role of IP in SCLC pts, we conducted two additional phase II studies. Methods: Between May 2003 and June 2006, a total of 196 SCLC pts (ED: 120, LD: 76) were enrolled in two separate trials. All pts were chemo-naive and ECOG PS of 0–2. Pts with ED-SCLC received irinotecan 60 mg/m2 intravenously (IV) and cisplatin 30 mg/m2 IV on days 1 and 8 every 21 days for 8 cycles followed by 6 cycles of irinotecan maintenance or observation. Treatment for LD-SCLC consisted of two 28-day cycles of cisplatin 30 mg/m2 IV on days 1 and 8 plus irinotecan 60 mg/m2 IV on days 1, 8, and 15, followed by two 21-day cycles of cisplatin 60 mg/m2 IV on day 1, plus etoposide 100 mg/m2 IV on days 1 to 3 with concurrent twice-daily thoracic radiation of total 45 Gy. Hoping to modify the treatment-related toxicity, 36 pts were given epoietin and 20 were given amifostine while 15 received neither during the concurrent chemo-radiation therapy. Results: For ED- SCLC, overall response rate was 92.6% with CR rate of 11.1%. The median survival was 13.8 mos (95% CI, 12.2 to15.3) with 1-and 2-year survival rates of 58.6% and 18.9%. The median progression-free survival (PFS) was 7.3 mos with 1-and 2-year PFS rates of 18.1% and 5.4%. Irinotecan maintenance did not affect the outcome, however. For LD-SCLC, the response rate was 97.1% with CR rate of 44.9%. The median survival was 24.9 mos (95% CI, 18.5 to 31.3) with 1-and 2-year survival rates of 75.2% and 51.4%. The median PFS was 11.0 mos (95% CI, 7.8–14.2) with 1-year PFS rates of 46.8%. The most common toxicity associated with IP treatment was grade 3 or 4 neutropenia (64.6% for ED, 45.3% for LD). Grade 3 diarrhea was developed in 12.4% for ED and 4% for LD pts. Conclusion: Significant antitumor activity of IP chemotherapy as shown suggests further progress in SCLC therapy. No significant financial relationships to disclose.

Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine (PCG) and gemcitabine/cisplatin (GC) in patients with locally advanced (LA) or metastatic (M) urothelial cancer without prior systemic therapy; EORTC30987/Intergroup Study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. LBA5030-LBA5030 ◽  
Author(s):  
J. Bellmunt ◽  
H. von der Maase ◽  
G. M. Mead ◽  
J. Heyer ◽  
N. Houede ◽  
...  
Keyword(s):  
Median Survival ◽  
Urothelial Cancer ◽  
Locally Advanced ◽  
International Study ◽  
Error Rates ◽  
Phase Iii ◽  
Comparable Efficacy ◽  
Logrank Test ◽  
Significant Difference ◽  
Phase Iii Study

