bluuebunny/crossref_metadata_2025_split huggingface dataset:
Final report of a randomized phase II study of docetaxel/oxaliplatin (DO) and docetaxel (D) in previously treated non-small cell lung cancer (NSCLC) patients (pts). A novel design, Alpe-Adria Thoracic Oncology Multidisciplinary group study (ATOM 019)
Authors: Belvedere O. , Follador A. , Rossetto C. , Sibau A. M. , Defferrari C. , Aita M. , Meduri S. , Fasola G. , Ceschia T. , Grossi F. 
Published: August 2020

e19010 Background: No combination regimen has proven superior to single agent chemotherapy as 2nd-line treatment for NSCLC. The absence of cross-resistance with cisplatin/carboplatin, favorable toxicity profile, along with both pre-clinical and clinical evidence of activity make O a good candidate for combination with D as 2nd-line therapy of NSCLC. We evaluated the activity of DO in this setting using a novel phase II trial design. Methods: This multicenter, non-comparative randomized phase II trial evaluated the activity of D (75 mg/m2 d1) and O (70 mg/m2 d2) every 3 weeks in previously treated NSCLC pts; the comparator arm was D (75 mg/m2 d1 every 3 weeks). This one-stage, three-outcome phase II trial design (Sargent, Control Clin Trials 2001) had 21 evaluable pts/arm. All had histologically confirmed NSCLC that progressed during/after platinum-based chemotherapy. Primary endpoint was response rate; secondary endpoints were toxicity, time to progression (TTP), 1-yr survival. Results: Fifty pts were enrolled. Pts characteristics: M/F, 76/24%; median age 62 yrs (range 43–69); ECOG PS 0/1, 36/64%; adenocarcinoma/other, 36/64%. With 48 pts evaluable, partial response was seen in 20% and 8% of pts; stable disease in 52% and 32% and progressive disease in 24% and 56% for DO and D, respectively; 1 pt was inevaluable due to early death (D arm). Main grade 3–4 toxicities were: neutropenia 56% and 64%; febrile neutropenia 4% and 8%; diarrhea 12% and 4% for DO and D, respectively. Median TTP was 4.9 and 1.8 months, median survival 10.9 and 6.9 months, and 1-yr survival 41% and 16% for DO and D, respectively. Conclusions: This study shows how novel phase II trial designs enrolling a limited number of pts may help identify promising regimens for subsequent study in phase III trials. The level of activity for DO we observed satisfied the pre-defined study primary endpoint and warrants further evaluation of this combination as 2nd-line therapy for NSCLC. Protocol developed at the 6th FECS/AACR/ASCO Workshop on Methods in Clinical Cancer Research, Flims 2004, with Professors Marc Buyse and Chris Twelves. [Table: see text]
Lung cancer symptoms with cetuximab/taxane/carboplatin in first-line advanced NSCLC: Analysis of the BMS099 trial
Authors: Patel T. , Dreisbach L. , McCleod M. , Heim W. J. , Hermann R. C. , Woytowitz D. , Lu H. , Weber M. R. , Lynch T. J. 
