bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I evaluation of vandetanib with radiation therapy (RT) ± cisplatin in previously untreated advanced head and neck squamous cell carcinoma (HNSCC)
Authors: Papadimitrakopoulou V. , Frank S. J. , Blumenschein G. R. , Chen C. , Kane M. , Cohen E. E. , Langmuir P. , Krebs A. D. , Lippman S. M. , Raben D. 
Published: August 2020

6016 Background: Vandetanib is a once-daily oral anticancer agent that selectively targets VEGF, EGF and RET receptor tyrosine kinases. We report preliminary results from an ongoing open-label phase I study of vandetanib with RT ± cisplatin in patients (pts) with previously untreated, unresected, locally advanced (stage III-IV) HNSCC. Methods: Eligible pts received once-daily vandetanib for 14 days followed by either 1) concomitant vandetanib + RT (2 Gy/d, 5 d/wk; total 70 Gy) + cisplatin (30 mg/m2, 2 h iv infusion/wk) for 7 wks, or 2) concomitant vandetanib + RT (2.2 Gy/d accelerated fractionation, 5 d/wk; total 66 Gy) for 6 wks. The primary objective was to determine the safety, tolerability and maximum tolerated dose (MTD) of vandetanib in both regimens. The first pt cohort received vandetanib 100 mg/day; escalation to 200 mg and 300 mg in subsequent cohorts was permitted providing <2/6 (33%) pts in the preceding cohort experienced a dose-limiting toxicity (DLT). Cohort expansion at the MTD of vandetanib was also planned. Results: As of Dec 1 2008, 24 pts (median age 53.5 yrs; 19 male; all M0) had received treatment with vandetanib + RT + cisplatin (n=18) or vandetanib + RT (n=6). In the triplet arm, no DLTs occurred in the initial vandetanib 100 mg cohort (n=6); an additional 6 pts were enrolled to receive vandetanib 200 mg but this dose was considered to exceed the MTD since DLTs were reported in 3/5 evaluable pts (Table). Vandetanib 100 mg was therefore declared the MTD with RT + cisplatin and cohort expansion at this dose continues. In regimen 2), 6 pts have received vandetanib 100 mg + RT and evaluation of this initial cohort is ongoing. Conclusions: This study, which continues to recruit, is the first to evaluate dual targeting of VEGFR/EGFR tyrosine kinases with chemoradiation or radiation alone in HNSCC pts. Among the 24 treated pts, 2 have completed the 2-year follow up, 1 death occurred that was causally related to cisplatin, and 21 remain in follow up or continue to receive treatment. [Table: see text] [Table: see text]
Final results of a phase I trial of chemotherapy combination with docetaxel, cisplatin, and S-1 (TPS) in patients with locally advanced or recurrent metastatic head and neck cancer (HNC)
Authors: Tahara M. , Araki K. , Kiyota N. , Okano S. , Fuse N. , Minashi K. , Yoshino T. , Doi T. , Minami H. , Ohtsu A. 
Published: August 2020

6021 Background: An oral fluoropyrimidine, S-1, has shown high efficacy against head and neck cancer (HNC), with a response rate of 34%. We investigated the maximum tolerated dose (MTD) of combination therapy with docetaxel, cisplatin and S-1 (TPS) in patients (pts) with locally advanced or recurrent/metastatic HNC. Methods: Eligibility criteria were histologically proven HNC, PS 0–1, age ≤75 years, adequate organ function, and no prior chemotherapy. Treatment consisted of 1-hour infusion of docetaxel at escalating doses of 50, 60 and 70 mg/m2, 2-hour infusion of cisplatin at 70 mg/m2/day on day 1, and S-1 twice daily on days 1–14 at escalating doses of 40, 60, and 80 mg/m2/day. This regimen was repeated every 3 or 4 weeks. Pts with locally advanced HNC received concurrent chemoradiotherapy after completion of 3 cycles of TPS. Results: Forty pts were enrolled, consisting of 33 males and 7 females with a median age of 50 years (range 22–74 years). Twenty-nine cases were locally advanced cancer and 11 were metastatic cancer. 116 cycles (median = 3, range 1–6) were administered in 6 dose levels. Grade 3 or 4 hematological toxicities were neutropenia (59%), febrile neutropenia (13%), and anemia (8%), whereas no grade 3 or 4 thrombocytopenia was seen. Two dose-limiting toxicities (DLTs) were observed at dose level 5 (TPS: 70/70/80 mg/m2/day every 3 weeks), namely one grade 3 infection and one grade 3 hyperbilirubinemia, establishing this as the MTD. Of 12 pts treated at dose level 6 (TPS: 70/70/60 mg/m2/day every 3 weeks), three DLTs were seen, namely one grade 3 diarrhea, one grade 3 ALT/AST and one grade 2 creatinine elevation. Of a total of 40 pts, 6 achieved a complete response and 22 a partial response according to RECIST, giving an overall response rate of 70%. Conclusions: The TPS combination was well tolerated. The recommended phase II dose was determined to be TPS at 70/70/60 mg/m2/day every 3 weeks. Antitumor activity was highly promising, and warrants further investigation. No significant financial relationships to disclose.
Phase II study of sunitinib in patients with recurrent and/or metastatic squamous head and neck carcinoma: The GORTEC 2006–01 study
Authors: Machiels J. H. , Henry S. , Zanetta S. , Kaminsky M. , Michoux N. , Bompas E. , Dillies A. , Faivre S. , Schmitz S. , Guigay J. 
Published: August 2020

