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.

DeCIDE: A phase III randomized trial of docetaxel (D), cisplatin (P), 5-fluorouracil (F) (TPF) induction chemotherapy (IC) in patients with N2/N3 locally advanced squamous cell carcinoma of the head and neck (SCCHN).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5500-5500 ◽  
Author(s):  
Ezra E. W. Cohen ◽  
Theodore Karrison ◽  
Masha Kocherginsky ◽  
Chao H Huang ◽  
Mark Agulnik ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Survival Rates ◽  
Phase Iii ◽  
High Survival ◽  
Open Label ◽  
Free Survival ◽  
Prior Therapy ◽  
Distant Failure ◽  
Grade 3

5500 Background: IC is associated with lower distant failure (DF) rates in SCCHN but an improvement in overall survival (OS) has not been validated. The goal of this trial was to determine whether IC prior to chemoradiotherapy (CRT) improves survival compared to CRT alone. Methods: In this phase 3, open-label trial, subjects with pathologically confirmed SCCHN; N2/N3 disease without metastases; no prior therapy; KPS ³ 70%; and intact organ function were randomized to CRT alone (CRT arm) [5 days of D (25 mg/m2), F (600 mg/m2), hydroxyurea (500 mg BID), and RT (150 cGy BID) followed by a 9 day break] or to 2 cycles of IC [D (75 mg/m2), P (75 mg/m2), F (750 mg/m2 day 1-5)] followed by the same CRT (IC arm). Primary endpoint was OS. Secondary endpoints included DF free survival, failure pattern, and recurrence-free survival (RFS). 280 subjects provided 80% power to detect a hazard ratio HR=0.5 for OS (a=0.05). Results: 280 subjects were accrued from 2004-09 with minimum follow-up 24 months. Of 142 patients randomized to IC, 91% received 2 cycles and 87% continued to CRT. Treatment adherence during CRT was high for docetaxel and hydroxyurea, but fewer than 75% of the patients received target dose of 5FU in both arms. RT was delivered without major deviations in 94% and 95% of patients on IC and CRT arms, respectively. The most common grade 3-4 toxicities during IC were febrile neutropenia (9%) and mucositis (8%), and during CRT (both arms combined) they were mucositis (45%), dermatitis (19%), and leukopenia (17%). Only grade 3-4 leukopenia and neutropenia rates were significantly higher in IC (p=0.002 and p=0.02, respectively). Table shows efficacy. Conclusions: High survival rates were observed in both arms. Further analysis and follow-up may provide insight into why the significant decrease in DF did not translate into improved OS. [Table: see text]

Induction chemotherapy with docetaxel, cisplatin, and 5FU (TPF) in unresectable advanced head and neck squamous cell carcinoma: Retrospective analysis of 300 cases and proposal for a prognostic index.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16055-e16055
Author(s):  
Alexandre Bozec ◽  
Nicolas Fakhry ◽  
Charlotte Dupuis ◽  
Benjamin Lallemant ◽  
Marc Alfonsi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Alcohol Intoxication ◽  
Locally Advanced ◽  
Neck Squamous Cell Carcinoma ◽  
Phase Iii ◽  
Grade 3

e16055 Background: Phase III studies have demonstrated that induction chemotherapy with TPF followed by cisplatin-based chemoradiation (CRT) is a valid option for the treatment of advanced unresectable head and neck squamous cell carcinoma. These studies have been done in highly selected patients. The aim of our study is to confirm these data in unselected patients and to identify prognostic factors of tolerance and survival. Methods: Between October 2005 and June 2010, 300 patients from 5 institutions with locally advanced neck and head cancer received at least one induction cycle, followed by locoregional radiotherapy (R) associated or not with platinum (P) or cetuximab (C)-based chemotherapy. Results: Mean age was 56 years old (range 31-76). Performance status was 0 or 1 in 97% of patients and 50 % of them presented current alcohol intoxication. 69% (n=208) received 3 cycles of TPF, and 91% (n=268) underwent R associated or not with P (n=167) or C (n=51). 52% of patients (n=156) received the conform treatment (ie 3TPF + RP or RC). Grade 3-4 toxicities have been reported in 19% (n= 57), including 3% febrile neutropenia (n=9) and 7% kidney failure (n=22). Grade 3-4 toxicity, during TPF induction, led systematically to permanently discontinuation of the chemotherapy. Overall response rate after TPF induction was of 88% with 23% of complete response. After a median follow-up of 21 months, median progression-free survival and cause-specific survival (SS) were not reached. Median overall survival (OS) was 49 months (95% CI 31.2-66.8). SS and OS were significantly improved (p<0.0001) in patients who received the conform treatment. In multivariate analysis the probability of death related to cancer or to toxicities induced by treatment was increased for hemoglobin level ≤ 12.6g/dl or GGT level ≥ 77U/I [HR = 3.45 (95% CI: 1.50-7.93) p=0.0029]. Conclusions: We propose to use a biological index based on baseline hemoglobin and GGT levels to select patient for induction therapy in SCCHN. This simple index, predictive of treatment conformity and specific survival, needs further prospectives investigations.

