bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autologous hematopoietic stem cell transplantation with a rituximab-containing preparative regimen for non-Hodgkin lymphoma
Authors: Kamble R. T. , May R. , Ganguly S. , Heslop H. E. , Brenner M. K. , Carrum G. 
Published: March 2020

7112 Background: We investigated the safety and outcome after adding Rituximab to our standard high-dose chemotherapy conditioning regimen with BEAM in patients receiving autologous hematopoietic stem cell transplantation. Methods: Between November 2002 and May 2006, 25 consecutive patients with relapsed high-risk NHL (diffuse large B cell = 15, transformed follicular =10) were enrolled. The high-dose chemotherapy regimen consisted of BEAM with rituximab administered at 375 mg/m2 IV on days −6, +14, +21 and +28. Rituximab associated delayed neutropenia was defined as ANC of < 500 occurring at least 4 weeks after the last dose of rituximab. B cell and T cell reconstitution data was measured using phenotypic analysis for CD3, CD4, CD8, CD56, CD19 and CD20. Results: The median age was 55 years (range 22–69 years). The disease status at transplant included advanced disease (≥CR-2) in 15 while 10 had primary refractory disease. The previous initial and or salvage chemotherapy included Rituximab in all 25 patients. A median of 4.47 ×10 6/kg CD 34 + cells were infused resulting in neutrophil and platelet engraftment at 11 (10–23) and 21 (14–56) days respectively. The median time to T cell reconstitution (CD3 >1,000/uL) was 32 days, B cell recovery was delayed beyond 1 year with median of 72 CD19+ve cells/uL at 1 year. 24 (96%) patients achieved complete remission after transplant and 1 had a partial response. There was no transplant related mortality. Nine patients relapsed at a median of 4 months (2–23 months). 6 patients died at a median of 15 months from transplant (relapsed lymphoma =4 and secondary MDS=2). At a median follow-up of 24 months, the disease free survival and overall survival is 52% and 75% respectively. Rituximab associated delayed neutropenia occurred in 3 (12%) patients at a median of 39 (31–64) days from the last dose of rituximab and resolved at a median of 14 days (7–38) with or without filgrastim support. There were no infectious complications associated with neutropenia or delayed B cell recovery. Conclusion: Incorporation of rituximab into a high dose chemotherapy conditioning regimen is safe. Delayed B cell reconstitution and Rituximab associated delayed neutropenia are common but not associated with significant infectious complications. No significant financial relationships to disclose.
Molecular analysis-directed individualized therapy (MADeIT) in advanced non-small cell lung cancer (NSCLC)
Authors: Simon G. R. , Williams C. C. , Chiappori A. A. , Haura E. B. , Tanvetyanon T. , Antonia S. J. , Bepler G. 
Published: March 2020

7502 Background: RRM1 (R1) is a crucial gene for nucleotide metabolism, and it is the dominant molecular determinant of gemcitabine efficacy. ERCC1 (E1), a component of the nucleotide excision repair complex, is important for platinum-induced DNA adduct repair. We hypothesized that selection of dual agent chemotherapy based on tumoral R1 and E1 expression would be feasible and beneficial for patients with advanced NSCLC. Methods: A prospective phase II clinical trial in patients with advanced NSCLC was conducted. Patients were required to have a dedicated tumor biopsy for determination of R1 and E1 gene expression by real-time quantitative RT-PCR. The primers and probes had been validated by sequencing of cDNA amplicons. Dual agent chemotherapy consisting of carboplatin (C), gemcitabine (G), docetaxel (D), and vinorelbine (V) was selected based on gene expression as follows: GC for low R1/low E1; GD for low R1/high E1; DC for high R1/low E1; and DV for high R1/high E1. Eligibility included pathologically confirmed advanced NSCLC (stage IV and wet IIIB); PS 0–1; no prior systemic therapy for NSCLC; age ≥18; adequate hematologic, hepatic, and renal function; and measurable or evaluable disease by RECIST. Disease response and patient survival were measured. Results: Sixty eligible patients were enrolled from 2/04 to 12/05. Tumor specimens were collected in all with one minor and clinically insignificant complication. Expression analysis was successful in 55 patients. R1 expression ranged from 0–1,637; E1 expression ranged from 1–8,103; and their expression was correlated (Spearman's rho=0.46, p<0.01). The partial response rate was 44% (95% CI 31–59%). OS and PFS and were 59% and 14% at 12 months with medians of 13.3 and 6.6 months respectively. Conclusion: Therapeutic decision making based on RRM1 and ERCC1 gene expression for patients with advanced NSCLC is feasible and promising for improvement in patient outcome. No significant financial relationships to disclose.
Randomized phase II study of maintenance vandetanib (ZD6474) in small cell lung cancer (SCLC) patients who have a complete or partial response to induction therapy: NCIC CTG BR.20
Authors: Arnold A. M. , Smylie M. , Ding K. , Ung Y. , Findlay B. , Lee C. W. , Djurfeldt M. , Seymour L. , Langmuir P. , Shepherd F. 
Published: March 2020

