bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase III randomized, placebo-controlled trial of docetaxel (D) with or without gefitinib (G) in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): A trial of the Eastern Cooperative Oncology Group (ECOG)
Authors: Argiris A. , Ghebremichael M. , Gilbert J. , Burtness B. , Forastiere A. 
Published: August 2020

6011 Background: G is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor with modest single-agent activity in SCCHN. We hypothesized that the addition of G to D will enhance therapeutic efficacy. Methods: Eligibility criteria included R/M SCCHN; any number of prior regimens (excluding D and EGFR inhibitors); ECOG performance status (PS) 2, if previously untreated, or ECOG PS 0–2, if prior chemotherapy for R/M SCCHN or as part of potentially curative therapy < 6 months (mo) earlier. Patients (pts) were randomly assigned to receive D 35 mg/m2 IV on days 1,8,15, every 28 days plus placebo (arm A) or the same D regimen plus G 250 mg orally, once daily (arm B) until disease progression. Stratification factors were PS, prior chemotherapy and weight loss. At the time of progression, treatment could be unblinded and, for pts in the placebo arm, single-agent G 250 mg/d initiated. We sought to demonstrate an improvement in median overall survival (OS) from 6 to 8.4 mo (28.6% reduction in HR). A total accrual of 314 eligible pts and 286 failures were needed to attain 80% power with 2.5% type I error. Results: 270 pts were enrolled (arm A, n = 136; arm B, n = 134). The study was terminated at interim analysis in November 2008 because it was highly unlikely that the primary endpoint could be met. 60% of pts had ECOG PS of 2; 72% had prior chemotherapy. 24 pts in arm A received G at progression. Data on subsequent treatment with EGFR inhibitors were not collected. Median OS was 6 mo in arm A versus 6.8 mo in arm B (p = 0.74); HR 1.04 (95% CI, 0.79–1.35). Objective response rate in 168 evaluable pts was 6% in arm A vs. 14% in arm B (p = 0.16). Median time to progression was 2 mo and 3.5 mo (p = 0.03) and median progression-free survival 2.2 mo and 3.3 mo (p = 0.18) in arms A and B, respectively. Common grade 3/4 adverse events (AE) in arm A (n = 121) vs. B (n = 115) were neutropenia 1/2 vs. 2/0; fatigue 16/4 vs. 14/0; diarrhea 3/0 vs. 11/1; nausea 4/1 vs. 5/0; vomiting 4/0 vs. 1/1; pneumonia 8/1 vs. 6/1. There were 2 grade 5 AE in arm A and 5 in arm B. Conclusions: The addition of G to D is well tolerated and improves time to progression but not survival in previously treated and poor PS pts with R/M SCCHN. [Table: see text]
Combined modality therapy with radiation therapy (RT), chemotherapy, bevacizumab, and erlotinib in the treatment of patients (pts) with locally advanced squamous carcinoma of the head and neck
Authors: Meluch A. A. , Spigel D. , Burris H. A. , Lane C. , Peyton J. D. , Shipley D. , Rubin M. , Stipanov M. , Greco F. A. , Hainsworth J. D. 
