bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized phase II trial of concomitant CT/RT versus TPF followed by concomitant CT/RT in locally advanced squamous cell carcinoma of the head and neck (LASCCHN)
Authors: Paccagnella A. , Buffoli A. , Koussis H. , D’Amanzo P. , Loreggian L. , Bonetti A. , Valduga F. , Gava A. , Ardizzoia A. , Sguotti C. 
Published: March 2020

5518 Background: Concomitant CT/RT is the standard treatment for LASCCHN. Induction chemotherapy followed by CT/RT vs CT/RT alone have not yet been compared. The feasibility of TPF followed by CT/RT has been evaluated in a previous study (Int J Rad Oncol Biol Phys 2004, 59:481). Methods: Pts with inoperable stage III-IVa, PS 0–1, were randomized to CT/RT [2 cycles of Cisplatin 20 mg/sqm days 1–4, 5FU 800 mg/sqm 96 hours c.i. weeks 1 and 6 during RT (66–70 Gy)] (Arm A) or 3 cycles of neoadjuvant TPF (Docetaxel 75mg/sqm day1, Cisplatin 80mg/sqm day1, 5FU 800mg/sqm 96 hours c.i) followed by the same CT/RT (Arm B). Pts were stratified according to tumor site, T stage and nodal status. Neck dissection was performed in N2-N3 patients with pathological CR on primary tumor. The planned sample size was 96 pts to detect a difference in CR (primary endpoint) up to 15% in favour of arm B. The radiological responses were evaluated by an internal committee according to RECIST criteria. Results: Preliminary data are available for 84/96 randomized pts (42 arm A, 42 arm B). Pts/tumor characteristics are well balanced in the two arms. Toxicities during induction TPF consisted primarily of G3–4 granulocytopenia 56% (febrile neutropenia: 7.5%). Grade 3–4 toxicities during CT/RT in arm A and B were mucositis (42% and 26%), dysphagia (20% and 9%), skin reaction (12% and 8.6%), asthenia (5% and 3%); G3 weight loss (2% and 3%), G3 dry-mouth (0% and 3%). Duration of CT/RT was equivalent: 6.1 wks (4.2–8.7) in arm A and 6.3 wks (3.8–9.5) in arm B. At the end of CT/RT, in the 82 pts evaluable for efficacy, radiological CR were 20% (95% CI 8–37%) in arm A and 64% (95% CI 45–80%) in arm B. Conclusions: Three cycles of neoadjuvant TPF are feasible and don’t compromise subsequent concomitant CT/RT with comparable toxicity pattern. At the end of the treatment sequence serious adverse events were 31% in arm A and 34% in arm B. The difference in CR of 40% in favour of arm B justifies the following phase III study. Final results including pCR and DFS will be presented at the meeting. [Table: see text]
Conditional survival probability for head and neck squamous cell cancer: Results from the SEER 11 Dataset
Authors: Fuller C. D. , Wang S. J. , Goldwein J. W. , Thomas C. R. , Weber R. S. , Hoffman H. T. , Rosenthal D. I. 
Published: March 2020

5519 Background: Survival for most cancers is typically reported as a 5-yr percentage from the time of diagnosis. Surviving patients e.g., desire to know if their likelihood for survival has improved, given that they have lived X-years since diagnosis. Conditional survival (CS) is a calculated probability of survival that demonstrates the changing likelihood of demise during a span of intervals after diagnosis. The specific aim of this study is to assess the CS for patients with head and neck squamous cell carcinoma (HNSCC). Methods: The study population included HNSCC patients from the Surveillance, Epidemiology, and End Results (SEER 11) Program. Cumulative survival rates were calculated using JMP v6 (SAS, Cary, NC) with the product-limit method, and derived on the basis of the subsequent annual survival data. Results were also sub-stratified by site of disease. Results: 90,526 patients with histologically confirmed HNSCC diagnosed from 1973 to 2001 were included. The cumulative HNSCC crude cohort 5-year CS at diagnosis is 33%, and 38% at one-year after diagnosis. 5-year CS is 43% at 2 years post-diagnosis, where it plateaus for the next 8 one-year intervals. Sub-site analysis reveals similar CS trends for all HNSCC sites except the nasopharynx. Nasopharynx cancer CS, in contrast, progressively increases over all intervals. Conclusions: HNSCCC 5-year mortality risk stabilizes within 2–3 years after diagnosis, and with the exception of nasopharyngeal cancers, does not substantially improve thereafter. The SEER data represent the largest pooled dataset for HNSCC, but do not necessarily address all relevant issues contributing to risk for death. These data, however, do provide useful estimates for HNSCC patients with known survival after diagnosis, and may have utility in the design of clinical trials which incorporate survival modeling. [Table: see text] No significant financial relationships to disclose.
Swallowing function for patients treated on E2399: A phase II trial of function preservation with induction paclitaxel/carboplatin followed by radiation plus weekly paclitaxel
Authors: Murphy B. A. , Smith K. , Cmelak A. , Forastiere A. 
Published: March 2020