6024 Background: Up to 90% of head and neck squamous cell carcinoma (HNSCC) express the vascular endothelial growth factor (VEGF) or the VEGF receptors (VEGFR) 1–3. Angiogenic factors could have prognostic implication making anti-angiogenic therapies an attractive treatment modality. Sunitinib inhibits multiple tyrosine kinase receptors including VEGFR1–3 and PDGFR. Methods: Palliative HNSCC in PD after platinum therapy received sunitinib 37.5 mg/day continuously. The primary endpoint was the disease control rate (SD, PR, CR) at 6–8 wks. A two-stage design was used (Simon; a = 0.15,b = 0.10, H0 = 10%, H1 = 25%) meaning that at least 6 patients out of 37 should achieve a SD. Dynamic contrast enhanced (DCE) magnetic resonance (MR) perfusion-weighted imaging before and 6 wks after treatment initiation was performed on a 3T system. Results: 37 pts (M/F:28/9;PS 0/1:5/32) were included.11 pts were not evaluable by imaging due to rapid clinical PD (7 pts) or toxicity (4 pts) and were considered in PD.PR was found in 1 pts, SD in 18, and PD in 18 (RECIST). Among the SD, 6 had a minor response and 5 had an unconfirmed PR (maximum % reduction in sum of the largest diameters: 2%, 4%, 7%, 10%, 16%, 17%, 30%, 45%, 48%, 65%, 73%). PR could not be confirmed due to PD within 4 wks (3 pts) or treatment termination due to toxicity (2 pts). 4 pts had MR DCE monitoring. In 3, a significant decrease in the volume transfer constant Ktrans measuring the tumor perfusion and endothelial permeability was found during sunitinib treatment. The main Gr3–4 toxicities (N pts) were fatigue (12), tumor bleedings (2), LVEF decrease (2), hypertension (2). Gr5 tumor bleedings occurred in 4 pts. Other local complications included apparition/worsening of tumor skin ulceration or tumor fistula in 15 pts. Conclusions: This trial met its primary endpoint with modest activity of sunitinib in HNSSC. The rate of complications (i.e., fatal bleedings) outlines the importance of a better patient selection. DCE-MRI may be useful to predict response. No significant financial relationships to disclose.
Use of DNA repair pathway analysis to predict overall survival in head and neck cancer patients treated with TFHX chemoradiotherapy
Authors: Seiwert T. , Weaver D. T. , Wang X. , Kutok J. , Cohen E. , Stenson K. , Vokes E. 
Published: August 2020

