bluuebunny/crossref_metadata_2025_split huggingface dataset:
Results of reduction of treatment intensity based on response to a novel induction therapy in stage III and IV head and neck cancer
Authors: Kudrimoti M. R. , Warren G. W. , Valentino J. , Spring P. M. , Mohiuddin M. , St. Clair W. H. , Brill Y. , Given C. , Regine W. F. , Arnold S. M. 
Published: March 2020

5561 Background: Concurrent cisplatinum based chemotherapy and qd radiotherapy (RT) to 70 Gy is standard therapy for stage III-IV head and neck (H/N) SCCA. Presented is a prospective IRB approved study tailoring the definitive therapy based on response to induction therapy. Methods: 25 patients with Stage III-IV H/N SCCA were treated with 2 cycles of induction therapy every 21 days comprised of carboplatin (AUC 6 day 1), paclitaxel (75 mg/m2 days 1, 8, and 15), and low dose RT (0.5 Gy BID days 1, 2, 8, and 15) for chemosensitization. The response rates of this mode of induction therapy have been presented previously (ASCO 2005 #3184). Patients with complete response (CR) to induction were treated with reduced dose RT at the primary site (reduced from 70 to 60–66 Gy) and 2 cycles of IV cisplatin (100 mg/m2) instead of 3. Those with partial response (PR) or stable disease (SD) were treated with surgery and adjuvant therapy or with altered fractionation regimens. The impact of dose reduction on survival (OS and DFS), failure patterns, compliance and toxicity (according to NCI CTCAE) were used as end points for the study. Results: Patients included 9 with tonsil, 5-L, 3-HP, 3-OC, and 5-BOT. There were 4-T1,9-T2,9-T3,and 3-T4 tumors. The nodal involvement was N0–5, N1–3, N2–13, N3–4. Patients presented with Stage III (28%), IVA (52%), and IVB (20%). Sixty percent had a CR, 32% had a PR, and 8% had SD after induction therapy. Two patients with CR were non-compliant after induction therapy and not further evaluated. With a median FU of 20.5 months (range 11–36 mo) the OS and DFS is 100% (13/13) in the dose reduced group (CR) and 60% (6/10) in the PR/SD treated with more aggressive regimens. The incidence of distant failure is 40% (4/10) in the PR vs 0% (0/13) in the CR. No patients in the dose reduced group required feeding tubes; however 30% (3/10) were required in patients with PR. Compliance with chemotherapy was 79% (10/13) in the CR vs 80% (8/10) in the PR. Conclusions: Our early results show that the patients showing a CR to induction chemotherapy are a favorable group of patients and they may be treated with reduced treatment intensity. This report provides strong evidence that RT dose deescalation for head and neck cancers may be feasible following assessment after induction therapy. [Table: see text]
Results of intraarterial cisplatin and hyperfractionated radiotherapy in locally advanced cancer of the oropharynx and oral cavity
Authors: Arnold S. M. , Graham W. W. , Valentino J. , Brill Y. , Regine W. , Spring P. , Given C. , Mohiuddin M. , St Claire W. , Kudrimoti M. 