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 Induction Chemotherapy Followed by Cetuximab Radiotherapy Is Not Superior to Concurrent Chemoradiotherapy for Head and Neck Carcinomas: Results of the GORTEC 2007-02 Phase III Randomized Trial

2018 ◽  
Vol 36 (31) ◽  
pp. 3077-3083 ◽  
Author(s):  
Lionnel Geoffrois ◽  
Laurent Martin ◽  
Dominique De Raucourt ◽  
Xu Shan Sun ◽  
Yungan Tao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Free Survival

Purpose Both concurrent chemoradiotherapy (CT-RT) and cetuximab radiotherapy (cetux-RT) have been established as the standard of care for the treatment of locally advanced squamous cell carcinoma of the head and neck. It was not known whether the addition of induction chemotherapy before cetux-RT could improve outcomes compared with standard of care CT-RT. Patients and Methods The current trial was restricted to patients with nonmetastatic N2b, N2c, or N3 squamous cell carcinoma of the head and neck and fit for taxotere, cisplatin, fluorouracil (TPF). Patients were randomly assigned to receive three cycles of TPF followed by cetux-RT versus concurrent carboplatin fluorouracil and RT as recommended in National Comprehensive Cancer Network guidelines. The trial was powered to detect a hazard ratio (HR) of 0.66 in favor of TPF plus cetux-RT for progression-free survival at 2 years. The inclusion of 180 patients per arm was needed to achieve 80% power at a two-sided significance level of .05. Results Between 2009 and 2013, 370 patients were included. All patients and tumors characteristics were well balanced between arms. There were more cases of grade 3 and 4 neutropenia in the induction arm, and the induction TPF was associated with 6.6% treatment-related deaths. With a median follow-up of 2.8 years, 2-year progression-free survival was not different between both arms (CT-RT, 0.38 v TPF + cetux-RT, 0.36; HR, 0.93 [95% CI, 0.73 to 1.20]; P = .58). HR was 0.98 (95% CI, 0.74 to 1.3; P = .90) for locoregional control and 1.12 (95% CI, 0.86 to 1.46; P = .39) for overall survival. These effects were observed regardless of p16 status. The rate of distant metastases was lower in the TPF arm (HR, 0.54 [95% CI, 0.30 to 0.99]; P = .05). Conclusion Induction TPF followed by cetux-RT did not improve outcomes compared with CT-RT in a population of patients with advanced cervical lymphadenopathy.

Once-a-Week Versus Once-Every-3-Weeks Cisplatin Chemoradiation for Locally Advanced Head and Neck Cancer: A Phase III Randomized Noninferiority Trial

2018 ◽  
Vol 36 (11) ◽  
pp. 1064-1072 ◽  
Author(s):  
Vanita Noronha ◽  
Amit Joshi ◽  
Vijay Maruti Patil ◽  
Jaiprakash Agarwal ◽  
Sarbani Ghosh-Laskar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Head And Neck ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Absolute Difference ◽  
Comparable Efficacy ◽  
Advanced Head ◽  
Adjuvant Setting ◽  
Free Survival

