bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined modality therapy with carboplatin, irinotecan and radiation therapy followed by consolidation docetaxel for patients with stage III NSCLC
Authors: Raez L. E. , Roman E. , Negret L. , Takita C. , Lobo C. , Kummar P. , Lopes G. , Farfan N. , Karr M. , Rocha-Lima C. 
Published: March 2020

17088 Background: Irinotecan (I) has an active role and potential as a radiosensitizing agent in patients with NSCLC. SWOG 9504 established the concept of “consolidation” chemotherapy with 3 cycles of docetaxel (D) after chemo/radiation (CRXT). We evaluated the efficacy and safety of administering weekly doses of carboplatin/irinotecan (CI) concomitantly with radiation therapy followed by D chemotherapy for patients (pts) with stages IIIA/B NSCLC. Methods: We have enrolled 23 pts, treatment included: C: (AUC = 2) and I: 30 mg/m2, weekly concomitant with radiation therapy, and D: 75 mg/m2 every 3 weeks for 3 times after CRXT was finished. The daily administered dose of radiation was 1.8 Gy, 5 days a week for 5 weeks, 25 fractions, (45 Gy) to the primary tumor and mediastinum (primary planning target volume: PPTV. After 45 Gy, the primary tumor and involved nodal metastasis (secondary planning target volume: SPTV) was boosted at 2 Gy per day to 18 Gy in 9 fractions. The total dose given was 63 Gy in 35 fractions over seven weeks. Evaluation of response has been done with RECIST criteria. Results: Median age is 55 years (range: 42–78), 18 (78%) of the pts are female, 17 (74%) are white, 13 (57%) are Hispanic, and 14 (65%) had an ECOG 1. Most common histologies are poorly differentiated and squamous cell carcinomas: 14 pts (61%), and half of the pts are stage IIIB. 111 weeks of CI and 39 cycles of D have been administered and we have documented 22 grade 3/4 adverse events (AE) among them: 4 pts pneumonia (17%), 3 pts radiation pneumonitis (13%), 2 pts: dehydration o neutropenia o dyspnea (9%) and 1 pt with diarrhea, nausea and vomiting (4.5%). No grade 4 neutropenia, esophagitis or diarrhea was reported. 12 severe AE were reported including: 2 pts with pneumonia (9%), 2 pts with dehydration (9%), and 2 pts with radiation pneumonitis (9%) requiring hospitalization. The rest of SAE were unrelated to therapy. Data for response is available in 18 pts. A partial response was seen in 10 pts (56%), and stable disease in 6 pts (33%). 2 pts are ineligible for response. Median survival (and PFS) has not been reached and it will be presented in the meeting. Conclusions: CI administered with radiation therapy and followed by D is safe and efficacious in the treatment of stage III NSCLC. [Table: see text]
Biweekly schedule of cisplatin with prolonged infusion of gemcitabine in advanced non small cell lung cancer (NSCLC)
Authors: López-Vivanco G. , Rubio I. , Mañé J. , Viteri A. , Ancizar N. , Muñoz A. , Barceló R. , Fuente N. , Ruiz de Lobera A. , López-Argumedo G. 
Published: March 2020

