bluuebunny/crossref_metadata_2025_split huggingface dataset:
Irinotecan, carboplatin and etoposide regimen in extensive disease small cell lung cancer: Phase II trial
Authors: Syrigos K. , Katirtzoglou N. , Charpidou A. , Botsis T. , Karapanagiotou E. , Dilana K. , Gkiozos I. , Pantazopoulos K. 
Published: March 2020

18153 Background: The prognosis for the patients with small cell lung cancer (SCLC) is very poor with metastases often present at the time of diagnosis. Despite the initial chemo-sensitivity the majority of the patients will relapse and die of their disease. Irinotecan, a topoisomerase I inhibitor, has been reported as an active new agent in SCLC. In combination with cisplatin, it has showed superiority in response rates and progression free survival over the standard regimen of cisplatin and etoposide. We conducted a phase II study in order to evaluate the efficacy and safety of Carboplatin, Irinotecan and Etoposide (CIE) combination in extensive-disease SCLC (ED-SCLC) Methods: Forty six chemo-naïve patients with ED-SCLC and PS 0–2 were enrolled. Forty of theme were men and 6 women. All of them were smokers and the median age was 59.6 years. We administered carboplatin AUC 5 on day 1, irinotecan 120 m2 on day 2 and etoposide 75 mg/m2 on days 1, 2, 3 in a 21 days repeated cycles. The treatment was continued for up to 6 cycles. Response assessments were performed after cycles 3 and 6 and every 2 months subsequently. The patients were evaluated for response, survival and toxicity. Clinical (as site of metastasis) and laboratory (such as LDH) parameters were tested as prognostic factors for survival. Results: Two hundred and two cycles were administered with an average of 4.5 cycle per patient. Overall response rate was 52.2% (partial and complete), mean overall survival was 16.3 months (CI: 95%: 13.0–19.7) and there was a 1 year survival rate of 43.47%. Patients with brain metastasis had worse prognosis (P:0.004). The three drug regimen was well tolerated. Only 1 patient had diarrhea grade II, 6 had grade III/IV and 1 patient was referred with abdominal pain. One was presented with fatal thrombocytopenia while two toxic deaths were reported. Nine patients (19.5%) had neutropenia grade III/IV, without being fatal, and 3 were presented with grade III anemia which need blood transfusions. Conclusions: CIE regimen is effective and well tolerated for the treatment of the poor prognosis group of ED-SCLC patients with responses and overall survival comperable to standard regimen (CE). No significant financial relationships to disclose.
Randomized phase II trial of two sequential schedules of docetaxel (D) and cisplatin (C) followed by gemcitabine (G) in patients with advanced non-small cell lung cancer
Authors: Galligioni E. , Gebbia V. , Cartenì G. , Gamucci T. , Grossi F. , Ferraù F. , Nardi M. , Pollera C. , Rossi S. , De Marinis F. 
Published: March 2020