Purpose Chemoradiation with cisplatin 100 mg/m2 given once every 3 weeks is the standard of care in locally advanced head and neck squamous cell cancer (LAHNSCC). Increasingly, low-dose once-a-week cisplatin is substituted because of perceived lower toxicity and convenience. However, there is no level 1 evidence of comparable efficacy to cisplatin once every 3 weeks. Patients and Methods In this phase III randomized trial, we assessed the noninferiority of cisplatin 30 mg/m2 given once a week compared with cisplatin 100 mg/m2 given once every 3 weeks, both administered concurrently with curative intent radiotherapy in patients with LAHNSCC. The primary end point was locoregional control (LRC); secondary end points included toxicity, compliance, response, progression-free survival, and overall survival. Results Between 2013 and 2017, we randomly assigned 300 patients, 150 to each arm. Two hundred seventy-nine patients (93%) received chemoradiotherapy in the adjuvant setting. At a median follow-up of 22 months, the estimated cumulative 2-year LRC rate was 58.5% in the once-a-week arm and 73.1% in the once-every-3-weeks arm, leading to an absolute difference of 14.6% (95% CI, 5.7% to 23.5%); P = .014; hazard ratio (HR), 1.76 (95% CI, 1.11 to 2.79). Acute toxicities of grade 3 or higher occurred in 71.6% of patients in the once-a-week arm and in 84.6% of patients in the once-every-3-weeks arm ( P = .006). Estimated median progression-free survival in the once-a-week arm was 17.7 months (95% CI, 0.42 to 35.05 months) and in the once-every-3-weeks arm, 28.6 months (95% CI, 15.90 to 41.30 months); HR, 1.24 (95% CI, 0.89 to 1.73); P = .21. Estimated median overall survival in the once-a-week arm was 39.5 months and was not reached in the once-every-3-weeks arm (HR, 1.14 [95% CI, 0.79 to 1.65]; P = .48). Conclusion Once-every-3-weeks cisplatin at 100 mg/m2 resulted in superior LRC, albeit with more toxicity, than did once-a-week cisplatin at 30 mg/m2, and should remain the preferred chemoradiotherapy regimen for LAHNSCC in the adjuvant setting.

scholarly journals Induction Chemotherapy in Head and Neck Squamous Cell Carcinoma: A Question of Belief

Cancers ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 15 ◽  
Author(s):  
Andy Karabajakian ◽  
Max Gau ◽  
Thibault Reverdy ◽  
Eve-Marie Neidhardt ◽  
Jérôme Fayette
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Neck Squamous Cell Carcinoma ◽  
Larynx Preservation ◽  
Distant Failure

Induction chemotherapy (IC) in locally advanced head and neck squamous cell carcinoma (LA HNSCC) has been used for decades. However, its role is yet to be clearly defined outside of larynx preservation. Patients with high risk of distant failure might potentially benefit from sequential treatment. It is now widely accepted that TPF (docetaxel, cisplatin, and fluorouracil) is the standard IC regimen. Essays that have compared this approach with the standard of care, concurrent chemoradiotherapy (CCRT), are mostly inconclusive. Radiotherapy (RT) can be used in the post-IC setting and be sensitized by chemotherapy or cetuximab. Again, no consensus exists but there seems to be trend in favor of potentiation by cisplatin. Less toxic schemes of IC are tested as toxicity is a major issue with TPF. IC might have an interesting role in human papilloma virus (HPV)-related LA HNSCC and lead to CCRT de-escalation.

scholarly journals RACE-trial: neoadjuvant radiochemotherapy versus chemotherapy for patients with locally advanced, potentially resectable adenocarcinoma of the gastroesophageal junction - a randomized phase III joint study of the AIO, ARO and DGAV

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Sylvie Lorenzen ◽  
Alexander Biederstädt ◽  
Ulrich Ronellenfitsch ◽  
Christoph Reißfelder ◽  
Stefan Mönig ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Preoperative Chemotherapy ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Neoadjuvant Radiochemotherapy ◽  
Perioperative Chemotherapy ◽  
Free Survival ◽  
Link Type

