bluuebunny/crossref_metadata_2025_split huggingface dataset:
Updated results of a phase II trial integrating gefitinib (G) into concurrent chemoradiation (CRT) followed by G adjuvant therapy for locally advanced head and neck cancer (HNC)
Authors: Ahmed S. M. , Cohen E. E. , Haraf D. J. , Stenson K. M. , Blair E. , Brockstein B. E. , Lin S. , Lester E. , Dekker A. , Williams R. , Vokes E. E. 
Published: March 2020

6028 Background: This study was undertaken to evaluate the tolerability and efficacy of substituting G for paclitaxel into a well- described CRT regimen (Clin Cancer Res 9: 5936; JCO 21: 320) and continuing G as adjuvant therapy. Endpoints included complete response (CR) rate to CRT, progression-free (PFS), disease-specific (DSS) and overall survival (OS), and local & distant control rates. Methods: Previously untreated subjects with stage III, IVa, or IVb squamous cell, poorly differentiated carcinomas, or lymphoepithelioma were enrolled. Organ sparing surgery was allowed. Subjects received 2 cycles of carboplatin/paclitaxel induction followed by CRT with G (250 mg PO qd), 5- fluorouracil, hydroxyurea, and twice daily radiation on day 1–5 of five 14d cycles. G was continued for 2 years from the start of CRT. Results: From 2/03 to 10/04, 67 eligible subjects accrued including 51 males; median age 56; ECOG PS 0 in 47, 1 in 19, and 2 in 1; stage IV in 61 (91%). With median follow-up of 858 days, 9 have had progressive disease (PD, 3 distant, 5 local, 1 with both) and 15 have died (12 related to HNC). Estimated OS=83% at 2y, 73% at 3y; PFS=77% at 2y, 64% at 3y; and DSS=86% at 2y, 80% at 3y. In 56 evaluable subjects we observed 51 CR (91 %), 4 partial responses and 1 PD after CRT. Non-evaluable subjects underwent surgery prior to CRT (10), or died prior to evaluation (1). Grade 3/4 toxicity included mucositis (75%/10%), dermatitis (29%/3%), rash (4%/0%) and diarrhea (1%/0%). Sixty-two patients received maintenance gefitinib, with 60 reliably reporting doses (median days on gefitinib=667). Reasons for holding G included LFT abnormalities, patient refusal, diarrhea, rash, recurrence, hospitalization for acute illness, and early death. Conclusions: Adding G to concurrent CRT after induction therapy, and as adjuvant therapy is tolerable and feasible. Favorable survival and CR data suggest that this is a promising regimen for patients with locally advanced HNC. [Table: see text]
Analysis of magnetic resonance imaging (MRI) in the detection of mammographically occult breast carcinoma
Authors: Vallow L. , Packianathan S. , Feigel D. , DePeri E. , Buskirk S. , Perez E. A. 
Published: March 2020

603 Background: Breast MRI may be useful for detecting mammographically occult ipsilateral carcinoma in newly diagnosed breast cancer. Our initial experience with breast MRI, demonstrated 16% of patients to have additional breast disease detected only by preoperative MRI. We further analyzed our findings to identify an association between patient factors and MRI detected disease. Methods: Preoperative MRI scans of 390 women with newly diagnosed breast cancer were reviewed. Using only patients with pathologic verification, the incidence of mammographically occult ipsilateral cancer was determined. Patient and tumor characteristics were further analyzed to identify factors which may predict pathologically positive MRI findings. Results: Of the 390 women undergoing preoperative MRI, 120 (31%) had ipsilateral findings requiring biopsy. Pathologically verified additional ipsilateral cancer was detected in 62 (16%). Multicentric disease was detected in 32 (52%) and multifocal or more extensive local disease in 30 (48%). The median age of all patients was 62 (27% premenopausal) whereas the median age of those with MRI detected additional carcinoma was 55 (44% premenopausal). Of those with additional disease detected by MRI, 74% had index lesions =1 cm and 63% node negative. The most common histology of the index lesion was infiltrating ductal carcinoma in 64%. In the 62 patients found to have additional disease by MRI the most common histology included infiltrating ductal carcinoma (58%), ductal carcinoma-in-situ (34%) and infiltrating lobular (8%). The histology of the MRI detected additional disease was identical to the index lesion in 71%. Conclusions: In women with newly diagnosed breast cancer, there was a 16% incidence of pathologically proven, mammographically occult ipsilateral disease detected by MRI. Patients found to have additional disease tended to be younger, premenopausal or have index tumors =1cm. The contribution of preoperative MRI in breast cancer management continues to evolve. A lower threshold for obtaining breast MRI may be appropriate in selected subsets of breast cancer patients. No significant financial relationships to disclose.
Phase 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. , Pineda R. M. , Fonseca A. J. , Bezerra M. , Ferreira C. G. , Knust R. E. , Fontão K. , Martins R. G. 
Published: March 2020

