bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized phase II study of cisplatin plus gemcitabine administered either as short infusion or at a fixed dose rate in non-small cell lung cancer (NSCLC)
Authors: Pereira J. R. , Fein L. , Carvajal P. , Giglio A. , Blajman C. , Richardet E. , Schwartsmann G. , Orlando M. , Hall B. J. , Van Kooten M.
Published: March 2020

17037

Background: Previous studies have indicated that, in combination with cisplatin (cis), fixed dose rate gemcitabine (gem) may be more efficacious than standard infusion gem. This open-label, randomized, multicenter Phase II study (B9E-LA-S350) was aimed to compare the efficacy and safety of these regimens as treatment for advanced NSCLC in Latin American patients (pts). Methods: Major eligibility criteria included histologic/cytologic diagnosis of stage IIIB/IV NSCLC not amenable to curative surgery; and at least one measurable lesion. Pts were randomized to receive up to 6 cycles of treatment with cis 75 mg/m2 on Day 1 plus either gem 1000 mg/m2 over 30 min on Days 1 and 8 of a 21-day cycle (standard arm) or gem 1000 mg/m2 at a fixed dose rate of 10 mg/ m2/min on Days 1 and 8 of a 21-day cycle (FDR arm). The primary endpoint was the objective response rate (ORR; assessed by RECIST criteria) and secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of tumor response (TR), and toxicity. Results: The results from this interim analysis assessed all objectives. Sixty-four pts were randomized to treatment (N = 33 standard arm; N = 31 FDR arm): 22 females; mean age 60 ± 9 yrs; 20% stage IIIB, 80% stage IV. In the standard arm, 9 (27%) pts responded (CR or PR) compared to 6 (20%) pts in the FDR arm (Odds ratio: 0.67, 95% CI 0.21–2.2, p = .56). As shown in the table below, there were no statistically significant differences in median ORR, OS, PFS, TR times, and Grade (G) 3/4 toxicities. Conclusions: The standard and FDR gem and cis treatment regimens produced similar results for both efficacy and toxicity in this patient population. This trial does not support the use of a FDR administration of gem in Latin American pts with NSCLC.

[Table: see text]

[Table: see text]
Phase II study of genexol (paclitaxel) and carboplatin as first-line treatment of advanced or metastatic non-small-cell lung cancer (NSCLC)
Authors: Kim C. , Bae S. , Lee N. , Lee K. , Park S. , Kim D. , Won J. , Hong D. , Park H.
Published: March 2020

17049

Background: Genexol is a polymeric micelle loaded paclitaxel without Cremophor EL (CrEL). CrEL has been shown to cause hypersentivity reaction and neuropathy. To evaluate and efficacy, we conducted a phase II study of CrEL-free paclitaxel (genexol) and carboplatin in patients (pts) of advanced or metastatic NSCLC. Methods: Eligibility criteria included: stage IIIB or IV NSCLC without previous chemotherapy and radiotherapy; written informed consent; measurable lesion; age 18–75; ECOG PS 0–3; adequate bone marrow, liver, and renal function; and no CNS disease. The patients received genexol 225 mg/m2 IV on day 1, followed by carboplatin AUC = 6 IV on day 1 every 3 weeks. Primary end points are response and toxicity. Response evaluations were performed after cycles 2, 4, and 6 of chemotherapy according to the RECIST criteria. Results: 36 pts were enrolled between November 2002 and November 2005. Pts characteristics: median age 63 years (range 45–73), median ECOG PS 1 (range 0–3), 13 stage IIIB and 23 IV, 21 adenocarcinoma and 14 squamous cell carcinoma, and 1 large cell carcinoma. At present, 30 pts were evaluable for response and toxicity. Meidan number of treatment cycles was 4 (range 1–6). Seven pts needed dose reduction. Thirteen pts achieved partial response and 13 pts had stable disease. The response rate 43.3%. Grade (gr) 4 neutropenia occurred in 11 pts (36.7%). Gr 1/2 sensory neuropathy occurred in 13 pts (43.3%) and gr 3/4 sensory neuropathy occurred in 5 pts (50%) among 10 pts over 65 year old. Other toxicities included neutropenic fever in 9 pts (30%), gr 4 thrombocytopenia 3 patients (10%), gr 2 hepatic dysfunction 3%, and gr 3 fatigue 10%. Treatment related mortality was not occurred. Complete analysis will be presented. Conclusions: In this trial, the combination of genexol and carboplatin showed a significant activity with acceptable and manageable toxicities as first line treatment for patients with advanced or metastatic NSCLC and dose reduction needed in older patients.