Abstract Background Despite obvious advances over the last decades, locally advanced adenocarcinomas of the gastroesophageal junction (GEJ) still carry a dismal prognosis with overall 5-year survival rates of less than 50% even when using modern optimized treatment protocols such as perioperative chemotherapy based on the FLOT regimen or radiochemotherapy. Therefore the question remains whether neoadjuvant chemotherapy or neoadjuvant radiochemotherapy is eliciting the best results in patients with GEJ cancer. Hence, an adequately powered multicentre trial comparing both therapeutic strategies is clearly warranted. Methods The RACE trial is a an investigator initiated multicenter, prospective, randomized, stratified phase III clinical trial and seeks to investigate the role of preoperative induction chemotherapy (2 cycles of FLOT: 5-FU, leucovorin, oxaliplatin, docetaxel) with subsequent preoperative radiochemotherapy (oxaliplatin weekly, 5-FU plus concurrent fractioned radiotherapy to a dose of 45 Gy) compared to preoperative chemotherapy alone (4 cycles of FLOT), both followed by resection and postoperative completion of chemotherapy (4 cycles of FLOT), in the treatment of locally advanced, potentially resectable adenocarcinoma of the gastroesophageal junction. Patients with cT3–4, any N, M0 or cT2 N+, M0 adenocarcinoma of the GEJ are eligible for inclusion. The RACE trial aims to enrol 340 patients to be allocated to both treatment arms in a 1:1 ratio stratified by tumour site. The primary endpoint of the trial is progression-free survival assessed with follow-up of maximum 60 months. Secondary endpoints include overall survival, R0 resection rate, number of harvested lymph nodes, site of tumour relapse, perioperative morbidity and mortality, safety and toxicity and quality of life. Discussion The RACE trial compares induction chemotherapy with FLOT followed by preoperative oxaliplatin and 5-Fluorouracil-based chemoradiation versus preoperative chemotherapy with FLOT alone, both followed by surgery and postoperative completion of FLOT chemotherapy in the treatment of locally advanced, non-metastatic adenocarcinoma of the GEJ. The trial aims to show superiority of the combined chemotherapy/radiochemotherapy treatment, assessed by progression-free survival, over perioperative chemotherapy alone. Trial registration ClinicalTrials.gov; NCT04375605; Registered 4th May 2020;

Randomized phase II trial of concomitant CT/RT versus TPF followed by concomitant CT/RT in locally advanced squamous cell carcinoma of the head and neck (LASCCHN)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5518-5518 ◽  
Author(s):  
A. Paccagnella ◽  
A. Buffoli ◽  
H. Koussis ◽  
P. D’Amanzo ◽  
L. Loreggian ◽  
...  
Keyword(s):  
Standard Treatment ◽  
Locally Advanced ◽  
Phase Iii ◽  
Serious Adverse Events ◽  
Randomized Phase Ii ◽  
Phase Iii Study ◽  
The Difference ◽  
Grade 3 ◽  
Toxicity Pattern ◽  
Pathological Cr

5518 Background: Concomitant CT/RT is the standard treatment for LASCCHN. Induction chemotherapy followed by CT/RT vs CT/RT alone have not yet been compared. The feasibility of TPF followed by CT/RT has been evaluated in a previous study (Int J Rad Oncol Biol Phys 2004, 59:481). Methods: Pts with inoperable stage III-IVa, PS 0–1, were randomized to CT/RT [2 cycles of Cisplatin 20 mg/sqm days 1–4, 5FU 800 mg/sqm 96 hours c.i. weeks 1 and 6 during RT (66–70 Gy)] (Arm A) or 3 cycles of neoadjuvant TPF (Docetaxel 75mg/sqm day1, Cisplatin 80mg/sqm day1, 5FU 800mg/sqm 96 hours c.i) followed by the same CT/RT (Arm B). Pts were stratified according to tumor site, T stage and nodal status. Neck dissection was performed in N2-N3 patients with pathological CR on primary tumor. The planned sample size was 96 pts to detect a difference in CR (primary endpoint) up to 15% in favour of arm B. The radiological responses were evaluated by an internal committee according to RECIST criteria. Results: Preliminary data are available for 84/96 randomized pts (42 arm A, 42 arm B). Pts/tumor characteristics are well balanced in the two arms. Toxicities during induction TPF consisted primarily of G3–4 granulocytopenia 56% (febrile neutropenia: 7.5%). Grade 3–4 toxicities during CT/RT in arm A and B were mucositis (42% and 26%), dysphagia (20% and 9%), skin reaction (12% and 8.6%), asthenia (5% and 3%); G3 weight loss (2% and 3%), G3 dry-mouth (0% and 3%). Duration of CT/RT was equivalent: 6.1 wks (4.2–8.7) in arm A and 6.3 wks (3.8–9.5) in arm B. At the end of CT/RT, in the 82 pts evaluable for efficacy, radiological CR were 20% (95% CI 8–37%) in arm A and 64% (95% CI 45–80%) in arm B. Conclusions: Three cycles of neoadjuvant TPF are feasible and don’t compromise subsequent concomitant CT/RT with comparable toxicity pattern. At the end of the treatment sequence serious adverse events were 31% in arm A and 34% in arm B. The difference in CR of 40% in favour of arm B justifies the following phase III study. Final results including pCR and DFS will be presented at the meeting. [Table: see text]

