A phase II study of cisplatin (P), S-1 (S), and concurrent thoracic radiotherapy (TRT) for locally advanced non-small cell lung cancer (LA-NSCLC): Okayama Lung Cancer Study Group trial 0501.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7042-7042
Author(s):  
Daizo Kishino ◽  
Naoyuki Nogami ◽  
Yoshihiko Segawa ◽  
Keisuke Aoe ◽  
Hiroshi Ueoka ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Survival Data ◽  
Response Rate ◽  
Locally Advanced ◽  
Active Agent ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Lung Cancer Study Group ◽  
Sensitizing Effect

7042 Background: We previously reported an efficacy and safety of fractionated schedule ofP and docetaxel (D) (days 1, 8, 29, and 36, each) and concurrent TRT (DP-TRT) for LA-NSCLC (JCO 2010). Although the median survival time (MST: 26.3 months) was excellent, grade 3 or greater pneumonitis (10%) and esophagitis (14%) were observed and treatment-related death was 3%.Thus, further improvement in the safety as well as efficacy is strongly warranted. S, an oral fluoropyrimidine, is a new active agent possessing a radio-sensitizing effect. Additionally, combining S and P offered an active and safe regimen for metastatic NSCLC. The objective of this study was to assess the efficacy and safety of S + P with concurrent TRT for LA-NSCLC. Methods: Patients with stage IIIA/IIIB, aged ≤75 years and PS 0-1, and without any prior chemotherapy were eligible for this study. Patients were treated with P (40 mg/m² on day 1, 8, 29 and 36) and S (40 mg/m²/dose b.i.d. on days 1-14 and 29-42) and TRT (60 Gy/30 fr over 6 weeks starting on day 1). Primary endpoint was response rate (RR), and required sample size was 48 patients. Results: Between 2006 and 2009, 48 patients were enrolled (37 men; median age, 66 years; PS 0/1, 36/14; IIIA/IIIB, 23/25; sq/non-sq, 22/26). Partial response was observed in 37 patients (77%; 95% confidence interval: 63-88%). The response rate was higher in older patients (≥65 yrs) than younger (<65 yrs) (89% vs. 64%, p=0.041). At a median follow-up of 40 months, median progression-free survival and MST were 9.3 months and 31.3 months, respectively. No difference in efficacy (response and survivals) was observed stratified by histology (sq vs. non-sq). Toxicities were generally mild, including G3/4 neutropenia (44%), G3/4 thrombocytopenia (13%), G3 febrile neutropenia (8%) and G3 pneumonitis (4%). No one developed Gr3/4 esophagitis. No toxic deaths occurred. Conclusions: This chemoradiotherapy regimen yielded a favorable overall survival data. Also, it was well-tolerated in patients with LA-NSCLC as compared with concurrent DP-TRT therapy especially in term of TRT-related toxicities. A phase III trial of this regimen vs. DP-TRT is now planned.

A phase II-III study comparing concomitant chemoradiotherapy (CRT) versus cetuximab/RT (CET/RT) with or without induction docetaxel/cisplatin/5-fluorouracil (TPF) in locally advanced head and neck squamous cell carcinoma (LASCCHN): Efficacy results (NCT01086826).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6003-6003 ◽  
Author(s):  
Maria Grazia Ghi ◽  
Adriano Paccagnella ◽  
Daris Ferrari ◽  
Paolo Foa ◽  
Maria Cossu Rocca ◽  
...  
Keyword(s):  
Survival Data ◽  
Response Rate ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Analysis Data ◽  
Phase Iii ◽  
Grade 3 ◽  
Asco Meeting ◽  
Present Response ◽  
Ecog Ps