Published: August 2020

6012 Background: Concurrent chemotherapy/RT is the standard of treatment for locally advanced head and neck cancer. Agents targeting EGFR and the angiogenesis pathway have also demonstrated activity. In this phase II trial, we added bevacizumab and erlotinib to an active combined modality regimen in the first-line treatment of pts with locally advanced head and neck cancer. Methods: Eligible pts had previously untreated squamous carcinoma of any head and neck site, with T3/T4 primary lesions and/or N1-N3 nodal involvement. Additional eligibility: ECOG PS 0 or 1; adequate organ function; indwelling central venous catheter; standard bevacizumab exclusions. All pts received induction therapy with 2 courses of paclitaxel (200mg/m2), carboplatin (AUC 6.0), 5-FU (200mg/m2 per day, 24 hour CI days 1–21), and bevacizumab (15 mg/kg); cycles were repeated at 21-day intervals. Pts then received concurrent RT (68.4 Gy, 1.8 Gy/day), paclitaxel (50 mg/m2 weekly x 6), bevacizumab (15 mg/kg weeks 1 and 4), and erlotinib (150 mg daily x 7 weeks). PFS was the primary endpoint. Results: Between December 2006 and July 2008, 60 pts were enrolled; the first 48 pts are included in this preliminary report. The median age was 56 years; T3/T4 = 9/8; N1/N2/N3 = 13/27/4. 45 pts (94%) completed the 6-week induction therapy, and 41 pts (85%) completed all therapy. After induction therapy, 56% of pts had objective response; 77% had objective response after completion of therapy. After a median follow-up of 16 months, the 18-month progression-free and overall survivals are 85% and 87%, respectively. Grade 3/4 toxicity during induction therapy included neutropenia (46%), neutropenic fever (6%), mucositis (14%), diarrhea (14%), and hand/foot syndrome (11%). Severe local toxicity (mucositis/esophagitis) occurred in 31 patients (76%) during combined modality therapy (56% grade 3/20% grade 4). Conclusions: The addition of bevacizumab and erlotinib to concurrent chemotherapy/RT was feasible, with no unexpected toxicity. After short followup, the regimen appears highly active. Updated results will be presented. [Table: see text]
EORTC 24051: Unexpected side effects of a phase I study of TPF induction chemotherapy (IC) followed by chemoradiation (CRT) with lapatinib (LAP), a dual EGFR/ErbB2 inhibitor, in patients with locally advanced larynx and hypopharynx squamous cell carcinoma (LA-LxHxSCC)
Authors: Specenier P. M. , Lalami Y. , Vermorken J. , Lacombe D. , El-Hariry I. , Bogaerts J. , Awada A. 
Published: August 2020

6017 Background: CRT is considered a standard approach for LA-LxHxSCC. TPF IC regimen seems to improve outcome in locally advanced head and neck SCC. The addition of LAP was investigated in combination with a sequential therapeutic approach (IC→ CRT). Methods: Eligible tumors were SCCHN: T3-T4 larynx (Lx), T2-T4 hypopharynx (Hx) N0–3 M0. The objective of this trial is to determine MTD, DLT and recommended dose of LAP when administered with TPF IC (docetaxel (T) 75mg/m2 (60 mg/m2 for the first cycle) d1, CDDP 75mg/m2 d1, 5FU 750mg/m2/d continuous infusion d1-d5 q3weeks) followed by CRT (weekly carboplatin AUC 1.5 and RT 70Gy in 7 weeks; 2Gy/fx). LAP is administered concomitantly with IC (escalating dose 500–1500mg po daily) and during CRT (1,500 mg daily). Results: Seven male patients were included; tumor sites: LX (n = 3) / Hx: (n = 4), median age 59 years (range: 47–79), WHO PS 0–1, no severe or uncontrolled comorbidity. Three pts were included in the first cohort, at dose level 1 (LAP 500 mg daily plus TPF IC). Renal toxicity was observed among these 3 pts (grade 4 [n = 1], grade 2 [n=1] and grade 1 [n=1]), with 1 DLT, leading to treatment interruption in this group. This nephrotoxicity was reversible after stopping lapatinib and hydration of the patients. As LAP plus cisplatinum plus RT was feasible in another study, a second cohort was conducted in 4 pts, receiving LAP at the same dosage, and docetaxel (T) was only introduced from cycle 2 of IC to see what is the role of T in the observed side effect. Two DLTs were observed among this second cohort of subjects: one pt presented a grade 2 renal toxicity, grade 3 diarrhea and dehydration and a second pt presented a grade 3 anorexia and grade 3 stomatitis. Based on the occurrence of 3 DLTs at the first dose level of LAP, patient recruitment was closed. Despite these safety issues, all patients recovered and were treated off-study. They will receive follow-up as foreseen by the protocol. Conclusions: These data suggest that LAP should not be combined with TPF IC regimen for LA-LxHxSCC due to prohibited toxicity. [Table: see text]
Phase II randomized trial of bortezomib (B) plus irinotecan (I) or B with addition of I at progression in recurrent (R) or metastatic (M) squamous cell carcinoma of the head and neck (SCCHN) (E1304): A trial of the Eastern Cooperative Oncology Group
Authors: Gilbert J. , Lee J. , Argiris A. , Feldman L. , Haigentz M. , Burtness B. , Forastiere A. 