Published: August 2020

e19011 Background: The phase III BMS099 trial investigated cetuximab (C) added to taxane/carboplatin (TC) for 1st line treatment of advanced NSCLC. Progression-free survival (PFS) was not significantly different with C; response rate (RR) was significantly higher. Median overall survival (OS) was longer, with a difference not statistically significant, but similar in magnitude to the significant OS improvement from the FLEX trial (cisplat/vinorelb±C). A secondary objective of the BMS099 study was to assess the effect of C on Lung Cancer Symptoms (LCS). Methods: Chemonaïve patients (pts) with stage IIIB/IV NSCLC (any histology or EGFR expression status) were randomized to TC±C. LCS were measured using the functional assessment of cancer treatment-lung cancer subscale questionnaire (FACT-LCS), given at baseline and before each therapy cycle until disease progression (scoring 7 symptoms: breath loss, weight loss, clear thinking, coughing, appetite, chest tightness, breath ease, on a 0–4 scale). The main endpoints were rates of symptom response/progression (≥ 2 point improvement/decrease from baseline in 2 consecutive assessments), compared between arms with a stratified Cochran-Mantel-Haenszel (CMH) test; a stratified log-rank test was used to compare time to symptomatic progression. A Wei-Lachin test was used to compare between arms the changes from baseline in LCS score, and a longitudinal model was constructed to measure treatment effect on those score changes. Results: With 676 patients randomized, the baseline compliance rates for the FACT-LCS questionnaire were 99.4% and 99.1% for CTC and TC respectively, decreasing by week 18 to 74.0% and 66.4%. Baseline FACT-LCS scores were similar across treatment arms (median, 19.0). Symptom response rates were similar with CTC vs TC (32.6% vs 28.5%, CMH P=0.26), and time to symptomatic progression was not significantly different (log-rank P=0.58). Changes from baseline in FACT-LCS scores did not differ significantly between arms (Wei Lachin P=0.912; longitudinal model P=0.81). Conclusions: The addition of C to TC for the 1st treatment of advanced NSCLC resulted in similar symptom response/progression rates and did not affect trends in LCS score changes throughout treatment. [Table: see text]
Optimal duration of chemotherapy (CT) for advanced non-small cell lung cancer (NSCLC) in the first- and second-line settings
Authors: Grossi F. , Belvedere O. , Defferrari C. , Brianti A. , Follador A. , Rijavec E. , Ceschia T. , Pronzato P. , Fasola G. , Aita M. 
Published: August 2020

e19037 Background: No difference in efficacy has been observed between 3 or 4 vs 6 cycles of 1st line CT in patients (pts) with advanced NSCLC. Although longer treatment may improve progression-free survival, this must be weighed against increased toxicity and potential for worse quality of life. There are no prospective, randomized data on the optimal duration of 2nd line CT. The aims of this retrospective study were to (i) confirm the lack of impact of treatment duration on response rate in 1st line NSCLC and (ii) investigate the impact of treatment duration in the 2nd line setting. Methods: Eligible pts had received at least 4 cycles of 1st line (n=95) or 2nd line (n=55) CT for stage IIIB/IV NSCLC in clinical trials of the ATOM group, Udine, Italy, or the National Cancer Institute, Genoa, Italy and achieved stable disease or responded to treatment; trials included one in the elderly, and the addition of biological agents to CT. Response was assessed according to RECIST after alternate CT cycles and tumor dimensions recorded. The proportion of pts achieving a complete or partial response, as well as its timing and any subsequent tumor shrinkage, were analyzed by treatment line. Results: In the 1st line setting, 48 of 95 pts responded; they did so after 2 (29 pts, 61%), 4 (15 pts, 31%) and 6 cycles (4 pts, 8%). In these pts, 16 (55%) and 9 (41%) pts who had responded by the 2nd and 4th cycle respectively and continued on treatment showed further tumor shrinkage; the median further reduction in tumor size was 16% (range 1–52%) and 6% (range 1–11%), respectively. In the 2nd line setting, 12 of 55 pts responded; they did so after 2 (3 pts, 25%), 4 (7 pts, 58%), and 6 cycles (2 pts, 17%). One and two pts who had responded by the 2nd and 4th cycle respectively and continued on treatment showed further tumor shrinkage of 25%, 5% and 24%, respectively. Conclusions: Approximately 90% of CT-naive pts who responded did so by the 4th cycle; most such pts achieved only minor tumor reduction with further CT and did so at the likely expense of increased toxicity. In the 2nd line setting the achievement of response appeared slower. These results support the discontinuation of 1st CT after 4 cycles and suggest the same is true for 2nd line CT. No significant financial relationships to disclose.
