bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality-of-life (QOL) evaluation for advanced non-small cell lung cancer (NSCLC): Comparison between vinorelbine and gemcitabine followed by docetaxel (VGD), and paclitaxel and carboplatin (PC) regimen on protocol JMTO LC00–03 (BRI LC03- 01)
Authors: Tada H. , Tokoro A. , Ishiwata R. , Teramukai S. , Fukushima M. , Kubota K. , Kawahara M. , Furuse K. 
Published: March 2020

18043 Background: JMTO LC00–03, a randomized trial of VGD versus PC in patients with advanced NSCLC, showed differences between the two treatment groups in response rate (25 vs 37.1%) and regimens’ specific toxicities including taxane-related toxicities such as numbness (0 vs 16.2%) and neuropathy (0.5 vs 9.6%), but not in overall survival (MST, 13.6 vs 14.1 mos) and progression-free survival (MST, 5.5 vs 5.8 mos). (Kawahara et al, # 7013, ASCO, 2006). Methods: Patients with advanced NSCLC were randomly assigned to VGD or PC. The patients were assessed with Functional Assessment of Cancer Therapy- FACT-L and FACT-Taxane score in baseline, and at 6-, 12-, 18-weeks after the treatment. The longitudinal analysis was used to compare mean changes of the QOL score over the two treatment groups. Results: Sixty-eight patients from the trial (VGD: 34, PC: 34) who submitted both baseline questionnaire and at least one questionnaire over the course of the treatment were subjects of the study. The table presents the estimated changes in mean scores in treatment arms over the time period. The longitudinal analysis showed significant difference in FACT-Taxane (p<0.001) in the treatment over time, but no significant difference in the FACT-L score (p=0.261). The analysis assuming non-random missing mechanism resulted in slightly larger differences in the mean change. Conclusions: There was no statistically significant difference in FACT-L between the two groups, but VGD group was numerically better than PC group at any point from baseline. The significant difference in FACT-Taxane score favoring VGD would be due to the difference in frequency of neuropathy with docetaxel than with paclitaxel. [Table: see text] [Table: see text]
Smoking and prognostic factors in advanced non-small cell lung cancer (NSCLC)
Authors: Altug S. , Li C. , Marek M. , Guclu S. , Kim Y. , Meshref M. , Qin S. , Krejcy K. , Reece W. 
Published: March 2020

18048 Background: The aim of this prospective, multi-country, observational study (B9E-AA-B004) is to estimate the effect of prognostic factors, including continued smoking during therapy, on treatment outcomes in patients (pts) with advanced NSCLC receiving first- line chemotherapy with a gemcitabine (gem)-platinum combination as part of their routine care. Methods: Major eligibility criteria included: tissue diagnosis of advanced stage IIIB/IV NSCLC not amenable to curative surgery/radiotherapy; no prior chemotherapy; ECOG performance status (PS) 0 or 1; and written informed consent. A predictive model was constructed and validated by splitting the data at random by centre into two datasets in a ratio of 3:1 Construction:Validation. The primary and secondary endpoints are the effect of prognostic factors on survival and selected adverse events (AEs), respectively. The association of smoking with outcomes was tested in the Construction dataset. Results: This interim analysis to assess the effect of prognostic factors on AEs occurred when all pts had completed treatment. 1214 pts were enrolled: 75.1% male; mean age 60.5 yr, range 23–86 yr; 57.1% Stage IV; 66.2% PS 1; 69.4% received gem-cis, 30.5% gem-carb; 25.7% had never smoked, 70.8% had ever smoked and 11.2% continued smoking during therapy. 22.0% of pts had =1 AE. After variable selection in the Construction database (891 pts) the following factors were associated with an AE possibly related to therapy: disease stage (IV vs III, odds ratio (OR) =1.48, p=0.034), weight loss >10% (OR=0.60, p=0.017), age (<70 vs =70, OR=0.66, p=0.046), treatment (gem- carb vs gem-cis, OR=1.5, p=0.04), pain at baseline (present vs absent, OR=1.5, p=0.03), country (OR vs Taiwan ranged from 0.32 (Israel) to 4.2 (Egypt), p<0.0001). Sex (F vs M, OR=0.86) was then added to the model because of its clinical importance. There was a trend towards a higher probability of an AE with continued smoking during therapy (OR=1.4), but this was not statistically significant (p=0.28). Conclusions: This model can be used to improve the prediction of whether patients are likely to experience treatment-related AEs. While the trend was for a greater AE rate in pts who continued to smoke during therapy, this was not proven. [Table: see text]
A phase II study of weekly docetaxel/cisplatin and concurrent radiotherapy followed by surgery in patients with stage III non-small cell lung cancer (NSCLC)
Authors: Maas K. W. , Phernambucq E. C. , Sharouni S. Y. , Stigt J. A. , Groen H. J. , van den Borne B. E. , Senan S. , Smit E. F. , Paul R. A. , Schramel F. M. 