7522 Background: Vandetanib (V) is an inhibitor of vascular endothelial and epidermal growth factor receptors. This trial sought to determine whether maintenance V, given after standard chemotherapy (CT) and radiation (RT), prolonged progression-free survival (PFS) in responding patients with SCLC. Secondary endpoints: overall survival (OS) and toxicity. Methods: Phase II randomized, study of V 300 mg PO daily or placebo (P). Eligibility: complete (CR) or partial response (PR) to platinum-based CT, ECOG PS 0–2 and completion of RT (thoracic or prophylactic cranial). Statistics: 80% power to detect a 2.5 months improvement in median PFS (estimate for P of 4 months) using a 1-sided 10% level test (100 eligible patients; 77 events). Results: Between May 2003 and March 2006, 107 patients were accrued from 17 centres. Median follow up: 13.5 months. 46 had limited disease (LD); 61 extensive disease (ED). There were fewer PS 0 patients (11 vs. 20), and fewer had CR to initial CT (4 vs. 8) in the V arm. V patients were more likely to experience toxicity and require dose modification. The most frequent toxicities leading to dose modifications were gastrointestinal and rash. Clinically asymptomatic QTc prolongation was observed in 8 V patients. 83 of 107 patients developed progressive disease (43 on V; 40 on P). The median PFS for V was 2.7 months (80% C.I.: 1.1 –4.5) and 2.8 months for P (80% C.I.: 1.9 –5.6); estimated hazard ratio (HR) was 1.01 for V vs P (80% C.I.: 0.75 –1.36, 1-sided P-value = 0.51). Median OS for V was 10.6 months vs. 11.9 months for P; HR was 1.43 for V vs. P (80% C.I.: 1.00 –2.05, 1-sided P-value = 0.90). In a planned subgroup analysis, a significant interaction was noted (P-value = 0.01); with LD patients randomized to V having a longer OS (HR: 0.45, 1-sided P-value = 0.07), whereas ED patients randomized to V had a shorter OS compared to P (HR: 2.27, 1-sided P-value = 0.996). Conclusion: V failed to demonstrate efficacy as maintenance therapy for SCLC. Future targeted therapies should probably be explored concurrently with chemotherapy. This study was supported by the Canadian Cancer Society and AstraZeneca. [Table: see text]
Randomized, phase III study of mitomycin/vindesine/cisplatin (MVP) versus weekly irinotecan/carboplatin (IC) or weekly paclitaxel/carboplatin (PC) with concurrent thoracic radiotherapy (TRT) for unresectable stage III non-small cell lung cancer (NSCLC)
Authors: Kimura T. , Uejima H. , Satouchi M. , Nakagawa K. , Hida T. , Kawahara M. , Sugiura T. , Kashii T. , Tamura K. , Fukuoka M. 
Published: March 2020