Published: March 2020

5563 Background: Intraarterial cisplatin and hyperfractionated radiation (HYPERADPLAT) is an accepted therapy for Stage III and IV head and neck cancer. We present long-term follow-up of patients with OP and OC cancer treated with HYPERADPLAT at a single institution. Methods: 44 patients with Stage III-IV squamous cell carcinomas of the OP or OC were treated with the HYPERRADPLAT regimen consisting of external beam radiotherapy (76.8–81.6 Gy) delivered in 1.2 Gy BID fractions with intraarterial cisplatin (150 mg/m2) administered when patients had reached 60 Gy. Tumor response, disease free survival (DFS), overall survival (OS), and toxicity were assessed for all patients according to NCI CCT criteria. Results: Of 44 patients, 21 had tumors of the base of tongue, 14-tonsil, 4-floor of mouth, and 5-other. Eighty eight percent of patients had T4 tumors and 7% had T3 tumors. Complete tumor response was observed in 86% of patients and 14% had a partial response. Lymph node metastases were present in 84% of patients with 78% of node positive patients having a complete nodal response and 19% with a partial response to treatment. Three-year DFS was 55% and OS was 45%. Locoregional recurrence was noted in 30% of patients and 16% had distant failure. Overall recurrence was noted in 47% of patients with a median time to recurrence of 8 months (range 4–55 months). Median weight loss during treatment was 9% of initial body weight and 28 patients required a feeding tube within 6 months of starting treatment. Grade 3 mucositis was noted in 68% of patients and 3 patients developed Grade 4 toxicity (2 mucosal, 1 hematologic). Conclusions: HYPERRADPLAT results in excellent tumor control that is well tolerated with minimal Grade 4 toxicity in patients with advanced poor prognosis cancers of the OP and OC. These results compare favorably with historically reported control rates and response for patients with a significantly high percentage of T4 tumors of the oropharynx and oral cavity. No significant financial relationships to disclose.
Randomized, phase III trial comparing liposomal platin with cisplatin in patients (pts) with advanced squamous cell carcinoma of the head & neck (SCCHN) regarding safety and efficacy profiles
Authors: Luftner D. , Siepmann S. , Christian J. , Pollmann D. , Pecher G. , Wernecke K. D. , Possinger K. 
Published: March 2020

5564 Background: Based on a metanalysis of > 16,000 patients (Bourhis, ASCO 2004), cisplatin emerges as the essential agent for the treatment of advanced SCCHN. However, its clinical use is impeded by its severe adverse reactions, as renal toxicity. In a randomized, phase III trial we replaced conventional cisplatin by a liposomal formulation of cisplatin (lipoplatin) and compared the safety and efficacy profiles. Methods: The study was designed for two treatment arms: A: 100 mg/m2/d lipoplatin (d 1,8,15) plus 1,000 mg/m2/d 5-FU (d 1–5) q3w for 6 cycles; B: 100 mg/m2/d cisplatin (d 1) plus 1000 mg/m2/d 5-FU (d 1–5) q3w for 6 cycles. Main inclusion criteria selected pts with primary metastatic, relapsed or progressive SCCHN between 18–75 years and creatinin clearance >50ml/min. Main endpoints for this interims analysis were hemato- and nephrotoxicity. First response data were collected. The study was designed for non-inferiority. Results: Out of 41 randomized pts, 30 pts are evaluable for toxicity (15 pts for every arm) and 27 pts (15 pts for lipoplatin, 12 pts for cisplatin) for outcome. In the cisplatin arm hematotoxicity was more frequent (leucopenia grade I/II: 5 pts, grade III/IV: 3 and 1 pts vs 5 pts with grade I/II in the lipoplatin arm). The rate of anemia was similar between the treatment arms. A total of 11 pts in the lipoplatin arm experienced renal toxicity grade I/II as measured by a reduction of the creatinine clearance and 12 pts in the cisplatin arm (grade I/II: 7 pts; grade III: 5 pts). No renal toxicity grade III was developed in the lipoplatin arm until now. Outcome was as follows: lipoplatin arm: PR: 1 pt; SD: 6 pts; PD: 8 pts; cisplatin arm: PR: 7 pts; SD: 3 pts; PD: 2 pts. Thus, the non-PD pts (PR or SD) is 7/15 (47%) in the lipoplatin arm vs 10/12 (83%) cases in the cisplatin arm. Conclusions: Liposomal platin seems to reduce both the hematological and non-hematological toxicity profiles as compared to conventional cisplatin to a clinically relevant extent. As patients with advanced SCCHN have an increased risk of renal toxicity due to poor hydration, the observed reduction of side effects will influence the chance to preserve the dose density of chemotherapy, and thereby, the efficacy of treatment. No significant financial relationships to disclose.
A phase II study of lapatinib (GW572016) in recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN)
Authors: Abidoye O. O. , Cohen E. E. , Wong S. J. , Kozloff M. F. , Nattam S. R. , Stenson K. M. , Blair E. A. , Day S. , Dancey J. E. , Vokes E. E. 