Published: March 2020

18050 Background: Concurrent chemoradiotherapy treatment is standard of care for patients with stage III NSCLC in good performance. Optimal chemotherapy have yet to be defined and the role of surgery is still unclear. This prospective phase II study analysed the feasibility and efficacy of weekly docetaxel/cisplatin (DC) and concurrent involved-field thoracic radiotherapy (CRT) followed by surgery in good performance status patients with stage IIIA/B NSCLC. Primary endpoint is radiological response of DC and CRT. Secondary endpoints included toxicity, efficacy of surgery, postoperative morbidity and mortality, time to progression and overall survival. Methods: DC consisted of IV docetaxel 20 mg/m2 and cisplatin 20mg/m2 at days 1,8,15,22,29 and 36. CRT was given in once-daily fractions of 1.8 Gy, 5 fractions a week to a total dose of 45 Gy during days 8 to 36. CT-based planning was used to minimise radiation to the contralateral lung. Invasive and non-invasive investigations were performed after induction treatment in order to restage the mediastinum. when mediastinal downstaging was achieved, surgery was performed in order to achieve radical resection. Results: Between January 2005 until August 2006, 45 patients were included, of whom 43 patients were evaluable. Stage IIIB disease was present in 18 patients (cT4N2=9, cT4N0/N1=5 and cN3=4) and 25 had stage IIIA-N2 disease. Radiologic response was seen in 20 patients (47%) and 8 (19%) showed progressive disease. Toxicity was mild. Explorative thoracotomy was performed in 24 (56%) patients. Of these, 14 were initially staged as IIIA and ten as stage IIIB (4 of whom had N3 metastases). Twenty patients (47%) underwent a radical resection without residual mediastinal malignant disease, and ten pneumonectomies (8 left sided) were performed. Three patients showed complete pathological response. The 30 days mortality after operation was 4% (one patient) due to ARDS. Conclusions: Weekly DC and CRT is possible in stage III NSCLC, with limited toxicity and nearly half of the treated patients (47%) could undergo a radical surgical resection (R0) without residual mediastinal malignant disease. This promising tri-modality regimen should be tested in future phase II or III trials. No significant financial relationships to disclose.
Phase I trial of extrapleural pneumonectomy [EPP], and intracavitary intraoperative hyperthermic [IOHC] cisplatin with amifostine cytoprotection for malignant pleural mesothelioma. [MPM]
Authors: Zellos L. , Richards W. G. , Capalbo L. , Jaklitsch M. , Bueno R. , Johnson B. , Sugarbaker D. J. 
