Phase III trial of modulation of cisplatin/fluorouracil chemotherapy by interferon alfa-2b in patients with recurrent or metastatic head and neck cancer. Head and Neck Interferon Cooperative Study Group.

1998 ◽  
Vol 16 (3) ◽  
pp. 1054-1059 ◽  
Author(s):  
D Schrijvers ◽  
J Johnson ◽  
U Jiminez ◽  
M Gore ◽  
P Kosmidis ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Median Survival ◽  
Neck Cancer ◽  
Controlled Trial ◽  
Local Therapy ◽  
Interferon Alfa ◽  
Phase Iii ◽  
Treatment Center ◽  
Multicenter Randomized Controlled Trial

PURPOSE In preclinical experiments, interferon alfa modulates the anticancer activity of fluorouracil (5-FU) and cisplatin (CDDP). To test this effect clinically in patients with recurrent or metastatic head and neck cancer (RMHNC), a multicenter randomized controlled trial with CDDP and 5-FU with or without interferon alfa-2b (IFNalpha) was performed. PATIENTS AND METHODS Eligible patients had histologically confirmed RMHNC; a good performance status; measurable disease; adequate bone marrow, hepatic, and renal function; no prior chemotherapy for recurrent or metastatic disease; only one chemotherapy regimen administered with previous local therapy; and a treatment-free interval of at least 3 months following previous local therapy. Patients were randomized and stratified according to treatment center, and prior radiotherapy and chemotherapy. The treatment regimen consisted of CDDP 100 mg/m2 on day 1 and 5-FU 1,000 mg/m2/d by continuous infusion for 96 hours (days 1 to 4), without (arm A) or with (arm B) IFNg alpha 3 x 10(6) U/d subcutaneously on days 1 to 5. Cycles were repeated every 21 days. RESULTS One hundred twenty-two patients were entered on each arm. The response rate (RR) was similar in both arms (arm A: complete response [CR] 10.7%, partial response [PR] 36.4%; arm B: CR 6.8%, PR 31.6%) (.70 < P < .50). There was no difference in median survival between the two arms (arm A 6.3 months v arm B 6.0 months; P = .49). Anorexia, fever, leukopenia, and thrombocytopenia grade III to IV were significantly more frequent in the IFNalpha arm. CONCLUSION Modulation of CDDP and 5-FU with IFNalpha as used in this study does not improve the RR or the median survival in patients with RMHNC. Patients on both study arms had a poor prognosis, which indicates the need for novel therapies.

First results of a phase III multicenter randomized controlled trial of intensity modulated (IMRT) versus conventional radiotherapy (RT) in head and neck cancer (PARSPORT: ISRCTN48243537; CRUK/03/005)

2009 ◽  
Vol 27 (18_suppl) ◽  
pp. LBA6006-LBA6006 ◽  
Author(s):  
C. Nutting ◽  
R. A'Hern ◽  
M. S. Rogers ◽  
M. A. Sydenham ◽  
F. Adab ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Controlled Trial ◽  
Late Toxicity ◽  
Primary Treatment ◽  
Phase Iii ◽  
Significance Level ◽  
Multicenter Randomized Controlled Trial ◽  
Secondary Endpoints

LBA6006 Background: Xerostomia is the most common late toxicity of RT to the head and neck. IMRT dose distributions reduce the dose delivered to parotid gland. PARSPORT investigated the role of IMRT in reducing xerostomia in patients with head and neck cancer. Methods: The PARSPORT trial compared two radiotherapy delivery methods in the treatment of patients with pharyngeal tumors (T1–4, N0–3, M0). Patients received 65Gy in 30 fractions over 6 weeks delivered using either CT planned parallel opposed lateral fields or parotid-sparing IMRT. Stratification was by site of tumor and center. The primary endpoint was incidence of LENT-SOMA ≥G2 xerostomia one year after treatment. Secondary endpoints included acute toxicities (CTCAE v3) and other late RTOG and LENT-SOMA radiation toxicities. Proportions of patients with ≥G2 toxicity were compared using exact tests. For secondary endpoints a significance level of 1% was used. Results: 94 patients (47 RT; 47 IMRT) were randomized between 2003 and 2007 from six UK centers. 80 patients had oropharyngeal tumors and 14 hypopharyngeal. Radiotherapy was given as primary treatment in 71 patients and post-operatively in 23. 22 patients had AJCC stage I/II disease. Median follow-up was 31.9 months (IQR: 26.6 –38.8). Twelve month LENT-SOMA ≥G2 xerostomia scores were observed in 74% (25/34) of RT and 40% (15/38) of IMRT patients (p=0.005). Corresponding values at 18 months were 71% (15/21) and 29% (9/31) (p=0.004). On the RTOG scale, 12 month ≥G2 xerostomia was reported in 64% (21/33) RT vs 41% (15/37) IMRT patients (p=0.06). The 18 month incidence was 81% 17/21 RT vs 20% (6/30) IMRT (p<0.001). Acute radiotherapy related ≥G2 fatigue was more prevalent in the IMRT group (76% vs 41% p=0.001). No differences in acute mucositis or pain scores were seen. At 12 months, no statistically significant differences were seen in other late toxicities. No differences were observed between overall survival and locoregional control rates. Conclusions: Sparing the salivary glands through use of IMRT significantly reduces the incidence of xerostomia in patients with pharyngeal tumors. [Table: see text]