17093 Background: Firstly, we conducted a phase I of a biweekly schedule of cisplatin with prolonged infusion of gemcitabine (10 mg/m2/min) and stablished the dose to perform a phase II. We present final results of a phase II with this combination. Methods: Patients with cytologically or histologically confirmed NSCLC stage IIIB and IV were included. Treatment consisted of Cisplatin 50 mg/m2 days 1 and 15 with Gemcitabine 1600 mg/m2 in 160 minutes (10 mg/m2/min), days 1 and 15 every 28 days. Chemotherapy was administered to a maximum of 6 cycles; if radiotherapy was planned, patients received 4 cycles. Results: From March-04 to January-05, 55 patients were included. Patient characteristics: Median age 59 years (35–75). Gender: 51 male 4 female. ECOG performance status 0/1/2: 8/43/4. Histology: Squamous cell carcinoma 26 (47.3%), adenocarcinoma 22 (40%), large cell carcinoma 2 (3.6%), undifferentiated 5 (9%). Stage: IIIA 2 (3.6%), IIIB 27 (49.1%) and IV 26 (47.3%). Treatment compliance: Administrations: Mean 6.7 and median 8 (1–12). Dose intensity: Cisplatin 20.35 mg/m2/week (81%) Gemcitabine 632.61 mg/m2/week (79%). Toxicity: Extrahematological toxicity grade 3/4 per patient: nausea 10/0, emesis 6/0, asthenia 31/1, anorexia 14/0, mucositis 1/0, diarrhoea 1/1, infection 4/0, hepatic 2/0, vascular 0/1 (pulmonary thromboembolism). Neurotoxicity grade 1, 13 pt and grade 2, 1 pt. Hematological toxicity grade 3/4: anemia 1/0, thrombocytopenia 5/1, neutropenia 21/9 and neutropenic fever 4/0. Nine patients were hospitalised due to toxicity. There was one toxic death. Response rate: Response was evaluated in 52 pt (3 pt died after first cycle). Overall response rate was 38.1% (95% CI 50.93–25.26%). Complete response 2 (3.6%), Partial response 19 (34.5%), Stable disease 23 (41.8%), Progressive disease 8 (14.5%). Survival: Overall median survival was 9.6 months (95% CI 7.76–11.43): stage III 10.46 and stage IV 8.8. Overall progression-free survival was 8.06 months (95% CI 5.95–10.18): stage III 8.9 and stage IV 6.3. Conclusions: Biweekly cisplatin with prolonged infusion of gemcitabine is an active regimen for advanced NSCLC with a good toxicity profile. This better rational way of gemcitabine infusion should be more profoundly explored. No significant financial relationships to disclose.
Gemcitabine (G) and vinorelbine (V) in patients (pts) with recurrent advanced non-small cell lung cancer (NSCLC): Sequence of administration matters
Authors: Juergens R. , Brahmer J. R. , Ettinger D. 
Published: March 2020

17101 Background: G and V have demonstrated clinical efficacy as single agents and in combination in pts with metastatic NSCLC. Methods: This single-institution, prospective, phase II trial evaluated a biweekly combination of G and V in NSCLC pts who had received 1 prior chemotherapeutic regimen and had disease progression. Eligibility criteria included: Age ≥ 18; PS ≤ 2; and adequate organ function. Pts with stable brain metastases were allowed. A Simon two-stage design specified enrollment of 15 evaluable pts in stage I. If 1 response was seen, 20 more pts would be enrolled. The power of this study to detect an increase in response from 10% to 30% was 90% with a two-sided alpha of 5%. G (1200 mg/m2 IV over 30 min.) was followed by V (30 mg/m2 IV over 6–10 min.) on days 1 and 15 of each 28 day cycle. Chemotherapy was given for 6 cycles unless disease progression or unacceptable toxicity was seen. Results: From 11/1998 to 10/2000, 15 of 20 pts enrolled (6 males, 9 females) were evaluable for response. Two pts had grade 4 neutropenia, and 1 pt had grade 4 thrombocytopenia. The only non-hematologic grade 3 toxicities were fatigue, phlebitis, and arthralgias. No objective responses were observed, but 11 pts had stable disease for a mean of 6 mos. The median survival time was 9.4 mos (95% CI = 4.2, 14.8), with a median time to progression of 4.2 mos (95% CI = 1.9, 5.6). The one year survival was 47%. Conclusions: While this schedule of GV was well tolerated, it was felt to be inactive. In vitro and pharmacokinetic studies published after the completion of our trial, suggest G followed by V may have antagonistic effects leading to lower dose delivery of both drugs. Our study was the only study of GV in 2nd-line NSCLC in the literature (n = 6) without an objective response. Our study, as well, was the only 2nd-line study that administered G prior to V. 1st-line studies in the literature (n = 12) that administered V prior to G had, on average, a 1.7 month higher median survival (10.0 vs 8.3 mos) which was statistically significant (p-value < 0.001). Based on this data, sequence of GV should be a consideration in future clinical trials. Because of the lack of response, further studies using this drug sequence, dose, and schedule for GV are not recommended. [Table: see text]
Gefitinib-induced cell death in short term fresh tumor cultures predicts for long term patient survival in previously-treated non-small cell lung cancer
Authors: Weisenthal L. 
Published: March 2020