18154 Background: C based doublets remain the cornerstone for first line treatment of advanced NSCLC but the role of sequential use of chemotherapy is still investigational. Aim of this study was to assess the activity and toxicity of 3 courses of C and D followed by 3 courses of single agent G, to reduce C exposure and sequentially administer 2 second generation cytotoxic drugs. The weekly D/C schedule was further investigated, to reduce toxicity. Methods: Chemotherapy naive stage IIIB or IV measurable NSCLC pts, aged 18–70 and PS 0–1, were stratified by stage (IIIB vs IV) and randomized, after local ethic committee approval and signed informed consent, to D and C (both 75 mg/m2 on day 1) q21 days for 3 cycles (Arm A), or to D and C (both 25 mg/m2 on days 1, 8, 15) q28 days for 3 (Arm B). Responding or stable pts of each arm, were treated with 3 additional cycles of G (1,200 mg/m2 on days 1, 8) q 21 days. Primary endpoint of the study was response rate (RECIST). Sample size was calculated of 42 pts per arm, considering worthy of further investigation a regimen with =14 objective responses. Results: Between May 2005 and October 2006, 88 pts were enrolled (Arm A/B: 43/45), with 69 evaluable so far (median age 63 yrs, median PS 0, and M/F ratio 53/16). Toxicity (NCI-CTG criteria) after 3 cycles, evaluable on 67 (32/35) pts, was mainly hematological, with grade 3/4 neutropenia in 17 pts (17/0), neutropenic fever in 1 (arm A), infections in 2 (arm B), grade 3/4 thrombocytopenia in 3 (1/2) and grade 3/4 anemia in 2 (arm A). Non-hematological grade 3/4 toxicity consisted of fatigue (4/1), diarrhea (4/1), pulmonary toxicity (1/4), pain (2/3), stomatitis (1/2) and alopecia (2/0). Fifty one pts (A/B: 29/22) are evaluable for response after 3 cycles, with 16 PR (55%) and 7NC in arm A and 1CR+6PR (32%) and 7NC in arm B. Objective responses after 6 cycles, available only in few pts so far, show 1CR+10PR in arm A and 2PR in arm B. At a median FU of 6.5 months, 60/85 pts are alive (33/27) and 25 are dead (8/17), with 3 pts, never treated, lost to f. up. Conclusions: From these preliminary results, CD combination appears active and manageable while the activity of G, cannot be defined yet. Data collection is continuing and analysis will be completed and mature, by the time of the meeting. [Table: see text]
A preliminary report of a phase II trial of single-agent vinflunine as second-line treatment of advanced non-small cell lung cancer
Authors: Joppert M. , Boccia R. , Dakhil S. , Steis R. 
Published: March 2020

18156 Background: In preclinical and early clinical trials, single-agent vinflunine (a novel microtubule inhibitor) has shown activity in a variety of tumors, including non-small cell lung cancer (NSCLC). The purpose of this phase II, single-arm study is to evaluate the safety and efficacy of vinflunine administration every 3 weeks to patients with advanced NSCLC who have progressed after prior treatment with a platinum-based doublet. The primary endpoint is 1-year survival rate. This report presents preliminary safety information demonstrating the safety and tolerability of this combination. Methods: Patients = 18 years with confirmed advanced NSCLC (stage IIIB with malignant pleural effusions or stage IV) that have progressed after receiving a platinum-based doublet as first-line therapy, received vinflunine (320 mg/m2) as a 20-minute IV infusion on Day 1 of each 21-day cycle. Results: At the time of analysis, 36 patients (of a planned total of 75) have received study treatment. Patient characteristics include: gender male/female, 24/12; median age 68.5 years (range 42–86); ECOG performance status 0/1, 10/26; and race Caucasian/Black, 34/2. The median number of cycles administered was 2 (range 1–9). Fourteen patients are still on study. The most common toxicities (NCI CTC version 2), regardless of causality, were Grade 3 fatigue (14.3%), asthenia (8.6%), neutropenia (8.6%), constipation (5.7%), cough (5.7%), dehydration (5.7%), vomiting (5.7%), dyspnea (5.7%), and ileus (5.7%). Grade 4 toxicities were neutropenia (22.9%) and change in mental status (5.7%). There were 5 deaths (2 from progressive disease, 1 from respiratory distress, 1 from coronary artery disease, and 1 case of sepsis possibly related to study drug). Conclusions: These preliminary results suggest that vinflunine has a manageable safety profile when used as a single agent for second-line treatment of patients with advanced NSCLC. Supported by Bristol-Myers Squibb. [Table: see text]
Efficacy and tolerability of a weekly schedule of docetaxel-cisplatin as first-line treatment for advanced non-small cell lung cancer (NSCLC)
Authors: Binder D. , Hackenthal M. , Graseck L. , Schweisfurth H. , Schäper C. , Krüll M. , Temmesfeld-Wollbrück B. , Suttorp N. , Beinert T. , Hellriegel K. 
Published: March 2020