5524 ECOG 2399 is a phase II organ preservation study using induction chemotherapy followed by concomitant chemoradiation in unresectable patients with squamous cancer of the larynx or oropharynx. A correlative study was undertaken to assess acute and long-term swallowing. Methods: Swallow evaluations were done at baseline, 3, 12 and 24 months posttreatment. Self-report measures consisted of the PSS-HN and FACT-HN. Objective measures include the Modified Barium Swallow (MBS) scored using a physiologic measure, the Dysphagia Outcome Severity Scale (D) and a functional measure, the Functional Communication Measure (F). Both D and F are graded on a 7-point scale (7 = normal through 1 = absent swallow/unable to take p.o). Results: The number of evaluable D and F assessments at each time point: baseline 97/99, 3 months 72/73, 12 months 40/41, 24 months 24/26. The scores presented in the table are expressed in percentages. Conclusions: The majority of patients presented with objective abnormalities on MBS, but swallow function remained largely intact. At 3 months, swallowing was markedly impaired (severe 18 and 24%, moderate 20 and 21%). By 12 months, swallowing had improved for most patients; however, a significant percentage of patients had persistent mild deficits (5–6). Severe swallowing abnormalities were found in less than 10% of patients at 12 and 24 months. Sponsored, in part, by Bristol-Myers-Squibb. [Table: see text] [Table: see text]
A Phase II study of axitinib (AG-013736), a potent inhibitor of VEGFRs, in patients with advanced thyroid cancer
Authors: Kim S. , Rosen L. S. , Cohen E. E. , Cohen R. B. , Forastiere A. , Silva A. M. , Liau K. F. , Archer R. L. , Bycott P. , Vokes E. E. 
Published: March 2020

5529 Background: Elevated levels of VEGF have been found in thyroid tumor tissue compared to normal thyroid. Axitinib (AG-013736) is a novel small molecule inhibitor of the receptor tyrosine kinases with picomolar potency against VEGFR 1, 2 & 3 and nanomolar potency against PDGFR-beta and KIT. A phase I study in solid tumors identified 5 mg BID as the therapeutic dose. A phase II study in renal cell cancer demonstrated significant efficacy with a response rate (RR) of 46% (Rini et al, ASCO 2005). This study examined the safety and efficacy of AG-013736 (AG) therapy for advanced thyroid cancer. Methods: 32 patients (pts) refractory to or not suitable candidates for Iodine (131I) treatment were treated with AG 5 mg p.o. BID. Eligibility included measurable disease and ECOG performance status (PS) of 0 or 1. A Simon 2 stage minimax design was used (alpha = 0.1; beta = 0.1; null response rate (RR) = 5%; alternative RR = 20%). Results: The median age of 32 enrolled pts was 63 yrs (35–81), 20 (63%) were male, 12 (38%) were female. Histological subtypes include papillary: 19 pts (59%); follicular- 9 pts (28%), medullary- 2 pts (6%) and anaplastic-2 pts (6%). 25 pts (78%) had prior surgery, 19 pts (59%) had prior 131I treatment, 15 pts (47%) had prior RT, 6 pts (19%) had prior Adriamycin. Best response as assessed by RECIST criteria is PR in 3 pts with 38%-48% regression and additional unconfirmed PRs in 3 pts. Two pts (follicular) have PR>12 mos. Response assessments are ongoing. 12 patients have discontinued treatment: 6 pts (19%)-progression, 3 pts-adverse events (AEs) and 3 pts-other. Twenty pts (63%) remain on study. The range for time on study is (6, 469) days. Median progression free survival has not been reached. Preliminary safety data for 17 pts indicate most common treatment emergent AEs as fatigue (9 pts), nausea (5 pts), proteinuria ( 5pts ), dizziness (4pts). Gr. 3 AEs include proteinuria ( 2pts ), cough (1pt), dyspnea (1 pt), abdominal pain (1pt), dysphagia (1pt), fatigue (1pt), muscle weakness (1pt), anorexia (1pt). Gr. 2 hypertension was observed in 2 pts. Conclusions: AG-013736 has substantial anti-tumor activity in advanced thyroid cancer. Therapy is well tolerated with manageable toxicity. Further investigation in this setting is warranted. [Table: see text]
A phase I, open-label study of lapatinib plus chemoradiation in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: Harrington K. J. , Bourhis J. , Nutting C. M. , Rosine D. , Theodosiou A. M. , Gardiner S. , Berger M. S. , Beelen A. P. , Stead A. G. , El-Hariry I. A. 
Published: March 2020