6003 Background: This is the first phase III study directly comparing CRT vs CET/RT in LASCCHN. Primary endpoints of this study were to compare: 1) overall survival (OS) of induction vs. no induction arms; 2) Grade 3-4 in-field toxicity of CRT vs. CET/RT. Preliminary toxicity results of concomitant treatments (primary endpoint for this comparison) were reported at the 2012 ASCO meeting. Here we present response rate and survival data for the two concomitant treatments (CRT vs. CET/RT), irrespective of induction chemotherapy. Methods: Untreated patients with unresectable LASCCHN, stage III-IV, ECOG PS 0–1 were randomized to a 2x2 factorial design: Arm A1: CRT (2 cycles of cisplatin/5fluorouracil concomitant to RT); Arm A2: CET/RT; Arm B1: 3 cycles of TPF followed by the same CRT; Arm B2:3 cycles of TPF followed by CET/RT. Results: A total of421 patients were randomized: 261 received CRT (131 Arm A1+ 130 Arm B1) and 160 received CET/RT (80 Arm A2+ 80 Arm B2). 82% were male; median age was 60y; PS of 0 (79%) or 1 (21%). Stage was III (32%) or IV (68%). Sites of disease were: oral cavity 20%, oropharynx 57%, hypopharynx: 23%. No significant differences were observed in patients’ characteristics distribution. At a median follow-up of 32.9 months, a total of 174 deaths occurred (204 required for final OS analysis). Data on activity and efficacy of CRT and CET/RT are shown in the Table. Conclusions: No significant differences were observed in response rate, progression free survival and OS between CRT and CET/RT. Pts are still being followed-up to assess OS of induction vs. no induction arms. Clinical trial information: NCT01086826. [Table: see text]

Phase III trial of thoracic irradiation with or without cisplatin for locally advanced unresectable non-small-cell lung cancer: a Hoosier Oncology Group protocol.

1995 ◽  
Vol 13 (6) ◽  
pp. 1425-1429 ◽  
Author(s):  
C Blanke ◽  
R Ansari ◽  
R Mantravadi ◽  
R Gonin ◽  
R Tokars ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Response Rate ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Free Survival

PURPOSE Here we report the results of a phase III study, to evaluate whether the addition of cisplatin to radiation therapy (XRT) would improve progression-free survival or overall survival for patients with locally advanced unresectable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Two hundred forty patients with biopsy-proven unresectable NSCLC without distant metastases or lower-stage medically inoperable patients were randomized to one of two treatment arms. Arm A consisted of thoracic XRT alone, 60 to 65 Gy total tumor dose in daily fractions of 1.80 to 2.00 Gy; and arm B consisted of identical XRT with the addition of cisplatin 70 mg/m2 every 3 weeks for three cycles beginning on the first day of irradiation. RESULTS Two hundred fifteen patients were eligible and assessable. The overall response rate was 50% on the combination arm versus 38% on the XRT-alone arm (P = .076). The median progression-free survival time was 23 versus 22 weeks, respectively (P = .0537). The median survival time was 43 weeks on the combination arm versus 46 weeks on the XRT arm (Poverall = .3469). The 1-, 2-, and 5-year survival rates were 43%, 18%, and 5% on the combination arm versus 45% 13%, and 2% on the XRT arm, respectively. CONCLUSION Cisplatin, administered every 3 weeks, does not significantly improve response rate, progression-free survival, or overall survival when added to thoracic XRT for locally advanced unresectable NSCLC.

A randomized phase III multicenter trial of neoadjuvant docetaxel plus cisplatin and 5-fluorouracil (TPF) versus neoadjuvant PF in patients with locally advanced unresectable squamous cell carcinoma of the head and neck (SCCHN). Final analysis of EORTC 24971

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5516-5516 ◽  
Author(s):  
E. Remenar ◽  
C. Van Herpen ◽  
J. Germa Lluch ◽  
S. Stewart ◽  
T. Gorlia ◽  
...  
Keyword(s):  
Response Rate ◽  
Locally Advanced ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Distant Metastases ◽  
Phase Iii ◽  
Treatment Center ◽  
Severe Thrombocytopenia ◽  
Phase Ii Studies