6033 Background: Preclinical data indicates synergy of erlotinib with both cisplatin and radiotherapy (RT). We previously reported the phase I results with the dose of erlotinib defined as 150 mg/day. Methods: Patients (pts) with stages III and IV SCCHN were included. Treatment consisted of RT (70.2 Gy in 8 weeks), and cisplatin (C) (100mg/m2, q 21 days for 3 doses), both starting on Day 8. Erlotinib (E) was started on Day 1 and continued until the end of RT. Patients with N2/N3 disease were evaluated for elective neck dissection post RT. Results: Thirty one pts have been accrued to the study. Median age was 55 years (35–73), 13 pts had larynx carcinoma (stage III 9pts, IVA 3pts, IVB 1pts), 13pts oropharynx (stage III 2pts, IVA 8pts, IVB 3pts) and 5pts hypopharynx (stage III 1pt, IVA 4pts). Twenty five pts completed treatment and are evaluable for response and toxicity. Grade III or IV toxicity included: in-field dermatitis (14pts), nausea (13pts), mucositis (9pts), emesis (8pts), cutaneous infection (3pts), acneiform rash (7pts), fatigue (7pts), dysphagia (6pts), respiratory infection (4pts), neutropenia (1pt), diarrhea (1pt) and 1pt died due to sepsis. The dose of C was reduced in 4pts and withheld in 3pts; RT was delayed in 6 pts (median of 8 days). Twenty one pts (84%) required enteral feeding. Response was accessed by endoscopy with biopsy and CT/MRI scans. Twenty one pts (84%) had complete pathological response, 2 had residual disease and were submitted to salvage surgery, and 1 had disease progression. The median follow-up is 10.8 months. Five pts (23%) had a local relapse. Nineteen pts are disease-free (16 with organ preserved), 2 alive with disease, and 3 pts died due to disease progression. Conclusions: The combination of RT+C+E showed a high complete pathological response and acceptable toxicity, despite the high incidence of grade III/IV in-field dermatitis. These results encourage the design of a phase III trial. Final results will be presented at the meeting. No significant financial relationships to disclose.
A phase II trial of gefitinib in recurrent and metastatic nasopharyngeal carcinoma pretreated with platinum-based chemotherapy
Authors: Chua D. T. , Sham J. , Au G. 
Published: March 2020

6042 Background: Epidermal growth factor receptor (EGFR) is commonly expressed in nasopharyngeal carcinoma (NPC) and strong EGFR expression appears to correlate with poor survival. Gefitinib, a small-molecule inhibitor of the EGFR tyrosine kinase, has been shown to inhibit the growth of NPC cell lines. Methods: Nineteen patients with recurrent or metastatic NPC were recruited into the study. Eligibility criteria included: radiographic progression of disease, ECOG PS < 2, 1 or more prior platinum-based chemotherapy regimens, normal organ function. Fifteen patients were treated for first relapse, 3 for second relapse, and 1 for third relapse. Local disease was present in 8, nodal disease in 3, and distant metastases in 14. All patients had previously received platinum-based chemotherapy as adjuvant and/or palliative treatments, and 89.5% had 2 or more regimens. Patients received gefitinib 250 mg po daily. Median treatment duration was 10 weeks and median follow-up time was 9 months. Results: Minor response was observed in 2 patients treated for advanced local recurrence. There were no complete or partial responders. Seven patients had stable disease and 12 had progressive disease. Median time to progression was 4 months and median survival was 14 months. Progression-free rate at 6 months was 22% and 1-year survival rate was 70%. Treatment was generally well tolerated and only grade 1–2 adverse events were observed, with acneiform rash (68.5%), fatigue (36.9%), diarrhea (31.6%), and anorexia (31.6%) most common. In 15 patients with symptoms related to NPC, 5 reported improvement, 5 reported no changes, and 5 reported worsening during gefitinib treatment. Conclusions: Gefitinib has little activity in terms of response rate in recurrent and metastatic NPC, although disease stabilization and symptomatic improvement were observed in some patients. Evaluation of markers of EGFR pathway on tumor tissue is currently being performed. No significant financial relationships to disclose.
Interaction of EGFR and IGF-1R signals to modulate the anti-proliferative and biochemical responses of head and neck squamous cancer (HNSCC) cells to EGFR inhibitors
Authors: Thomas C. Y. , Jameson M. , Beckler A. 
Published: March 2020