18159 Background: Docetaxel-cisplatin, administered every 3 weeks, is an effective first-line chemotherapy for locally advanced or metastatic NSCLC. However, this regimen is commonly associated with neutropenia and neutropenic infections. Moreover, the extensive hydration required with cisplatin given every 3 or 4 weeks makes outpatient treatment difficult. We assessed the efficacy and tolerability of weekly docetaxel-cisplatin, which may be better tolerated than the standard regimen. Methods: Patients (pts) with histologically confirmed stage UICC IIIB (malignant effusion) or IV NSCLC were treated with docetaxel (35 mg/m2, 30 min. infusion) and cisplatin (25 mg/m2, 30-min. infusion) on Days 1, 8, and 15, every 4 weeks for 4–6 cycles. Pts received ondansetron 8 mg iv and dexamethasone 8 mg iv preceding every day of chemotherapy and oral dexamethasone 2 x 4 mg daily from the day before until the day after chemotherapy. NK1-antagonists were given at the investigator’s discretion. On each day of therapy, 2750 mL of fluid was infused over 3.5 h. Most pts were treated in an outpatient department. Safety was assessed using CTCAE v3.0. The primary endpoint was response rate (RECIST). Results: 45 pts were enrolled; efficacy and tolerability data were available for 43 pts. 12/45 pts achieved an objective response (11 partial; 1 complete; ITT response rate 27%). Median time to progression was 3.9 months. Pts received a median of 3 full cycles. 4 pts (9%) required dose reductions. No cases of neutropenic fever/infections or grade 2–4 thrombocytopenia were observed. Only 2 pts (5%) had grade 3 neutropenia. One pt (2%) experienced grade 3–4 nausea/vomiting. 5 pts died during therapy for reasons not unequivocally attributable to tumor progression (bacterial meningitis with normal neutrophil counts [n=1], pneumonia with normal neutrophil counts [n=1], pulmonary arterial embolism [n=1], unknown [n=2]). Conclusions: Docetaxel-cisplatin administered weekly was well tolerated. Hematologic toxicity and neutropenic fever were uncommon. Docetaxel-cisplatin can be safely administered with relatively low hydration volumes in an outpatient setting. Survival data will be presented. No significant financial relationships to disclose.
Phase II study of docetaxel and carboplatin in elderly patients with advanced non-small cell lung cancer: Final results
Authors: Yoshimura N. , Kudoh S. , Kimura T. , Mitsuoka S. , Yana T. , Hirata K. 
Published: March 2020

18161 Background: Single-agent chemotherapy has been considered as standard treatment for elderly patients with non-small cell lung cancer (NSCLC). However recent subset analyses suggest that platinum-based combination chemotherapy may be safely administered to the elderly with good performance status (PS). We evaluated the efficacy and safety of carboplatin and docetaxel in a phase II study of elderly patients aged 70 years or older. Methods: Chemotherapy-naive patients aged =70 years with advanced NSCLC (IIIB-IV), ECOG performance status (PS) of 0–2, a measurable lesion, and adequate organ functions were enrolled. Patients received carboplatin (AUC 5) and docetaxel (60 mg/m2) administered on day 1 every 3 weeks. The primary endpoint was response rate (RR). This study, with a planned sample size of 25, had 80% power to support the hypothesis that the true RR was >30%, and 5% significance to deny the hypothesis that the true RR was <10%. Results: Between October 2003 and April 2006, 30 elderly patients with NSCLC were enrolled in the study and all patients were treated. Demographics: M/F 20/10; PS 0/1/2 2/23/5; median age 75 (range 70–84). Median number of treatment cycles was 3.5. Responses in the 30 evaluable patients included 1CR; 13PR; for an objective RR of 46.7% (95% CI 28.8–64.6%). By January 4, 2007, 21 (70.0%) of 30 patients had died. Median follow-up for survival was 8.4 months. The median time to tumor progression was 4.4 months, and the median survival was 9.9 months. The 1-year survival rate was 43.3%.Grade 3/4 hematologic toxicities included leukopenia (80.0%), neutropenia (86.7%), anemia (16.7%) and thrombocytopenia (3.3%). Non-hematologic toxicities were mild with no grade 4 toxicities; grade 3 nausea (10.0%), anorexia (30.0%), diarrhea (13.3%), fatigue (6.7%), allergic reaction (6.7%), pneumonitis (3.3%), febril neutropenia (16.7%) and infection (10.0%) were observed. Conclusions: The combination of carboplatin and docetaxel was safe and promising for the treatment of chemotherapy-naive elderly patients with advanced NSCLC. This regimen warrants further evaluation in a phase III trial. No significant financial relationships to disclose.
Medical resource utilization (MRU) and costs associated with paclitaxel poliglumex (PPX) compared to gemcitabine (Gem) or vinorelbine (Vin) in non-small cell lung cancer (NSCLC) patients
Authors: Oldham F. B. , Anastassopoulos K. P. , O'Byrne K. , Maxon M. S. , Schaefer C. P. 
Published: March 2020

