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 Bevacizumab in combination with fluoropyrimidine-based chemotherapy for the first-line treatment of metastatic colorectal cancer

2010 ◽  
Vol 14 (Suppl 2) ◽  
pp. 47-53
Author(s):  
S Whyte ◽  
A Pandor ◽  
M Stevenson ◽  
A Rees
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Absolute Difference ◽  
First Line ◽  
Open Label ◽  
Open Label Study ◽  
Free Survival

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of bevacizumab in combination with fluoropyrimidine-based chemotherapy for the first-line treatment of metastatic colorectal cancer based on the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. Evidence was available in the form of one phase III, multicentre, multinational, randomised, open-label study (NO16966 trial). This two-arm study was originally designed to demonstrate the non-inferiority of oral capecitabine plus oxaliplatin (XELOX) compared with 5-fluorouracil plus folinic acid plus oxaliplatin (FOLFOX)-4 in adult patients with histologically confirmed metastatic colorectal cancer who had not previously been treated. Following randomisation of 634 patients, the open-label study was amended to include a 2 × 2 factorial randomised (partially blinded for bevacizumab) phase III trial with the coprimary objective of demonstrating superiority of bevacizumab in combination with chemotherapy compared with chemotherapy alone. Measured outcomes included overall survival, progression-free survival, response rate, adverse effects of treatment and health-related quality of life. The manufacturer’s primary pooled analysis of superiority (using the intention-to-treat population) showed that after a median follow-up of 28 months, the addition of bevacizumab to chemotherapy significantly improved progression-free survival and overall survival compared with chemotherapy alone in adult patients with histologically confirmed metastatic colorectal cancer who were not previously treated [median progression-free survival 9.4 vs 7.7 months (absolute difference 1.7 months); hazard ratio (HR) 0.79, 97.5% confidence interval (CI) 0.72 to 0.87; p = 0.0001; median overall survival 21.2 vs 18.9 months (absolute difference 2.3 months); HR 0.83, 97.5% CI 0.74 to 0.93; p = 0.0019]. The NO16966 trial was of reasonable methodological quality and demonstrated a significant improvement in both progression-free survival and overall survival when bevacizumab was added to XELOX or FOLFOX. However, the size of the actual treatment effect of bevacizumab is uncertain. The ERG believed that the modelling structure employed was appropriate, but highlighted several key issues and areas of uncertainty. At the time of writing, NICE was yet to issue the guidance for this appraisal.

scholarly journals Radiation therapy treatment facility and overall survival in the adjuvant setting for locally advanced head and neck squamous cell carcinoma

Cancer ◽  
2019 ◽  
Vol 125 (12) ◽  
pp. 2018-2026 ◽  
Author(s):  
Nicholas C. J. Lee ◽  
Jacqueline R. Kelly ◽  
Yi An ◽  
Henry S. Park ◽  
Benjamin L. Judson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Radiation Therapy ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Locally Advanced ◽  
Advanced Head ◽  
Adjuvant Setting ◽  
Treatment Facility ◽  
Therapy Treatment

Gemcitabine versus cisplatin concurrent with radiation therapy in locally advanced head and neck squamous cell carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5557-5557
Author(s):  
Magda Mostafa ◽  
Hesham Atif ◽  
Mahmoud Fawzy ◽  
Amr Yehia Sakr ◽  
Ahmed Alashwah
Keyword(s):  
Squamous Cell Carcinoma ◽  
Radiation Therapy ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Advanced Head ◽  
Free Survival ◽  
Weekly Cisplatin