Results of a phase III, randomized, double-blind, placebo-controlled trial of pegfilgrastim (PEG) in patients (pts) receiving first-line FOLFOX or FOLFIRI and bevacizumab (B) for colorectal cancer (CRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3575-3575
Author(s):  
Tamas Pinter ◽  
Esteban Abella ◽  
Alvydas Cesas ◽  
Adina Croitoru ◽  
Jochen Decaestecker ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Double Blind ◽  
Free Survival ◽  
Clinically Significant ◽  
Grade 3

3575 Background: The literature reports that adding biologics to chemotherapy (ctx) may increase the incidence of clinically significant neutropenia. his trial was conducted to evaluate the efficacy of PEG in reducing the incidence of febrile neutropenia (FN) in pts with locally-advanced (LA) or metastatic (m)CRC receiving first-line treatment with either FOLFOX/B or FOLFIRI/B. Methods: Key eligibility: ≥ 18 years old; measurable, nonresectable CRC per RECIST 1.1. Pts were randomly assigned 1:1 to either placebo or 6 mg PEG ~24 h after ctx/B. The study treatment period included four Q2W cycles, but pts could continue their assigned regimen until progression. Pts were stratified by region (North America vs rest of world), stage (LA vs mCRC), and ctx (FOLFOX vs FOLFIRI). Estimated sample size (N = 800) was based on the expected incidence of grade 3/4 FN (primary endpoint) across the first 4 cycles of ctx/B, powered for PEG superiority over placebo. Other endpoints included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: 845 pts were randomized (Nov 2009 to Jan 2012) and received study treatment; 783 pts completed 4 cycles of ctx/B. Median age was 61 years; 512 (61%) pts were male; 819 (97%) had mCRC; 414 (49%) received FOLFOX, and 431 (51%) received FOLFIRI. Grade 3/4 FN (first 4 cycles) for placebo vs PEG was 5.7% vs 2.4%; OR 0.41; p = 0.014. A similar incidence of other ≥ grade 3 adverse events was seen in both arms (28% placebo; 27% PEG). See table for additional results. Conclusions: PEG significantly reduced the incidence of grade 3/4 FN in this pt population receiving standard ctx/B for CRC. Follow-up is ongoing. Clinical trial information: NCT00911170. [Table: see text]

Adjuvant chemotherapy with S-1 after curative treatment in patients with head and neck cancer (ACTS-HNC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6004-6004 ◽  
Author(s):  
Takahide Taguchi ◽  
Akira Kubota ◽  
Kunitoshi Yoshino ◽  
Kichinobu Tomita ◽  
Naoyuki Kohno ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Head And Neck ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Curative Treatment ◽  
Free Survival ◽  
End Point ◽  
Phase Iii Study ◽  
P 16 ◽  
Grade 3

6004 Background: To establish the efficacy of adjuvant chemotherapy with S-1 (tegafur gimeracil oteracil potassium) after curative treatment in patients with advanced squamous cell carcinoma of the head and neck (SCCHN), we conducted a randomized phase III study to investigate whether S-1 is superior to UFT (uracil/tegafur). Methods: Patients with SCCHN who had received curative treatment and were confirmed to be tumor-free were randomly assigned to receive UFT (300 or 400 mg/day for 1 year) or S-1 (80, 100, or 120 mg/day for 1 year). The primary end point was disease-free survival (DFS). Secondary end points were overall survival (OS), relapse-free survival (RFS), and safety. We estimated that 500 patients were needed to establish the primary end point. Results: From April 2006 through November 2008, a total of 526 patients (262 assigned to UFT; 264 assigned to S-1) were enrolled. The 3-year DFS rate was 66.0% in the UFT group and 64.1% in the S-1 group (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.66 to 1.16; [log-rank], P = .34). The 3-year OS rate was 75% in the UFT group and 82.9% in the S-1 group (HR, 0.64; 95% CI, 0.44 to 0.94; [log-rank], P = .022). The 3-year RFS rate was 63.6% in the UFT group and 68.2% in the S-1 group (HR, 0.81; 95% CI, 0.60 to 1.09; [log-rank], P = .16). There were no significant differences in 3-year DFS or RFS; however, the 3-year OS was significantly better in the S-1 group. The incidence of the following grade 3 or 4 events was significantly higher in the S-1 group: oral mucositis/stomatitis (2.4%), leukopenia (5.2%), neutropenia (3.6%), and thrombocytopenia (5.0%). Conclusions: S-1 was not demonstrated to be superior to UFT in terms of 3-year DFS; however, 3-year OS was significantly better with S-1 than with UFT. Clinical trial information: NCT00336947.

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