No significant financial relationships to disclose.
A phase II trial of biweekly pemetrexed (P) and gemcitabine (G) in the first-line treatment (tx) of patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: Peacock N. W. , Spigel D. R. , Hainsworth J. D. , Yardley D. A. , Burris H. A. , Barton J. H. , Patton J. F. , Shipley D. L. , Simons L. , Greco F. A.
Published: March 2020

17054

Background: P and G are active and well-tolerated non-platinum agents used in the tx of NSCLC. Previous trials have combined P and G in the first-line NSCLC setting using a 21D schedule. This trial examined the safety and activity of biweekly P/G. Methods: Theprimary endpoints of this single center community-based phase II study were toassess the safety and response rate (RR) of P/G in pts with previously untreated stage III (unresectable) or IV NSCLC. Tx included: P 500mg/m2 IV D1 and G 1500mg/m2 IV D1 Q 14D for 8–12 cycles. Pts also received folate and B12 prophylaxis. Pts were restagedafter 4 cycles. Eligibility included:measurable disease, ECOG PS 0–2, adequate organ function, informed consent, and no active brain metastases. Analysis was by intent to treat. Results: Thirty-five pts were enrolled between 5/05 and 8/05. The median follow-upis 6 months (3.5–7.5 months). Baseline characteristics include: medianage 65 years (41–85); male/female, 71%/29%; ECOG PS 0,1,2:17%/71%/12%; and histology, adenocarcinoma (34%), large cell (29%), squamous (11%), mixed or not specified (26%). The median number of cycles delivered was 8 (1–12). Grade (G)3/4 non-hematologic toxicity included:chest pain (6%), constipation (6%), fatigue (17%), hypercalcemia (6%), dyspnea (9%), and tachyarrhythmia (9%). G3/4 hematologic toxicity included: neutropenia(51%), anemia (8%), and thrombocytopenia (3%). G3/4 febrile neutropenia occurred in 14%. There were notx-related deaths. Response data are availablefor 35 pts. Complete/partial responses for all pts were observed in 0 pts/7pts, respectively, for an overall RR of 20% (95% CI 10%-36%, 1 pt unconfirmed by RECIST criteria). Fifty-four percentof pts had stable disease, and 14% had disease progression(4 pts were unevaluable.) Six-month progression-free survival (PFS) andoverall survival (OS) were 51% and 67%, respectively. Median PFS and OS have not been reached. Conclusions: Biweekly P/G is a safe and well-tolerated regimen with RRsimilar to other standard first-line regimens for the tx of pts with advanced NSCLC, and further study is warranted. Median and 1-year PFSand OS endpoints have not been reached in this trial.

[Table: see text]
A phase I dose-escalating study of combination S-1 and carboplatin (CBDCA) in patients with chemo-naïve advanced non-small cell lung cancer (NSCLC)
Authors: Tamura K. , Okamoto I. , Ozaki T. , Shimizu T. , Kashii T. , Takeda K. , Matsui K. , Kudoh S. , Kurata T. , Fukuoka M.
Published: March 2020