Published: March 2020

5568 Background: Epidermal growth factor receptor (EGFR) inhibitors have demonstrated reproducible activity in patients with R/M SCCHN. HER2 is the preferred dimerization partner for EGFR. Lapatinib is a dual EGFR and HER2 kinase inhibitor that has demonstrated promising preclinical activity in SCCHN models. Methods: This phase II multi-institutional study enrolls patients with R/M SCCHN into 2 cohorts: those without prior exposure to an EGFR inhibitor (arm A) and those with prior exposure to an EGFR inhibitor (arm B). All subjects were treated with lapatinib 1500mg OD. Primary endpoints were response rate (arm A) and progression-free survival (arm B). Results: 42 subjects have been enrolled (27 arm A, 15 arm B; 35 male, 7 female, median age 60 years). Toxicity was generally mild without any dose reductions or patient withdrawal due to adverse effects. Diarrhea was the most frequent toxicity occurring in 40% of patients. Other toxicities observed included fatigue (21%), rash (21%) and nausea (14%). 2 patients experienced grade 3 toxicity (1 diarrhea, 1 emesis). 1 patient had a reduction in left ventricular ejection fraction (60% to 40%) which was asymptomatic and recovered to baseline upon discontinuation of lapatinib. No objective responses were observed in either arm. In an intent-to-treat analysis stable disease was the best response observed in 37% of arm A and 20% of arm B subjects. Median PFS was 1.6 months in arm A and 1.7 months in arm B. Conclusions: Lapatinib as a single agent in R/M SCCHN, although well tolerated, appears to have little activity in either EGFR inhibitor naïve or refractory subjects. No significant financial relationships to disclose.
Antitumor effects of combined bortezomib and tipifarnib in head and neck squamous cell carcinoma (HNSCC) cells
Authors: Klass C. M. , Chen Z. G. , Zhang X. , Lonial S. , Khuri F. R. , Shin D. M. 
Published: March 2020

5581 Background: The dysregulation of the NF-κB and Ras/PI3K/AKT pathways in HNSCC supports our hypothesis that combined treatment with the proteasome inhibitor (PI) bortezomib (B) and the farnesyl transferase inhibitor (FTI) tipifarnib (T) leads to synergistic growth inhibition of HNSCC cells. Methods: Growth inhibitory effects of single agents (B 2.5–100 nM; T 0.625–5μM), combination (B+T) (B 12.5–17.5 nM; T 0.625–5 μM) or sequential treatment (B→T after 2h or T→B) were examined in three HNSCC lines (Tu212, 686LN and Sqcc/Y1) using a sulforrhodamine B assay after 72 h of drug exposure. Combination effect in cells treated concomitantly or sequentially was assessed using the combination index (C.I.: < 1.0, synergy; >1.0, antagonism; ≈1.0, additivity). Apoptosis was measured by flow cytometry. Relevant protein markers were evaluated by Western blot. Cell cycle analysis after flow cytometry used FlowJo software. Statistical analysis was done using a two-sided t-test. Results: Growth inhibition by B alone is very effective in all three lines (IC50 = 9–22nM). T used alone is active only in μM range (IC50 = 0.625–5 μM). The inhibitory effects of B and T were sequence dependent. Simultaneous treatment with 12.5 nM B and 5μM T showed synergistic growth inhibition in all 3 lines [C.I., 0.281–0.54]. B→T showed synergistic effects in all three cell lines [C.I., 0.36–0.76]. However, T→B was less synergistic in two of the three lines [Sqcc/Y1 C.I. = 0.404; Tu212 C.I. = 0.748]. Apoptosis was also sequence dependent with B+T or B→T treatment showing significantly more apoptosis than T→B (p = 0.03). Apoptosis induced by T→B was not different from treatment with single agent B (p = 0.22). Sqcc/Y1 cells treated with B and T showed accumulation in G2M phase and an increased percentage of cells in sub-G1. The observed synergistic inhibitory effect of B+T was associated with downregulation of p-AKT. Conclusions: We conclude that treatment with B+T and B→T synergistically enhances HNSCC growth inhibition and results in both significantly increased apoptosis and G2M arrest. These studies strongly support the clinical development of the sequential combination of a PI and a FTI. (Supported by Millenium Pharm. and the Georgia Cancer Coalition). [Table: see text]
Anthracycline regimens versus CMF in the adjuvant treatment of early breast cancer (EBC): A matter of difference
Authors: Gennari A. , Sormani M. , Costantini M. , Pronzato P. , Rosso R. , Bruzzi P. 
