Radiosensitization with a COX2 inhibitor with chemoradiation for head and neck cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5582-5582 ◽  
Author(s):  
P. Prellop ◽  
G. Peters ◽  
W. Carroll ◽  
L. Nabell ◽  
S. Spencer ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Febrile Neutropenia ◽  
Head And Neck ◽  
Local Control ◽  
Neck Cancer ◽  
Survival Data ◽  
Locally Advanced ◽  
Radiation Dermatitis ◽  
Published Data ◽  
Cox2 Inhibitor

5582 Background: Cyclo-oxygenase 2 (COX2) inhibitors have shown promise as radio- and chemosensitizers. We conducted a phase IB/II study to evaluate the toxicity and efficacy of celecoxib, a selective COX2 inhibitor, administered concurrently with carboplatin, paclitaxel, and radiation for locally advanced or recurrent head and neck cancer. Methods: Patients with stage III/IV or recurrent squamous cell carcinoma of the oropharynx, oral cavity, hypopharynx, or larynx were eligible. Primary endpoints were toxicity, local control and survival. Patients were treated with weekly carboplatin (AUC = 2.0), paclitaxel (30 mg/m2) and concurrent radiation (70 Gy). Celecoxib (400 mg bid) was started 1 week prior to the initiation of radiotherapy and was given for a total of 2 years. In 12/04, the study closed due to concerns of cardiotoxicity with COX-2 inhibitors. Celecoxib was discontinued in all patients. The study restarted in 5/06 with the modification that celecoxib would be given only during radiation. Results: Between 12/02 and 1/06, a total of 28 patients were enrolled: 89% were male, median age was 56.5, 3 with recurrent cancer and 25 treated definitively. Five patients have been treated on the modified study. Grade 3/4 toxicities include: mucositis (35% G3), dermatitis (18% G3; 7% G4), febrile neutropenia (21% G3; 3% G4), dysphagia (57% G3), nausea/vomiting (29% G3). Thirty percent did not complete prescribed chemotherapy due to myelosuppression. Acturarial 2 year outcomes in the 20 evaluable, definitively treated patients: 65% survival, 76% local control. Conclusions: Compared to published data using carbo/taxol and RT, an unexpectantly high incident of febrile neutropenia was observed but no increase in radiation dermatitis or mucositis. Two year survival data is comparable to published data. No significant financial relationships to disclose.

A phase I/II study of radiation therapy, paclitaxel poliglumex, and cetuximab in locally advanced head and neck cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16047-e16047
Author(s):  
Seung Shin Hahn ◽  
Jeffrey Bogart ◽  
Chung Taik Chung ◽  
Jack Hsu ◽  
Robert Kellman ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Phase I ◽  
Head And Neck ◽  
Phase Ii ◽  
Local Control ◽  
Neck Cancer ◽  
Survival Benefit ◽  
Locally Advanced ◽  
Radiation Dermatitis ◽  
Advanced Head

e16047 Background: In patients with locally advanced head and neck cancer (LA-HNC), radiotherapy (RT) + cisplatin showed survival benefit over RT alone, but with significant toxicity. The addition of cetuximab to RT demonstrated survival benefit without increased RT-related toxicity. Paclitaxel poliglumex (PPX) is a novel conjugate consisting of paclitaxel linked to a biodegradable, water-soluble polymer of glutamic acid. PPX has a radiation enhancement factor of ≈8 and improved curability in a murine carcinoma model. In a phase I study of PPX + RT in esophageal cancer, no dose-limiting toxicities (DLTs) occurred at PPX doses up to 70 mg/m2/week and an encouraging rate of pathological CRs was observed. This phase I/II study addresses the combined use of intensity modulated RT (IMRT), PPX, and cetuximab in patients with LA-HNC. Methods: Eligible patients had untreated stage III or IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx; ECOG PS 0-1; and adequate bone marrow function. In the phase I portion, patients received cetuximab 400 mg/m2 day 1 and 250 mg/m2 days 8, 15, 22, 29, 36, 43, and 50. PPX was administered at 40 mg/m2 days 8, 15, 22, 29, 36, 43, and 50 for Cohort 1 (n = 3) then escalated or decreased for Cohorts 2-5 (3 patients each) until the maximum tolerated dose (MTD) was established. IMRT began on day 8 and consisted of 69.96 Gy delivered in 2.12 Gy daily fractions. In the phase II portion, patients received PPX at the MTD + cetuximab and IMRT at the phase I dose and schedule. Results: In total, 14 patients were treated (9 phase I, 5 phase II). The PPX MTD was determined to be 40 mg/m2. The majority of adverse events (AEs) were grade 1/2 and consistent with known toxicities of individual agents. The most common grade 3 AEs were mucositis (n = 8), radiation dermatitis (n = 4), and cetuximab rash (n = 3). Of 13 patients evaluable for response, 9 had CR and 4 had PR. After a median 17-month follow up, the local control rate was 11/11 and the median survival was 20 months. Two patients with stage IVC disease were excluded for local control and survival analysis. Conclusions: The combination of IMRT, PPX, and cetuximab is tolerable and shows promising clinical activity in patients with LA-HNC.