LBA5030 Background: GC is a standard alternative to M-VAC for LA/M urothelial cancer (UC) based on comparable efficacy and a more favorable toxicity profile. Based on a phaseII trial, it has been suggested that the PCG triplet might provide improved response and survival. To evaluate the role of paclitaxel when added to GC, a randomized, international study (EORTC30987/Intergroup Study) comparing GC with PCG in LA/M UC was initiated in 2001, with the main endpoint being overall survival (OS). Methods: Chemo naive patients with histologic evidence of LA or M transitional UC, with GFR>60ml/min were eligible. After stratification for institution, PS(WHO 0–1) and presence/absence of metastatic disease, patients were randomized to receive PCG(armA) or GC(armB). PCG treatment included: paclitaxel(P) 80mg/m2 d1&8, cisplatin(C) 70mg/m2 d1 and gemcitabine(G) 1000mg/m2 d1&8, every 21d. GC: C70mg/m2 d1 or 2, G1000mg/m2 d1,8,15 every 28d. To detect an increase in median survival from 14 to 18m(HR=0.778) based on a two sided logrank test at error rates a=0.05 and β=0.20, 498 deaths were required. The planned sample size was of 610 pts. Results: From June 01 to May 04, 627pts (82% primary bladder) were included, (312 PCG, 315 GC). Median age was 61y with 81% males and similar baseline prognostic characteristics on both arms. PS 1 in 47%PCG and 46%GC pts. On PCG 47% had visceral and 83% M; on CG 49%-83% respectively. Overall response rate (RR): 57,1% for PCG (CR15%) and 46,4% for GC (CR10%), p=0.02. Median PFS: 8.4m and 7.7m for PCG and GC, p=0.10. 478 pts have died; the EORTC IDMC has released the study because the required number of events will occur prior to presentation. Median survival is 15.7m for PCG and 12.8m for CG, with no significant difference in OS (p=0.10, HR0.86, CI95% 0.72–1.03, p=0.12 adjusted for risk factors). Both treatments were overall well tolerated, with more thrombopenia and bleeding on GC (12%vs7%) and more febrile neutropenia on PCG (13%vs4%). Conclusions: This large, multicenter, Phase III study shows that PCG provided a better RR when compared with GC in LA/M UC; however the predefined endpoint for PFS and OS improvement was not reached. [Table: see text]

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.

JUPITER-02: Randomized, double-blind, phase III study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC).

2021 ◽  
Vol 39 (18_suppl) ◽  
pp. LBA2-LBA2
Author(s):  
Rui-hua Xu ◽  
Hai-Qiang Mai ◽  
Qiu-Yan Chen ◽  
Dongping Chen ◽  
Chaosu Hu ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Double Blind ◽  
Grade 3 ◽  
First Line Treatment

LBA2 Background: Gemcitabine-cisplatin (GP) chemotherapy is the standard 1st line treatment for locally advanced, recurrent or metastatic (r/m) NPC. Toripalimab, a humanized IgG4K monoclonal antibody specific for PD-1, provided durable responses in patients (pts) with r/m NPC as monotherapy in the ≥2nd line setting (POLARIS-02 study). The results of JUPITER-02, a randomized, placebo-controlled, double-blinded Phase III trial of toripalimab in combination with GP chemotherapy as first-line treatment for r/m NPC are summarized. Methods: Pts with advanced NPC with no prior chemotherapy in the r/m setting were randomized (1:1) to receive toripalimab 240 mg or placebo d1 in combination with gemcitabine 1000 mg/m2 d1, d8 and cisplatin 80 mg/m2 d1 every 3 weeks (Q3W) for up to 6 cycles, followed by monotherapy with toripalimab or placebo Q3W until disease progression, intolerable toxicity, or completion of 2 years of treatment. Stratification factors were ECOG PS (0 vs. 1) and extent of disease (recurrent vs. primary metastatic) at enrollment. Progression-free survival (PFS) and response were assessed by independent review committee (IRC) per RECIST v1.1. The primary endpoint was PFS by IRC in the ITT population. Secondary end points included ORR, DOR and OS. There was one prespecified interim analysis of PFS at 130 PFS events with a planned final analysis at 200 PFS events. Results: 289 pts were randomized: 146 to the toripalimab arm and 143 to the placebo arm. By May 30, 2020 as the interim analysis cutoff date, the median treatment duration was 39 weeks in the toripalimab arm and 36 weeks in the placebo arm. A significant improvement in PFS was detected for the toripalimab arm compared to the placebo arm (HR = 0.52 [95% CI: 0.36-0.74] two-sided p = 0.0003), with median PFS of 11.7 vs. 8.0 months. The 1-year PFS rates were 49% and 28% respectively. An improvement in PFS was observed across relevant subgroups, including all PD-L1 subgroups. The ORR was 77.4% vs. 66.4% (P = 0.033) and the median DOR was 10.0 vs. 5.7 months (HR = 0.50 [95% CI: 0.33-0.78]). As of Jan 15, 2021, OS was not mature, with 25 deaths in the toripalimab arm and 35 in the placebo arm (HR = 0.68 [95% CI: 0.41-1.14], P = 0.14). The incidence of Grade ≥3 adverse events (AEs) (89.0% vs 89.5%); AEs leading to discontinuation of toripalimab/placebo (7.5% vs 4.9%); and fatal AEs (2.7% vs 2.8%) were similar between two arms; however, immune-related (irAEs) (39.7% vs. 18.9%) and Grade ≥3 irAEs (7.5% vs. 0.7%) were more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to GP chemotherapy as 1st-line treatment for pts with advanced NPC provided superior PFS and ORR and longer DOR than GP alone with a manageable safety profile. These results support the use of toripalimab with GP chemotherapy as the new standard care for this population. Clinical trial information: NCT03581786.