17055

Background: S1, a novel oral fluoropyrimidine derivative, has promising results in the treatment of advanced gastric or colorectal carcinoma. Response rate/median survival time of single S1 and the combination S1 plus cisplatin for advanced NSCLC were 22.0%/309 days and 47.3%/335 days, respectively in the previous phase II. Platinum doublets including a novel active drug is a potent standard for advanced NSCLC as 1st line chemotherapy. Carboplatin has advantage of low gastrointestinal or renal dysfunction in comparison with cisplatin. The primary objective of this study was to determine the maximum tolerated dose (MTD) of combination S-1 and carboplatin, the toxicity profile and the recommend dose (RD) for a multi-center randomized trial of platinum doublets including S1. Methods: Eligibility criteria includes histologically diagnosed NSCLC stage IIIB/IV, no prior chemotherapy, ECOG PS 0–1, 75 > age >20, adequate organ function, and written informed consent. Pts receive carboplatin intravenously over 30 minutes on day 1, and S1 daily for 2 weeks, every 3 weeks. Results: Total 10 patients were registered (M/F: 6/4; median age:67 (37–73); Ad/Sq:7/3; IIIB/IV: 0/10 PS 0/1:3/7) Three patients were enrolled at the dose level 1 (CBDCA AUC = 5 and S1 65 mg/m2), 3 patients at level 2 (CBDCA AUC=5 and S1 80 mg/m2) and 4 patients at level 3 (CBDCA AUC=6 and S1 80 mg/m2), respectively. No DLTs (dose-limiting toxicities) occurred at both level 1 and 2. DLTs were observed in 2 out of 4 patients at level 3. One is significant delay starting of 2nd cycle caused by thrombocytopenia. One is G3 anorexia and vomiting at 1st cycle and results in stop the treatment. A total 27 courses were assessable for safety. Two pts with G3 neutropenia, 2 pts with G3 anorexia, 1 pts with G3 liver dysfunction and 1 pts with G3 infection were observed during total courses. Five out of 6 patients at Level 1 or 2 have completion of 4 cycle’s treatment. Objective response was obtained in three patients out of 10. Conclusions: MTD was level 3. RD for the future trial was Level 2 (CBDCA AUC = 5 and S1 80 mg/m2). This combination was well tolerated and produced an antitumor effect for advanced NSCLC.

No significant financial relationships to disclose.
Gefitinib-induced platelet-derived microparticle and ICAM-1 in Japanese patients with non-small cell lung cancer
Authors: Kanazawa S. , Kinoshita Y. , Yamaguchi K. , Nomura S.
Published: March 2020

17056

Background: We recently discovered that platelet activation is observed in patients receiving gefitinib. Nomura et al. reported that activated platelets generated platelet-derived microparticle (PDMP) and this PDMP could induce adhesion molecules and an interaction between white blood cells and endothelial cells. Theaim of the present study was to identify the clinical significance between PDMP and intercellular adhesion molecule-1 (ICAM-1) in lung cancer patients receiving gefitinib. Methods: Patients with a diagnosis of non-small cell lung cancer were entered into this study. Blood samples were withdrawn before and one week and two weeks after the administration of gefitinib. PDMP and ICAM-1 were measured using an enzyme-linked immunosorbent assay kit. A total of 25 patients was recruited in the study. The characteristics of the study subjects were: age: 42–78 years (median: 68 years); gender: male vs. female = 14 vs. 11; tumor histology: adenocarcinoma vs. squamous cell carcinoma = 17 vs. 8. Nine patients were responders and the other 16 patients were non-responders. Results: The plasma concentration of PDMP significantly increased after receiving gefitinib (before vs. one week vs. two weeks = 14.1±12.0 U vs. 17.9±16.9 U (p<0.05) vs. 14.6±12.0 U n = 25). The plasma concentration of ICAM-1 significantly increased after receiving gefitinib (before vs. one week vs. two weeks = 296.2±85.1 ng/ml vs. 319.4±78.9 ng/ml vs. 344.8±74.0 ng/ml (p<0.05) n = 16). Conclusions: Platelets were activated by gefitinib therapy, and the effect of gefitinib is related to a reaction of not only blocked EGFR but also platelet activation and in part endothelial cells and leukocytes through activated platelets. The mechanisms underlying some adverse events in gefitinib-treated patients are poorly understood. Our results suggest that one of the mechanisms causing gefitinib-related adverse effects depends on platelet activation.