7530 Background: Concurrent chemoradiotherapy plays an important role in the treatment of unresectable stage III NSCLC. Our group demonstrated a superiority of MVP with concurrent TRT over that with sequential TRT (Furuse, JCO, 1999), while weekly chemotherapy with concurrent TRT has acceptable toxicities and expected efficacy. We conducted a randomized phase III trial to compare the efficacy and toxicity of weekly chemotherapy with concurrent TRT against MVP by a non-inferiority design. Methods: Patients were assigned to 3 regimens; MVP: cisplatin (80 mg/m2 on days 1, 29), vindesine (3 mg/m2 on days 1, 8, 29, 36) and mitomycin (8 mg/m2 on days 1, 29) with concurrent TRT (60 Gy). After then, pts received 2 courses of consolidation chemotherapy with MVP; IC: weekly irinotecan (20 mg/m2) / carboplatin(AUC 2) for 6 weeks and TRT (60 Gy) followed by 2 courses of irinotecan(50 mg/m2) / carboplatin(AUC 5); PC: weekly paclitaxel (40 mg/m2)/carboplatin (AUC 2) and TRT (60 Gy) followed by 2 courses of paclitaxel (200 mg/m2) / carboplatin (AUC 5). Primary endpoint was overall survival. Results: From Sep 2001 to Sep 2005, 456 pts were randomized; 429 pts had evaluated responses. Pretreatment characteristics were well-balanced between 3 arms (median age 63 years (30–74), PS0/1 41/55%, Ad/Sq/others 43/45/12%). The achievement rates of full treatment in MVP, IC and PC were 39.9, 29.7, and 49.3 %; those of full-dose TRT/2 courses of consolidation chemotherapy were 81.1/41.3%, 41.4/29.7% and 59.7/50.0%, respectively. Major toxicities were as follows; G4 neutropenia in MVP, IC, PC were 76.9, 13.1, 4.2% (p<0.001), and G3–4 non-hematological toxicities (decrease in PS, and febrile neutropenia) were 13.3, 6.2, 4.2% (p=0.01), and 29.4, 6.9, 4.9% (p<0.001), respectively. The overall response rates were 65.7% (95% CI 57.9–73.5), 58.6 % (95% CI 50.5–66.1) and 62.9% (95% CI 55.0–70.8), in MVP, IC and PC, respectively. Complete analysis will be fixed in Oct 2008. Conclusions: Weekly PC with TRT appears good compliance with high achievement rate and MVP appears poor compliance with severe hematological and non-hematological toxicities. No significant financial relationships to disclose.
A phase II study of cetuximab (C225) in combination with chemoradiation (CRT) in patients (pts) with stage III A/B non-small cell lung cancer (NSCLC): An interim report of the RTOG 0324 trial
Authors: Blumenschein G. , Moughan J. , Curran W. , Robert F. , Fossella F. , Werner-Wasik M. , Doescher P. , Choy H. , Komaki R. 
Published: March 2020

7531 Background: Cetuximab (C225) is a chimerized monoclonal antibody that targets the epidermal growth factor receptor (EGFR). NSCLC commonly expresses the EGFR, which is associated with aggressive tumor behavior and poor clinical outcome. Preclinical model systems demonstrate radiosensitization following molecular inhibition of EGFR signaling. Methods: We report a phase II trial testing the combination of C225 with CRT in unresectable stage III NSCLC with a planned sample size of 84 PTS. Eligibility criteria included Zubrod performance status (PS) = 1, weight loss = 5% over past 3 months, FEV1 = 1.2 l, adequate hematologic, hepatic, and renal function. PTS received an initial dose of C225 (400 mg/m2) on day 1 of week 1, then weekly doses of C225 (250 mg/m2) until completion of therapy (weeks 2 –17). During week 2, patients started CRT (63 Gy/35 fractions) with weekly carboplatin (C) AUC 2 and paclitaxel (P) 45 mg/m2 × 6 doses followed by C (AUC 6) and P (200 mg/m2) × 2 cycles (weeks 12–17). Interim monitoring for severe (grade = 3) or excessive non-hematologic toxicities occurred after pts had been treated and followed for at least 90 days after RT. Primary endpoints include safety and compliance of concurrent C225 and CRT. Results: 93 pts were enrolled with 87 evaluable pts. Pts characteristics: 57% male, median age 64 years (range 42–85), 47% PS 0, 46% stage IIIA. Median follow-up is 14 months. Response rate is 62% (n=54) and 12 month overall survival (OS) is 68% (# at risk=56). Adverse events related to treatment include 20% (n=17) of pts with grade 4 hematologic toxicities and 7 pts who had grade 3 esophagitis. There was 1 infection related death, 1 death NOS, and 3 pts who died of pulmonary complications (adult respiratory distress syndrome, pneumonitis, and hypoxia). Conclusions: The combination of C225 with CRT is feasible. Further study will be needed to determine whether the addition C225 to CRT enhances toxicity or efficacy. Complete compliance and toxicity data along with 18 month OS will be reported. No significant financial relationships to disclose.
Are timing of chemoradiation and early therapy response as detected by PET prognostic factors of a multimodality treatment approach for NSCLC stage III? (LUCAS-MD)
Authors: Schmuecking M. , Schneider C. P. , Presselt N. , Baum R. P. , Leonhardi J. , Hoeffken K. , Niesen A. , Mueller K. M. , Wendt T. G. , Bonnet R. 
Published: March 2020