Published: March 2020

569 Background: Anthracycline-based adjuvant chemotherapy (CT) in EBC was found, in the latest EBCTCG overview, to be associated with a 15% reduction in mortality, when compared to CMF. However, differences among trials, and specifically the use of suboptimal experimental arms (underdosed anthracyclines) and non conventional CMF (i.v.), require a careful interpretation of this finding. Methods: To evaluate the reduction in mortality, associated to different anthracycline and CMF regimens, we performed a systematic overview of abstracted data from published randomised trials comparing CMF with anthracyclines. Those studies including other drugs were excluded. Fifteen retrieved trials, comprising 15.831 women, were divided into 6 groups according to the type of CMF (oral or i.v.), and to the type of anthracycline regimen: 3 drugs (FAC/FEC), 2/1 drugs (AC/EC, A/E) and sequential schedules (Anthra→CMF). From each study, the estimates of the Hazard Ratio (HR; anthra vs CMF) and of its variance were abstracted or estimated from the presented results. HRs from studies of the same group were combined according to standard meta-analytic techniques. Summary estimates of HR for oral or i.v. CMF and for different anthracycline schedules were similarly obtained. Results: The overall comparison confirms a superiority of anthracyclines over CMF (HR 0.83 - 95%CI 0.77–0.90, p<0.001). HRs in the 6 groups of studies are reported in the table . When i.v. CMF is compared to any anthracycline regimen, the HR is 0.76 (95%CI 0.67–0.86, p<0.001; heterogeneity p 0.01), while with oral CMF, the HR is 0.88 (95%CI 0.80–0.97, p 0.01; heterogeneity p 0.06). Conclusions: The magnitude of the survival benefit of anthracyclines over CMF seems to be strongly affected by the type of anthracycline regimen and by the type of CMF, the largest effect being observed in trials using sequential schedules and i.v. CMF. Final results will be presented at the meeting, including evaluation of regimen type and its effects on toxicity and quality of life. [Table: see text] No significant financial relationships to disclose.
Phase III study of docetaxel weekly (DW) versus every 3 weeks (D) in patients with metastatic breast cancer: Final results
Authors: Rivera E. , Mejia J. A. , Arun B. , Adinin R. , Walters R. , Brewster A. , Broglio K. , Yin G. , Esteva F. J. , Hortobagyi G. N. , Valero V. 