Published: March 2020

18059 Background: Despite aggressive multimodality treatment, MPM remains a disease with poor survival. Innovative strategies that improve cytoreduction are needed. We sought to determine the maximum tolerated dose (MTD) and quantify the toxicity of cisplatin IOHC with amifostine cytoprotection in the setting of EPP for MPM. Methods: 42 MPM patients (pts) were enrolled in an IRB approved protocol. Those who underwent EPP with cytoreduction to < 1 cm3 received 910 mg/m2 of amifostine followed by 1-hour perfusion of the chest and abdomen with cisplatin dose escalation (75–200 mg/m2). Pts were monitored prospectively. Results: 13 pts were unresectable (9 with chest wall invasion, 3 with chest wall and mediastinal invasion and 1 with cardiac invasion). The 29 resected pts had median age 57 years; median stay 15 days, and mortality rate 6.8% (2/29 pts.). Complications were: atrial fibrillation 65.5% (19 pts.), deep vein thrombosis 31% (9 pts.), and grade 3 renal toxicity 31% (9 pts.). Renal toxicity was unrelated to cisplatin dose and no MTD was determined. Median follow-up was 17 months. Median survival (MS) for 42 enrolled pts was 17 months. The 13 unresected pts experienced a 10-month MS. The 29 resected pts had a 20-month MS while 24 epithelial pts experienced a 29-month MS and 5 non-epithelial pts 13 month MS (p=0.006). The 15 pts receiving higher cisplatin doses (175–200 mg/m2) had a 26-month MS while the 14 pts receiving lower doses (75–150 mg/m2) had 16-month median survival. (p=NS) The 10 pts with negative margins has a MS of 25.8 months while 19 pts with positive margins had a 13.4 month MS (p=NS). MS for 20 pts with N2 (-) nodes was 30 months and for 9 pts with N2 (+) 13 months (p= 0.0115). MS for 18 pts with BWH/DFCI stage 1–2 was 32 months and for the 11 stage 3 pts 14 months (p=0.0022). Conclusions: 1) IOHC was technically feasible with acceptable morbidity and mortality 2) Single dose amifostine was inadequate against cisplatin renal toxicity and MTD was not determined. 3) Stage 1–2, epithelial type or N2 (-) pts demonstrated survival greater that expected historic controls. No significant financial relationships to disclose.
Combined evaluation of Rad51 and ERCC1 expressions for sensitivity to platinum agents in non-small cell lung cancer (NSCLC)
Authors: Yoshino I. , Takenaka T. , Koso H. , Ohba T. , Yohena T. , Osoegawa A. , Shoji F. , Maehara Y. 
Published: March 2020

18085 Background: DNA repair enzyme expression in tumor cells possibly affects sensitivity to anti-cancer agents. The aim of this study was to determine the relationship between expression status of DNA repair proteins and chemosensitivity in patients with NSCLC. Rad51 and ERCC1 play important roles in repair of double and single strand breaks of DNA, respectively, and may protect cells from cytotoxic effect of platinum agents. Methods: NSCLC tissues prepared from the surgical specimens of 41 patients were subjected to an immunohistochemical analysis for Rad51 and ERCC1 proteins and to a chemosensitivity test using the MTT assay. The relationships between the expression status of the DNA repair enzymes and ex vivo chemosensitivity to various agents were evaluated. Results: A positive expression for Rad51 and ERCC1 was observed in 17 cases (41%) and 20 cases (49%), respectively. The positivity of Rad51 was closely related to a certain histologic type of squamous cell carcinoma and poor differentiation, and the positivity of ERCC1 tended to be related to squamous cell carcinoma. In chemosensitivity tests, sensitivities to CDDP and CBDCA were significantly lower when both two enzymes were positive (p = 0.012 and 0.04 in CDDP, 0.014 and 0.03 in CBDCA), but not when either or neither of them was positive. Both Rad51 and ERCC1 expressions showed no significant relationship with sensitivities to paclitaxel, etoposide, vinorelbine, gemcitabine, 5-FU, or irinotecan. Conclusions: Combined expression of Rad51 and ERCC1 is associated with resistance to platinum agents in the ex vivo study of clinical NSCLC, and evaluation of expression status of both DNA repair enzymes would be a predictor for clinical response to platinum-based chemotherapies. No significant financial relationships to disclose.
A population-based study of incidence, diagnostic approaches and therapy of thymic epithelial tumors
Authors: Schaapveld M. , De Jong W. K. , Timens W. , Klinkenberg T. J. , Blaauwgeers J. L. , Groen H. J. 