18172 Background: NSCLC accounts for 80% of lung cancer cases and is commonly treated with taxanes. PPX is a phase III, biologically-enhanced, investigational, chemotherapeutic for treatment of NSCLC that links paclitaxel to a biodegradable polyglutamate polymer that potentially spares normal tissue exposure to chemotherapy toxicities. Methods: MRU data were collected as part of a multinational, randomized trial that compared PPX (n=191) to Gem or Vin (n=190) in chemotherapy-naïve advanced NSCLC patients with a performance status of 2. MRU and costs associated with chemotherapy administration and non-protocol-driven care were compared over the study period. Costs (2005 U.S. dollars) were assigned from a U.S. payer perspective. Results: Patient demographics were similar (p>0.05) between groups (mean age: 62 yrs, 72% male, 89% Caucasian). PPX had slightly longer median survival (220 vs. 198; p=0.686) with significantly fewer adverse events (all grades; 2.0 vs. 3.0; p=0.011) and significantly more chemotherapy cycles (3.4 vs. 3.9; p=0.007), per subject. Additionally, PPX had fewer outpatient visits (0.6 vs. 1.7; p<0.001), diagnostic tests (0.6 vs. 1.9; p<0.001), and days on non-chemotherapy medications (64.4 vs. 91.2; p<0.001), per subject. There was no significant difference in number of hospitalizations (0.04 in both groups; p=0.786), length of stay among those hospitalized (8.4 days PPX vs. 6.1 days Gem or Vin; p=0.301), or procedures (0.02 PPX vs. 0.04 Gem or Vin; p=0.238), per subject. Average costs per subject were significantly lower in PPX for outpatient visits ($34 vs. $78; p=0.014), non-chemotherapy medications ($717 vs. $911; p<0.001), and chemotherapy administration ($1,557 vs. $3,601; p<0.001) and similar for inpatient stays ($210 PPX vs. $244 Gen or Vin; p=0.794). Conclusions: This analysis suggests that, in addition to providing a clinical benefit of fewer adverse events, PPX results in reduced MRU and associated costs compared to Gem or Vin in treating NSCLC. These cost savings can be weighed against the cost of PPX and may provide a pharmacoeconomic advantage. Further research is warranted to confirm these results in routine clinical practice. [Table: see text]
A phase II trial of adjuvant UFT after sequential chemotherapy and radiotherapy in patients with stage IIIB non-small cell lung cancer and non-oriental ethnicity
Authors: Melo A. C. , Lima D. S. , Small I. A. , Olmedo D. B. , Toscano E. , de Biasi P. , Martins R. , Ferreira C. G. , Zukin M. 
Published: March 2020

18175 Background: The goals of chemoradiotherapy in non-small cell lung cancer (NSCLC) with stage III disease are to achieve local control, for which radiotherapy plays the main role, and eradicate occult distant metastases by chemotherapy. Systemic progression remains a significant cause of morbidity and mortality in these patients. Japanese trials showed that the combination of uracil and tegafur (UFT) improves survival in patients with early NSCLC. The Brazilian National Cancer Institute (INCA) conducted a phase II trial to evaluate the use of adjuvant UFT in patients with IIIB NSCLC treated with sequential chemoradiation. Methods: The eligibility requirements were stage IIIB NSCLC, an ECOG performance status 0 or 1 and normal end organ function. Patients were treated with induction chemotherapy with cisplatin (100 mg/m2 - days 1 and 29) and vinblastine (5 mg/m2/week for 5 weeks) followed by 60 Gy of thoracic radiotherapy. Two weeks after the end of radiotherapy they started a fixed UFT oral dose (400 mg/day), administered continuously for one year if no progression was detected in this interval. Results: Between May 1999 and October 2003, 22 patients were enrolled; 15 were male (68.2%); 65% were white (no patients had oriental ethnicity); 11 were adenocarcinoma (50%), 9 squamous cell (40.9%); the median age was 55.5 years (range: 45–74 years). UFT’s toxicity was manageable with 13.6% of grades 3 and 4 toxicities (mainly fatigue, diarrhea, nausea and vomiting). Two patients discontinue UFT due to limiting toxicity (1 patient due to diarrhea and 1 due to nausea and fatigue). Median time on UFT was 5 months (range: 0.5–12 months). Median follow-up was 13.5 months (range: 6–77 months) and five patients are still alive. The median overall survival (OS) was 14 months (95% CI: 10.6–17.3) and the median progression-free survival was 8 months (95% CI: 3.4–12.5). Conclusions: UFT in this fixed dose schedule was well tolerated, but our results are almost identical to the Dillman′s original report with sequential chemotherapy and radiotherapy in stage IIIB NSCLC (13.7 months OS). Despite our limited sample size these data may suggest that adjuvant UFT do not add any benefit to sequential chemoradiation in this non-oriental population. No significant financial relationships to disclose.
A phase I study of amrubicin (AMR) and irinotecan (CPT-11) in relapsed small cell lung cancer
Authors: Mio T. , Kawahara M. , Fukushima M. , Yanagihara K. , Daimon T. , Furuse K. 
Published: March 2020