Published: August 2020

6020 Background: B, inhibits activation of NF- κβ and inhibits growth of SCCHN cell lines. NF-κβ dysregulation contributes to chemoresistance, including I. Pretreatment with B increases tumor sensitivity to I in vitro. Methods: Eligibility: 0–1 prior chemo regimens, ECOG PS 0–1. Pts randomized to B 1.3 mg/m2 IV d 1, 4, 8, 11 and I 125 mg/m2 IV d 1, 8 every 21 days (Arm 1) or B with addition of I at time of progression (Arm 2). Primary endpoint was response rate (RR) using RECIST and Simon's optimal 2-stage design. Results: 62 pts analyzable (Arm 1, N = 23; Arm 2, N = 39) of 71 enrolled . Pt. characteristics: median age 61 yrs., ECOG PS 1 - 53 %, and 71% had prior chemo. To date, RR (all PRs) 13% Arm 1 and 3% Arm 2 with SD 17% Arm 1 and 23% Arm 2. However, 3 patients remain on active therapy in Arm 2 and PFS and updated RR will be reported. 7 patients (including 3 pts on Arm 2) received 6–10 cycles of therapy. No responses in all 11 analyzable pts in Arm 2 with I added at progression. Median OS 9.1 months - Arm 1 and 7.3 months - Arm 2. Toxicity of B + I (125 mg/m2): grade 3/ 4 neutropenia (31%), vomiting (15%), diarrhea (15%), dehydration (23%). Grade 5 toxicity in 3 pts, 2 possibly related to therapy. Trial amended to decrease I to 90 mg/m2 3 patients (33%) - grade 3 / 4 diarrhea; no grade 3/ 4 neutropenia or grade 5 toxicities. Arm 2: grade 3 / 4 fatigue (15%). Conclusions: B alone is well tolerated. To date, RR low but prolonged stable disease noted in some pts. B in combination with I is a toxic regimen with disappointing activity. [Table: see text]
Antitumor activity of cediranib in patients with metastatic or recurrent head and neck cancer (HNC) or recurrent non-small cell lung cancer (NSCLC): An open-label exploratory study
Authors: Saura C. , Baselga J. , Herbst R. , del Campo J. , Marotti M. , Tessier J. , Collins B. , Heymach J. 
Published: August 2020

6023 Background: Cediranib is an oral, highly potent and selective inhibitor of VEGF signaling, with activity versus VEGFR-1, -2 and -3. FDG-PET has previously been shown to provide early assessment of the effectiveness of anticancer treatment in solid tumors after chemotherapy. The objectives reported here were to assess the effects of cediranib on 1) tumor metabolic activity using FDG-PET (standardized uptake value, SUVmax) and 2) tumor size (RECIST longest diameter). Methods: Eligible pre-treated patients with metastatic or recurrent HNC or NSCLC received cediranib monotherapy 30 mg/day for 3 weeks, or until disease progression or unacceptable toxicity. Patients showing evidence of response (FDG-PET) or clinical benefit at day 22 could continue study treatment and were assessed on days 43 and 71 by RECIST/FDG-PET. Evaluable patients had baseline and at least one post-baseline measurement available. Results: A total of 19 patients were treated; 17 patients had baseline and day 22 FDG-PET and 18 patients had baseline and at least one post-baseline RECIST assessment. Consistent changes in FDG-PET were observed (Table). At days 22, 43 and 71, a total of 5 (29%), 7 (41%) and 6 (35%) patients had ≥25% decrease in SUVmax (FDG metabolic response), respectively. The combined (HNC/NSCLC) best mean % change in tumor size from baseline for all patients was -25.9%. Best responses of PR and SD were seen in 18.8% and 50% of HNC patients, respectively (Table). The most common adverse events were proteinuria (7 [37%]), fatigue, diarrhea and hypertension (each 6 [32%]). Conclusions: This study provided evidence of antitumor activity with cediranib monotherapy as measured by decreases in FDG uptake, reductions in tumor size and RECIST response rate. Cediranib 30 mg/day was generally well tolerated, with a manageable adverse event profile consistent with previous studies. Further studies are warranted in these tumor types. [Table: see text] [Table: see text]
Frequency of HPV-associated tonsillar cancer in Sweden
Authors: Attner P. , Näsman A. , Marklund L. , Hammarstedt L. , Lindholm J. , Ramquist T. , Dalianis T. , Munck-Wikland E. 