The palliative effect of EGFR inhibitors in platinum-resistant NSCLC
Authors: Tassinari D. , Tamburini E. , Scarpi E. , Santelmo C. , Carloni F. , Castellani C. , Lazzari Agli L. 
Published: August 2020

e19053 Background: To assess the clinical benefit of EGFR-inhibitors (erlotinib or gefitinib) in terms of quality of life and symptoms control in platinum-resistant NSCLC. Methods: A systematic review of literature in the MEDLINE and EMBASE data bases from 2000 to 2007 was independently performed by two authors (DT and ET) The 2 randomized phase III trials comparing erlotinib or gefitinib (the BR21 and ISEL trials respectively) with placebo were considered eligible and included into the pooled analysis. Overall quality of life was the primary outcome of the pooled analysis; symptoms control the secondary one. Heterogeneity between the trials was analysed using the I2 test; the outcome analysis was performed using a random effects model and an alpha error lower than 5%. Results: The outcomes of 2423 patients enrolled into the BR21 and ISEL trials were compared in the pooled analysis. 1129 patients were treated with gefitinib, 488 with erlotinib and 806 with placebo. A methodological heterogeneity was detected in the preliminary qualitative analysis of the trials (the 2 trials assessed quality of life and symptoms control with different tools), while a relative homogeneity was documented from a statistical point of view, using the I2 test (I2=0, p=0.733). An absolute improve of quality of life was documented in favour of the treatment with EGFR-inhibitors (+8%, p<0.001) and symptoms control (+4%, p=0.034). Nevertheless, as quality of life and symptoms control were assessed with different tools in the 2 trials, the comparisons of the 2 main outcomes have uniquely a descriptive aim. Conclusions: Although a comparison of the outcomes of quality of life and symptoms control in a pooled analysis of the BR21 and ISEL trials is quite difficult for the intrinsic heterogeneity between the trials, our preliminary analysis seems to suggest a benefit in favour of patients treated with EGFR-inhibitors when compared with placebo. Further trials comparing EGFR-inhibitors with chemotherapy (mainly docetaxel and pemetrexed) are probably needed to identify the gold standard of second line chemotherapy for NSCLC, whose main aims are quality of life and symptoms control. No significant financial relationships to disclose.
Phase I trial of vorinostat in combination with erlotinib in advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations after erlotinib progression
Authors: Reguart N. , Cardona A. F. , Isla D. , Cardenal F. , Palmero R. , Carrasco-Chaumel E. , Rolfo C. , Massuti B. , Moran T. , Rosell R. 
Published: August 2020

e19057 Background: Vorinostat (SAHA) is a histone deacetylase inhibitor that induces differentiation, growth arrest and apoptosis of malignant cells. In vitro, there is a synergistic interaction of vorinostat in combination with gefitinib in NSCLC cell lines. Moreover, vorinostat increases levels of E-cadherin, p21, and downregulates expression of phospho-AKT and phospho-ERK1/2. These molecular findings could reverse resistance to erlotinib in mutant patients. Methods: We conducted a standard 3+3 Phase I trial of oral erlotinib 150 mg QD in combination with oral vorinostat (dose level 1 [DL1], 300 mg QD on days 1–7 every 21 days; DL2, 400 mg QD on days 1–7 every every 21 days, and; DL3, 400 mg QD on days 1–7 and 15–21 in a 28-day cycle). Cycles were repeated for a maximum of 6 cycles until progressive disease (PD) or intolerable toxicity. Pts with advanced NSCLC with EGFR mutations (Exon 19 and 21) after erlotinib progression and ECOG ≤2 were eligible. The main objectives were to determine the maximum tolerated dose (MTD), drug activity and safety of the combination regimen. Results: Thirteen patients have been enrolled up to date, with 9 patients available for this interim analysis (median age, 59 years; range 41–77). One patient (DL3 cohort) experienced a dose limiting toxicity (Grade 3 diarrhoea). The MTD has not been reached. The most common drug-related toxicities of any grade in the first cycle of treatment were anemia (77.8%), skin alterations (66.7%), diarrhoea (66.7%), xerostomy (55.6%), asymptomatic changes in liver function tests (55.6%), and asthenia (55.6%). There were no Grade ≥3 drug-related adverse events during first cycle of treatment and the global analysis of cycles showed asthenia (11.1%), somnolence (11.1%) and hyporexia (11.1%). Four pts discontinued treatment, all due to PD. Of 9 evaluable pts for efficacy, 6 had stable disease as best response (median duration of treatment 6.0 months, range 4–12). Final data will be presented at ASCO meeting. Conclusions: Although accrual continues to determine the MTD, the combination of vorinostat and erlotinib appears to be well tolerated and effective in this group of advanced NSCLC pts with EGFR mutations after erlotinib progression. No significant financial relationships to disclose.