17117 Background: Gefitinib (GEF) may act by inhibiting anti-apoptotic signals transduced by mutant EGFR kinase (Science 305:1163,04). Cell culture assays with cell death endpoints could be informative for GEF activity. Methods: We tested 568 biopsies of fresh human tumors (TUM) with 2 concentrations of GEF (22 and 11 μg/ml) for 96 hrs, each with 2 separate cell death endpoints (DISC and MTT), detailed methods http://weisenthal.org/w_ovarian_cp.pdf . Results classified as resistant (RES), intermediate (INT), or sensitive (SEN) based on means and standard deviations of training set data (ref ibid), reported prospectively to 3 different physicians: surgeon, pathologist, and oncologist. Assay evaluability rate > 90%. Results: Based on overall % control cell death, the following TUM showed (on average) no greater RES or SEN than the universe of 568 assays: NSCLC (n = 72), colon (33), breast (106), ovarian (109), melanoma (23), pancreatic (20), endometrial (12). The following showed (on avg) significantly greater RES: soft tissue sarcomas (n = 24), carcinoid/islet (16), renal (15), and mesothelioma (8). For NSCLC, there was no avg difference between female (32) vs male (35) or untreated (34) vs previously treated (38). For 32 unRxd pts with survival data, there was no significant difference in overall surv for 20 pts with prospectively reported GEF RES (GR) assays vs 12 pts with SEN or INT (GSI) assays. For 31 pts with prior chemoRx (med surv = 155 days), there was significant survival disadvantage for 14 pts with prospectively reported GR vs 17 pts with GSI (median 85 vs 380 days, P2 < 0.0001, HR 3.7; 95% C.I. 2.6–19). For pts with known post-assay Rx, there were 7 pts with GSI subsequently receiving GEF or erlotinib (ERLOT), with med surv = 485 days; 9 pts with GSI not receiving GEF or ERLOT, med surv = 135 days; 10 pts with GR not receiving GEF or ERLOT, med surv = 76 days, and 3 pts with GR receiving GEF or ERLOT, med surv = 75 days. Survival of group of 7 pts was significantly greater than those of groups of 9, 10, and 3 pts (P2 = 0.02, P2 < 0.0001, and P2 = 0.002, respectively). Conclusions: GEF-induced cell death in cultures of fresh TUM from prev-treated NSCLC pts may identify pts with favorable prognosis, particularly when treated with GEF or ERLOT. [Table: see text]
Interim analysis of the triplet association cisplatin (P), gemcitabine (G) and vinorelbine(V) for advanced small cell lung cancer (SCLC)
Authors: Eyll B. M. , Pereira J. R. , Yamaguchi J. Y. , Arruda M. T. , Feio F. S. , Costa C. M. , Melo M. A. , Rangel J. E. , Santana A. P. , Almeida C. 
Published: March 2020

17125 Background: Small cell lung cancer (SCLC) is an aggressive disease characterized by rapid growth and early metastasis. Actually, the treatment of choice for advanced SCLC is cisplatin combined with etoposide. For these patients 9 to 12 months are the expected survival, overall response is 61%–78 % and complete response rate is 10%–14%. Despite of these results 5 years overall survival is less than 5% justifying the search for more effective treatment scheme. Methods: Fourteen patients were analyzed between January and October 2005. They received Cisplatin 80 mg/m2 d1, Gemcitabine 1,500 mg/m2 d1 and Vinorelbine 30 mg/m2 d1, every 3 weeks. The response was evaluated by chest X-ray after each cycle. Thorax CT was performed at beginning and end of treatment. Results: Patients received 2–6 cycles (median = 3.78 ); KPS was 50%–90% (median 80%); median age 57 yrs (range 21–75). Thirteen patients had objective response (92.8%), 4 complete response (28.6%) and 9 partial response (64.3%). Non-hematological grade (G) 3–4 toxicity consisted of nausea and vomiting (28.6%); anorexia (42.8%); neurotoxicity (14.5%). Only one patient (7.1%) had neutropenia G3 and another subject (7.1%) had thrombocytopenia G3. There were no febrile neutropenia cases. Conclusions: Although a large study should be performed to confirm these results, PGV association shows promising activity in SCLC patients. Toxicity profile was very favorable too. [Table: see text] No significant financial relationships to disclose.
Comparison and analysis among expression of CRP and tumor markers in advanced non-small cell lung cancer patients
Authors: Dong W. , Ren X. , Liu P. 
Published: March 2020