Published: March 2020

18086 Background: Diagnostic and therapeutic approaches to thymic epithelial tumors are not standardized. Also, opinions differ on the biological behavior of thymomas. The purpose of this population-based study was to assess the incidence of the whole spectrum of thymomas and thymic carcinomas and to assess the diagnostic approaches, therapy, and survival of these tumors. Methods: The Dutch National Pathological Archives (PALGA) were used to evaluate the incidence of thymomas and other thymus neoplasms between 1994- 2003. Clinical and pathological characteristics were obtained from PALGA and the Netherlands Cancer Registry. Results: We identified 537 thymic epithelial tumors, male/female 262/275, median age 59 years (range 1–94). WHO classification was type A 12%, AB 21%, B1 16%, B2 18%, B3 12%, C 11%, unknown 10%. Clinical disease stage according to Masaoka was I in 26%, II 23%, III 13%, IV 12%, unknown 26%. Incidence of all thymic epithelial tumors in the Netherlands is 3.2/1,000,000 and of thymomas (WHO classes A-B2) is 2.2/1,000,000. Primary resection as first procedure for obtaining a diagnosis was performed in 56% of patients, and was associated with smaller tumors (p<0.001), younger age (p=0.006), and the presence of myasthenia gravis (p<0.001). Survival data were available for 232 patients. Five- year overall observed survival was 69%. Not only thymic carcinomas but also thymomas showed tumor-related mortality. The majority of patients (78%) was treated with resection, and had a better survival than non-operated patients (median survival more than 10 years versus 1.1 years, p<0.001). Among the surgically treated patients (n=180), the completeness of resection was not prognostic (p=0.17). Conclusions: Thymic epithelial tumors are rare and the majority shows tumor-related mortality. Primary resection is the most frequently used procedure to obtain a definite diagnosis and is also advisable in cases with questionable resectability. No significant financial relationships to disclose.
The efficacy of second line chemotherapy (CHT) in platinum-sensitive advanced/metastatic small cell lung cancer (SCLC) patients: Results of an ongoing Italian multicenter survey
Authors: Martelli O. , Cinquini M. , Mancuso A. , Borgonovo K. , Petrelli F. , Sergi C. , Paleari D. , Fatigoni S. , Sdrobolini A. , Aglione S. 
Published: March 2020

18090 Background: Despite CHT and radiotherapy for SCLC, most patients (pts) die within 2 years. Response rates for second-line CHT are low, with a median survival of 5 months in platinum-refractory pts. Re-challenge with platinum salts or salvage regimens is a standard option for pts with platinum-sensitive disease with a median overall survival (OS) of 6.5–8 months (Chua et al., Cancer Treat Rev. 2004). The purpose of this study was to explore the benefits of different second line regimens in this platiunum sensitive population. Methods: Clinical records of 73 platinum sensitive SCLC pts (first line relapse free survival > 6 months) were reviewed from 13 medical oncology departments in Italy from January 1993 to December 2006. Pt. characteristics: 59 males, 14 females, median age 64 years (range 27–93), median ECOG performance status (PS): 1, limited/extended disease: 33/40 pts. Pts received salvage chemotherapy which consisted of monotherapy in 37% and platinum-containing doublets in 55%. Doublets without platinum salts were administered in the remaining 8%. Results: Of 67 evaluable pt, second line CHT produced partial responses (PR) in 58 (79%) and stable disease (SD) in 9 pts (12%) by RECIST criteria. Overall tumor growth control (PR+SD) was 91%. Despite these encouraging results, the median TTP was 3 months and OS for all evaluable pts was 6.5 months. Survival at 1 year was 11%. Multivariate analysis revealed that the most important prognostic factor for response was age ( p<0.04) and there was no statistically significant difference between platinum-based regimens and monotherapy. Multivariate analysis showed no impact on survival by prior response to first line treatment, female sex or smoking status. Conclusions: Within the limits of a retrospective study, despite the high rate of responses obtainable in this setting, TTP and OS do not appear significantly improved by salvage regimens. Second line CHT has marginal activity and should be considered only in younger pts with a good PS. On the basis of these results, re-treatment with platinum salts could be avoided in these pts. No significant financial relationships to disclose.