Safety and efficacy of gefitinib monotherapy for patients (pts) ≥80 years (yrs) with advanced non-small cell lung cancer (NSCLC): A phase II subset analysis
Authors: Ebi N. , Semba H. , Tokunaga S. , Takayama K. , Wataya H. , Kuraki T. , Yamamoto H. , Akamine S. , Okamoto I. , Nakanishi Y. ,   Lung Oncology Group in Kyushu (LOGIK)
Published: August 2020

e19059 Background: Lung cancer is a disease of the elderly with median age at diagnosis of 70 yrs. The very elderly pts (age ≥80 yrs) with advanced NSCLC have not been well studied, even though this proportion is increasing over coming years. There are no data to evaluate the safety and efficacy of gefitinib treatment for pts ≥80 yrs with advanced NSCLC. Methods: We reported the phase II trial of gefitinib monotherapy in chemotherapy-naïve pts of 75 yrs or older with advanced NSCLC (J Thorac Oncol. 2008;3: 1166–1171). We analyzed data for pts ≥80 yrs, comparing with those <80 yrs in our trial. Results: A total of 28 pts were 80 yrs old and over in our trial. Patient characteristics: male/female = 12/16, median age = 82 (range 80–90), ECOG PS 0/1/2=7/13/8, stage IB/IIIA/IV=1/3/24, and adenocarcinoma (Ad)/non-Ad= 22/6. Five pts achieved partial response. The response rate was 18% (CI 95%, 6–39). The disease control rate was 50%. Median survival time was 9 months and 1-year survival rate was 39%. The most frequent adverse events were skin disorders (86%). Nine pts (32%) experienced toxicities ≥grade 3. There were two pts with possible interstitial lung disease including one treatment-related death. Tumor samples from 10 pts were analyzed for EGFR mutation status. EGFR mutations were detected in tumor tissues from 5 pts, of which 3 had partial responses (60%). Table shows the difference between the pts ≥80 yrs and those <80 yrs. Conclusions: Gefitinib monotherapy is effective and relatively well tolerated for pts ≥80 yrs with advanced NSCLC. Gefitinib has potential as a first-line therapeutic option even if elderly pts are more than 80 yrs old. [Table: see text] No significant financial relationships to disclose.
Use of an Internet-based protocol to collect clinical information and blood from patients with lung cancer who never smoked cigarettes
Authors: Girard N. , Klein R. , Riely G. J. , Reddy R. , Kris M. G. , Pao W. 