No significant financial relationships to disclose.
The inter-relationship of hypoxia and phospho-Akt in the pathobiology of malignant pleural mesothelioma
Authors: Stewart D. , Edwards J. , Richardson D. , Jones L. , Burke B. , Waller D. , Zeigler-Heitbrock L. , Wardlaw A. , O’Byrne K.
Published: March 2020

17057

Background: Poor outcomes with conventional oncological treatments for malignant pleural mesothelioma (MPM) have driven the imperative to advance understanding of the disease pathobiology. Carbonic Anhydrase (CA)-IX is a surrogate marker of hypoxia over-expressed in solid tumours. Protein Kinase B, or Akt, known to have important intracellular roles including resistance to apoptosis, is activated in human malignancies and upregulated in hypoxic conditions. This study examined the expression of CA-IX and phosphorylated Akt (pAkt) in tumour samples from patients with MPM, correlating expression with established prognostic factors. The role of pAkt in the survival of an MPM cell line exposed to hypoxic conditions was also examined. Methods: Full local regional ethics committee approval was obtained for this work. Tumour samples from 200 patients with MPM were stained using pAkt and CA-IX specific antibodies. The effect of hypoxia on Akt and pAkt was evaluated in the JU77 mesothelioma cell line in the presence or absence of the phosphatidylinositol-3-kinase inhibitor, LY294002. Results: There was a positive association between the level of CA-IX and pAkt staining, implying that intra-tumoural hypoxia may be a stimulus for Akt phosphorylation. On multivariate analysis increased expression of nuclear pAkt was found to be associated with a poor survival. In-vitro cell culture work showed that, although pAkt is expressed in normoxic conditions in the JU77 cell line, the rates of apoptosis were significantly increased in hypoxic conditions when the phosphorylation of Akt was blocked by LY294002. Conclusions: This work provides evidence for the anti-apoptotic role of pAkt in hypoxic conditions in solid human malignancies. Phospho-Akt may represent a novel therapeutic target in MPM.

No significant financial relationships to disclose.
Stereotactic body radiotherapy (SBRT) and medical inoperability of early stage non-small cell lung cancer
Authors: Franks K. N. , Bezjak A. , Pearson S. , Cho B. C. , Payne D. , Sun A. , Waddell T. K. , Shepherd F. A. , Keshavjee S.
Published: March 2020

17074

Background: Early stage NSCLC is commonly diagnosed in elderly patients who often have significant medical co-morbidity. SBRT is emerging as a treatment alternative that can provide 80–97% local control for peripheral tumors. We performed a literature review and a retrospective review of 24 patients referred to Princess Margaret Hospital for consideration of SBRT to assess what criteria were used to determine patient selection for this new treatment. Methods: Published papers reporting treating stage I NSCLC with SBRT were reviewed. Clinical and demographic characteristics of patients referred for consideration of SBRT over the last 15 months were analyzed. All patients were assessed by experienced thoracic surgeons to determine their operability status. Patients were retrospectively scored as average or high risk for surgery on the basis of accepted PFT guidelines (FEV1 and DLCO <40% predicted); Charlson Index of Comorbidity (CCI) was calculated (score >2 associated with impaired survival). Results: Of 13 papers reporting Stage 1 SBRT results, 8 included details of medical inoperability. 2 papers had strict guidelines for PFTs, in addition to other criteria. In 6 studies reporting 276 pts, the most common reason for inoperability was non-specific medical comorbidity (60%). Our cohort (24 patients) referred for SBRT (median age 75, range 57–89) had a mean tumour size of 2.32cm (S.D. 1.11); 50% of patients had a good (0–1) Zubrod Performance status. Based upon PFT tests alone 10 patients (42%) were high risk and 5 (21%) average risk for surgery. The CCI score was ≥3 in 10 patients (42%). 3 patients who scored average risk and CCI ≤2 were deemed medically inoperable due a single severe medical comorbity. In 23/24 pts the surgeon recommended against surgery; one patient refused surgery. Conclusions: With an aging population and increased detection due to incidental finding or screening, it is important to know that there is effective alternative therapy for patients deemed too high risk for surgical resection. Comorbidity is an important factor influencing surgical mortality; defining explicit criteria for inoperability remains a clinical challenge.