A phase II trial of combination chemotherapy with irinotecan and amrubicin in pretreated patients with non-small cell lung cancer
Authors: Segawa Y. , Nogami N. , Shinkai T. , Kiura K. , Tabata M. , Takigawa N. , Hotta K. , Shibayama T. , Ueoka H. , Tanimoto M. 
Published: March 2020

18111 Background: Amrubicin, a totally synthetic anthracycline, is a topoisomerase II inhibitor and highly effective for non-small cell lung cancer (NSCLC) as a single agent with response rates of 25% to 28%. We previously conducted a phase I trial of combination chemotherapy with irinotecan and amrubicin for NSCLC and found acceptable toxicity profiles with a favorable efficacy in patients with pretreated NSCLC. The aim of this phase II trial was to further evaluate its efficacy and toxicity in this population. Methods: Primary endpoint was objective response. Patients with NSCLC previously treated with one or two chemotherapy regimens were enrolled in this trial. Irinotecan and amrubicin were both administered on days 1 and 8, every 3 weeks at doses of 100 and 40 mg/m2, respectively. Response and toxicity were assessed according to the RECIST guideline and NCI Common Terminology Criteria for Adverse Events v3.0. Results: Thirty-one pretreated NSCLC patients were enrolled between 2004 and 2006. A median number of courses administered was 3 (range: 1 to 6). All patients and courses were assessable for efficacy and safety. Demographics of the patients were as follows: M/F: 21/10, Ad/others: 21/10, ECOG-PS 0/1: 12/19, and smoker/non-smoker: 21/10. Platinum-based regimens were commonly used as the prior chemotherapy. Objective response was obtained in 9 of the 31 patients with a response rate of 29.0% (95%CI: 12.1–46.0%). Grade 4 leukopenia and neutropenia were observed in 6 (19%) and 14 (45%) patients, respectively, whereas thrombocytopenia were generally mild. Grade 3 febrile neutropenia was observed in 7 patients (23%), of whom two patients further developed Grade 4 and 5 septic shock each. Other grade 3 or greater non-hematological toxicities included diarrhea, vomiting, pneumonitis, liver dysfunction in 4, 1, 1 and 2 patients, respectively. At the time of this analysis with a median follow-up time in the surviving patients of 7.5 months, median survival time and median progression-free survival time were 11.9 and 4.0 months, respectively. Conclusion: This combination seemed highly effective for pretreated NSCLC despite the moderate toxicity profiles. Development of efficient patient selection is needed to avoid the serious toxicities. No significant financial relationships to disclose.
Retrospective review of stage III non-small cell lung cancer (NSCLC) patients treated with carboplatin/paclitaxel plus radiotherapy followed by docetaxel
Authors: Patel M. R. , Weidner M. , Lynch J. W. , Walden E. , George T. J. 