5557 Background: In locally advanced head and neck squamous cell carcinoma (HNSCC) weekly cisplatin concurrent with radiation therapy is the standared treatment. However some patients cannot tolerate cisplatin. So we conduct a prospective randomized trial comparing cisplatin versus gemcitabine. Methods: This trial was done in Kasr El-Ainy Center of Clinical Oncology and Radiation therapy (NEMROCK), during the period from March 2010 till June 2011. Sixty patients with locally advanced HNSCC were randomized to receive Cisplatin (30 mg/m2) weekly for 6 consecutive weeks (30 patients) or Gemcitabine (50 mg/m2) weekly for 6 consecutive weeks (30 patients) both concomitant with radiation therapy reaching a dose of 70 Gy over 7 weeks. Primary end points include response rate, progression free survival and toxicity. Toxicities were graded according to NCI-CTCAE v3.0. Results: Thewhole study group included 48 (80%) males and 12 (20%) females. Mean age was 47.9 (± 6.5) years (range 26-61). Both arms were comparable regarding their age, gender, performance status and stage. There were 9 (30%) CR, 7 (23.3%) PR, 2 (6.7%) SD and 12 (40%) PD in cisplatin arm versus 12 (40%) CR, 4 (13.3%) PR, 1 (3.3%) SD and 11 (36.7%) PD in gemcitabine arm. Median progression free survival (PFS) in cisplatin arm was 9 months versus 11months in gemcitabine arm with a hazard ratio of 0.08 (95% CI 0.005 – 1.47). We did not reach median overall survival. Radiotherapy induced skin toxicity (slight or patchy atrophy), nausea, vomiting, mucositis, salivary gland affection and weight loss were equally distributed in both arms. Dysphagia and fatigue were markedly higher in gemcitabine arm. While infection and neutropenia were slightly higher in cisplatin arm. Conclusions: Weekly gemcitabine 50mg/m2 concomitant with radiotherapy was found to be of equal efficacy and toxicity comparable with weekly cisplatin in the treatment of locally advanced HNSCC.

Phase III randomized trial comparing weekly versus three-weekly (W3W) cisplatin in patients receiving chemoradiation for locally advanced head and neck cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6007-6007 ◽  
Author(s):  
Vanita Noronha ◽  
Amit Joshi ◽  
Vijay Maruti Patil ◽  
Jaiprakash Agarwal ◽  
Sarbani Ghosh Laskar ◽  
...  
Keyword(s):  
Head And Neck ◽  
Dose Reduction ◽  
Cell Cancer ◽  
Locally Advanced ◽  
Phase Iii ◽  
Absolute Difference ◽  
Relative Reduction ◽  
Advanced Head ◽  
Total Treatment Time ◽  
Weekly Cisplatin

6007 Background: Chemoradiation (CRT) with cisplatin 100mg/m2 given 3-weekly is the standard of care in locally advanced head and neck squamous cell cancer (HNSCC). Substituting low dose weekly cisplatin has pharmacological rationale due to lower toxicity and enhanced radiosensitization but has never been compared to 3-weekly cisplatin. Methods: Phase III non-inferiority trial (CTRI/2012/10/003062) in patients with Stage III or IV (non-metastatic) HNSCC planned for radical CRT. Pts were stratified for T-category, N-category and intent of therapy (adjuvant versus definitive) and centrally randomized 1:1 to cisplatin 30mg/m2 weekly or 100mg/m2 3-weekly concurrently with radiotherapy. Primary endpoint was locoregional control (LRC); secondary endpoints included toxicity, compliance, response, progression-free survival and overall survival. The upper boundary of non-inferiority margin was set at 15%, assuming LRC of 60% with power 80% and alpha 0.05. Results: 300 pts were randomized,150 to each arm; median age 44 years (range: 25-67), males 89%; 71% were smokeless tobacco users. 61% were T4, 71% > N2. 93% pts received CRT as adjuvant therapy for high-risk disease; indication was perinodal extension in 84%, close/ positive margins 8%. Median total treatment time was 86 days (IQR: 79-95). Median RT dose was 60 Gy (IQR 60-60 Gy) using shrinking field technique. In the weekly arm, 133 pts (88.7%) received > 6 cycles; 14 (9%) required dose reduction, median cumulative cisplatin dose 210 mg/m2 (IQR 180-210). In the 3-weekly arm, 143 pts (95%) received > 2 cycles, median cumulative cisplatin dose 300 mg/m2 (IQR 200-300); 12 (8%) required dose reduction. At a median follow up of 20 months (range: 1-49), locoregional relapses (LRR) occurred in 42.2% pts in the weekly arm and 29.6% pts in the 3-weekly arm, leading to an absolute difference in LRR of 12.7% (95%CI:1.89-23.41), p=0.035 by Gray’s test, HR-1.58 (95%CI:1.02-2.46). Acute > grade 3 toxicity occurred in 85.3% pts in 3-weekly arm and 70.7% pts in weekly arm, p=0.002; 30.7% pts in the 3-weekly arm and 14% patients in the weekly arm required hospitalization for management of toxicity, p=0.001. Conclusions: 3-weekly cisplatin leads to 42% relative reduction in locoregional recurrence; it is superior to weekly cisplatin and should be the preferred regimen in CRT for HNSCC. Clinical trial information: CTRI/2012/10/003062.