Published: August 2020

e19064 Background: At least 10% of patients develop lung cancer despite smoking <100 cigarettes in a lifetime. These “never smokers” with lung cancer have a unique clinical course and likely represent a subgroup genetically distinct from lung cancer patients with a history of cigarette smoking. Few genes associated with the development of lung cancer in this population have been found. To identify genetic risk factors, we plan to perform genome-wide association studies (GWAS) but need to study a large group of cases - more than that seen at a single institution in a reasonable timeframe. To speed accrual, we hypothesized that we could use the internet to collect clinical information and blood from never smokers with lung cancer. Methods: We established an IRB- approved protocol to collect prospectively clinical information and blood samples from patients recruited via the internet. Interested patients enroll via the website ( www.mskcc.org/neversmokerswithlungcancer ), or by email ( neversmokerswithlungcancer@mskcc.org ). Eligibility criteria: age ≥18 yo, pathologic diagnosis of lung cancer, smoking history <100 cigarettes in a lifetime, resident of the U.S. Study materials (information packet, screening questionnaire, consent form, and tissue sample collection kit) are directly sent to patients. Bloods are drawn at routine local doctor visits and returned to study investigators by free overnight shipping. All data are kept confidential. Results: The website went online on 14 Sept 2008. As of 5 Jan 2009, 70 patients from 25 states contacted us via the internet. 33 patients signed the consent form, 27 were eligible, and 19 sent blood samples. For those who sent blood, the median time between first email contact and receipt of blood was 29 days. Conclusions: Collection of clinical information and blood samples from cancer patients is feasible over the internet. We are expanding efforts to connect with individuals appropriate to this study, with a target of 2000 patients. The identification of risk variants associated with lung cancer through GWAS can facilitate the development of new strategies for prevention, diagnosis, and treatment. No significant financial relationships to disclose.
Dose-ranging study of the combination of paclitaxel poliglumex and pemetrexed in advanced non-small cell lung cancer (NSCLC)
Authors: Slagle B. M. , Rigas J. R. , Dragnev K. H. , Williams I. , DiSalvo W. , Engman C. , Lipe B. , Simeone S. 
Published: August 2020

e19090 Background: Taxanes continue to play an important role in the treatment of advanced NSCLC. Paclitaxel poliglumex (XyotaxTM) is an ester α-poly-L-glutamic acid conjugate of paclitaxel allowing for solubility in aqueous solution, not requiring Cremophor or ethanol for intravenous administration or premedications. This is a non-randomized single-arm, single-institution open label dose-ranging study was designed to evaluate the combination of pemetrexed and paclitaxel poliglumex. Methods: The primary objective of this study was to evaluate the safety of this combination. Patients (pts) were enrolled in 2 different dosing levels. The first 6 received 135 mg/m2 paclitaxel poliglumex and 500 mg/m2 pemetrexed intravenously every 3 wks. None of the 6 pts experienced an initial dose limiting toxicity (IDLT) following 2 cycles of therapy and the paclitaxel poliglumex was then escalated to 175 mg/m2 with 500 mg/m2 pemetrexed. Eligibility included advanced NSCLC, one or more measurable lesions (RECIST), ECOG = 0–2, prior chemotherapy and radiation allowed, no grade 2+ peripheral neuropathy, no untreated brain metastases, and no active cardiac disease. Results: Twelve pts were enrolled, 6 pts to each dose level. Four of the pts were female, the median age was 65 years (48- 74), 11 had a performance status of 0–1, and only 1 pt received prior chemotherapy. There were no IDLTs at the first dose level, and there was one IDLT of infection with neutropenia at the second dose level. The median number of cycles completed was 5 (range 1–12 cycles). Aside from grade 3 fatigue in 2 pts there were no grade 3 or greater non-hematologic toxicities. Common non-hematologic toxicities included peripheral neuropathy, constipation, fatigue, and alopecia. Of the 12 pts, the best response was stable disease in 9 pts, 2 are without disease progression, and 6 pts are alive to date. The median progression free survival was 3.3 months (range 0.7–10.7 months). Conclusions: The combination of paclitaxel poliglumex and pemetrexed was well tolerated at the proposed phase II dose of 175 mg/m2 and 500 mg/m2. The PFS is encouraging and future studies of this combination are recommended. No significant financial relationships to disclose.