Cisplatin and fluorouracil chemotherapy does not yield long-term benefit in locally advanced head and neck cancer: results from a single institution.

1991 ◽  
Vol 9 (8) ◽  
pp. 1376-1384 ◽  
Author(s):  
E E Vokes ◽  
R Mick ◽  
E P Lester ◽  
W R Panje ◽  
R R Weichselbaum
Keyword(s):  
Head And Neck Cancer ◽  
Adjuvant Chemotherapy ◽  
Head And Neck ◽  
Induction Chemotherapy ◽  
Neck Cancer ◽  
Survival Data ◽  
Locally Advanced ◽  
Local Therapy ◽  
Complete Response ◽  
Advanced Head

Fifty-one patients with locally advanced head and neck cancer were treated with three cycles of cisplatin at 100 mg/m2 followed by 5-day continuous infusion fluorouracil (5-FU) at 1,000 mg/m2/d as induction chemotherapy. Subsequent local therapy consisted of surgery for patients with resectable disease and/or radiotherapy. Three cycles of adjuvant chemotherapy were administered to patients with partial response (PR) or complete response (CR) to induction chemotherapy. Twenty-two patients (43%) had a clinical CR that was pathologically confirmed in 12 patients (24%), and 24 patients (47%) had a PR for an overall response rate of 90%. Local therapy included surgery in 24 patients (47%) and radiotherapy alone in 22 patients (43%). Adjuvant chemotherapy was administered to 32 patients (63%) frequently at great dose reduction. At a median follow-up of 90 months, the median survival is 22 months (95% confidence interval, 15 to 36 months), and the 5-year survival is 25%, with only five patients known to be alive and disease-free at this time. The median time to progression is 14 months, with 29 patients (57%) having documented progression of their head and neck cancer and eight (16%) having progression of a second neoplasm. Seven patients died of intervening medical events. This high incidence of second malignancies supports the continued investigation of chemoprevention for patients in CR. Despite the known high response rates achieved with cisplatin and 5-FU induction chemotherapy, the overall poor survival data reported here should lead to a thorough reexamination of the frequent administration of this regimen in the community.

First-line docetaxel (Dx) and capecitabine (Cap) in advanced head and neck cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16505-16505 ◽  
Author(s):  
A. Gil-Negrete ◽  
J. M. Mañe ◽  
A. Ruiz de Lobera ◽  
A. Martinez-Bueno ◽  
I. Rubio ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Febrile Neutropenia ◽  
Head And Neck ◽  
Neck Cancer ◽  
Locally Advanced ◽  
Early Death ◽  
First Line ◽  
Kaplan Meier ◽  
Nail Changes ◽  
Hand Foot Syndrome