A phase I dose escalation study of eryaspase in combination with modified FOLFIRINOX in locally advanced and metastatic pancreatic ductal adenocarcinoma.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS453-TPS453
Author(s):  
Marcus Smith Noel ◽  
Philip Agop Philip ◽  
Mohamedtaki Abdulaziz Tejani ◽  
John Marshall ◽  
Aiwu Ruth He ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase I ◽  
Pancreatic Adenocarcinoma ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

TPS453 Background: FOLFIRINOX remains the standard of care for the first line treatment of patients with locally advanced and metastatic pancreatic adenocarcinoma, however the prognosis remains poor, thus novel treatment options are indicated. Eryaspase, asparaginase (ASNase) encapsulated in red blood cells (RBCs) is an investigational product under development. Following infusion, asparagine and glutamine are actively transported into RBCs where they are hydrolyzed by the encapsulated ASNase. A randomized phase IIb study in patients with advanced pancreatic cancer whose disease progressed following first-line treatment (NCT02195180) was previously conducted. Eryaspase in combination with gemcitabine monotherapy or FOLFOX combination therapy improved overall survival (OS) and progression free survival (PFS). The safety profile of eryaspase was acceptable. A second line pivotal randomized phase III trial (Trybeca-1) is currently enrolling (NCT03665441). We design this phase I study to determine the safety of mFOLFIRINOX combined with Eryaspase in the first line of treatment. Methods: Patients with locally or metastatic biopsy proven pancreatic adenocarcinoma will be treated with the combination of mFOLFIRINOX plus Eryaspase. This will be a standard 3+3 design with 4 possible doing levels. mFOLFIRINOX dosing will include 5-Fluorouracil 2400 mg/m2 over 46 hours, Oxaliplatin 85 mg/m2, Irinotecan 150 mg/m2 plus Eryaspase 75 Units/kg at dose level 0. Eryaspase will be dose escalated up to 100 Units/kg. The study will enroll at three academic centers. Key eligibility criteria include performance status 0 or 1; locally advanced or metastatic tumor disease; adequate organ function. The primary objective is to determine the maximum tolerated dose and safety of this novel combination. Key secondary objectives include objective response rate, progression-free survival, overall survival, pharmacokinetics, pharmacodynamics, and biomarker research. A data safety monitoring committee will review data every 3 months. Clinical trial information: 04292743.

scholarly journals Induction Chemotherapy with Docetaxel, Cisplatin and 5-Fluorouracil (TPF) Followed by Chemoradiotherapy for Locally Advanced Head and Neck Cancer: Can It Achieve Its Potential?

2020 ◽  
pp. 1-10
Author(s):  
Nicholas P Rowell ◽  
Nicholas P Rowell
Keyword(s):  
Overall Survival ◽  
Induction Chemotherapy ◽  
Treatment Time ◽  
Locally Advanced ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Advanced Head ◽  
Free Survival ◽  
The Mean ◽  
Delivered Dose

Objective: In view of concerns about toxicity and deliverability of induction chemotherapy and its impact on subsequent chemoradiotherapy, a retrospective review was carried out with patients treated for locally advanced head and neck cancer (LAHNC) in a single centre between 2007-2017. Patients and Interventions: Patients with LAHNC and good performance status receiving induction chemotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF) followed by chemoradiotherapy to 70Gy in 35 daily fractions with platinum-based chemotherapy. Main Outcome Measures: Overall and cause-specific survival, rates of locoregional recurrence or distant metastasis, treatment-related toxicity. Results: One hundred and eight patients with LAHNC were treated with 1-4 cycles of TPF (95 receiving two cycles) followed by chemoradiotherapy. The mean delivered dose intensity was 97.6% for all TPF cycles. Median interval from the start of the final cycle of TPF to the start of radiotherapy was 24 days, with 92/103 (89%) starting radiotherapy within 28 days. Median radiation treatment time was 47 days. The mean delivered dose intensity for chemotherapy delivered concurrently with radiotherapy was 97%. There were significantly fewer dose reductions in those receiving platinum/5FU combinations than platinum only regimes (P < 0.0001). For those receiving two cycles of TPF, 90% of patients completed the whole course of treatment within 14 weeks (median overall treatment time 13.1 weeks). There were four treatment-related deaths during induction chemotherapy and none during radiotherapy. Twenty-five developed locoregional failure and 13 distant metastases (both in eight). Actuarial overall survival was 60.7% at five years, with progression-free survival of 77.9% at two years and 74.1% at five years. For oropharynx cancers, overall survival was 70.4% and progression-free survival 80.8% at five years. Conclusion: Although significant toxicity from TPF was observed, with appropriate support, it is possible to complete treatment without undue compromise of subsequent treatment.