Published: March 2020

18123 Background: Concurrent chemoradiotherapy is standard of care for unresectable patients and the most widely cited trials include the locally advanced multi-modality protocol (LAMP) study, SWOG S9019 and S9504. Our institutional approach represents a merger between the protocols utilized in two of these phase II studies: chemoradiotherapy from the LAMP study and consolidation therapy from SWOG S9504. Methods: We identified all stage III patients treated at the NF/SG VHS from Jan 2001 to Dec 2005. Eligible patients who had unresectable stage III NSCLC were included in the analysis. We treated 34 patients with weekly paclitaxel 45 mg/m2 plus carboplatin AUC 2 and concurrent TRT 63.0 Gy over 7 weeks. Four weeks after the completion of chemoradiotherapy, docetaxel 75 mg/m2 was given every 3 weeks for 21 days for 3 cycles as consolidation. Our primary endpoints were overall and progression free survival. The secondary endpoints were response rate and toxicity. Results: With a median age of 65 years and follow-up time of 25.9 months, median overall survival was 13.7 mos. Median progression free survival was 9.8 mos. The overall response rate was 68% including 5 CRs (15%). The most common grade 3/4 toxicities included pneumonitis (21%), esophagitis (21%), neutropenia (21%) [febrile neutropenia (9%)], neuropathy (18%), anemia (15%) and hypersensitivity to paclitaxel (9%). 62% of patients were able to complete the planned treatment. There were no treatment related deaths. At the time of this analysis, 9 patients were alive (26%) including 7 without progression (21%). Conclusions: Chemoradiotherapy with weekly carboplatin and paclitaxel followed by consolidation therapy with docetaxel is associated with comparable outcomes to other combined modality regimens. Given the advanced age and co-morbidities of our population, this regimen was generally well tolerated with the expected toxicities and can be considered as an option in the treatment of patients with unresectable stage III NSCLC. No significant financial relationships to disclose.
Effects of dexamethasone (Dex) pretreatment on toxicity and efficacy of carboplatin and gemcitabine (Carbo/Gem) in patients with non-small cell lung cancer (NSCLC)
Authors: Leggas M. , Kuo K. , Cloud G. , Li M. , Wang H. , Zhang R. , Robert F. , Rinehart J. J. 
Published: March 2020

18124 Background: Our preclinical data showed that treating mice with Dex 4 days prior to chemotherapy increased efficacy and decreased toxicity of Carbo/Gem in nude mice bearing human NSCLC by increasing drug concentration in tumors, and decreasing drug concentration in normal tissue without altering plasma pharmacokinetics (PK). Thus, we undertook a Phase I/II trial to determine the optimal dose of Dex, and the effect of Dex on Carbo/Gem plasma PK. Methods: Patients (n=30) with untreated, stage IV NSCLC and PS =2 received Gem, 1g/m2 days 1&8, and Carbo, AUC 5.5 on day 1. Patients were randomized (1:2:2) to receive no Dex (arm 1), or Dex at 8 and 16 mg bid po 4 days before and on day 1 (arms 2 and 3). Dex was administered in courses 2, 3, and 4 (only) to allow course 1 vs course 2 intra-patient toxicity and Carbo/Gem plasma PK assessment. Plasma samples were analyzed by HPLC for Carbo/Gem. Plasma PK analysis was performed with NONMEM v5 using a 5-compatment or 2-compartment structural models for Gem and Carbo. Results: Patients in arms 1, 2, and 3 were similar in PS, age, gender, and histology. In arms 1, 2, and 3, patients completing 4 planned courses of therapy: 1/6, 6/12, 9/12; partial responses (RECIST): 2/6, 7/12, and 8/12. Hematologic toxicity in arms 1 (no Dex), 2, and 3 (Dex) was compared. Platelet nadirs (course2÷course1): 0.6±0.2, 3.77±2.0, 3.4±0.72 (p<0.02); AGC nadirs: 1.1±0.3, 2.32±0.4, 4.95±1.04 (p< 0.01); Change in median time to recovery from day 1 (course 2-course 1) of AGC to 1,500 mm3 in days: +9, -15, -19; Change in median time to recovery of platelets to 100,000 mm3: +5, -1, -1.5. Comparison of nadir AGC and platelets between courses 2, 3, and 4 consistently demonstrated superiority of arm 3 over arm 2. No significant differences in non-hematologic toxicities were seen between arms 1, 2 and 3. Gem and Carbo clearance values were not significantly different among arms or courses. Area under the time-concentration curves (course2÷course1): 0.91±0.18, 0.77±0.15, 0.80±0.16. Conclusions: Dex pretreatment appears to reduce toxicity and improve efficacy of Carbo/Gem in NSCLC patients, with arm 3>2. These effects are not due to alteration of plasma PK since no significant decrease in chemotherapy exposure was observed in arms 2 and 3. [Table: see text]