bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial safety results of an open-label phase II trial of erlotinib in non-small cell lung carcinoma (NSCLC)
Authors: García-Velasco A. , Pérez-Carrión R. , de Castro J. , Garrido P. , García R. , González-Larriba J. L. , Martín G. , Provencio M. , Amador M. L. , Paz-Ares L. 
Published: March 2020

18038 Background: Erlotinib is an orally selective and reversible inhibitor of HER1/EGFR tyrosine kinase. Erlotinib has demonstrated to be effective in the treatment of advanced non-small-cell lung cancer, in terms of longer survival, better quality of life and delayed symptom progression. The TargeT trial is a large open-label, non-randomized, phase II study carried out in 101 Spanish institutions. Methods: Eligibility criteria included stage IIIB-IV previously treated patients (p) with confirmed NSCLC. Patients harboring mutations in EGFR gene or p unsuitable for chemotherapy were also allowed to enter the study and received erlotinib as first line treatment. Subjects were treated with 150 mg/day po until disease progression or unacceptable toxicity. Dose reductions were allowed. Primary end-point was time to progression. Results: By the time of this analysis, data from 1,522 p were available. Median age: 65 y (range 26–95); most p were male (71.9%); active/former a smoker (78.3%). Around half of the p had adenocarcinoma histology, including bronchioloalveolar carcinoma (53%) and 81.8% exhibited stage IV. ECOG PS 0/1/2 were (%) 21/54/25. The % p receiving erlotinib as 1st/2nd/3rd-line treatment were 29/38/33. Safety data were available for 1,255 p. 6.9% p did not experience any adverse event. As expected most common adverse events were rash (any grade: 61%; gr. 3/4: 11%), and diarrhea (any gr.: 31%; gr. 3/4: 4%) 5.6% p withdrew prematurely the trial due to AE. Erlotinib-related AEs leading to treatment discontinuation were cutaneous toxicity in 21 p (17 gr. 3/4), diarrhea in 6 p (4 gr. 3/4), hepatic toxicity in 1 p, cholestasis in 1 p, and interstitial pneumonitis in 1 p. No unexpected toxicities were reported. 10% of p had dose reductions mainly due to rash and diarrhea. Response rate in these p was 18.7%; time to progression 3.8 months (95% CI: 3.5–4.2); and overall survival 6.0 months (95% CI: 5.5–6.4). Conclusions: These initial interim safety results of erlotinib in real-life clinical setting in a large number of unselected patients with advanced non-small-cell lung cancer confirm the favorable toxicity profile and good tolerability of erlotinib. No significant financial relationships to disclose.
Vinorelbine (VRB) plus gemcitabine (GEM) as first-line treatment for elderly patients (p) with advanced non-small cell lung cancer (NSCLC): Molecular correlates
Authors: Maestu I. , Isla D. , Diz P. , Muñoz J. , Oramas J. , Garcia R. , del Barco S. , Provencio M. , Taron M. , Rosell R. 