Critical Impact of Radiotherapy Protocol Compliance and Quality in the Treatment of Advanced Head and Neck Cancer: Results From TROG 02.02

2010 ◽  
Vol 28 (18) ◽  
pp. 2996-3001 ◽  
Author(s):  
Lester J. Peters ◽  
Brian O'Sullivan ◽  
Jordi Giralt ◽  
Thomas J. Fitzgerald ◽  
Andy Trotti ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Phase Iii ◽  
Treatment Center ◽  
Tumor Control ◽  
Advanced Head ◽  
Number Of Patients ◽  
Protocol Compliance ◽  
The Impact

Purpose To report the impact of radiotherapy quality on outcome in a large international phase III trial evaluating radiotherapy with concurrent cisplatin plus tirapazamine for advanced head and neck cancer. Patients and Methods The protocol required interventional review of radiotherapy plans by the Quality Assurance Review Center (QARC). All plans and radiotherapy documentation underwent post-treatment review by the Trial Management Committee (TMC) for protocol compliance. Secondary review of noncompliant plans for predicted impact on tumor control was performed. Factors associated with poor protocol compliance were studied, and outcome data were analyzed in relation to protocol compliance and radiotherapy quality. Results At TMC review, 25.4% of the patients had noncompliant plans but none in which QARC-recommended changes had been made. At secondary review, 47% of noncompliant plans (12% overall) had deficiencies with a predicted major adverse impact on tumor control. Major deficiencies were unrelated to tumor subsite or to T or N stage (if N+), but were highly correlated with number of patients enrolled at the treatment center (< five patients, 29.8%; ≥ 20 patients, 5.4%; P < .001). In patients who received at least 60 Gy, those with major deficiencies in their treatment plans (n = 87) had a markedly inferior outcome compared with those whose treatment was initially protocol compliant (n = 502): −2 years overall survival, 50% v 70%; hazard ratio (HR), 1.99; P < .001; and 2 years freedom from locoregional failure, 54% v 78%; HR, 2.37; P < .001, respectively. Conclusion These results demonstrate the critical importance of radiotherapy quality on outcome of chemoradiotherapy in head and neck cancer. Centers treating only a few patients are the major source of quality problems.

Prophylaxis of Radiation-Associated Mucositis in Conventionally Treated Patients With Head and Neck Cancer: A Double-Blind, Phase III, Randomized, Controlled Trial Evaluating the Clinical Efficacy of an Antimicrobial Lozenge Using a Validated Mucositis Scoring System

2002 ◽  
Vol 20 (19) ◽  
pp. 3956-3963 ◽  
Author(s):  
S. El-Sayed ◽  
A. Nabid ◽  
W. Shelley ◽  
J. Hay ◽  
J. Balogh ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Clinical Efficacy ◽  
Neck Cancer ◽  
Scoring System ◽  
Controlled Trial ◽  
Phase Iii ◽  
Double Blind ◽  
Almost All ◽  
Severe Mucositis

PURPOSE: Mucositis occurs in almost all patients treated with radiotherapy for head and neck cancer. The aim of this multicenter, double-blind, prospective, randomized trial was to evaluate the clinical efficacy of an economically viable antimicrobial lozenge (bacitracin, clotrimazole, and gentamicin [BcoG]) in the alleviation of radiation-induced mucositis in patients with head and neck cancer. PATIENTS AND METHODS: One hundred thirty-seven eligible patients were randomized to treatment with either antimicrobial lozenge (69 patients) or placebo lozenge (68 patients). The primary end point of the study was the time to development of severe mucositis from the start of radiotherapy. Secondary end points included severity and duration of mucositis, pain measurement, radiation therapy interruption, and quality of life. Mucositis was scored using a validated mucositis scoring system. RESULTS: Toxicity profiles were similar between the two arms of the study. The median time to development of severe mucositis from the start of radiotherapy was 3.61 weeks on BCoG and 3.96 weeks on placebo (P = .61). There were no statistically significant differences between the arms in the extent of severe mucositis as measured by physician, in oral toxicities as recorded by patients, or in radiotherapy delays. CONCLUSION: This study was conducted on the basis of a pilot study that demonstrated the BCoG lozenge to be tolerable and microbiologically efficacious. A validated mucositis scoring system was used. However, in this group of patients treated with conventional radiotherapy, the lozenge did not impact significantly on the severity of mucositis. Whether such a lozenge would be beneficial in treatment situations where rate of severe mucositis is higher (ie, in patients treated with unconventional fractionation or with concomitant chemotherapy) is unknown.