5516 Background: So far, the Wayne State regimen combining 100 mg/m2 cisplatin on day 1 and 1000 mg/m2/d continuous infusion 5-fluorouracil over 5 days (PF), is the gold standard in advanced SCCHN. Improvement of PF induction chemotherapy by adding a taxane has been suggested from phase II studies and 2 randomized phase III trials. We now report the final analysis of EORTC 24971. Methods: Eligible were patients (pts) with unresectable stage III/IV SCCHN (no distant metastases), 18 to 70 yrs of age, PS≤1, and adequate hematologic, renal and hepatic function. Pts were stratified by primary disease site (oral cavity, oropharynx, hypopharynx, larynx) and treatment center and randomized to PF (as above) or TPF (T 75 mg/m2/1h, P 75 mg/m2/1h, both d1, F 750 mg/m2/d, d1–5) q 3 wks, for 4 cycles unless progression (PD) or unacceptable toxicity, or refusal. Thereafter (interval 4–7 wks), all pts not in PD received radiotherapy (RT: conventional [66–70 Gy], accelerated [max. 70 Gy] / hyperfractionated [max. 74 Gy]). Surgery was allowed before RT (neck) or 3 months after RT (primary, neck). Primary endpoint was progression-free survival (PFS), and 348 pts and 260 events were needed to detect a 50% increase in median PFS (10 vs 15 mo) with 85% power. Results: Between April 1999 and March 2002, 358 pts were accrued (181 PF, 177 TPF). At a median follow-up (FUP) of 32 mo, PFS was significantly improved with TPF (HR 0.72, p = 0.0071; median 8.2 vs 11.0 mo). A 51 mo median FUP showed an overall survival (OS) benefit with TPF (HR 0.71, p = 0.0052; median 14.2 vs 18.6 mo). Estimated 3-yr survival rates are 23.9% (95% CI: 17.9%;30.5%) for PF and 36.5% (29.3%;43.6%) for TPF. Response rate also favored TPF (53.6% vs 67.8%, p = 0.006). There was more severe (G3+4) leucopenia (41.6% vs 22.9%) and neutropenia (76.9% vs 52.5%) with TPF, and more severe thrombocytopenia with PF (17.9% vs 5.2%). Severe alopecia occured more with TPF (55.5% vs 11.7%); hearing loss (2.8% vs 0%) and toxic death (7.8% vs 3.7%) more with PF. Conclusions: TPF (→ RT) is superior to PF (→ RT) for PFS, OS (including long-term), response rate, and is better tolerated. [Table: see text]

scholarly journals FIGHT-302: first-line pemigatinib vs gemcitabine plus cisplatin for advanced cholangiocarcinoma with FGFR2 rearrangements

2020 ◽  
Vol 16 (30) ◽  
pp. 2385-2399 ◽  
Author(s):  
Tanios S Bekaii-Saab ◽  
Juan W Valle ◽  
Eric Van Cutsem ◽  
Lorenza Rimassa ◽  
Junji Furuse ◽  
...  
Keyword(s):  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Survival Duration ◽  
Efficacy And Safety ◽  
First Line ◽  
Open Label ◽  
Clinical Trial Registration ◽  
Duration Of Response

FGFR2 rearrangements resulting in dysregulated signaling are drivers of cholangiocarcinoma (CCA) tumorigenesis, and occur almost exclusively in intrahepatic CCA. Pemigatinib, a selective, potent, oral inhibitor of FGFR1–3, has demonstrated efficacy and safety in a Phase II study of patients with previously treated locally advanced/metastatic CCA harboring FGFR2 fusions/rearrangements. We describe the study design of FIGHT-302, an open-label, randomized, active-controlled, multicenter, global, Phase III study comparing the efficacy and safety of first-line pemigatinib versus gemcitabine plus cisplatin in patients with advanced CCA with FGFR2 rearrangements (NCT03656536). The primary end point is progression-free survival; secondary end points are objective response rate, overall survival, duration of response, disease control rate, safety and quality of life. Clinical Trial Registration: NCT03656536 ( ClinicalTrials.gov )

Randomized phase III trial of docetaxel and cisplatin combination chemotherapy versus mitomycin, vindesine and cisplatin combination chemotherapy with concurrent thoracic radiation therapy for locally advanced non-small cell lung cancer: Preliminary report

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7101-7101 ◽  
Author(s):  
K. Kiura ◽  
Y. Segawa ◽  
M. Tabata ◽  
N. Takigawa ◽  
H. Kamei ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Response Rate ◽  
Locally Advanced ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Stage Iiia ◽  
Phase Iii Trial ◽  
Thoracic Radiation