No significant financial relationships to disclose.
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.
Effects of gefitinib (G) on bone metatases (BMs) in non-small cell lung cancer patients
Authors: Garfield D. , Zampa G. , Cadranel J. , Bell D. W. , Moscato M. , Normanno N.
Published: March 2020

17147

Background: Selected pts with advanced NSCLC might have particular benefit from EGFR tyrosine kinase (TK) inhibitor treatment. We have identified 4 NSCLC pts with BMs who had major responses to G. Methods: Pts characteristics: Pt 1, 62 y/o female, never-smoker (ns), NSCLC, brain and BMs with bone pain; pt 2, 51 y/o male, former smoker (fs), ADC and BMs; pt 3, 51 y/o male, ns, ADC and BMs; pt 4, 50 y/o male, fs, ADC, pleural effusion, BMs and bone pain. Pts 1 and 4 had mixed osteolytic-sclerotic BMs; pts 2 and 3 had osteolytic BMs. Pts were treated with 250 mg/day of G; the dose was increased to 375 mg/day in pt 1 for maximum CNS control. Pts 1 and 4 received G as first-line therapy, pts 2 and 3 as second-line following failure of platinum-containing therapy. Pts 1–3 also received zoledronic acid. Results: Pts 1 and 4 experienced significant decrease in bone pain with G, within hours in pt 1 and by day 3 in pt 4. Pts 1–3 developed rash. Objective regression of primary tumor was observed in all 4 pts. After 3 months of G the bone scan did not change in pt 1 but many lesions became more sclerotic. Bone scans became negative after one year of treatment in pts 2 and 3. Pt 2 had resection of the primary tumor with no recurrence, 26+ months (mos) from diagnosis, 9+ mos from surgery. Pt 1 has had disease control for 7+ mos, pt 3 for 15+ mos. Pt 1 had CNS regression with G. Pt 3 was found to have asymptomatic CNS mets at 6 mos of G, received whole-brain radiation, and remains on G at >1 year. Pt 4 died 6 weeks after starting G from unrelated causes but showed dramatic BMs response by PET. Tumor tissue was available for molecular analyses for pts 2 and 4, who respectively showed EGFR-TK domain G719C mutation in exon 18 and L858R mutation in exon 21. Both mutations have been previously described in NSCLC patients responding to G. Conclusions: G may be effective in the treatment of BMs in some NSCLC patients.

[Table: see text]
Modified gemcitabine regime in advanced lung cancers
Authors: Agarwal S. , Agarwal P.
Published: March 2020

17148

Background: Gemcitabine is established treatment modality for NSCLC. However it’s introduction on day 8 is sometimes delayed because of low counts or poor patient acceptance because of effects of d1 dose. Methods: We have used gemcitabine 10000 mg/m2 as d1,d10 regimen in 32 patients of advanced lung cancer incombination with either cisplatin or carboplatin .Colony stimulating factors were required in 2 patients. Results: The patients tolerated the chemotherapy (4 to 6 cycles) satisfactorily and none of the patient required delaying of the d10 therapy. Complete regression was seen in 2 patients,partial regression in 22 patients.the median survival was 10.2 months. Conclusions: The d1–10 schedule of gemcitabine based chemotherapry is safe,effective and better tolerated then the d1-d8 schedule.

No significant financial relationships to disclose.
Predictors for toxicity profiles of weekly docetaxel in non-small cell lung cancers
Authors: Chen J. P. , Lo Y. , Yu C. J. , Hsu C. , Shih J. Y. , Cheng A. , Yang P. C. , Yang C. H.
Published: March 2020