7532 Background: A randomized multicenter phase III trial was designed to assess if timing of chemoradiation may alter treatment outcome for patients (pts) with stage III NSCLC in a multimodality treatment approach. Additionally, the role of F-18 FDG PET within clinical trials is evaluated for staging, therapy management, molecular radiation treatment planning (MRTP) and early therapy response and its effect on survival as compared to regression grade (RG). Methods: Inclusion criteria: histologically confirmed NSCLC stage IIIA/IIIB. ECOG PS 0–1. Primary end points: OS, DFS. Secondary end points: TTP, QoL, RR. Neoadjuvant treatment: 2–3 cycles of paclitaxel/carboplatin and a block of chemoradiation (45 Gy, 1.5 Gy b.i.d., concomitant paclitaxel/carboplatin) followed by surgery. Randomization: late (Arm1) vs. early (Arm2) chemoradiation. Staging: PET in addition to CT and/or MRI after randomization, second PET after completion of neoadjuvant therapy. Assessment of standardized uptake values (SUV) in primary tumor (PT) and all metastatic lymph nodes (LN). Documentation of involved LN as detected by PET and LN sampling during surgery according to Naruke/ATS-LCSG classification. Evaluation of RG and correlation with PET for PT and each LN. MRTP using fused PET/CT data. Intent to treat analyses using Kaplan-Meier estimates, log rank tests, Cox multivariate models. Results: 210 eligible pts were enrolled (Arm1: 106, Arm2: 104, well-balanced on all factors). Paraoperative lethality 4.3%. Treatment-related deaths in Arm1: 8.3%, in Arm2: 5.9%. Up-staging in 26/210 pts due to distant metastases, down-staging in 5/210 pts resulting in 15% stage migration. Actuarial tumor specific survival after 60 months: complete vs. incomplete metabolic remission: 56% vs. 24% (p =0.005), RG III/IIb (no/less than 10% of vital tumor cells) vs. RG IIa/I (more than 10% vital tumor cells): 61% vs. 25% (p <0.001). Late vs. early chemoradiation: 30% vs. 45% (p =0.313). Multivariate Cox regression for initial SUV: p >0.05. Conclusions: Long-term survivors with early chemoradiation have a trend to better survival being not statistically significant. Metabolic remission correlates well with RG and may predict therapeutic outcome. No significant financial relationships to disclose.
Oral talactoferrin extends survival in patients with refractory NSCLC in a randomized, placebo-controlled, phase 2 trial
Authors: Parikh P. K. , Wang Y. , Ranade A. A. , Vaid A. K. , Advani S. H. , Raghunadharao D. , Nag S. , Madhavan J. P. , Varadhachary A. 
Published: March 2020

7540 Background: Talactoferrin alfa (TLF), an immunomodulatory protein with a novel anti-cancer mechanism of action, was active preclinically and in non-small cell lung cancer (NSCLC) patients in Phase 1b studies. Randomized Phase 2 studies in NSCLC were conducted with TLF as a single agent and combined with chemotherapy. The 110-patient combination therapy study, which was previously presented (ASCO 2006, #7095), met its primary endpoint with an improved BOR over chemotherapy alone. We now present results from the placebo- controlled single agent study. Methods: 100 Stage IIIB/IV NSCLC patients who had progressed after first or second line therapy were enrolled at 10 leading Indian cancer centers, and randomized to receive best supportive care plus either oral TLF (1.5 g bid) or placebo. TLF/placebo was administered until disease progression, for up to three 14-week cycles (12 weeks on, 2 weeks off), in a centrally monitored trial. The primary endpoint was overall survival (OS) with 80% power to detect an improvement in median OS with an a=0.05. Results: All patients had previously received a 1st line platinum based regimen; 26 also received 2nd line therapy. The TLF and placebo arms enrolled 47 and 53 patients, respectively. Baseline characteristics were similar in both groups, including proportion of patients receiving 1 or 2 prior regimens. All patients were included in the Intent To Treat (ITT) analysis. The trial met its primary endpoint with a 55% increase (2.1 month; p<0.05) in median OS. TLF was well tolerated. Adverse Events (AEs) were generally mild. No drug- related SAEs were reported. Incidence of AEs and Grade 3/4 AEs was similar in both arms. Conclusion: Oral talactoferrin, a promising new anti-cancer agent, significantly improved survival in patients with refractory NSCLC in this randomized, placebo-controlled trial. TLF was well tolerated in this population. Given its favorable toxicity profile, TLF may be particularly attractive in refractory patients with poor performance status. [Table: see text] [Table: see text]
Prognostic implication of the EGFR gene mutations in a large cohort of Japanese patients with early stage lung adenocarcinoma
Authors: Kosaka T. , Yatabe Y. , Onozato R. , Mitsudomi T. 
Published: March 2020