7101 Background: Standard treatment of locally advanced non-small cell lung cancer (NSCLC) is cisplatin-based chemotherapy with concurrent thoracic radiation therapy (TRT). Furuse et al. demonstrated a superiority of mitomycin, vindesine and cisplatin (MVP) chemotherapy with concurrent TRT over that with sequential TRT (JCO 17, 1999). We demonstrated that docetaxel plus cisplatin (DP) chemotherapy with concurrent TRT shows better response rate and survival (Kiura K et al. BJC 89, 2003). We conducted a randomized phase III trial that compared DP with MVP in locally advanced NSCLC patients when concurrently administered with TRT. Methods: We randomly assigned patients with good performance status (PS)-stage IIIA/IIIB NSCLC to receive DP or MVP chemotherapy. Chemotherapy consisted of docetaxel 40 mg/m2 and cisplatin 40 mg/m2 on days 1, 8, 29, & 36 in the DP arm and mitomycin 8 mg/m2 on days 1 & 29, vindesine 3 mg/m2 on days 1, 8, 29, & 36, and cisplatin 80 mg/m2 on days 1 & 29 in the MVP arm. In the both groups, TRT began on day 1 at a dose of 60 Gy (2 Gy per fraction and 5 fractions per week for a total of 30 fractions). Results: Two hundred patients entered the trial between July 2000 and July 2005. Pretreatment characteristics were well balanced between the two treatment arms as follows: male/female 92/7, 88/13; median age (range) 65 (40–75), 64 (34–75); stage IIIA/IIIB 33/66, 33/68; and PS of 0/1 46/53, 50/51, for the DP arm and for the MVP arm, respectively. The response rates for the DP arm and the MVP arm were 78.8% and 70.3%, respectively. The 1- and 2-year survival rates were 81.8% and 59.9% for the DP arm, and were 68.8% and 49.1% for the MVP arm, respectively. Median follow up time is 1.4 years in January 2006. Complete analysis will be fixed in July 2007. Conclusions: The DP arm is exactly reproducing the response rate and survival of the phase II trial we have previously reported. The MVP arm seems to reveal better results than that we expected. Radiation dose and schedule might explain the difference because Furuse et al. splitted 56 Gy of TRT in the MVP arm whereas we did not split 60 Gy of TRT. No significant financial relationships to disclose.

Outcomes for elderly advanced stage non-small cell lung cancer (NSCLC) patients (pts) treated with bevacizumab (B) in combination with carboplatin (C) and paclitaxel (P): Analysis of Eastern Cooperative Oncology Group (ECOG) 4599 study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7535-7535 ◽  
Author(s):  
S. S. Ramalingam ◽  
S. E. Dahlberg ◽  
C. J. Langer ◽  
R. Gray ◽  
C. P. Belani ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Response Rate ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
The Elderly ◽  
Phase Iii ◽  
Motor Neuropathy ◽  
Seer Data ◽  
Elderly Cohort ◽  
Nsclc Patients