Published: March 2020

574 Background: D is a semi-synthetic taxane with significant activity in breast cancer. D is usually administered on an every 3-weeks schedule, however, studies have demonstrated drug efficacy and a different toxicity profile when administered on a weekly basis. In this study we compared the weekly schedule versus every 3-weeks to define the safest schedule with the highest efficacy. Methods: Patients (Pts) were enrolled if they had stage IV breast cancer and had received no more than one prior chemotherapy regimen for metastatic disease. Prior treatment with D was not allowed but adjuvant paclitaxel (P) was allowed if > 12 months since the last dose. Pts were randomized to receive D at a starting dose of 75mg/m2 on day 1 or DW at a dose of 35 mg/m2/week for 3 weeks followed by 1 week of rest every 28 days. Doses could be escalated to 100 mg/m2 and 40mg/m2, respectively at the discretion of the investigator. Premedication with dexamethasone was given with each regimen. Results: From 1/2001 until 9/2004, a total of 125 pts were enrolled, 63 in the DW arm and 62 in the D arm. Thirty-nine and 10 pts had received prior anthracycline (A) and P respectively in the D arm while 32 and 11 pts had A and P in the DW arm. Median ages were 56 and 54 years in the D and DW arm, respectively. 118 pts were eligible for an efficacy analysis with a response rate of 35.6%; (95% CI, 23.6%, 49.1%) for the D arm vs 20.3%; (95% CI, 11.0%, 32.8%) for DW. There was no difference between D and DW in median PFS and OS, 5.7 vs 5.5 months (p = 0.46) and 18.3 vs 18.6 months (p = 0.34), respectively. There was a higher overall toxicity rate (grade 3 and 4) in the D arm vs DW, 88.1% vs 55.9% (p = 0.0001). There were 48 (81%) and 6 (10%) pts with grade ¾ granulocytopenia with 6 (10%) and 2 (3%) episodes of neutropenic fever in D vs DW, respectively. Grade 3/4 fatigue and myalgias were reported more often in D than DW, 15 (25%) and 8 (13.5%), and 16 (27%) and 2 (3%), respectively. Grade 3 epiphora was similar in both arms, 4 (7%) and 5 (8%) for D and DW, respectively. Conclusions: D has a higher response rate compare to DW but with a more pronounced toxicity profile. This needs to be kept in mind when making a treatment recommendation for patients with metastatic breast cancer. No difference in PFS or OS was observed between both arms. No significant financial relationships to disclose.
Phase III study of gemcitabine plus vinorelbine (VG) versus vinorelbine (V) in patients (pts) with metastatic breast cancer (MBC) previously treated with anthracyclines (A) and taxanes (T). Final results of GEICAM 2000–04 study
Authors: Muñoz M. , Martín M. , Ruiz A. , Balil A. , García-Mata J. , Calvo L. , Jara C. , Alba E. , Salas F. , Soto C. 
Published: March 2020

575 Background: VG has shown to be efficacious and safe in MBC in pts previously treated with AT. This study compared treatment (TT) V with the combination of VG. Primary objective was progression free survival (PFS). Methods: pts previously treated with AT, aged ≥18, ECOG ≤ 2, were randomized to V: 30 mg/m2 day (d) 1, d8, or VG 30/1200 mg/m2 d1, d8, both every 21 days until disease progression. Stratification criteria were previous lines of TT for MBC (0 vs.1 vs.2) and visceral disease (yes vs. no). 126 pts per arm were needed to demonstrate a prolongation in PFS of 2 months (m) (from 3 to 5; HR = 1.67; α and β errors 0.05 and 10). Results: 252 pts (127 V and 125 VG) were recruited between 2001 and 2005. Arms were well balanced: median age was 57 years; median number of metastatic sites 2; visceral disease was present in 75% of pts; 17%, 53% and 29% of pts received study TT as first, second and third line respectively. Median number of cycles were 4 (1–21) in V and 6 (1–26) in VG. Median PFS was 6.3 m (95% CI, 5.3–7.3) for VG and 4.1 m (95% CI, 3.3–4.9) for V (p=0.0011). Objective response rate was 37% (CI 95% 29–46) for VG and 25% (CI 95%: 17–33) for V (p= 0.035). CTC grade 3–4 hematologic toxicity was significantly higher with VG vs. V (65% vs. 43% neutropenia, 33% vs. 17% leucopenia, and 11% vs. 2% thrombocytopenia); febrile neutropenia was present in 10.5% of pts on VG and 6% of pts in V (p=ns). Non-hematological toxicity was low and manageable in both arms. Conclusions: VG demonstrated significant efficacy advantages over V in pts with MBC previously treated with AT, with manageable toxicity. This favorable risk-benefit profile supports the use of this combination in this patient population. [Table: see text]
Breast cancer epidemiologic risk factors by HER2/neu status
Authors: Chen W. Y. , Colditz G. A. , Rosner B. 