6033 Background: Concurrent chemoradiotherapy is a standard-of-care for head and neck cancer. Radiotherapy and chemotherapeutic agents damage DNA; lack of adequate repair induces tumor cell death. The network of DNA repair pathways was examined to predict TFHX chemoradiotherapy outcomes. Methods: Biopsy specimens (paraffin) from 60 HNC patients were evaluated from tissue microarrays. Samples originated from patient groups from phase I/II studies: 1) poor-prognosis radiation-naïve, 2) re-irradiation. All were treated with TFHX-based chemoradiotherapy. DNA repair biomarkers XPF, pMK2, PAR, pH2AX, FANCD2, ATM, BRCA1, RAD51, ERCC1 (clone 8F1), and p53 were explored using IHC, automated image processing, and machine reading (>500 cells/read), for nuclear and cytoplasmic quantity, area, and intensity, and correlated with clinical outcome. Results: There was low inter-core variability per tumor with median patient ranking signal to noise ratio of 15.0 across all markers. Patients were stratified into short and long survival groups by determination of critical marker thresholds. Five DNA repair biomarkers (RAD51, ATM, BRCA1, XPF, FANCD2) exhibited univariate significance for overall survival (p = 2.65e-3, 1.53e-2, 4.77e-4, 8.57e-5, 1.32e-3)(additional clinical parameters multivariate analysis was not feasible due to sample size). ERCC1 was not statistically significant (p = 1.0). Pairwise biomarker combinations improved survival group discrimination. Combination of 4 DNA repair biomarkers (FANCD2, BRCA1, ATM, XPF) was also significant (p = 1.31e-4). Discriminant analysis demonstrated higher fractions of correctly identified patients in good/poor survival groups from four-marker tests. Conclusions: Five DNA repair biomarkers predicted overall survival following TFHX-based chemoradiotherapy. By contrast ERCC1 (8F1) was not significant. Combination of markers improved predictive ability in this study. The analysis of DNA repair pathways, particularly in homologous recombination, DNA damage response, and nucleotide excision repair, may be clinically useful. Validation in a larger, homogeneous patient population, and using platinum-based chemoradiotherapy, is indicated and currently ongoing. [Table: see text]
Feasibility and toxicity of docetaxel before or after fluorouracil, epirubicin, and cyclophosphamide as adjuvant chemotherapy for early-stage breast cancer
Authors: Abe H. , Umeda T. , Kawai Y. , Tanaka M. , Shimizu T. , Chou H. , Kubota Y. , Mekata E. , Kurumi Y. , Tani T. 
Published: August 2020

604 Background: As adjuvant chemotherapy for breast cancer, the addition of docetaxel to regimens containing anthracyline has been shown to be effective. However, tolerance and safety associated with the administration order of the two drugs have not been evaluated. Methods: Breast cancer patients with node-positive or high-risk patients with node-negative were eligible. The treatment completion rate and toxicity were evaluated in 2 arms who underwent a total of 6 courses of the following regimens: Arm A: 3 courses of fluorouracil 500 mg/m2, epirubicin 100 mg/m2 and cyclophosphamide 500 mg/m2 (FEC100: q3w) followed by 3 courses of docetaxel (DOC100: 100 mg/m2, q3w); and Arm B: 3 courses of DOC100 (q3w) followed by 3 courses of FEC100 (q3w). Results: June 2006 to April 2008, 42 patients were registered. To the present, analysis has been completed in 21 patients in arm A and 21 in arm B. The mean age of patients was 49.1 years and 53.8 years, respectively. In arm A, the stage of cancer was 1 in 4 patients, 2a in 10, and 2b in 7, in arm B, the stage of cancer was 1 in 3 patients, 2a in 9, and 2b in 9. The adjuvant chemotherapy completion rate was 100 % for arm A and 95.2 % for arm B. The relative dose intensity (RDI) was 94.2 % for FEC100 and 97.8 % for DOC100 in arm A, and 98.9 % for DOC100 and 95.2 % for FEC100 in arm B. In arm A, grade 3 or higher hematological toxicity was observed in 9 patients, and febrile neutropenia developed in 3 patients with FEC100. In arm B, grade 3 or higher hematological toxicity was observed in 7 patients, but febrile neutropenia was not noted in any patients. Grade 3 or higher non-hematological toxicity was observed with FEC100 in 2 patients each in the two arms. Grade 1 or 2 edema developed in 11 patients with DOC100 in the two arms. Conclusions: In both arm A and B, adverse events associated with FEC100 were frequently observed but spontaneously recovered, or adequate management was possible by supportive therapy. Adverse events associated with DOC100 were mild. The regimens in both arms A and B were safe regarding adjuvant chemotherapy for early stage breast cancer. However, DOC100 followed by FEC100 may be more tolerable and effective. No significant financial relationships to disclose.
Upfront chemotherapy and accelerated radiotherapy with EGFR inhibition for locally advanced inoperable head and neck cancer
Authors: Mercke C. , Wickart-Johansson G. , Sjödin H. , Adell G. , Nyman J. , Haugen H. 
Published: August 2020