16505 Background: Dx and Cap are useful drugs in head and neck cancer. Our purpose was to establish the efficacy and safety of this combination in non selected patients (pts) with advanced or metastatic (M1) head and neck cancer. Methods: : Between Apr 2005 and Nov 2006, 33 pts with squamous cell locally advanced or M1 head and neck cancer received the following chemotherapy (Ct) schedule: Dx 75 mg/m2 day 1 and Cap 950 mg/m2/12h days 2–14, every 3 weeks.30 pts (90.9%) had received previous local radiotherapy, 11 of them with concomitant Ct. Results: Mean age was 60 years old (range 46–75). M/F: 32/1. PS 0/1/2: 1/29/3. Location of disease: only local 49%; local and M1 36%; only M1 15% (Main M1 site: lung 76.5%, nodes 11.8%, bone 5.9%, soft tissue 5.9%). Mean number of Ct cycles: 4 (range 1–7). Worst hematologic toxicities per patient G3/G4 (%): neutropenia 6/39; febrile neutropenia 36/0; anemia 3/0; trombopenia 3/3. Non-hematologic toxicities G2/G3 (%): vomiting 3/3; neuropathy 6/0; asthenia 33/6; diarrhea 21/3; mucositis 33/18; nail changes 12/0; hand foot syndrome 3/12. Other events to remark: 4 pts had neumonia (2 toxic deaths), 1 pts had angor and required a different Ct schedule, 2 pts had massive hemorrage (1 exitus). There were 7 pts not evaluable for response (4 not yet evaluated, 1 early death due to massive hemorrage, 1 toxic death due to neumonia, 1 early disphagia). Among the evaluated pts, responses were: 2 CR (7.7%), 10 PR (38.5%), 9 SD (34.6%) and 5 PD (19.2%). Median TTP was 21 weeks (95%CI 17.5 - 24.2). Median OS was 39.8 weeks (95%CI 32.4 - 47.4) by Kaplan-Meier method. Conclusions: This combination appears to be active in pts with advanced or M1 head and neck cancer. Main toxicities were neutropenia, febrile neutropenia, mucositis and asthenia. Global toxicity was important with two toxic deaths documented No significant financial relationships to disclose.

Predicting survival and local control after radiochemotherapy in locally advanced head and neck cancer by means of computed tomography based radiomics

2019 ◽  
Vol 195 (9) ◽  
pp. 805-818 ◽  
Author(s):  
Luca Cozzi ◽  
Ciro Franzese ◽  
Antonella Fogliata ◽  
Davide Franceschini ◽  
Pierina Navarria ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Local Control ◽  
Neck Cancer ◽  
Locally Advanced ◽  
Advanced Head

Phase II trial of concurrent 5-fluorouracil, hydroxyurea, cetuximab, and intensity moduled radiation therapy (IMRT) for locally advanced head and neck cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6014-6014
Author(s):  
J. Kao ◽  
L. Policarpio ◽  
M. Teng ◽  
R. Burri ◽  
E. Genden ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Phase Ii ◽  
Neck Cancer ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Locally Advanced ◽  
Radiation Dermatitis ◽  
Advanced Head ◽  
Patient Reported

6014 Background: This phase II study was conducted to evaluate the tolerability and efficacy of incorporating cetuximab and simultaneous integrated boost intensity modulated radiation (SIB-IMRT) into a well-described 5-fluorouracil (5-FU) and hydroxyurea (HU)-based chemoradiation regimen. Endpoints included overall survival (OS), locoregional (LRC) and (DC), quality of life and toxicity. Methods: Patients with stage IVa-IVb or high-risk stage III squamous cell carcinomas were enrolled on a phase II trial. Prior organ-conserving surgical therapy or induction chemotherapy was allowed off protocol. SIB-IMRT was prescribed to low (43.2 to 48 Gy) and intermediate (54 to 63 Gy) risk volumes. A separate IMRT conedown plan was targeted to gross disease (72 Gy). The median radiation dose was 72 Gy (range 60 to 72 Gy) administered in 1.5 Gy fractions BID on weeks 1, 3, 5, 7 ± 9. Concurrent systemic therapy consisted of 5-FU (600 mg/m2), HU (500 mg BID) and cetuximab (250 mg/m2). Results: From January 2007 to April 2008, 33 subjects enrolled. Characteristics included 24 males; median age 59; ECOG performance status was 0 in 12. Disease was stage IVa-b disease in 31 (94%), T3–4 in 16 (48%), N2–3 in 23 (70%), and oropharynx primary in 15 (45%). Median follow-up in surviving patients is 15 months (range 6 to 22 months). The 1 year LRC, DC and OS is 91%, 82%, and 92%, respectively. Grade 3 toxicity consisted of mucositis (33%), radiation dermatitis (15%), anemia (15%), and leukopenia (15%), and neutropenia (9%). There were no grade 4–5 events. The majority of patients (64%) were able to tolerate treatment without a feeding tube. Median patient reported University of Washington QOL-R scores before, immediately after, 3 months and 8 months after chemoradiation were 85.5 (±14), 65 (±13), 76.5 (±15), and 84.5 (±9), respectively. Conclusions: Concurrent 5-FU, HU, cetuximab, and SIB-IMRT is a promising and reasonably well tolerated approach to incorporating molecularly targeted therapy in the curative therapy of locally advanced head and neck cancer. [Table: see text]

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