5553 Background: Lapatinib is a selective and potent dual, competitive inhibitor of EGFR and ErbB2. A high level of expression of EGFR is reported in SCCHN (ranging from 55% to 90%), which is a negative prognostic factor, whereas ErbB2 expression ranges between 40% to 60%. The rationale for EGFR inhibition in combination with fractionated radiotherapy is to enhance radiosensitivity and inhibit cellular proliferation, including accelerated repopulation, during treatment. Methods: Patients (pts) with locally advanced SCCHN were enrolled at escalating dose levels of lapatinib (500–1,500 mg/d) in combination with radiotherapy (66–70 Gy/6–7 weeks given 5 days a week in 2 Gy daily fractions) and intravenous cisplatin (100 mg/m2, days 1, 22 and 43 of radiotherapy). Each cohort was to include 3 pts, with expansion to 6 in the event of dose-limiting toxicity (DLT). Main eligibility criteria were confirmed SCCHN, excluding nasopharynx, stage III, IVa,b, and adequate organ function. Regular safety assessments were performed during therapy and follow-up period. Cardiac assessments using MUGA or ECHO scans were also performed. Results: Seventeen pts were treated (500 mg - 7; 1,000 mg - 7; 1,500 mg - 3; expanded cohort of 9 additional pts is currently recruiting). The most common side effects were Grade 1-3 dysphagia, mucositis and dermatitis, typically observed with cisplatin and radiotherapy in this population. Lapatinib-related adverse events were minor. In the 500mg cohort: 2 pts had diarrhea (Gr 1), 1 pt had tinnitus (Gr 1); in the 1,000mg cohort: 2 pts had nausea (Gr 2) and vomiting (Gr 2), 1 pt had transient elevated liver enzymes (Gr 3); in the 1,500mg cohort 2 pts had nausea (Gr 1) and 3 pts vomiting (1 pt Gr 1, and 2 pts Gr 2). One DLT was reported both at 500 mg and 1,000 mg dose levels; no further DLT were reported at the final 1,500 mg dose level. The optimally tolerated regimen was lapatinib 1,500 mg OD, given concurrently with conventional radiotherapy and cisplatin. Preliminary evidence of clinical activity was encouraging. Conclusions: The combination of lapatinib and concomitant chemoradiation is well tolerated, has demonstrated encouraging clinical activity in this population of locally advanced SCCHN patients, and warrants phase II studies in this disease. [Table: see text]
Phase I/II study of erlotinib combined with cisplatin and radiotherapy for locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: Herchenhorn D. , Dias F. L. , Ferreira C. G. , Bezerra M. , Fonseca A. J. , Mora P. , Pineda R. M. , Fontão K. , Knust R. E. , Martins R. G. 
Published: March 2020