Published: March 2020

585 Background: Although breast cancers categorized by estrogen receptor (ER) and progesterone receptor (PR) status are recognized to differ in their associations with standard breast cancer risk factors, little data exist on differences by HER2/neu status. Methods: The Nurses’ Health Study is a prospective cohort study of 121,700 registered nurses aged 30–55 in 1976 who answered biennial questionnaires to update medical and lifestyle factors and disease occurrence. Medical record review was used to confirm invasive breast cancer and abstract ER, PR, and HER2/neu status. Statistical analyses included both proportional hazards models to estimate relative risks and control for potential confounders and polytomous logistic regression to compare the effects. Only cases diagnosed from return of the 1998 questionnaire until June 2002 were included in the analysis since HER2/neu was only routinely assessed beginning with the 1998 follow-up cycle. Results: 211 HER2/neu positive and 770 HER2/neu negative cases were included in the analysis. In this predominantly postmenopausal group aged 52–77 in 1998, HER2neu negative cancers were more likely to be ER+/PR+ (72%) and less likely to be ER-/PR- (11%) than HER2/neu positive ones (58% ER+/PR+ and 24% ER-/PR-), but the majority of cancers were still ER+/PR+. In multivariate models, risk factor associations by HER2/neu status were similar with positive associations seen for family history, benign breast disease, body mass index, current postmenopausal hormone use, and cumulative alcohol consumption. However, when the subgroup of ER-/PR-/HER2/neu negative cancers were evaluated separately (N=83), most of these risk factor associations disappeared with the only significant risk factor being a prior history of benign breast disease. Conclusions: This is the first prospective data study to report on risk factor association by HER2/neu status. For the standard epidemiologic breast cancer risk factors, ER and PR status appear to better represent separate etiologic pathways, rather than HER2/neu status. However, the subgroup of ER/PR/HER2neu negative breast cancers appears to be distinct, although power was limited and HER2/neu status was not confirmed by central review. Additional analyses stratified by ER/PR status will also be presented. No significant financial relationships to disclose.
Outcome of phase II oncology clinical trial abstracts presented at annual meeting of the American Society of Clinical Oncology (ASCO)
Authors: Hoeg R. T. , Lee J. A. , Mathiason M. A. , Rokkones K. , Serck S. L. , Crampton K. L. , Emmel A. , Jumonville A. J. , Severson E. A. , Go R. S. 
Published: March 2020

6010 Background: Translation of evidence-based medicine into clinical practice depends on timely and full publication of clinical trials. Previous studies have shown that a substantial number of phase I and III trials presented at the annual meetings of ASCO remain unpublished more than 5 years after presentation. We investigated the outcome of phase II trials presented at ASCO. Methods: We searched for phase II trials using the 1997 ASCO Annual Meeting Proceedings. We excluded trials reporting only preliminary data or interim analyses. The following information were extracted from each study: type of presentation, country of origin, sample size, sponsor, treatment modality, novelty of treatment, and efficacy. A literature search was performed using the Medline and EMBASE databases up until January 2006 for full publications in peer-reviewed journals. If a trial was not found, the authors were contacted by E-mail. Results: We identified 124 phase II trials with 13.7%, 30.6%, and 55.6% presented orally, in poster, and in print, respectively. Most trials were either submitted from countries in North America (50.8%) or Europe (34.7%). Funding came from the pharmaceutical companies (24.2%), governments (20.2%), study institutions (15.3%), private foundations (9.7%), or was not specified (30.6%). The top 5 cancers studied were lung, breast, ovarian, gastric, and sarcoma. Treatment included mostly chemotherapy, either alone (87.1%) or in combination with other modalities (3.2%). To date only 70.2% of the trials have been published. The median time to publication for all abstracts was 23 months. The cumulative rates of publication were 12.9%, 34.7%, 51.6%, 64.5%, and 68.5% at 1, 2, 3, 5, and 7 years, respectively. None of the factors we analyzed, including type of presentation, country of origin, sample size, sponsor, novelty of treatment, and efficacy, influenced the likelihood of or time to publication. Conclusions: About a third of phase II oncology clinical trials initially presented as abstracts at the 1997 ASCO annual meeting have not been published almost a decade later. Similar to phase I and III trials, underreporting of phase II trials is an important problem with serious implications for clinical practice that needs to be addressed. No significant financial relationships to disclose.