6040 Background: Concomitant chemoradiotherapy (CT/RT) is the standard treatment for locally advanced head and neck squamous cell carcinoma. However, late toxicity is substantial.This phase II trial explores the feasibility and efficacy of combining neoadjuvant TPF and accelerated RT where the concomitant cytostatic component is replaced with cetuximab (E), a chimeric IgG1 mAb against EGFR. Methods: Patients (pts) had previously untreated stage III/IV M0,WHO 0–1, unresectable squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx and were scheduled for 2 cycles of TPF (docetaxel 75 mg/m2 and cisplatin 75 mg/m2 day 1 and 5-FU 1,000 mg/m2 96 hours CI) every 3 weeks followed by RT (68 Gy/4.5 weeks) with E given one week before (400 mg/m2) and weekly during RT (250 mg/m2). A brachytherapy boost of 8 Gy was given to pts with oral cavity or oropharyngeal tumours. Neck dissection was planned for pts with N2–3 and complete response (CR) at the primary tumour. Tumour response was evaluated according to RECIST with CT, MRI or PET/CT after CT and at 6 weeks follow up. Toxicity (CTC 3.0) and quality of life (EORTC QLQ 30) was registered during and after treatment. Results: From 070401 to 081115 68 pts were enrolled, 56 had stage IV disease (T4, n = 14, N3, n = 9). Median age 57, 60 males, 3 oral cavity, 44 oropharynx, 10 larynx, and 11 hypopharynx. 30 pts were followed beyond 6 weeks and evaluated for response and early toxicity: stage IV disease 24 (T4, n = 6, N3, n = 3), median age 60, 25 males, 18 oropharynx, 5 larynx, and 7 hypopharynx. Remissions after TPF/after RT: CR 1/10, PR 15/18, SD 14/1, and PD 1. TPF as prescribed: 28/30 (pat refusal 1, renal insuff 1, dose reduction 0/28); E as prescribed: 22/30 (dermatitis 4, hypersensitivity 3, liver tox 1). Vital tumour in resected specimen 0/13. Alive at follow-up 29/30 (1 local failure). Conclusions: TPF followed by RT concomitant with E is feasible with manageable toxicities. Dermatitis in the irradiated neck, at least with the present accelerated fractionation, is troublesome to some patients but does not interrupt treatment and heals rapidly. To dispose of feeding tubes after disappearance of acute mucosal reactions has not been a problem. Early survival results are promising. Toxicity and survival results will be updated. [Table: see text]
TPF induction chemotherapy (CT) followed by concomitant cisplatin/radiotherapy (cCTRT) in locally advanced nasopharyngeal cancer (LANPC)
Authors: Bossi P. , Parolini D. , Bergamini C. , Locati L. D. , Orlandi E. , Franceschini M. , Palazzi M. , Olmi P. , Potepan P. , Licitra L. 
Published: August 2020

6046 Background: Recent meta-analysis showed better event free survival in LANPC with induction CT. In head and neck cancer, docetaxel, cisplatin and 5 FU (TPF) induction chemotherapy led to survival gain over cisplatin and 5FU alone. We studied feasibility and activity of TPF induction CT followed by cCTRT in LANPC. Methods: From October 2004 to May 2008, 45 pts with LANPC were treated at our Institution with 2 to 4 cycles (median 3) of induction TPF (docetaxel 75 mg/sm and cisplatin 75 mg/sm on day 1, and 5-FU 750 mg/sm/day ci for 96 hrs. Prophylactic ciprofloxacin was administered for 10 days each cycle, while use of G-CSF was not allowed. Following CT, pts received full doses radiotherapy (RT) concurrent with cisplatin 100 mg/sm q 21 days. Intensity modulated radiotherapy (IMRT) was delivered to 34 pts (76%). All but two pts had non-keratinizing carcinoma. Stage IV pts were 60%, stage III 34%, and 6% stage II. T4 was present in 24% and N3 disease was diagnosed in 42% of the pts. Results: TPF was well tolerated, with main toxicity consisting in neutropenia (31% G3–4). Response rate was 87%. RT dose ranged from 64 Gy to 70 Gy (median 70 Gy). Main toxicities during cCTRT were: neutropenia (38% G3, 4% G4), febrile neutropenia (11% G3), thrombocytopenia (7% G3–4) and mucositis (40% G3, 4% G4). Nasogastric tube was placed in 33% of pts and maintained for a median of 40 days. During cCTRT, platinum compounds mean dose delivery was 75%, with 6 pts shifting to carboplatin for renal function impairment. Observed late toxicities were xerostomia (G3 in 38% of cases) and peripheral neurotoxicity (G1 in 27%, G2 in 7% and G3 in 2% of the pts). After treatment completion, complete and partial response were recorded in 78% and 20% of the pts respectively, while 1 pt showed stable disease. With a median follow up of 22 months (range 7 to 47), 9 pts showed recurrence or progressive disease (7 at local and/or regional level, 2 distant metastases and 1 at both sites), with a 2-years event free survival of 78% and an overall survival of 85%. Conclusions: TPF followed by cCTRT is feasible in LANPC. In this high-stage nonendemic population local-regional disease control still remains the main therapeutic goal. Supported in part by AIRC. [Table: see text]
A phase II trial evaluating weekly docetaxel and capacitabine in patients with metastatic or advanced, locally, recurrent head and neck cancer
Authors: Zhang J. , Lee J. S. , Urba S. , Worden F. 
Published: August 2020