7574 Background: Prognostic impact of epidermal growth factor receptor (EGFR) gene mutations in lung adenocarcinoma remains controversial. We examined a large cohort of lung adenocarcinoma resected in a single institution for EGFR mutations and evaluated its prognostic implication. Methods: We analyzed 402 patients with lung adenocarcinoma who underwent potentially curative pulmonary resection at our department, from May 2000 through December 2005. Total RNA was extracted and direct sequencing of exons 18–21 of EGFR gene was performed after reverse transcription - polymerase chain reaction. KRAS and TP53 gene mutations were also analyzed in 209 adenocarcinoma patients from this cohort. Results: We found that 196 patients (49%) had EGFR mutations. Of them, exon 19 deletion mutations were 83 (42%) and L858R mutations were 92 (47%). EGFR mutations were significantly frequent in female (P<0.0001), never smokers (P<0.0001), and well to moderately differentiated adenocarcinoma (P<0.0001). In 347 patients who were not treated with gefitinib, prognostic effect of EGFR mutations was evaluated. Patients with EGFR mutations survived for a longer period than those without the mutations after surgery in univariate analysis (P=0.0046, log rank test). We did not detect any difference in overall survival between the patients with exon 19 deletion mutations and those with L858R mutations (P=0.3962). There were tendencies that patients with KRAS mutations or TP53 mutations survived for a shorter period than those without mutations, although there was no statistical significance (P=0.2534 and 0.0859). Multivariate analysis using the Cox proportional hazards model revealed that never smokers (P=0.0253) and disease stage (P<0.0001) were independent prognostic factors. However, all gene mutations were not independent prognostic factors (EGFR; P=0.4763, KRAS; P=0.7998, TP53; P=0.3464). Conclusion: EGFR mutations were not independently associated with prognosis of patients with early stage adenocarcinoma of the lung. Furthermore, there was no difference between exon 19 deletion mutations and L858R mutations in their prognostic impact. No significant financial relationships to disclose.
Epidermal growth factor receptor (EGFR) immunohistochemistry: Comparison of antibodies (Abs) and cut points to predict benefit from gefitinib in a phase III placebo-controlled study in advanced non-small cell lung cancer (NSCLC)
Authors: Dziadziuszko R. , Hirsch F. R. , Varella-Garcia M. , Thatcher N. , Mann H. , Watkins C. , Speake G. , Holloway B. , Bunn P. A. , Franklin W. A. 
Published: March 2020

7576 Background: Tumor tissues obtained from the ISEL phase III trial assessing the efficacy of gefitinib vs placebo in chemotherapy-pretreated NSCLC were used to evaluate two Abs (DAKO and Zymed) and assess whether different cut points of EGFR protein expression improved prediction of response and survival benefit from gefitinib. Methods: EGFR protein expression in tumor samples was assessed by immunohistochemistry using DAKO EGFR pharmDx kit (scoring percent of tumor cells with positive staining, predefined cut point of =10%) and Zymed monoclonal Ab clone 31G7 (scoring proportion of positive cells times staining intensity [scale 0–400], predefined cut point of =200). Results: Clinical characteristics of the patients (pts) assessed with DAKO (n=379) and Zymed (n=357) Abs reflected the overall study population (N=1692) with the exception of fewer never-smokers and Asians. Of the pts evaluated with DAKO/Zymed Abs, females represented 32%/31%; never-smokers, 13%/14%; Asians, 6%/4%; adenocarcinomas, 44%/42%; and 88%/88% of pts were refractory to most recent chemotherapy. With the above criteria, 70% of tumor samples were scored as positive using DAKO Ab and 68% using the Zymed Ab (agreement between assessments 76%). The objective response rates in gefitinib treated EGFR-positive pts defined with various cut points with DAKO Ab (=1% to =90%) varied between 8% and 12%, and with Zymed Ab (score =50 to =350), between 10% and 13%. Lower cut points with the DAKO Ab provided the best discrimination between EGFR positive and EGFR negative patients in terms of survival hazard ratios (HRs) comparing gefitinib to placebo, with a significant treatment/cut point interaction for the 10% cut point (p=0.049). A similar trend was noted for Zymed Ab, although the discrimination between HRs was less apparent and not significant for any cut point analyzed. Conclusion: Assessment with DAKO PharmDx kit, according to percentage of positive staining, may provide more accurate prediction of survival benefit for gefitinib-treated pts than assessment with Zymed Ab and staining index. Use of higher cut points to define positivity does not improve discrimination of the test. No significant financial relationships to disclose.