Published: March 2020

18040 Background: The clinical benefit of non-cisplatin doublets vs a single agent in elderly or unfit p is still controversial. The present study focuses on clinical outcome with VRB/GEM in elderly p and the role of functional status and comorbidities. Genetic predictive markers of response to VRB/GEM will also be examined in genomic and cDNA from tumor and circulating tumor DNA. Methods: 145 chemonaive p with stage IIIB (pleural effusion or supraclavicular lymph nodes)-IV or recurrent NSCLC and age > 70 years were accrued at 32 sites between April 2004 and January 2006. Treatment consisted of VRB 25 mg/m2 IV or 60–80 mg/m2 oral plus GEM 1200 mg/m2, days 1, 8 every 21 days. Activities of daily living (ADL), instrumental activities of daily living (IADL) and comorbidities were evaluated. DNA samples were collected from primary tumors for the assessment of microtubule associated protein 4 (MAP4) and from serum for the checkpoint with forkhead-associated and ring finger (CHFR) methylation. Results: Data on 130 p is available. Median age 76 years (69–83); males: 86.8%; smokers: 70.5%; PS 0–1: 83.9%; adenocarcinoma: 34.4% / squamous: 48%; stage IIIB: 22.7%, IV: 77.3%. Self-sufficiency in ADL and IADL was 77.4% and 45.2% of the p analyzed. 68% of the p had comorbidities. Median cycles: 3 (1–8). Hematological toxicities (%p): grade 3/4 neutropenia, 7.8%/4.7%; grade 3/4 thrombocytopenia, 2.3%/0.8%; grade 3 anemia, 3.1%. Efficacy in evaluable population: PR, 23.2% (95% CI, 15.1% to 32.9%); SD, 41.1%. 24 p died during the treatment period (non toxicity related) and 21 p were not evaluable. With a median follow up of 5.8 months, median survival for the whole population was 4.97 months (m), progression free survival 4.53 m, event free survival 3.43 m, 1-year survival 26.6%. Statistically significant differences in median survival were observed among subgroups: PS 0–1/2, 6.5/2.3 m (p<0.001); sex male/female, 4.5/9.7 m (p 0.027); ADL <6/=6, 3.4/7.1 m (p 0.023). Conclusions: This trial confirms that VRB/GEM is effective, presenting a favorable toxicity profile in elderly p with advanced NSCLC. Complete data on genetic markers will be presented. No significant financial relationships to disclose.
The relationship between pemetrexed exposure (AUC) and clinical outcome in Japanese NSCLC patients
Authors: Adachi S. , Tamura T. , Nakagawa K. , Falcoz C. , Musib L. , Calvert H. 
Published: March 2020

18041 Background: The efficacy of pemetrexed (PEM) 500 mg/m2 administered with vitamin B12 and folic acid (FS) has been established in previously treated NSCLC. The 500 mg/m2 dose is based on the MTD determined for PEM without FS. Recently completed phase I studies have shown the recommended dose of PEM single agent with FS to be 900–1,000 mg/m2. A randomized phase II study conducted in Japan (ASCO 2007) showed PEM 500 mg/m2 and 1,000 mg/m2 with FS to have similar efficacy for patients with 2nd and 3rd line NSCLC. PEM is renally excreted and a PK model characterizing the relationship between CrCL and PEM AUC has been previously established. The exposure response relationships (ERRs) between AUC and progression free survival (PFS), individual patient’ tumor response, and toxicity were explored in these analyses. Methods: Eligible patients had a histologic or cytologic diagnosis of NSCLC, had been previously treated by 1 or 2 chemotherapy regimens, and were randomized to 500 mg/m2 (N = 108 pts) or 1,000 mg/m2 (N = 108 pts) of PEM once every 3 weeks. A previously established PK model was used to estimate AUC based on patient CrCL and dose administered. AUCs were linked to clinical outcome to identify ERRs. Efficacy models assumed a distribution of events with hazard dependent on prognostic factors and mean AUC at cycle over the treatment period. The AE model assumed probability of toxicity as a function of AUC at each cycle. Results: Median CrCL for patients in 500 mg/m2 and 1,000 mg/m2 groups were 85 ml/min (42–167) and 83 ml/min (38–146), respectively; median estimated PEM AUCs were 158 mg.h/L (107–221) and 318 mg.h/L (215–468). The relationship between model-estimated AUC and PFS was not significant. This is consistent with the clinical findings: PFS for the 500 mg/m2 and 1,000 mg/m2 groups of 3.0 months and 2.4 months, respectively; overall response rate (RR) of 18.5% and 14.8%, respectively. ERR analyses for individual patient tumor response, neutropenia and thrombocytopenia are ongoing at this time. Conclusions: Estimated PEM AUCs, based on CrCL, does not correlate with PFS for pretreated NSCLC at 500 mg/m2 and 1,000 mg/m2. The ERRs for individual tumor response and toxicity are ongoing and will be presented at the meeting. No significant financial relationships to disclose.
Low incidence of brain metastasis as first site of relapse in patients with stage II and III non-small cell lung cancer
Authors: Moazzam N. , Kratzke R. 