5575 Background: Erlotinib has single agent activity in SCCHN. Preclinical data indicates synergy with both cisplatin and radiotherapy (RT). Methods: This phase I/II study included patients (pts) with stages III and IV SCCHN. Pts received therapy with RT 70.2 Gy for 8 weeks and cisplatin (C) 100 mg/m2, 3 doses every 3 weeks, both starting on Day 8. Erlotinib (E) was started on Day 1 and continued until the end of RT. Phase I doses were escalated in cohorts of 3 pts/dose level: level 1–50 mg, level 2–100 mg and level 3–150 mg. In case of grade IV toxicity leading to RT interruption, 3 additional pts were included in the same dose level. Frozen tissue for molecular studies was collected before and after treatment. Results: Phase I was completed with 9 patients. No patient had RT interruption due to grade IV toxicity. Consequently 150 mg/day was established as the phase II dose. Twelve patients have been included in the phase II part of the trial. Final toxicity data is available for 13 patients (9 from phase I and 4 from phase II). Median age was 58 years, 10 pts had laryngeal carcinoma (stage III 4pts, IVA 3 pts, IVB 3 pts) and 3 oropharyngeal carcinoma (stage III 1pt, IVA 1pt, IVB 1 pt). The dose of C was reduced or held in 3 pts due to ototoxicity (2 pts) and neutropenia (1 pt). Other grade III or IV toxicity included dermatitis (8 pts), skin rash (3 pts), respiratory infection (2 pts), nausea (2 pts), neutropenia (2 pts), mucositis (2 pts) and cutaneous infection (1 pt). Response was accessed by direct visualization/biopsy and CT/MRI scans. Among the 13 patients who have completed treatment, 11 (84.6%) achieved complete pathological response, 1 had residual disease and 1 disease progression. Conclusions: This trial establishes the standard dose of erlotinib, 150 mg/day, as safe to be combined with full dose cisplatin and radiotherapy, in locally advanced SCCHN. Accrual for the phase II study is ongoing and additional response and toxicity data will be presented at the meeting. No significant financial relationships to disclose.
Combination therapy of docetaxel, carboplatin or paclitaxel, carboplatin for patients with metastatic/recurrent carcinoma of the head and neck (SCCHN)
Authors: Bickmann A. , Holzgraefe M. , Wolf M. , Schröder M. 
Published: March 2020

5576 Background: The five-year survival for patients with recurrent disease has not been significantly increased in the last years. Despite aggressive initial management of the primary tumor, patients suffer from locoregional recurrence in up to 50% and distant metastasis is seen in about 25% of cases. Materials and Methods: 96 patients with recurrent or metastatic carcinoma of the head and neck received therapy as follows. From August 1996 to May 2000, 52 patients received chemotherapy with paclitaxel 100 mg/m2 in combination with carboplatin AUC2. Between May 2000 and October 2004, 44 patients with recurrent or metastatic disease were treated with docetaxel 35 mg/m2 in combination with carboplatin AUC2. Both chemotherapy regimens were administered weekly for a maximum of six cycles. Results: Most of the patients underwent a combination first line therapy with CT/Surg/RT (48%/47.7%) or CT/RT (36%/23%) before suffering from rec. disease. After recurrence local, regional or distant, we observed 9.6% complete response for the combination-therapy with paclitaxel/carboplatin and 25% with docetaxel/carboplatin, partial response in 38.5% and 34.1% of the patients, yielding an overall response rate of 48.1% with weekly paclitaxel/carboplatin and 59.1% with weekly docetaxel/carboplatin. Stable disease was documented for 25% of the patients treated with paclitaxel/carboplatin and 18.2% after treatment with docetaxel/carboplatin. Median survival was measured after first diagnosis of recurrence or metastatic disease. We observed a median survival of 10.9 month for the group treated with paclitaxel/carboplatin and 37 month for patients treated with docetaxel/carboplatin. Therapy with both treatment-options was well tolerated, all 96 patients received six cycles. Most frequent toxicity was leucopenia (Grade I/II/III: paclitaxel 12%/27%/15%; docetaxel 25%/23%/16%). Conclusions: Chemotherapy for recurrent carcinoma of the head and neck with weekly docetaxel/carboplatin is well tolerated and effective. The toxicitiy profile makes this combination favourable for an outpatient setting. No significant financial relationships to disclose.
Phase II study of combretastatin A4 phosphate (CA4P) in patients with advanced anaplastic thyroid carcinoma (ATC)
Authors: Cooney M. M. , Savvides P. , Agarwala S. , Wang D. , Flick S. , Bergant S. , Bhakta S. , Lavertu P. , Ortiz J. , Remick S. 
Published: March 2020