Randomized Phase III Trial of Gemcitabine Plus Cisplatin Compared With Gemcitabine Alone in Advanced Pancreatic Cancer

2006 ◽  
Vol 24 (24) ◽  
pp. 3946-3952 ◽  
Author(s):  
Volker Heinemann ◽  
Detlef Quietzsch ◽  
Frank Gieseler ◽  
Michael Gonnermann ◽  
Herbert Schönekäs ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Median Overall Survival ◽  
Statistical Significance ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Free Survival

Purpose To compare the effectiveness and tolerability of gemcitabine plus cisplatin with single-agent gemcitabine as first-line chemotherapy for locally advanced or metastatic pancreatic cancer. Patients and Methods Patients with advanced adenocarcinoma of the pancreas were randomly assigned to receive either gemcitabine 1,000 mg/m2 and cisplatin 50 mg/m2 given on days 1 and 15 of a 4-week cycle (GemCis arm) or gemcitabine alone at a dose of 1,000 mg/m2 on days 1, 8, and 15 of a 4-week regimen (Gem arm). The primary end point was overall survival; secondary end points were progression-free survival, response rate, safety, and quality of life. Results One hundred ninety-five patients were enrolled and showed baseline characteristics well balanced between treatment arms. Combination treatment in the GemCis arm was associated with a prolonged median progression-free survival (5.3 months v 3.1 months; hazard ratio [HR] = 0.75; P = .053). Also, median overall survival was superior for patients treated in the GemCis arm as compared with the Gem arm (7.5 v 6.0 months), an advantage which did not, however, reach statistical significance (HR = 0.80; P = .15). Tumor response rates were comparable between treatment arms (10.2% v 8.2%). The rate of stable disease was, however, greater in the combination arm (60.2% v 40.2%; P < .001). Grade 3 to 4 hematologic toxicity did not exceed 15% in both treatment arms. Conclusion These results support the efficacy and safety of an every-2-weeks treatment with gemcitabine plus cisplatin. Median overall survival and progression-free survival were more favorable in the combination arm as compared with gemcitabine alone, although the difference did not attain statistical significance.

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.

Recurrent Epithelial Ovarian Carcinoma: A Randomized Phase III Study of Pegylated Liposomal Doxorubicin Versus Topotecan

2001 ◽  
Vol 19 (14) ◽  
pp. 3312-3322 ◽  
Author(s):  
Alan N. Gordon ◽  
John T. Fleagle ◽  
David Guthrie ◽  
David E. Parkin ◽  
Martin E. Gore ◽  
...  
Keyword(s):  
Overall Survival ◽  
Ovarian Carcinoma ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Epithelial Ovarian Carcinoma ◽  
Phase Iii ◽  
Comparable Efficacy ◽  
Bulky Disease ◽  
Free Survival

PURPOSE: To compare the efficacy and safety of pegylated liposomal doxorubicin (PLD) and topotecan in patients with epithelial ovarian carcinoma that recurred after or didn’t respond to first-line, platinum-based chemotherapy. PATIENTS AND METHODS: Patients with measurable and assessable disease were randomized to receive either PLD 50 mg/m2 as a 1-hour infusion every 4 weeks or topotecan 1.5 mg/m2/d for 5 consecutive days every 3 weeks. Patients were stratified prospectively for platinum sensitivity and for the presence or absence of bulky disease. RESULTS: A total of 474 patients were treated (239 PLD and 235 topotecan). They comprised the intent-to-treat population. The overall progression-free survival rates were similar between the two arms (P = .095). The overall response rates for PLD and topotecan were 19.7% and 17.0%, respectively (P = .390). Median overall survival times were 60 weeks for PLD and 56.7 weeks for topotecan. Data analyzed in platinum-sensitive patients demonstrated a statistically significant benefit from PLD for progression-free survival (P = .037), with medians of 28.9 for PLD versus 23.3 weeks for topotecan. For overall survival, PLD was significantly superior to topotecan (P = .008), with a median of 108 weeks versus 71.1 weeks. The platinum-refractory subgroup demonstrated a nonstatistically significant survival trend in favor of topotecan (P = .455). Severe hematologic toxicity was more common with topotecan and was more likely to be associated with dosage modification, or growth factor or blood product utilization. CONCLUSION: The comparable efficacy, favorable safety profile, and convenient dosing support the role of PLD as a valuable treatment option in this patient population.

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