scholarly journals Using the Systemic Immune-Inflammation Index (SII) as a Mid-Treatment Marker for Survival among Patients with Stage-III Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

2020 ◽  
Vol 17 (21) ◽  
pp. 7995
Author(s):  
Tithi Biswas ◽  
Kylie H. Kang ◽  
Rohin Gawdi ◽  
David Bajor ◽  
Mitchell Machtay ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Locally Advanced ◽  
Small Cell ◽  
Phase Iii ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Cancer Data ◽  
Immune Inflammation

The Systemic Immune-Inflammation Index (SII) is an important marker of immune function, defined as the product of neutrophil-to-lymphocyte ratio (NLR) and platelet count (P). Higher baseline SII levels have been associated with improved survival in various types of cancers, including lung cancer. Data were obtained from PROCLAIM, a randomized phase III trial comparing two different chemotherapy regimens pemetrexed + cisplatin (PEM) vs. etoposide + cisplatin (ETO), in combination with radiotherapy (RT) for the treatment of stage III non-squamous non-small cell lung cancer (NSCLC). We aimed to determine if SII measured at the mid-treatment window for RT (weeks 3–4) is a significant predictor of survival, and if the effect of PEM vs. ETO differs by quartile (Q) level of SII. Hazard-ratios (HR) for survival were estimated using a proportional hazards model, accounting for the underlying correlated structure of the data. A total of 548 patients were included in our analysis. The median age at baseline was 59 years. Patients were followed for a median of 24 months. Adjusting for age, body mass index, sex, race, and chemotherapy regimen, SII was a significant mid-treatment predictor of both overall (adjusted HR (aHR) = 1.6, p < 0.0001; OS) and progression-free (aHR = 1.3, p = 0.0072; PFS) survival. Among patients with mid-RT SII values above the median (6.8), those receiving PEM (vs. ETO) had superior OS (p = 0.0002) and PFS (p = 0.0002). Our secondary analysis suggests that SII is an informative mid-treatment marker of OS and PFS in locally advanced non-squamous NSCLC.

scholarly journals Sequencing of Androgen-Deprivation Therapy With External-Beam Radiotherapy in Localized Prostate Cancer: A Phase III Randomized Controlled Trial

2020 ◽  
Vol 38 (6) ◽  
pp. 593-601 ◽  
Author(s):  
Shawn Malone ◽  
Soumyajit Roy ◽  
Libni Eapen ◽  
Choan E ◽  
Robert MacRae ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
Localized Prostate Cancer ◽  
Definitive Treatment ◽  
Rank Test ◽  
Log Rank Test ◽  
Significant Difference ◽  
Grade 3