5580 Background: CA4P is the first tubulin-binding vascular disrupting agent tested in the clinic. Phase I studies were devoid of significant myelosuppression, DLT included cardiovascular side effects, and there was demonstrable activity in ATC (Cancer Res 2002; 62:3408; Clin Cancer Res 2004; 10:96). Methods: Patients with metastatic ATC, good performance status, normal ECG and cardiac function, and no prior therapy for disseminated disease were eligible for study. CA4P at a dose of 45 mg/m2 was administered as 10-minute IV infusion on days 1, 8 and 15 every 28 days (1 cycle) until progression of disease. Results: A total of 18 patients (pts) (11M/7F), median age 62 (range 40–71 yrs), received a total of 55.67 cycles of treatment. Therapy was well tolerated with mild to moderate nausea, vomiting, headache, and tumor pain (3 pts with grade 3) all of which essentially resolved within first 24 hrs. There was no clinically meaningful myelosuppression or cardiac toxicity. No objective responses were seen; 6 pts with stable disease and 12 pts progressed. Median progression free survival (PFS) was 7.4 wks (range 2–84+ wks); with 28% of pts progression free > 3.0 mos. (12.0+, 14.3, 15.3, 25.6 and 84.0+ wks). Pts without bulky disease tended to do better. Fourteen pts have died; 4 are alive; and 2 are alive and on-study at 12.0+ and 84.0+ wks. Median survival is on the order of approximately 20 wks. Conclusions: Approximately a quarter of patients treated with single-agent CA4P experience greater than 3 mos. freedom from progression. Combined modality strategies with CA4P and either chemotherapy and other targeted agents or with radiation are warranted. [Supported in part by a clinical grant from OXiGENE, Inc., Waltham, MA and NIH grant nos. M01 RR-00080]. No significant financial relationships to disclose.
Phase III adjuvant trial of concurrent epirubicin/taxane vs. sequential epirubicin/cyclophosphamide followed by taxane for node positive breast cancer
Authors: Lambert-Falls R. , Deutsch M. A. , Desch C. , Zhou K. , Perez E. 
Published: March 2020

573 Background: This study evaluates whether concurrent epirubicin/taxane (ET) improves disease-free survival (DFS) at 3 yrs compared to the sequential combination of epirubicin/cyclophosphamide followed by a taxane (EC>T) in pts with operable node (+) breast cancer. Methods: Eligible pts were randomized to receive either ET (E 75 mg/m 2) for 8 cycles q21 days or EC>T (E 90 mg/m 2, C 600 mg/m2) for 4 cycles, followed by 4 cycles of a taxane q21 days. Choice of T (paclitaxel 175 mg/m2 or docetaxel 75 mg/m 2) was at the physician’s discretion. The primary endpoint is DFS. A 0.10 increase in the probability of DFS at 3 yrs for the ET arm would be considered clinically relevant. To detect 82 events, 300 subjects per arm are required to provide 90% power at 5% significance level. Results: 617 pts were enrolled from Nov 2000 to June 2003; 308 pts received ET and 309 pts received EC>T. Both treatment arms were well balanced with respect to age, nodal+, ER status, Her-2+ and PS; median age 52.5 (42%<50 years old); 70% ER+; 61% LN (1–3); 16% Her-2+; 87% PS 0. Total of 2206 cycles of treatment were given to ET compared 2314 cycles of treatment to EC>T. At 30 months of median follow-up there were DFS 102 events occurred; 47 events in ET arm (16%) and 55 events in EC>T arm (18%); 63 total deaths; 29 deaths in ET arm and 34 deaths in EC>T arm. The most common toxicities include alopecia (50%), fatigue (31%), nausea and vomiting (30%), dyspepsia (27%), febrile neutropenia (15%), constipation (12%), diarrhea (10%), arthralgia (11%), stomatitis (10%). In cardiac safety f/u, only one pt in ET arm remained LVEF drop >15. Conclusions: Epirubicin can be combined with taxanes in both sequential and concurrent therapies and both regimens are effective and well tolerated. The study is sponsored by Pfizer Inc. No significant financial relationships to disclose.
Update of cardiac dysfunction on NSABP B-31, a randomized trial of sequential doxorubicin/cyclophosphamide (AC)→paclitaxel (T) vs. AC→T with trastuzumab (H)
Authors: Geyer C. E. , Bryant J. L. , Romond E. H. , Ewer M. S. , Keefe D. L. , Shannon R. P. , Levine T. B. , Rastogi P. , Swain S. M. , Wolmark N. 
Published: March 2020