Published: March 2020

18051 Background: Lung cancer remains the leading cause of cancer mortality in both women and men in the United States. Despite recent advances in treatments, many patients with stage II and III non-small cell lung cancer (NSCLC) die of recurrent disease. Methods: A retrospective review was conducted to determine the incidence of brain metastasis as first site of relapse as well as other patterns of failure in patients with stage II and III NSCLC. From 1995 to 2003, 239 patients were identified from Minneapolis Veterans Affairs Medical Center tumor registry. Data was collected on the following variables to identify prognostic factors for brain metastasis and others patterns of failure: patient’s age, tumor histology, tumor size, nodal status, use of adjuvant chemotherapy, and type of adjuvant chemotherapy. Results: Of the 239 patients, only 12 (5%) had brain metastasis as first site of relapse. Median survival for patients with brain metastasis was 0.9 year (95% CI, 0.75–1.50). Out of 12 patients, 8 (67%) developed brain metastasis between 6 and 12 months after the initial diagnosis, 3 (25%) developed brain metastasis between 12 and 18 months and 1 (8%) developed brain metastasis as first site of relapse more than 18 months after initial diagnosis. Other patterns of failure were as follows: Thorax 36%, primary site 22%, primary + thorax 14% and distant metastasis 32%. Among 88 patients who underwent surgery as a part of definitive therapy, thorax was again the most common site of relapse (23%). Multivariate analysis showed that use of non-platinum based chemotherapy is a significant risk factor for relapse (p=0.02). Conclusion: Brain metastasis as first site of relapse is uncommon in patients with stage II and III NSCLC. Due to very low incidence of brain metastasis in this cohort of patients, prophylactic cranial radiation (which is the focus of few ongoing clinical trials) may cause more harm than good. No significant financial relationships to disclose.
P63 in cytologic material is helpful for detection of squamous differentiation in non-small cell carcinomas of lung and treatment selection
Authors: Jorda M. , Mousavi F. , Gomez-Fernandez C. , Maleki Z. , Walker G. , Ganjei-Azar P. 
Published: March 2020

18052 Background: Bevacizumab in combination with carboplatin and paclitaxel improves overall response and survival in patients with advanced or recurrent non-small cell lung carcinoma. However, this drug is not recommended in patients with carcinomas with squamous differentiation. Therefore, identification of squamous cell component is desirable. In many instances, cytology is the diagnostic tool of choice; however, routine cytomorphology is limited in classification of non small-cell carcinomas into squamous and non-squamous subtypes. The aim of this study is to identify the value of immunocytochemistry for p63 in this distinction. Methods: Review of cytology records identified 51 consecutive pulmonary specimens with the diagnosis of non-small cell carcinoma (9 squamous cell carcinomas and 42 carcinomas without squamous differentiation). Histologically, they proved to be 26 squamous cell carcinomas and 25 non-small cell carcinomas without squamous differentiation. P63 immunocytochemical stain was performed on archival alcohol-fixed Papanicolaou stained cytology slides, using standard immunocytochemical methods. Results: Twenty-three (88 %) of the 26 histologically proven squamous cell carcinomas were positive for p63 on cytologic smears. Using p63, we detected 14 carcinomas with squamous differentiation not identified by cytomorphology. Smears from all carcinomas with squamous differentiation were positive for p63. Sensitivity of cytology for the detection of squamous differentiation increased from 35% to 88% using p63 immunocytochemistry (p=0.001, McNemar’s test). Four carcinomas with squamous differentiation were detected only in cytologic and not in corresponding histologic samples. Conclusions: 1- p63 is a useful marker for the detection of squamous differentiation in cytologic pulmonary samples; 2- p63 immunocytochemistry significantly increases the sensitivity for the identification of squamous cell carcinomas of lung from 35% to 88% (p=0.001); 3- p63 immunocytochemistry should be used in all pulmonary cytologic samples with a diagnosis of non-small cell carcinoma to improve therapeutic selection of patients; 4- Cytologic sampling may provide better representation of tumor subtypes. No significant financial relationships to disclose.
A phase I and pharmacologic study of belotecan in combination with cisplatin in patients with previously untreated extensive-stage disease small cell lung cancer
Authors: Lee J. , Lee D. , Bae K. , Kim S. , Suh C. , Shin J. , Hong J. , Kang Y. 