PURPOSE Dose-escalated radiotherapy (RT) with androgen-deprivation therapy (ADT) is a standard definitive treatment of localized prostate cancer (LPCa). The optimal sequencing of these therapies is unclear. Our phase III trial compared neoadjuvant versus concurrent initiation of ADT in combination with dose-escalated prostate RT (PRT). PATIENTS AND METHODS Patients with newly diagnosed LPCa with Gleason score ≤ 7, clinical stage T1b to T3a, and prostate-specific antigen < 30 ng/mL were randomly allocated to neoadjuvant and concurrent ADT for 6 months starting 4 months before RT (neoadjuvant group) or concurrent and adjuvant ADT for 6 months starting simultaneously with RT (concurrent group). The primary end point was biochemical relapse-free survival (bRFS). Stratified log-rank test was used to compare bRFS and overall survival (OS). Incidence of grade ≥ 3 late RT-related toxicities was compared by log-rank test. RESULTS Overall, 432 patients were randomly assigned to the neoadjuvant (n = 215) or concurrent group (n = 217). At 10 years, bRFS rates for the two groups were 80.5% and 87.4%, respectively. Ten-year OS rates were 76.4% and 73.7%, respectively. There was no significant difference in bRFS ( P = .10) or OS ( P = .70) between the two groups. Relative to the neoadjuvant group, the hazard ratio for the concurrent group was 0.66 (95% CI, 0.41 to 1.07) for bRFS and 0.94 (95% CI, 0.68 to 1.30) for OS. No significant difference was observed in the 3-year incidence of late RT-related grade ≥ 3 GI (2.5% v 3.9%) or genitourinary toxicity (2.9% v 2.9%). CONCLUSION In our study, there was no statistically significant difference in bRFS between the two treatment groups. Similarly, no difference was seen in OS or late RT-related toxicities. On the basis of these results, both neoadjuvant and concurrent initiations of short-term ADT with dose-escalated PRT are reasonable standards of care for LPCa.

scholarly journals Phase III Randomized Trial of Induction Chemotherapy in Patients With N2 or N3 Locally Advanced Head and Neck Cancer

2014 ◽  
Vol 32 (25) ◽  
pp. 2735-2743 ◽  
Author(s):  
Ezra E.W. Cohen ◽  
Theodore G. Karrison ◽  
Masha Kocherginsky ◽  
Jeffrey Mueller ◽  
Robyn Egan ◽  
...  
Keyword(s):  
Head And Neck ◽  
Induction Chemotherapy ◽  
Locally Advanced ◽  
Phase Iii ◽  
Serious Adverse Events ◽  
Free Survival ◽  
Distant Failure ◽  
Common Grade ◽  
Treatment Naïve ◽  
Grade 3

Purpose Induction chemotherapy (IC) before radiotherapy lowers distant failure (DF) rates in locally advanced squamous cell carcinoma of the head and neck (SCCHN). The goal of this phase III trial was to determine whether IC before chemoradiotherapy (CRT) further improves survival compared with CRT alone in patients with N2 or N3 disease. Patients and Methods Treatment-naive patients with nonmetastatic N2 or N3 SCCHN were randomly assigned to CRT alone (CRT arm; docetaxel, fluorouracil, and hydroxyurea plus radiotherapy 0.15 Gy twice per day every other week) versus two 21-day cycles of IC (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2 on days 1 to 5) followed by the same CRT regimen (IC + CRT arm). The primary end point was overall survival (OS). Secondary end points included DF-free survival, failure pattern, and recurrence-free survival (RFS). Results A total of 285 patients were randomly assigned. The most common grade 3 to 4 toxicities during IC were febrile neutropenia (11%) and mucositis (9%); during CRT (both arms combined), they were mucositis (49%), dermatitis (21%), and leukopenia (18%). Serious adverse events were more common in the IC arm (47% v 28%; P = .002). With a minimum follow-up of 30 months, there were no statistically significant differences in OS (hazard ratio, 0.91; 95% CI, 0.59 to 1.41), RFS, or DF-free survival. Conclusion IC did not translate into improved OS compared with CRT alone. However, the study was underpowered because it did not meet the planned accrual target, and OS was higher than predicted in both arms. IC cannot be recommended routinely in patients with N2 or N3 locally advanced SCCHN.

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