6045 Background: Epidermal growth factor receptor (EGFR) inhibitors improve the efficacy of radiotherapy for HNSCC and as single-agents induce tumor responses or stabilization in a minority of patients. The molecular mechanisms that dictate the spectrum of observed responses are not well understood. Methods/Results: Exposure of the HNSCC lines SCC-9 and SCC-25 in vitro to the EGFR inhibitors PD158780, lapitinib, or cetuximab suppressed cell proliferation and cell cycle progression into S-phase. Immunoblots showed that PD158780 inhibited autocrine activation of the EGFR, reduced phosphorylation of the downstream signaling proteins AKT and Erk, and affected cell cycle regulatory molecules (reduced Rb phosphorylation, decreased cyclin D1 levels, and induced p27kip1). However, stimulation of the cells with an insulin-like growth factor-1 (IGF-1) analog produced a dose-dependent resistance to the anti-proliferative effects of the EGFR inhibitors. The resistance of SCC-25 cells correlated with IGF-1-induced maintenance of AKT and Rb phosphorylation and cyclin D1 expression. Conversely, the EGFRs also acted downstream of the activated IGF-1 receptors as concomitant EGFR inhibition dampened the proliferative response of the cells, reduced Erk phosphorylation and increased p27kip1 expression. Experiments with the metalloproteinase inhibitor TAPI-2 suggested that the IGF-1 activates the EGFRs through proteolytic cleavage of precursor forms of EGFR ligands. Conclusions: The proliferative and biochemical responses of HNSCC cells to EGFR inhibitors are influenced by cross-talk between the EGFR and IGF-1 receptors. One implication of this work is that the clinical response of HNSCCs to EGFR inhibitors may depend on the relative contribution of autocrine EGFR signaling to activation of specific downstream growth factor signaling pathways, whether or not these receptors are the primary or secondary source of these signals. No significant financial relationships to disclose.
Plasma EBV DNA and cell-free GAPDH DNA as prognostic factors of locally advanced nasopharyngeal carcinoma
Authors: Chen J. , Ting L. , Ko J. , Lou P. , Wang C. , Yang T. , Hong R. 
Published: March 2020

6053 Background: Plasma cell-free nucleic acids have been investigated to be potential prognostic and predictive markers of treatment response, residual disease, and survival of cancer patients. However, these nucleic acids will be confounded by normal cell death, which might be caused by cancer-related inflammation, infection, or chemotherapy. Nasopharyngeal carcinoma is endemic in Taiwan, highly related to EBV infection. Plasma EBV DNA level has been suggested to be predictive of disease status and outcomes. We try to find out whether plasma EBV and cell-free glyceraldehydes-3-phosphate dehydrogenase DNA before definite treatment of locally advanced NPC predict tumor outcomes better. Methods: 144 stage IV (AJCC version 6) NPC patients received induction chemotherapy followed by concurrent chemoradiotherapy in National Taiwan University Hospital from 1998 to 1999. Pre-treatment blood samples were colleted for real-time quantitative polymerase chain reactions of EBV and GAPDH DNA. The results will be analyzed by SPSS version 13 to see if correlated with tumor extent, locoregional/distant failure, and overall survival. Results: Our patients were mainly composed of T4(97%) and N2(56%) patients. 23 % were in N3 stage. Plasma EBV and cell-free GAPDH DNA levels were not correlated with T stage. Plasma EBV DNA level was significantly correlated with N3 status(Mann-Whitney test p=0.021). After Cox regression model, only age (p=0.024) was a significant predictor of recurrence-free survival; N3 status(p=0.007) and positive plasma EBV DNA (p=0.002) predicted shorter metastasis-free survival. N3 status (p=0.031) and positive plasma EBV DNA (p=0.002) were significantly related to poor survival by log-rank test; whereas T4 lesions (p=0.524) and plasma cell-free GAPDH DNA level (p=0.182) were not. After multivariate Cox regression, positive plasma EBV DNA (hazard ratio 4.936 p=0.006) was the only significant predictor of poor survival. Conclusions: To use circulating DNA as prognostic marker, a specific one, such as EBV DNA, might be better than a non-specific one, like GAPDH DNA. This is important in the development of tumor markers for other solid tumors. No significant financial relationships to disclose.
A phase I dose escalation study of pemetrexed in patients with advanced head and neck squamous cell cancer (HNSCC)
Authors: Morrow P. H. , Glisson B. S. , Ginsberg L. E. , Lippman S. M. , Kies M. S. , Blumenschein G. R. , Ayuste R. C. , Feng L. , Papadimitrakopoulou V. A. , Kim E. S. 
Published: March 2020