Published: August 2020

6030 Background: Numerous studies has shown an increase of the incidence of tonsillar squamous cell carcinoma (SCC) both in the USA and in Sweden. This increase in incidence is despite a decreasing prevalence in smoking, a well-known risk factor for developing tonsillar cancer. The proportion of human papillomavirus (HPV) positive tonsillar SCC has also been shown to increase. This study aims to examine the incidence of tonsillar SCC and the proportion of HPV positive tonsillar SCC between 2003–2007 in the County of Stockholm, Sweden in correlation to data from 1970–2002. Methods: All patients (n = 120) diagnosed with tonsillar SCC during 2003–2007 in the County of Stockholm were included in this study. Ninety-eight pre-treatment biopsies were available and presence of HPV DNA and HPV-16 E6 and E7 mRNA were tested by PCR and RT-PCR. Incidence data between 2003–2007 for Sweden and in the County of Stockholm was obtained from the Swedish Cancer Registry. Data reported from 1970 to 2002 was also obtained for comparison. Results: HPV DNA was present in 83/98 (85%) of the tonsillar SCC biopsies from 2003–2007. Of the 77 HPV-16 positive tumors, HPV-16 E6 and E7 mRNA were found in 98% of the analyzed cases. The proportion of HPV-positive cancers had significantly increased both from 1970 to 2007 (p < 0.0001) as well from 2000 to 2007 (p < 0.01), with 68% (95% CI, 53–81) 2000–2002; 77% (95% CI, 63–87) 2003–2005; and 93% (95% CI, 82–99) 2006–2007. The incidence rate of HPV-positive tumors almost doubled each decade between 1970–2007, in parallel with a decline of HPV-negative tumors. Conclusions: Today, almost all tonsillar SCC in the County of Stockholm is HPV positive, and the incidence of HPV-positive cancers is still increasing. The data suggest that we are dealing with an epidemic of a virus-induced carcinoma, and that soon practically all tonsillar SCC will be HPV positive; a similar situation observed in cervical cancer. No significant financial relationships to disclose.
Blood biomarker modulation with dasatinib (D) and cetuximab (C) in patients (pts) with advanced solid malignancies
Authors: Egloff A. , Feinstein T. M. , Joyce S. C. , Kelly L. A. , Panelli M. C. , Yang T. , Siegfried J. M. , Grandis J. R. , Argiris A. 
Published: August 2020

6034 Background: Src is implicated in the resistance to epidermal growth factor receptor (EGFR) inhibitors. We studied biomarkers in the context of a phase I clinical trial of D, a small molecule inhibitor of several kinases, including Src, and C, a chimeric IgG1 monoclonal anti-EGFR antibody (Esteve et al. ASCO 2008; A14668). Methods: Plasma levels of EGFR, amphiregulin (AR), transforming growth factor-α (TGF-α), COX-2 and hepatocyte growth factor (HGF) were measured using a multiplex enzyme-linked immunosorbant assay (Searchlight TM) at day 0 and day 15. Blood mononuclear cell pSrc/Src levels were measured by Odyssey western blotting at day 0 (no C) and day 15 (with C) prior to and 2, 4, 8 and 24 hours after D. Clinical results were tested for association with biomarkers. The same biomarkers were also measured in plasma collected through an Early Detection Research Network- (EDRN-) sponsored effort from 22 squamous cell carcinoma of the head and neck (SCCHN) pts and 32 cancer-free matched controls. Results: 25 pts had baseline levels, 16 with paired samples. At day 15, EGFR plasma levels significantly decreased (p < 0.001), while AR (p < 0.001) and TGF-α (p < 0.001) significantly increased compared to pretreatment levels. HGF and COX 2 plasma levels did not change with treatment. Pre-daily D pSrc levels on day 0 and day 15 did not differ. pSrc levels decreased from pre-daily D levels by 8 hours post-D at day 0 (p = 0.036, n = 21) and day 15 (p = 0.027, n = 13) and returned to pre-D levels by 24 hours. In 17 pts evaluable for response, only low baseline levels of TGF-α were associated with an increased likelihood of disease control (p = 0.020). Elevated HGF at baseline was seen in treatment pts and SCCHN control pts compared to cancer-free controls (p = 0.006 and p = 0.001, respectively). Otherwise, there was no significant difference in plasma biomarker levels compared to the matched EDRN. Conclusions: D and C significantly decreased plasma levels of EGFR and increased EGFR ligands (AR and TGF-α). Similar data has been shown in vitro, suggesting that C binding to EGFR leads to fewer available receptors for ligand binding. pSrc transiently decreased after D dosing. We will evaluate C plus D and validate these biomarkers in a planned phase II trial in SCCHN. [Table: see text]
Higher dose per fraction and shorter overall treatment time using intensity-modulated radiation therapy versus conventional radiation therapy with concurrent carboplatin and 5-fluorouracil for locally advanced oropharyngeal carcinoma: A comparison of toxicity and efficacy
Authors: Clavel S. , Nguyen D. , Després P. , Fortin B. , Coulombe G. , Donath D. , Soulières D. , Charpentier D. , Guertin L. , Nguyen-Tan P. F. 