17126 Background: To investigate the correlation of C-reactive protein (CRP) and tumor markers such as carcinoembryonic antigen (CEA), CA125, cytokeratin 19 antibody (Cyfra 21–1) in non-small cell lung cancer (NSCLC) patients. Methods: CRP, CEA, CA125, Cyfra 21–1 were measured in the serum of 79 patients with advanced non-small cell lung cancer (stage III and IV ) by independent samples t test. Results: It showed statistically significant difference (P < 0.05) in the level of CRP, CEA, CA125, Cyfra211 between lung cancer patients (25.21 ± 19.12 mg/L, 62.89 ± 53.96 ng/L, 46.36 ± 30.03 U/L, 6.85 ± 2.42 ng/L, respectively) and the control subjects. CRP, CA125 showed no significant difference between squamous carcinoma and adenocarcinoma (P = 0.832, 0.406, respectively). CEA was higher in adenocarcinoma than in squamous carcinoma (P = 0.002). Cyfra211 was lower in adenocarcinoma than in squamous carcinoma (P = 0.039). The increase of CRP was accompanied with the increase of CEA, CA125 and Cyfra211 (p < 0.05). At the same time, CRP elevated while CEA, CA125, Cyfra211 increased (p < 0.05). Conclusions: All of CRP, CEA, CA125 and Cyfra211 increased in advanced non-small lung cancer. Combined monitoring on CRP with CEA, CA125, Cyfra211 may be a complementary method in advanced non-small cell lung cancer patients. No significant financial relationships to disclose.
Efficacy and tolerability of gemcytabine plus docetaxel in patients with locally advanced or metastatic adenocarcinoma of the lung
Authors: Krzakowski M. , Kowalski D. M. , Zajda K. , Denisso T. , Jaskiewicz P. , Lasota W. , Janowicz-Zebrowska A. 
Published: March 2020

17134 Background: Chemotherapy prolongs survival of patients with advanced non-small cell lung cancer (NSCLC). Subanalysis of a phase III trial suggests better outcome of treatment with platinum and gemcytabine containing combinations in patients with adenocarcinoma. Also docetaxel is active in NSCLC. The aim of this phase II trial was to wvaluate the efficacy and tolerability of third generation doublet (GCB and DXL) in cheminaive patients with advanced adenocarcinoma of lung. Methods: Chemonaive patients with biopsy proven stage IIIB or IV adenocarcinoma of lung not suitable for curative radical treatment witk KPS 80–100 received 2 to 6 chemotherapy cycles (DXL 80 mg/m2 day 1 plus GCB 1000 mg/m2 day 1 and 8; every 21 days). Response rate and tolerability were the primary endpionts, while the overall survival and 1-year survival were secondary objectives. Results: Twenty eigth patients (15 women, 13 men) with median age 59,04 (range 40–74) were treated. Twenty three patients was analysed. Stage IV was found in 23 (95.8%) and stage IIIB in 1 (4.2%) patients. Partial response was achiwed in 9 (37,5%), stable disease in 12 (50%) and pregressive disease in 3 (12,5%) patients. Median time to progression was 8, 37 months (range: 1.5–14 months). Median overall survival was 12,87 months (range: 4–35 months). Eleven (11) patients received second-line therapy (6-RT, 11-CTH). All patients received 94 cycles of chemotherapy (range: 2, median 3,9). Total dose of docetaxel on each patients was fro 120 to 960 mg (median 556 mg). Total dose of gemcytabine on each patients was from 2100 mg to 21000 mg (median 10475 mg). Treatment toxicicy presents on the table . Conclusions: First line gemcytabine and docetaxel containing chemotherapy is effective palliative treatment for patients with advanced AC of the lung. Toxicity was within acceptable limits. [Table: see text] No significant financial relationships to disclose.
Promising results of multi-intensified treatment of small-cell lung cancer (SCLC)
Authors: Brodin O. , Lamberg K. , Anjedani D. , Lödén B. , Henriksson R. , Wagenius G. 
Published: March 2020