6051 Background: Docetaxel has documented clinical efficacy in head and neck cancer and the synergy between docetaxel and capacitabine has been shown in preclinical studies. Phase I studies combining docetaxel and capacitabine demonstrated anti-tumor effects in breast, colon, and bladder cancers. We therefore test this combination in patients with metastatic or locally advanced head and neck cancer. Methods: To be eligible for this single arm safety/efficacy phase II study, patients must have documented measurable advanced, locally recurrent or metastatic head and neck cancers, which were untreatable by surgical resection or radiation therapy, a Zubrob performance status of 0–2, adequate marrow, hepatic and kidney functions. Prior chemotherapy with non-docetaxel containing regimen was allowed. Docetaxel 30 mg/m2 was given on day 1, 8 and 15, while capecitabine 1,000 mg bid was given on days 5–18 of the 28 days cycle. Response to treatment was assessed after every 2 cycles. Patients with complete response (CR) received 2 additional cycles of therapy. Patients with partial response (PR) or stable disease (SD) continued to receive the therapy until they developed CR or progressive disease (PD). Patients with PD or unacceptable toxicity will be off the study. Results: 39 patients (33 male, 6 female) with a median age of 58.4 years were enrolled between September 2003 and April 2008. At baseline, 14/39 patients (36%) had local regional disease, 17/39 (44%) had distant metastasis, and 7/39 (18%) had both. 31/39 (79%) of the patients had prior chemotherapy. Responses at 4 months were analyzed on 36 patients: 5 patients (13%) had confirmed responses (2 CR, 3 PR) and 8 patients (20%) had stable diseases. Progression-free survival at 6 month was 34% (95% CI 19% - 49%). Major grade 3 and 4 toxicities were lymphopenia (8/39, 20%), infection without neutropenia (5/39, 13%) and fatigue (4/39, 10%). Conclusions: Weekly docetaxel and capacitabine are well tolerated and the disease control rate (33%) is comparable with the historical controls in patients with metastatic or advanced, locally, recurrent head and neck cancers. No significant financial relationships to disclose.
Neoadjuvant chemotherapy followed by radiotherapy or chemoradiation for locally advanced nasal and paranasal sinus tumors
Authors: Hameed S. , Jamshed A. , Hussain R. , Ali M. , Iqbal H. , Majeed U. , Shah M. A. 
Published: August 2020

6055 Background: The treatment of locally advanced nasal and paranasal sinus tumors is controversial. The disease is chemosensitive and there is increasing interest in the use of chemotherapy with radiation in this group of patients. Our aim was to determine survival in patients with locally advanced nasal and paranasal sinus tumors treated with neoadjuvant chemotherapy followed by radiotherapy or chemoradiation (RT/CRT). Methods: Between August 2005 and August 2008, 21 patients with AJCC stage III or IV nasal and paranasal sinus tumors were treated with neoadjuvant chemotherapy followed by RT/CRT in our institution. There were 15 males and 6 females (M 71%:F 29%) with a median age of 49 years (range 19 - 70 years). Site of disease was nasal cavity 33% (7), ethamoid sinus 43% (9), maxillary antrum 19% (4), and frontal sinus in 5% (1) of patients. Histopathological diagnosis was squamous cell carcinoma 43% (9), undifferentiated carcinoma 29% (6), adenocarcinoma 19% (4), esthesioneuroblastoma in 9% (2) of patients. Induction chemotherapy consisted of cisplatin 75 mg / metre2 day 1 and gemcitabine 1 gm / metre2 day 1 and 8 every three weeks. Eighty-five percent (18/21) received 2 cycles of neoadjuvant chemotherapy (range 1–4 cycles) prior to radiotherapy. Radiotherapy dose was 54 Gy - 70 Gy (median radiation dose 66 Gy). Fifty-seven percent (12/21) received concomitant cisplatin with radiotherapy. Results: Response to neoadjuvant chemotherapy; complete in 19% (4), partial in 67% (14), no response/progression 14% (3). Following RT/CRT 86% (18/21) had complete regression of disease. Thirty-three percent (7/21) have failed treatment (local 3, regional 2, and distant metastasis in 2 patients). Among treatment failures 2 patients were successfully salvaged; surgery for local recurrence in one patient and in the other case radiation was given for regional recurrence. Disease free and overall survival at 40 months was 52% and 63%, respectively. Conclusions: Gemcitabine cisplatin chemotherapy has good activity in nasal and paranasal sinus tumors. In combination with RT/CRT survival rates are encouraging and the approach merits further investigations in clinical trials. No significant financial relationships to disclose.