A Phase III placebo-controlled trial of oral pilocarpine in patients undergoing radiotherapy for head-and-neck cancer

2002 ◽  
Vol 54 (1) ◽  
pp. 9-13 ◽  
Author(s):  
Padraig Warde ◽  
Brian O’Sullivan ◽  
Julie Aslanidis ◽  
Barbaranne Kroll ◽  
Gina Lockwood ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Controlled Trial ◽  
Phase Iii

ROMAN: Reduction in oral mucositis with avasopasem manganese (GC4419)–Phase III trial in patients receiving chemoradiotherapy for locally advanced, nonmetastatic head and neck cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6596-TPS6596
Author(s):  
Jon Holmlund ◽  
Jeffrey Mark Brill ◽  
Robert Fairbanks ◽  
Deborah Saunders ◽  
Stephen T. Sonis ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Oral Mucositis ◽  
Controlled Trial ◽  
Locally Advanced ◽  
Phase Iii ◽  
Open Label ◽  
Double Blind ◽  
Who Grade

TPS6596 Background: Approximately 70% of patients receiving intensity-modulated radiotherapy (IMRT) plus cisplatin for locally advanced head and neck cancer (HNC) develop SOM, defined as WHO Grade 3 or 4, which limits patients' ability to eat solids (Gr 3) or liquids (Gr 4, requiring enteral nutrition). An RT-induced burst of superoxide initiates oral mucositis (OM) development. GC4419, a superoxide dismutase mimetic, interrupts this process by converting superoxide to H2O2. It showed promising reduction of SOM in a published open-label Phase 1b/2a trial (IJROBP 1 Feb 2018). In a subsequent randomized, double-blind placebo-controlled trial in 223 patients receiving IMRT/cisplatin for HNC (ASCO 2018), 90 mg of GC4419 administered M-F prior to IMRT demonstrated statistically significant reduction in SOM duration (p=0.024, median 1.5 days @ 90 mg vs. 19 days placebo) and meaningful reductions @ 90 mg in SOM incidence (43% vs. 65%) and severity (incidence of Grade 4, 16% vs. 30%). The safety results were acceptable and consistent with the known toxicities of IMRT/cisplatin. Methods: 335 patients at multiple centers in the U.S. and Canada with locally-advanced, nonmetastatic head and neck cancer (oral cavity/oropharyngeal) receiving 70 Gy IMRT (>50 Gy to > 2 oral sites) plus cisplatin (40 mg/m2 qwk x 6-7, or 100 mg/m2 q3wk x 3) are being randomized (double-blinded) 3:2 to 90 mg of GC4419 or placebo, M-F before each RT fraction. Enrollment is stratified by cisplatin schedule and treatment setting (definitive vs. post-op). OM by the WHO scale will be assessed twice weekly during RT & weekly for 2 weeks post RT. The primary efficacy endpoint is incidence of SOM through the end of IMRT. Secondary efficacy endpoints include severity (incidence of Grade 4 OM through the end of IMRT), & days of SOM (days from first to last SOM for all patients, with patients never developing SOM having 0 days of SOM by definition). Days of SOM for the subset developing SOM will be analyzed descriptively. Patients will be followed for one year post IMRT for tumor progression/recurrence and for two years for survival. Clinical trial information: NCT03689712 .

Prevention of dental caries using low concentration fluoride gel in custom tray in head and neck cancer patients undergoing radiotherapy: a preliminary study

2019 ◽  
Author(s):  
Sakiko Soutome ◽  
Souichi Yanamoto ◽  
Madoka Funahara ◽  
Yumiko Kawashita ◽  
Masako Yoshimatsu ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Dental Caries ◽  
Head And Neck ◽  
Neck Cancer ◽  
Medical Information ◽  
Controlled Trial ◽  
University Hospital ◽  
Phase Iii ◽  
Low Concentration ◽  
Preliminary Study

Abstract Background: To prevent radiation-related dental caries, some studies reported topical application of 1.0 – 2.0% fluoride gel in custom tray for 4-5 minutes every day. However, in Japan, the concentration of fluoride used by patients is limited to less than 0.15 %. The efficacy of low concentration of fluoride gel in custom tray in preventing radiation-related dental caries has not been investigated. Methods: This is a preliminary study. Thirteen patients with head and neck cancer who underwent radiotherapy were enrolled in this study. They wore custom tray containing 0.145% sodium fluoride gel during sleep every night and were examined for newly developed dental caries a year later. Results: No new dental caries were found in the 13 patients one year after radiotherapy. Conclusions: Low concentration fluoride gel in custom tray during sleep could prevent radiation-related dental caries. We are planning to conduct a multicenter phase III randomized controlled trial to examine the efficacy of this method in preventing radiation-related dental caries. Trial registration: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), UMIN000025196. Registered 9 December 2016, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000028984

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