7535 Background: PC administered in combination with bevacizumab extends survival for advanced non-squamous NSCLC pts. Based on SEER data, elderly pts (age ≥70 years) represent >50% of all new cases of lung cancer and present unique therapeutic challenges. The ECOG 4599 database was analyzed to compare the outcomes in elderly pts treated with PCB vs. PC alone. Methods: Pts ≥ 70 years at study entry constituted the elderly cohort. Each arm (PCB vs. PC) and age group (≥70 vs. <70) was compared with respect to baseline pt characteristics, response rate (RR), progression-free survival (PFS), survival and toxicity. Results: Out of 850 eligible pts, 26% (N=224) were ≥ 70 years of age (1.6% ≥ 80 years). Median age for the elderly was 74 yrs; 44% were ≥ 75 yrs. Baseline characteristics of the elderly cohort were similar to the younger group except for a higher proportion of males (62% vs. 52%, P = 0.005). For the elderly pts, there was a trend towards superior response rate (29% vs. 17%, P = 0.067) and median PFS (5.9 mos vs. 4.9 mos, P = 0.063) with PCB when compared to PC, though there was no difference in overall survival (PCB = 11.3 mos; PC = 12.1 mos; P = 0.4). Grades 3–5 toxicities (CTC version 2.0) were noted in 87% of elderly pts treated with PCB compared to 61% with PC (P < 0.001). Treatment-related death rates with PCB vs. PC were 6.3% vs. 1.8% (NS) for the elderly. Febrile neutropenia (6% vs. 0.9%), proteinuria (8% vs. 0) and hypertension (6% vs. 0.9%) were more common with PCB than PC among the elderly. When compared to younger pts, the elderly experienced more neutropenia (34% vs. 22%), bleeding (7.9% vs. 3.2%), proteinuria (7.9% vs. 1.3%), muscle weakness (7.9% vs. 2.2%) and motor neuropathy (3.5% vs. 0.6%) with PCB. Conclusions: The proportion of elderly patients in ECOG 4599 is the highest recorded among ECOG phase III studies for advanced NSCLC. Increased toxicity with the addition of bevacizumab in those ≥ 70 yrs may have contributed to the absence of survival benefit for PCB vs PC, but this observation is limited by its post-hoc, retrospective nature. No significant financial relationships to disclose.

A phase II trial of ZD6474 plus docetaxel in patients with previously treated NSCLC: Follow-up results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7016-7016 ◽  
Author(s):  
J. V. Heymach ◽  
B. E. Johnson ◽  
D. Prager ◽  
E. Csada ◽  
J. Roubec ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Survival Data ◽  
Locally Advanced ◽  
Primary Objective ◽  
Phase Iii ◽  
Double Blind Study ◽  
Once Daily ◽  
Platinum Based Chemotherapy

7016 Background: ZD6474, a once-daily oral agent, targets key signaling pathways in cancer by inhibiting VEGF, EGF and RET receptor tyrosine kinases. ZD6474 in combination with docetaxel (Doc) was assessed in patients (pts) with refractory non-small-cell lung cancer (NSCLC). Methods: Pts eligible for this randomized, double-blind study had locally advanced or metastatic (stage IIIB/IV) NSCLC after failure of 1st-line platinum-based chemotherapy. The primary objective was to determine whether once-daily oral ZD6474 (100 or 300 mg) + Doc (75 mg/m2 i.v. infusion every 21 days) prolonged progression-free survival (PFS) vs Doc alone (80% power to detect 50% prolongation at P<0.2). Overall survival was a secondary objective. Results: A total of 127 pts (73 male/54 female; median age 59 yrs, range 29–82) received ZD6474 100 mg + Doc (n=42), ZD6474 300 mg + Doc (n=44) or Doc (n=41). The study met its primary objective of PFS prolongation with the addition of ZD6474: median PFS was 19 wks for ZD6474 100 mg + Doc (HR=0.64; P=0.074); 17 wks for ZD6474 300 mg + Doc (HR=0.83; P=0.461); and 12 wks for Doc. A total of 64 pts (50%) presented with histology other than adenocarcinoma, including 37 with squamous, and 13 pts (10%) entered with CNS metastases. Exploratory subgroup analyses suggest advantages in PFS for ZD6474 + Doc vs Doc both for adenocarcinoma and for other lung cancer histologies. Common adverse events (AEs) included diarrhea, rash and asymptomatic QTc prolongation, all responded to standard management or dose interruption/reduction. Four pts with squamous experienced hemoptysis (ZD6474 100 mg + Doc, n=2 CTC grade 1/2; Doc, n=2 CTC grade 3/4). No fatal episodes of hemoptysis or any CNS hemorrhage AEs were reported in pts receiving ZD6474. Overall survival data were immature at the time of PFS analysis, and a mature survival analysis will be conducted at ∼75% of deaths (anticipated April 2006, and will be presented at the meeting). As of December 2005, 40/127 (31%) pts were alive, 5 of whom continue to receive ZD6474. The minimum follow-up of pts still alive was 17 months. Conclusions: ZD6474 + Doc prolonged PFS vs Doc alone, and these promising data have led to the initiation of Phase III evaluation of ZD6474 + Doc in 2nd-line NSCLC. [Table: see text]

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