Published: March 2020

18053 Background: Belotecan (CKD602) is a novel camptothecin derivative antitumor agent. This phase I study was designed to determine the maximum-tolerated dose (MTD), toxicity profile, and dose-limiting toxicity (DLT) of belotecan in combination with cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer (ED SCLC). Furthermore, pharmacokinetics (PK) and preliminary antitumor activity of belotecan against SCLC were evaluated. Methods: Patients with ED SCLC, age 18–70, ECOG PS 0–2, no prior chemotherapy and adequate organ function were eligible. Cisplatin with fixed dose of 60 mg/m2 was administered intravenously (i.v.) over 2 hours on day 1. Belotecan was administered iv as intermittent 30-minute infusions on days 1 to 4, starting dose of 0.40 mg/m2/day with increment of 0.05 mg/m2/day. Modified Fibonacci escalation was used (3 to 6 patients per cohort) and intra-patient dose escalation was not allowed. PK of belotecan was determined during the first treatment using non-compartmental pharmacokinetic analysis. Results: Seventeen patients were treated at 4 dose levels (0.40 to 0.55 mg/m2/day). At 0.55 mg/m2/day of belotecan, the DLT of grade 4 neutropenia with fever occurred in 2 of 5 patients, and therefore the MTD was 0.50 mg/m2/day. Interestingly, out of 17 patients, there were 14 partial responses (82.4%; 95% CI, 63.4% to 100.0%). PK analysis revealed that at 0.50 mg/m2/day, plasma clearance of belotecan was 5.78 ± 1.32 L/hr and terminal half-life was 8.55 ± 2.12 hr. Fraction of excreted amount in urine was 37.36 ± 5.55 %. PK of belotecan were not altered by administration of cisplatin, as compared with historical control. Conclusions: The MTD of belotecan was 0.50 mg/m2/day for intermittent 30-min i.v. infusion for 4 days in combination with cisplatin 60 mg/m2 on day 1 every 3 weeks. Furthermore, very promising antitumor activity against SCLC was observed. The phase II study is being conducted now. No significant financial relationships to disclose.
A phase I dose escalation study of sunitinib in combination with gemcitabine + cisplatin for advanced non-small cell lung cancer (NSCLC)
Authors: Reck M. , Frickhofen N. , Gatzemeier U. , Fuhr H. , Lanzalone S. , Lechuga M. J. , Wang E. , Chao R. , Felip E. 
Published: March 2020

18057 Background: Sunitinib malate (SU) is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, RET, and FLT3, approved internationally for the treatment of advanced RCC and imatinib-resistant or -intolerant GIST. SU has also shown single- agent activity in NSCLC. In this study we assess the safety, tolerability, and pharmacokinetics (PK) of SU in combination with gemcitabine (G) and cisplatin (C). Methods: This is a phase I, dose-finding study in pts with untreated, stage IIIB/IV NSCLC not amenable to curative treatment. Planned dose levels include: oral SU (37.5 or 50 mg/day for 2 wks followed by 1 wk off treatment [2/1 schedule]) plus G (1000 or 1250 mg/m2 iv on days 1 and 8 of a 21-day cycle) and C (80 mg/m2 iv on day 1 of each cycle). SU doses are escalated in serial pt cohorts to determine the maximum tolerated dose (MTD) for both schedules. SU continuous dosing (CD) schedule will also be tested. PK and antitumor efficacy are also assessed. Results: As of Oct 2006, 13 pts were treated on the 2/1 schedule: 6 pts with SU 37.5 mg + G 1000 mg/m2 + C 80 mg/m2, and 7 pts with SU 50 mg + G 1000 mg/m2 + C 80 mg/m2. No dose-limiting toxicities (DLTs) were observed with SU 37.5 mg, while 2 pts experienced neutropenia and infection as DLTs with SU 50 mg. Grade 3/4 hematological AEs included neutropenia (n=3 at dose level 1 and n=5 at dose level 2), thrombocytopenia (n=1 and 5) and anemia (n=2 and 0). 3 pts achieved a partial tumor response at the SU 50 mg/day dose level. There were no apparent drug-drug interactions between SU in combination with G and C based on their systemic exposures in this study. Conclusions: The combination of SU (37.5 mg) on schedule 2/1 with G (1000 mg/m2) and C (80 mg/m2) in advanced NSCLC appears safe and tolerable in this pt population. Testing with G escalated to 1250 mg/m2 or with SU administered on a CD schedule is ongoing. No significant financial relationships to disclose.