Published: August 2020

6038 Background: The aim of this retrospective study was to compare toxicity and efficacy of two different radiotherapy regimens, the first one using intensity-modulated radiation therapy (IMRT) to that of conventional radiotherapy (CRT) in patients treated with concomitant chemotherapy for locally advanced oropharyngeal cancer. Methods: Between January 2000 and December 2007, 249 patients with stage III-IV squamous cell oropharyngeal carcinoma were treated at our institution with definitive concurrent chemoradiation using carboplatin 70 mg/m2/day for four days and 5-fluorouracil 600 mg/m2/day as a continuous infusion every 3 weeks. One hundred patients had 70 Gy in 33 fractions using IMRT (2.12 Gy per day) and 149 received CRT at 70 gy in 35 fractions (2 Gy per day), both administered five times a week. Toxicities were compared using Fisher's exact test. Overall survival (OS), disease-free survival (DFS), and locoregional control (LRC) were estimated using the Kaplan-Meier method and compared with the log-rank test. Results: Median follow-up was 33 months. Three year actuarial rates for OS, DFS, and LRC were 95.4 vs. 75.8% (p < 0.001), 89.3 vs. 71.6% (p < 0.001), and 92.4 vs. 85.3% (p = 0.050) for IMRT and CRT respectively. To minimize the effect of changes in treatment paradigm over time, analyses were performed for patients treated after January 2004 and still showed OS, DFS, and LRC differences. Comparison of toxicities demonstrated that IMRT was associated with fewer dermatitis than CRT (p < 0.01), but caused the same rates of mucositis, weight loss, enteral feeding, hospitalization and death during treatment. There was significantly less xerostomia at 24 and 36 months (p < 0.001) following the end of treatment with IMRT. Conclusions: In this retrospective study, higher dose per fraction and shorter overall treatment time using IMRT given concurrently with chemotherapy when compared to CRT is a safe regimen with better OS, DFS, LRC, and less long term xerostomia. Altered fractionation RT with chemotherapy seems to result in better outcome and future prospective trials are needed to confirm this hypothesis. No significant financial relationships to disclose.
Comparison of cisplatin (CDDP) and radiation (RT) to cetuximab (C) and RT for locally advanced head and neck cancer (LAHNC): A preliminary analysis
Authors: Koutcher L. , Fury M. , Wolden S. , Zhang Z. , Mo Q. , Zelefsky M. , Kraus D. , Sherman E. , Pfister D. , Lee N. 