A phase II trial of pemetrexed (P), gemcitabine (G), and bevacizumab (BV) in untreated patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: Wozniak A. J. , Kalemkerian G. P. , Gadgeel S. M. , Schneider B. J. , Valdivieso M. , Venkatramanamoorthy R. , Hackstock D. M. , Chen W. , Heilbrun L. K. , Ruckdeschel J. D. 
Published: August 2020

e19099 Background: P and G are active agents with acceptable toxicity profiles in the treatment of NSCLC. The addition of BV to chemotherapy has resulted in a significant improvement in survival for pts with non-squamous NSCLC. We are currently conducting a phase II trial of P, G and BV on a novel every two week schedule in untreated pts with advanced NSCLC. Methods: Advanced, non-squamous NSCLC pts with measurable/evaluable disease, no prior treatment for advanced disease, PS 0–1, adequate hepatic, renal and bone marrow function, treated brain metastases were eligible. No unstable hypertension/cardiac disease/vascular disease, hemoptysis, anti-coagulation, recent major surgery, no cavitation or close proximity of primary cancer to a major vessel were allowed. Pts received P 500 mg/m2, G 1,500 mg/m2, and BV 10 mg/kg every 2 weeks for 12 cycles. Doses were reduced to P 400 mg/m2 and G 1,200 mg/m2 when grade 4 neutropenia occurred in the first 2 patients. BV was continued until disease progression or toxicity. Planned accrual is 42 patients. Primary endpoint is progression-free survival. Secondary endpoints are response rate (RR), toxicity, time to progression and overall survival. Results: 20 pts have been accrued. Median age 57.5 yrs, males-55%, stage IV 90%, adenocarcinoma 75%. 18 pts are response evaluable (2 were too early to assess). 11/18 (61%) pts had a response (1 CR, 7 PR, 3 unconfirmed PR) (90% CI for RR is 0.42 - 0.77), and 3 had SD ( 17%) for a disease control rate of 78%. Currently the median treatment cycles for all pts are 6 (range 1–12). All pts are evaluable for toxicity. Grade 3- 4 toxicities: neutropenia 4, anemia 1, thrombocytopenia 2, lymphopenia 1, febrile neutropenia 1, fatigue 4, hypertension 1, GI 2, ALT/AST 3, pneumonitis 1, muscular weakness 1, metabolic 2, otitis media 1. Conclusions: The combination of P, G, and BV is a very active and tolerable treatment for NSCLC despite the preliminary nature of these results. Updated information will be presented at the meeting. This research is supported by Lilly Oncology and Genentech. [Table: see text]
Interest, attitudes, and participation in clinical trials among lymphoma patients with online access
Authors: Schwartz K. ,   Advisors to Patients Against Lymphoma
Published: August 2020

e19514 Background: There is an increasing number of investigational agents for lymphomas and a limited patient pool, approximately 5% of available patients. Thus, identifying and addressing obstacles to study enrollment is vital to making progress. Methods: This analysis was made from a non-random population of 251 lymphoma patients with online access to our survey. Results: In this cohort, 43% reported High Interest in clinical trials, 50% have Considered Trials, and 27% Have Participated. Patients who considered studies (126) ranked the following reasons for declining as significant: Randomization (70), Insurance (49), Study Risks / Toxicities (42), Travel and Lodging (30), Eligibility (28), Tests and Procedures (12), and a perception that Regular Treatment is superior (6). See Table 1 for associations with consideration of clinical trials and participation. Conclusions: In this cohort, interest in clinical trials and participation rates were much higher than generally cited. As expected, the discussion of clinical trials with the patient's oncologist was associated with the highest consideration (85%) and participation (53%) rates, suggesting a need to increase awareness of study protocols among treating physicians so that this discussion can become more routine. Patient issues and perceptions regarding randomization, study risk, eligibility, and tests and procedures suggest an opportunity to improve enrollment in clinical trials by focusing on these aspects of study design, specifically, attending to the rationale of the protocol as a treatment decision. [Table: see text] No significant financial relationships to disclose.