17135 Background: In spite of the obvious chemosensitivity of SCLC only 10–15% of patients with limited disease (LD) live for 5 years and hardly any of those with extensive disease (ED). Intensification of treatment has not got a break-through, though there are studies demonstrating an improved survival from shortened intervals, three drugs instead of two and higher doses at first treatment. We have performed a study combining these three ways of treatment intensification. Methods: Patients with confirmed SCLC, in performance status 0–2, below 76 were included in a randomized phase II study. Randomisation was performed between standard treatment (S): Carboplatin 6 AUC day 1 and Etopside 100 mg/m2 day1–3, 6 courses with 3 weeks intervals. Radiotherapy was given with 1.5 Gy bid to 45 Gy in patients with LD starting simultaneously with course 2. And between intensified treatment (I): Ifosfamide 5000 mg/m2 day 1 at first course, 3000 mg/m2 at courses 2–6 and Carboplatin and Etoposide as in the S-group. Six courses were given with 2 weeks interval which was possible by giving G-CSF (Neupogen) day 4 of each course. A dose escalation schedule, if low effect on bone-marrow was applied in the I-group. Radiotherapy was given as in the S-group. Results: Forty-two patients were included during three years. Inclusion rate, however, decreased spontaneously, and the inclusion was stopped. Twenty-four patients had ED and 18 LD. After four years follow-up 4/7 (57%) LD patients are still alive without disease in the I group and 3/11 (27%) in the S group, of which 1 has relapsed. In the ED patients 1/11 (9%) is alive without disease in the I group and 0/13 in the S group. Conclusions: The low number of patients does not permit any firm conclusion concerning survival even if the results are promising. Intensified treatment in this way is feasible even if mainly thrombocytopenia and fatigue are problems in the I group. No significant financial relationships to disclose.
Pertinence of sequential use of gemcitabine and irinotecan following docetaxel and cisplatin for non operable non small cell lung cancer
Authors: Nouyrigat P. , Madroszyk A. , Audigier-Valette C. , Escarguel B. , Andreotti D. , D’Amore D. , Marqueste L. , Tchiknavorian X. , Cals L. 
Published: March 2020

17138 Background: The objective of the study is to determine if the switch to a gemcitabin (G) and irinotecan (I) is efficient after low efficacy of a docetaxel (D) and cisplatin (C) regimen for advenced non small cells carcinoma (NSCLC). Methods: Eligible patients were above 18 years old and under 75, with stage IIIb or IV NSCLC. No previously chemotherapy, WHO = 0, 1, 2 under 60 and WHO = 0, 1 under 60. mesurable target. Treatment D and C = 75 mg/m2 were given wekks 1, 4 and 7. After evaluation on week 10: in case of objective response 3 more cycles of DC were administred, if not a switch was performed with G 1000 mg/m2 and I 100 mg/m2 given as 90 minutes infusion J1-J8 every 3 weeks before a new evaluation after 3 cycles. Results: 21 patients entered the study, median age 57 (37–74). Stage IIIb = 8, IV = 13. Efficacy: we observed 8 patients with objective response (38%). Among 13 patients without an objective response after 3 DC only 4 patients received the switch treatment of GI. We found no new objective respons among them. Conclusions: For non responsive NSCLC patients to docetaxel-cisplatin regimen the treatment by gemcitabin-irinotecan does not seem relevant. No significant financial relationships to disclose.
A phase I study of weekly topotecan and vinorelbine in recurrent lung cancer
Authors: Beldner M. A. 
Published: March 2020