6055 Background: Despite recent advances in therapy, patients (pts) with recurrent or metastatic HNSCC continue to demonstrate a poor median survival. In these pts, early trials with pemetrexed, a novel antimetabolite that acts upon several enzymes involved in pyrimidine and purine synthesis, have demonstrated promising efficacy and tolerability. Prior studies found that the administration of oral dexamethasone with pemetrexed reduced the incidence of skin rash. Later, vitamin supplementation (B12 and folic acid), given in addition to the dexamethasone, further diminished side effects. However, no trial has yet evaluated the appropriate steroid dose and its relation to the dosing of pemetrexed, in the setting of vitamin supplementation. We conducted a phase I trial to determine the maximum tolerated dose, toxicity, and preliminary efficacy of pemetrexed when given with different schedules of, or in the absence of, dexamethasone in pts with advanced HNSCC who had been treated with at least one or more chemotherapy regimens. Methods: Eligible pts had metastatic or recurrent HNSCC, prior treatment with one or more chemotherapy regimens, ECOG PS =2, and life expectancy >3 months. A conventional algorithm-based dose escalation design was applied, with three predefined dose levels (DL) of pemetrexed (500 mg/m2, 600 mg/m2, and 700 mg/m2) within each schedule of dexamethasone (none, 20 mg IV on day 1, and 4 mg orally bid for 3 days). Results: A total of 23 pts have been enrolled; 18 pts were evaluable. Median age was 57 years (range 47–82). Median ECOG PS was 1 (range 0–2), and 75% of pts were male. Number of prior chemotherapy regimens were as follows: 1 (40%), 2 (35%), 3 (15%), and 4 (10%). Preliminary data demonstrated only 2 treatment-related adverse events that were grade 3 or greater: anemia (DL1) and pneumonia (DL 1). In all, 13 pts have received pemetrexed with less than standard recommended dexamethasone dosing (none or IV), including 7 pts who received no dexamethasone. Of the 18 evaluable pts, 1 pt had a partial response and 2 pts had stable disease. Conclusions: This represents the first study that demonstrates that steroids may not be required as premedication with pemetrexed. Due to the limited toxicity observed, trial enrollment continues with dose escalation. [Table: see text]
Tumor response criteria and biomarkers associated with increased survival following adenoviral p53 gene therapy (ADVEXIN) in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN)
Authors: Nemunaitis J. J. , Clayman G. , Hamm J. , Bier-Laning C. , Minn H. , Van Echo D. , Yoo G. , Menander K. , Sobol R. E. , Goodwin W. J. 
Published: March 2020

6057 Background: There is a growing body of data indicating that conventional WHO and RECIST criteria do not optimally identify tumor responses associated with increased survival. Methods: We compared several response criteria to assess the efficacy of intratumoral adenoviral p53 gene therapy (Advexin) in a Phase 2 trial of 106 patients with recurrent SCCHN. Results: The percentage of patients with tumor responses defined by reductions in bi-dimensional tumor area by CT scans of 50%, 30%, 25%, 10% or stable disease of > 3 months were 8%, 10%, 11%, 16% and 20% respectively. The median survival for the entire population was 5.9 months while the responder populations defined by tumor decreases of 50%, 30%, 25%, 10% or stable disease > 3 months had median survivals of 40.8, 17.0, 13.7, 12.3 and 11.4 months respectively. There was a statistically significant increase in median survival for each of the responder populations compared to non-responders (p < 0.0009 for each comparison by logrank test). Statistical significance was maintained for the response definitions in landmark analyses excluding patients with survivals less than 3 and 6 months respectively. Locoregional disease control (CR + PR + SD > 3 months) was a stronger predictor of survival by Cox Proportional Hazard analysis (p = 0.0002) than conventional > 50% tumor reduction CR + PR response criteria (p = 0.005). With respect to abnormal p53 detected by immunohistochemistry (≥20% positive cells), 75% of patients (12/16) with p53+ tumors demonstrated locoregional disease control compared to only 18% (2/11) with p53− tumors p=0.0063 Fisher’s Exact Test. In addition, the median survival of patients with abnormal p53 was 11.6 months compared to only 3.5 months in patients with normal p53 (p=0.0007 Logrank Test). Conclusions: Our findings indicate that abnormal p53 is a predictive biomarker that identifies a subset of patients most likely to benefit from p53 gene therapy and that recurrent SCCHN tumor response definitions based upon smaller reductions in tumor size or the absence of progression (stable disease > 3 months) more accurately identified Advexin treated patients with increased survival than conventional response criteria. [Table: see text]
Phase II neoadjuvant docetaxel/cisplatin followed by concurrent cisplatin/radiotherapy for locally advanced nasopharyngeal cancer
Authors: Kandil M. S. , Alnasser H. S. , Bandey S. A. , Almutairy A. S. , Ammar F. A. , Saadeddin A. A. , Murshid E. M. , Asiri M. A. , Zahrani A. M. 
Published: March 2020