581 Trastuzumab (H) has been shown to improve 3-year disease-free survival (DFS) and overall survival (OS) in HER2 positive, node-positive breast cancer patients when combined with paclitaxel (T) following AC (Romond NEJM 2005:353;1673–1684). Cardiac dysfunction is the major toxicity associated with the addition of H to AC→T. The 3-year cumulative incidence of cardiac events (class III/IV CHF or cardiac death) with AC→TH was 4.1% compared to 0.8% with AC→T (Tan-Chiu JCO 2005:23;7811–7819). An updated analysis of cardiac safety on B-31 with an additional full year of follow-up is planned for March 2006 and will be presented. [Table: see text]
Relationship between numeracy and breast cancer patients’ estimates of adjuvant treatment benefit
Authors: Lipkus I. M. , Kimmick G. G. , Chui S. Y. , Fifield D. L. , Werner L. A. , Marcom P. K. 
Published: March 2020

586 Background: Based on clinical anecdotes and existing literature, the general population has trouble understanding and making use of statistical information. We explored the accuracy of breast cancer patients’ (pts) estimates of treatment outcomes (probabilities of remaining cancer free versus recurring) relative to data provided by ‘Adjuvant! Online‘ decision aid program, and whether accuracy differed by pts numeracy skills (i.e. use of mathematical concepts and operations). Methods: 43 ER+ women with early stage, node-negative breast cancer were recruited (mean age 56, 72% Caucasian). After signing an informed consent and completing an assessment of numeracy (Lipkus et al., 2001), pts discussed case-specific Adjuvant! print-outs with an oncologist. Pts then estimated their chances of being cancer free after receiving no further treatment, hormonal therapy only, chemotherapy only, or both. Pts also were asked to select the treatment option that afforded their best chance of remaining cancer free. Results: Compared to the estimates provided by Adjuvant! Online, pts underestimated their chance of being cancer free after receiving no further treatment (M=62 vs. 48 out of 100), hormonal therapy only (M=72 vs. 45), chemotherapy only, (M=71 vs.42), and combined therapy (M=78 vs. 54). 63% correctly selected the treatment option that afforded the highest estimate of being cancer free. More numerate patients were more likely to correctly specify which treatment option provided the best chance of being cancer free (OR=0.67, 95% CI: 0.50, 0.89, p<.006); and less likely to give personal estimates of being cancer free inconsistent with estimates provided by Adjuvant! for hormonal therapy (OR=0.17, 95% CI: 0.04, 0.72, p<.02), chemotherapy (OR=0.62, 95% CI: 0.39, 0.99, p<.05) and combined therapy (OR=0.44, 95% CI: 0.23, 0.85, p<.02). Conclusions: Findings suggest that pt numeracy skills are important in comprehending statistical data about adjuvant treatment outcomes. Numeracy skills may have implications for how statistical information about treatment is presented and discussed, affecting processes of informed decision-making and pt quality of life. No significant financial relationships to disclose.