Published: August 2020

6042 Background: Both concurrent CDDP/RT and C/RT have been shown in randomized trials to yield superior disease control compared to RT alone in LAHNC, but no randomized trial has compared them. We evaluated our center's experience with these regimens. Methods: From 3/1/06 - 4/1/08, 175 patients were retrospectively identified who received definitive treatment for LAHNC with CDDP (planned total dose 100 mg/m2 Q3 weeks X 3) and RT (n = 125) or C (400 mg/m2 load; 250 mg/m2 weekly) and RT (n = 50). Patients who received prior RT, additional systemic therapy, and/or surgery to the primary site were excluded. C was given for the following reasons: auditory 30%, renal 4%, cardiac 2%, performance status 18%, patient choice 16%, neuropathy 4%, unknown 2%, and a combination of factors 24%. The median age: CDDP group 56, 6% >71; C group 66.5, 40% >71. Additional CDDP and C features: male sex, 86 v 78%; stage IV, 70 v 68%; and oropharynx, 78 v 70%. Median RT dose (70 Gy), RT length (46 days), and Karnofsky performance status (KPS) (90%) were the same; alcohol/tobacco use was similar. Results: At a median follow up of 18.7 months, with death without local failure (LF) as a competing risk, the 18 month LF incidence rate was 2.5% in the CDDP group and 43.3% in the C group (p < 0.0001), with the latest event occurring at 16.5 months. The 18 month disease-free survival (DFS) and overall survival (OS) rates were 85.7 v 40.9%, and 96.8 v 73.1%, in favor of CDDP (p < 0.0001 for both). Initially, 21 variables were assessed for significance, and when Cox proportional hazards model was used for multivariate analysis to address prognostic imbalances, treatment with CDDP still predicted for improved LF, DFS, and OS (p < 0.0001 for LF and DFS; p = 0.0017 for OS). For OS analysis, the concordance probability estimates were .67 for using drug choice alone and .80 for using drug choice, T stage, RT dose, and KPS. Conclusions: CDDP/RT and C/RT were used to treat somewhat different populations with LAHNC. The observed superiority of CDDP/RT compared to C/RT in LF, DFS, and OS may reflect patient selection issues. However, preliminary multivariate modeling suggests that CDDP/RT remains the preferred option for fit patients pending further analyses and prospective studies comparing these regimens. [Table: see text]
Concurrent chemoradiotherapy for locally advanced cervical esophageal carcinoma: A phase II study of oral fluoropyrimidine agents (UFT, S-1) plus cisplatin with radiotherapy
Authors: Iwase H. , Shimada M. , Tsuzuki T. , Hirashima N. , Goto H. 
Published: August 2020

6043 Background: Carcinoma of the cervical esophagus is a highly virulent disease. Although surgery is the standard therapy, the results of surgery alone are poor. Oral fluoropyrimidines (UFT, S-1) are useful to treat head and neck cancer and enhance the effectiveness of radiotherapy. We evaluated concurrent chemoradiotherapy using an oral fluoropyrimidine (UFT, S-1) and cisplatin in patients with locally advanced cervical esophageal carcinoma. Methods: Chemoradiotherapy with UFT and cisplatin (R-U-P) consisted of 60Gy of radiotherapy during 6 weeks, with daily UFT (200 mg/m2/day) and a 24-h infusion of cisplatin (70 mg/m2) on Days 8 and 36. Chemoradiotherapy with S-1 and cisplatin (R-S-P) consisted of two courses. One included 30 Gy of radiotherapy over 3 weeks, with daily S-1 (80 mg/m2/day) for 2 weeks and a 24-h infusion of cisplatin (70 mg/m2) on Day 8. The other included chemoradiotherapy after 2 weeks. Responders received at least 2 four-week courses of the chemotherapy. Results: Twenty patients were enrolled: 8 were treated with R-U-P and 12 with R-S-P. Four patients had stage II tumors and 16 had stage III tumors. All patients completed the chemoradiotherapy. The most prominent toxicity was myelosuppression. Grades 3 and 4 leukocytopenia occurred in 5 (25%) and 2 (10%) patients, respectively. Nonhematologic toxicity was moderate: grade 2 nausea/vomiting, pain, oral mucositis, and renal dysfunction occurred in 25%, 25%, 20% and 10% of the patients, respectively. Complete response (CR) was attained in all 4 patients with stage II tumors. In stage III cases, CR, partial response (PR), and response rates were 81%, 13%, and 94%, respectively these reached 75%, 17%, and 92% in the R-U-P group, and 90%, 10%, and 100% in the R-S-P group, respectively. All stage II patients survived. In stage III cases, the one-year survival rate was 75% and the three-year survival rate was 50%. Conclusions: Chemoradiotherapy with an oral fluoropyrimidine (UFT, S-1) plus cisplatin is convenient, tolerable, and effective, and it is a promising nonsurgical management option for patients with locally advanced cervical esophageal carcinoma. No significant financial relationships to disclose.