17140 Background: Topotecan is a topoisomerase I (topo I) inhibitor that directs cytotoxic effects by stabilizing the topo I-DNA complex. Alone, topotecan has shown activity in extensive small cell lung cancer (SCLC). Vinorelbine is a vinca alkaloid, which interacts with tubulin and disrupts microtubule function exhibiting cytotoxic effects, and has demonstrated activity in both non-small cell lung cancer (NSCLC) and SCLC. The rationale for using the agents in combination therapy is based upon their single agent activity and published preclinical data demonstrating synergy with topo I inhibitors and mitotic spindle poisons. Previous trials using topotecan weekly demonstrated less myelosuppression and equivalent anti-tumor activity. In this phase I study, we evaluated the safety profile of escalating doses of topotecan and a fixed dose of vinorelbine. Methods: Patients (pts) with recurrent NSCLC or SCLC were enrolled. Vinorelbine was delivered as 20mg/m2 on days 1 and 8, every 21 days. Topotecan was initiated at 2mg/m2 given on the same days. If there was no dose limiting toxicity (DLT) in each 3 person cohort, then topotecan was incrementally increased by 0.5mg/m2. Tolerability was assessed prior to each cycle. Responses were assessed after two cycles. Pts were taken off study for disease progression or unacceptable toxicities. Results: To date 12 pts have been enrolled (10 NSCLC, 2 extensive SCLC). Average ECOG performance status was 0–1 (11 pts 92%). Patients were heavily pretreated, this representing on average 2nd to 4th line therapy. Cohorts 1–3 had no DLT. In each cohort there were dose delays for grade 2 and 3 neutropenia and thrombocytopenia. Cohort 4 enrolled 3 pts with a DLT of grade 4 neutropenia observed in 1 pt. Nonmyeloid toxicities included nausea (42%), fatigue (33%), and constipation (17%). In cohorts 1–3, no CRs or PRs were seen. SD was observed in 6 pts (67%), with a median duration of 11 weeks. Response rates for cohort 4 are not yet assessed. Conclusion: Results of this ongoing phase I trial indicate that weekly vinorelbine and topotecan x 2 every three weeks was fairly well tolerated with grade 4 neutropenia being the primary DLT. The best response achieved in assessable pts was SD. Once the MTD has been established, a phase II study examining this regimen in advanced SCLC and NSCLC will be performed. No significant financial relationships to disclose.
High efficacy of paclitaxel (P), carboplatin (C) and concurrent thoracic radiation therapy (TRT) for locally advanced non-small cell lung cancer (NSCLC)
Authors: Kishi K. , Okazaki A. , Takaya H. , Miyamoto A. , Sakamoto S. , Kawabata M. , Tsuboi E. , Homma S. , Yoshimura K. 
Published: March 2020

17143 Background: Combined modality therapy with P, C and radiation for locally advanced NSCLC is active, but its clinical data are limited in Japan. The aim of this study is to evaluate feasibility and efficacy of the therapy in a Japanese general hospital. Methods: Patients with previously untreated and locally advanced NSCLC with stage IIIA and IIIB (PS 0–1, weight loss less than 5% over past 3 months) were treated with P (40 mg/m2 on days 1,8,15, 22, 29, 36, 43), C (AUC 2 on days 1,8,15, 22, 29, 36, 43) and TRT (66 Gy/33fr over 6.5 weeks starting on day1). Results: Fifteen evaluable patients entered this study between December 2001 and March 2005. They were 12 males, 3 females, with median age 67 (57–76); 6 patients with ECOG PS 0, 9 with PS 1, 8 with stage IIIA, and 7 with IIIB. Chemotherapeutic agents were administered a median of 6 cycles (4–7) and 66 Gy of TRT done in 14 patients. It achieved 13 PRs, 1 SD and 1 PD with a response rate of 86.7%. Survival was 85.5% at 1 year, 66.0% at 2 year and 66.0% at 3 year. Eleven patients are still alive. A relapse occurred in 10 patients (66.7%) and 5 were disease-free (33.3%). The site of first relapse was distant in 5 patients, local in 3, and both local and distant in 2. Toxicity was mild: grade 3 neutropenia in 2 patients, grade 3 nausea in 1, and grade 3 esophagitis in 1. No grade 3/4 pneumonitis was observed. After completion of chemoradiotherapy scheduled, 2 patients received additional chemotherapy of PC and 1 underwent lobectomy. Conclusion: Although the number of patients is small in this study, concurrent PC and TRT for locally advanced NSCLC is feasible and highly effective for Japanese patients with good PS and minimal weight loss. No significant financial relationships to disclose.