Activity of patupilone for the treatment of recurrent or progressive brain metastases in patients (pts) with non-small cell lung cancer (NSCLC): An open-label, multicenter, phase II study
Authors: Abrey L. , Wen P. Y. , Govindan R. , Reimers H. J. , Rigas J. R. , Robins H. I. , de Bedout S. , O’Connell C. , Li X. , Johri A. 
Published: March 2020

18058 Background: Advances in systemic chemotherapy have improved overall survival for patients with advanced NSCLC; unfortunately, CNS metastasis is common and limits survival benefits with current therapies. Unlike taxanes, preclinical findings suggest that the novel epothilone, patupilone, crosses the blood-brain barrier in 3 animal species and also has antitumor effects in brain tumor models. Results of an ongoing phase I/II study of patupilone as second-line therapy in pts with NSCLC are encouraging. The present study is evaluating the efficacy of patupilone in pts with brain metastases from NSCLC who have failed or recurred after previous chemotherapy, surgery, and/or radiation to the brain. Methods: This open-label, single-arm, multicenter, phase II study has a 2-stage design (25 pts per stage). Eligible pts have histologically confirmed NSCLC and = 1 recurrent, bidimensionally measurable intracranial lesion = 2 cm. Patupilone was administered IV at 10 mg/m2 as a single 20-min IV infusion every 3 weeks until disease progression, satisfactory response, or unacceptable toxicity. The primary multinomial endpoint was a combination of early progression (disease progression or death before cycle 1, day 21) and response rate (alive without progression at cycle 4, day 1). Results: An interim analysis of 13 pts with a median age of 62 years (range, 40–67 years) is reported. The most common adverse events (AEs) related to study drug were NCI CTC grade 1/2 diarrhea in 7 (54%) pts, nausea in 3 (23%), and fatigue in 2 (15%). Only 2 serious AEs (grade 4 colitis and grade 3 diarrhea) and 2 additional grade 3 AEs (diarrhea, neutropenia) were reported in 1 pt each. Three (23%) pts experienced early disease progression. Five (38%) pts responded, receiving a median 10 cycles (range, 5 to 12 cycles) and were alive without progression on cycle 4, day 1. Conclusions: Patupilone has activity in patients with CNS metastases from advanced NSCLC and is well tolerated. Additional investigation of patupilone as a treatment for brain metastases from NSCLC is warranted. [Table: see text]
A randomized phase II study of carboplatin and paclitaxel (CP) versus gemcitabine and vinorelbine (GV) in performance status (PS) 2 patients with advanced non-small cell lung cancer (NSCLC): West Japan Thoracic Oncology Group 00
Authors: Iwamoto Y. , Saito H. , Nakagawa K. , Kashii T. , Katakami N. , Nakano T. , Kurata T. , Ando M. , Fukuoka M. 