17153

Background: Weekly docetaxel has been proved recently to be safer and equivalently effective compared with traditional tri-weekly docetaxel as second-line treatment for NSCLC. However, the risk factors for toxicity of weekly docetaxel in this group of patients are still unknown. Methods: We reviewed advanced NSCLC patients receiving 2nd line or 3rd line weekly docetaxel from 1999 to 2003 from cancer registry and pharmacy records in our hospital. Clinical characteristics, previous chemotherapy regimens, laboratory data, docetaxel administration schedules/dosage, and treatment efficacy were retrospectively collected. Logistic regression was performed to identify risk factors for adverse outcomes. Cox’s proportional hazards model was used to analyze cumulative-dose related adverse events. Results: A total 155 patients were analyzed for treatment effect and toxicity. The overall response rate of weekly docetaxel (36–40 mg/m2) was 5.16% and median survival of all patients was 8.1 months. The incidence of treatment withdrawal due to adverse events was 43.23 % and significantly related to previous anthracycline use (odds ratio 4.582; P = 0.0144) and chronic hepatitis B or C virus (HBV/HCV) infection(odds ratio 3.928; P=0.0058). The incidence of grade 3 or 4 neutropenia was 23.2% and was significantly associated with old age (odds ratio 7.232; P < 0.001), lower baseline white count(odds ratio 5.57; P < 0.05), and chronic HBV/HCV infection(odds ratio 3.25; P < 0.05). The incidence of fluid retention was 41.29% and the median cumulative dose of docetaxel at onset was 327 mg/m2. Abnormal liver function significantly increased the risk for fluid retention(odds ratio 2.368; P < 0.05); steroid premedication (odds ratio 0.184; P < 0.01), higher albumin(odds ratio 0.237; P < 0.01), and previous surgical resection(odds ratio 0.341; P < 0.05) decreased the risk. Conclusions: Salvage weekly docetaxel for NSCLC patients in Taiwan remains toxic. Part of the reasons for the significant toxicities is that chronic HBV/HCV infection, which occurs in around 20% of general populations in Taiwan, represents a significant risk factor for neutropenia, fluid retention, and treatment withdrawal. The role of prophylactic anti-viral agents in these patients should be explored in the future.

[Table: see text]
Gemcitabine, cisplatin and methylprednisolone (GEM-P) in patients with T-cell lymphoma: Results from The Royal Marsden Hospital
Authors: Arkenau H. , Trumper M. , Sirohi B. , Chong G. , Chau I. , Wotherspoon A. , Norman A. , Horwich A. , Matutes E. , Cunningham D. C.
Published: March 2020

17507

Background: There is a need for novel, effective therapies for T-cell non-Hodgkin’s lymphoma (NHL). The combination of gemcitabine, cisplatin and methylprednisolone (GEM-P) has shown activity in patients (pts) with relapsed Hodgkin’s disease and NHL (Chau I et al. Br J Haematol 2003, Baetz T et al. Ann Oncol 2003). We report a single institution retrospective analysis of GEM-P for pts with T-cell NHL. Methods: Sixteen pts with T-cell NHL treated at the Royal Marsden Hospital between June 2001 and March 2005 with GEM-P (gemcitabine 1 g/m2 D1, 8, 15; cisplatin 100 mg/m2 D15; methylprednisolone 1 g D1–5, repeated every 28D) were identified. Results: 16 pts (9 males and 7 females) were analysed. Histological subtypes were: angioimmunoblastic (n = 5), T-cell enteropathy (n = 2), NK/T cell nasal-type (n = 2), T-cell anaplastic (n = 3) and peripheral T-cell unspecified (n = 3). Median age was 55 years (range: 18–71 years), 69% had IPI-score ≥ 2 and 69% had stage III/IV disease. 15 /16 pts were pre-treated: median number of prior treatments: 1 (range: 0–4). At the start of GEM-P treatment pts presented with: primary refractory disease (n = 3), 1st relapse (n = 6), 1st relapse refractory (n = 3), 2nd relapse (n = 2) and 4th relapse (n = 1). Median time from diagnosis of T-cell NHL to start of GEM-P was 8.9 months(m) and median number of cycles given was 3 (range: 1–6). Of 16 evaluable patients, 3 pts (19 %) achieved complete remission (CR), 8 pts (50 %) achieved partial remission (PR), (ORR= 69%; CI-95% 41.4–89.0) and 5 pts (31%) progressed while on GEM-P. One pt received high dose chemotherapy (melphalan/etoposide) after CR to GEM-P. After a median follow up of 17.4m the mean progression free survival (PFS) was 9m (range 1.15–37.5). The median overall survival (OS) has not been reached and the survival probability at 1 year was 68.2% (95% CI: 40–85). The main grade 3/4 toxicities were myelosuppression (leucopenia 62%, neutropenia 62% and anaemia 12%) and required granulocyte colony stimulating factor (GCSF) in 3 pts with neutropenic sepsis and in 1 pt with neutropenia. Conclusion: GEM-P has encouraging efficacy with an acceptable toxicity profile in pts with previously treated T-cell NHL.

[Table: see text]