6059 Background: Neoadjuvant cisplatin/docetaxel are active agents for locally advanced nasopharyngeal cancer (LANPXCA). The efficacy and tolerability of neoadjuvant cisplatin/docetaxel followed by concurrent cisplatin with radiotherapy are explored in a phase II trial. Methods: From Jan 2003 to Jan 2005; 23 patients with LANPXCA stage III, IVA, IVB, (AJCC 2002), were treated with 3 cycles of neoadjuvant docetaxel 60mg/m2, 1 hour IV infusion D1 and cisplatin 60 mg/m2, 2 hours IV infusion D1 with prophylactic GSCF as 5μg/kg sc D3–7,(recycle D22). This was followed by 2 cycles of cisplatin 100 mg/m2, 2 hours IV infusion D1 , (recycle D22), concurrently with radiotherapy aiming at 70Gy / 35 fractions / 7 weeks. The median follow up was 27.9 months (18.3–47.3). Results: The median age was 38 years (16–68) and male to female ratio was 7.66:1. Neck mass 95.7%, neck pain 73.9%, nasal obstruction 65.2%, , headache 56.5%, impaired hearing 52.2%, and epistaxis 52.2% were the commonest symptoms. All patients had G3 squamous cell carcinoma. The majority of patients were stage IV 52.2% while 47.8 % were stage III. Grade one ECOG performance status was the commonest 52.2% while 47.8% were G2. The treatment was tolerable with commonest G3 acute toxicities were dysphagia 43.4% , and oral mucositis 8.7%. The commonest G3 late toxicities were dry mouth 17.4% and impaired hearing 13%. Complete remission was achieved in 22/23 patients 95.7% while 1/23 patients 4.3% was partial responder. Failure sites include; Distant; liver and/or bone 8.7%, local; skull base 4.3% or local and distant 4.3%.The Kaplan Meyer 47 month disease free survival was 82.61% while the 47 month overall survival was 91.3%. Conclusion: Neoadjuvant docetaxel / cisplatin followed by concurrent Cisplatin with radiotherapy is an effective and tolerable outpatient treatment for LANPXCA. No significant financial relationships to disclose.
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. , Takeuchi S. , Fuse N. , Minashi K. , Minami H. , Ohtsu A. 
Published: March 2020

6064 Background: An oral fluoropyrimidine, S-1, has shown high efficacy against head and neck cancer (HNC) with a response rate of 34% and preclinical data has demonstrated a possible synergy with platinums and taxanes. The aim of this study was to determine the maximum tolerated dose (MTD) of a combination therapy with TPS in patients (pts) with locally advanced or recurrent/ metastatic HNC. Methods: The eligibility criteria were: histologically proven squamous cell carcinoma of the head and neck with recurrent/metastatic and locally advanced lesions, PS 0–1, age =75 years, adequate organ function, and no prior chemotherapy. Chemotherapy consisted of 1-hour infusion of docetaxel at escalating doses of 50 and 60 mg/m2, 2-hour infusions 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. The treatment was repeated every 4-weeks. Results: Twenty two pts were enrolled. These were 17 males and 5 females with a median age of 50 years (22–74). There were 11 locally advanced and 11 metastatic cases. Median of 3 cycles were administrated (range 1–6; total 77 cycles). Anorexia, nausea, neutropenia and anemia were the most frequently observed adverse events. Grade 3 or 4 hematological toxicities were neutropenia (59%), febrile neutropenia (0%), anemia (14%) and thrombocytopenia (0%). Although a total of 12 pts were treated with TPS at doses of 60/70/80 mg/m2/day, one-dose limiting toxicity (grade3 infection) was observed at these doses, but MTD was not reached. As the approved dose of S-1 is 80 mg/m2, further dose escalation was not conducted. In a total of 22 pts treated with the TPS, 3 (1 locally advanced, 2 metastatic cases) achieved complete response and 11 (7 locally advanced, 4 metastatic cases) achieved partial response according to RECIST with an overall response rate of 64%. Conclusions: The TPS combination was well tolerated in pts with locally advanced or recurrent/ metastatic HNC. Although MTD was not reached and the data were preliminary, the antitumor activity was very promising, and this warrants further investigation. No significant financial relationships to disclose.