Published: March 2020

18060 Background: Although doublet chemotherapy is a standard treatment regimen for PS 0–1 patients with advanced non- small cell lung cancer (NSCLC), the optimal chemotherapy for PS 2 patients with advanced NSCLC still remains to be established. We conducted a randomized phase II study to compare the efficacy and safety of a platinum-doublet regimen (CP) versus a non-platinum doublet regimen (GV) in PS 2 patients with advanced NSCLC. Methods: Chemotherapy-naive patients with stage IIIB (malignant effusion) and IV NSCLC were eligible for this study. The patients were randomly assigned to carboplatin area under the curve of 6 plus paclitaxel 200 mg/m2 on day 1 every 3 weeks (the CP arm) or gemcitabine 1000 mg/m2 plus vinorelbine 25 mg/m2 on days 1 and 8 every 3 weeks (the GV arm). The primary endpoint was the 1-year survival rate while the secondary endpoints were the response rate, the time to progression and the quality-of-life (QOL). The sample size was 41 assessable patients in each arm. Results: Of the 89 patients enrolled, 84 were assessable for efficacy and toxicity: 41 patients (median age 65 years, male/female 30/11, stage IIIB/IV 7/34) in the CP arm and 43 patients (median age 67 years, male/female 31/12, stage IIIB/IV 7/36) in the GV arm. The overall response and 1-year survival rates were 29.3% (95% CI, 16.1 to 45.5%) and 22% (95% CI, 9.3 to 34.6%) for the CP and 20.9% (95% CI, 10 to 36%) and 27.9% (95% CI, 14.5 to 41.3%) for the GV arm, respectively. The median survival time and time to progression were 5.9 and 2.9 months, respectively, for the CP arms and 6 and 2.6 months for the GV arm. The selected Grade 3/4 toxicity in the CP and GV arms included neutropenia (67.5% vs 65.1%, respectively), anemia (12.5% vs 30.2%), thrombocytopenia (7.5% vs 11.6%), febrile neutropenia (17.1% vs 11.6%), infection (29.3% vs 23.3%), pneumonitis (4.9% vs 11.6%), liver dysfunction (2.5% vs 9.3%), and neuropathy (5.1% vs 0%). The QOL improved after each treatment and it was similar between the two arms. Conclusions: Both CP and GV appear to be active in PS 2 patients with advanced NSCLC . The toxicity profiles were different between the two arms. [Table: see text]
Phase II study of TS-1 (S) plus cisplatin (P) with concurrent thoracic radiotherapy for unresectable stage III non-small cell lung cancer (NSCLC)
Authors: Ohyanagi F. , Yamamoto N. , Horiike A. , Horai T. , Gomi K. , Murakami H. , Harada H. , Takahashi T. , Nakamura Y. , Nishio M. 
Published: March 2020

18070 Background: Although combined chemoradiotherapy is the standard of care in stage III NSCLC, the optimal chemotherapy regimen is not established. S-1, a fourth-generation oral fluoropyrimidine is an active new agent for NSCLC and the combination with cisplatin has a favorable toxicity profile. The objective of this study was to evaluate feasibility and efficacy of S plus P with concurrent radiation for unresectable stage III NSCLC. Methods: Patients with histologically or cytologically confirmed NSCLC, 20 to 75 years in age, performance status 0–1, with no prior chemotherapy were eligible for the study. Patients were treated with P (60 mg/m2 on day 1) and S (orally at 40 mg/m2/dose bid (80 mg/m2/d), on days 1 to 14) repeated every 3–4 weeks for 4 cycles and TRT (60 Gy/30 fr over 6 weeks starting on day 2). The primary endpoint was the response rate (RR), and planned sample size for this phase II study was 28 patients (Simon’s two-stage minimax design, P0=70%, P1=90%, a =0.1, β = 0.1). Results: Of 28 patients enrolled between August 2005 and October 2006, 28 were evaluable. There were 24 males and 4 females, median age of 63 (range 40–74) and 11 IIIA and 17 IIIB. Chemoradiotherapy was well tolerated; 2 cycles of SP and 60 Gy of TRT were administered in all patients and 24 (86%) patients received 4 cycles of SP. During concurrent chemoradiotherapy, grade 3 toxicities were neutropenia (8 pts), leukopenia (6 pts), fatigue (6 pts), anorexia (5 pts), febrile neutropenia (4 pts) and, esophagitis (4 pts). Only one grade 4 leukopenia were observed. During consolidation therapy, grade 3–4 neutropenia, anemia, esophagitis, and pneumonitis were developed in 4, 1, 1 and 2 patients, respectively. No toxic deaths have occurred. Overall RR was 85.7% (95% CI: 79.1- 98.7%) with 4 SDs and 24 PRs. The median progression-free survival and median survival is not mature enough to estimate as only 4 progression and no deaths have occurred. Conclusions: This chemoradiotherapy regimen produced promising response rate in patients with stage III NSCLC and it seems to be well-tolerated. No significant financial relationships to disclose.