18181 Background: AMR and CPT-11 have shown excellent activity in extensive small cell lung cancer (SCLC). The aim of this study was to determine the maximum tolerated dose (MTD) of amrubicin in combination with a fixed dose of CPT-11. Methods: Eligibility criteria were patients having pathologically proven SCLC, had relapsed after one or two previous chemotherapies, ECOG performance status (PS) of 0–2 and adequate organ function. Irinotecan was delivered as 50 mg/m2 on days 1 and 8, every 21 days. AMR was delivered on day 1. Doses of AMR were level 1: 80mg/ m2, level 2: 90 mg/m2 and level 3: 100 mg/ m2. Dose elevation was determined using continuous reassessment method (CRM). Tolerability was assessed after the 1st cycle. Another two cycles were conducted when disease progression or unacceptable toxicities were not observed. Results: Between June 2004 and October 2006, 18 patients were enrolled with the following characteristics: male/female, 15/3; median age, 66.3 years (range 57–61); PS 0/1/2: 4/14/0. Median number of previous treatment cycles was 5. A total of 40 courses were conducted. Grade 3/4 hematological toxicities of 1st cycle were: leukocytopenia: 67% (G3/4: 8/4); neutropenia: 89% (G3/4: 6/10), thrombocytopenia: 11% (G3/4: 1/1). Grade 3 febrile neutropenia occurred in 1 patient. Other grade 3 or greater non-hematological toxicities were observed in 4 of 40 courses (grade 3 infection in 3 courses and diarrhea in 1). In the first course, DLT was observed in 2 of 6 patients at dose level 2 (prolonged grade 4 neutropenia, febrile neutropenia), in 1 of 6 at dose level 3 (prolonged grade 4 neutropenia), MTD of amrubicin were determined by CRM to be 100 mg/m2 (level 3). Objective response was obtained in 4 patients (28%). Conclusions: This combination was well tolerated and showed activities in SCLC, though hematological toxicities were rather severe. Phase II trials are being planned in chemo naïve SCLC. No significant financial relationships to disclose.
Asbestos-related malignant mesothelioma in Japan
Authors: Kishimoto T. 
Published: March 2020

18182 Large amounts of asbestos use from 1960’s induced the increase of death caused by malignant mesothelioma in Japan. However, a national survey of the relationship between malignant mesothelioma and asbestos exposure, as well as diagnosis and treatment of malignant mesothelioma has not done up to today. One hundred and fifty-three cases of malignant mesothelioma diagnosed and treated in the Rosai Hospitals located all over Japan were studied, and 132 cases (80.4%) proved to be the definite diagnosis of malignant mesothelioma; another 21 cases were diagnosed as lung cancer, etc. As for definite 132 cases, 105 cases are male and other 27 cases are female with the ratio of 3.9:1. Ages ranges from 28 to 92 years old with the mean of 66.2 years old. One hundred and twelve cases originated from pleura, 18 cases from peritoneum, and each one case originated from pericardium and testicular tunica vaginalis. Final diagnosis of 104 cases (78.8%) was done by the tumor tissues. According to IMIG classification, stage I was 29 cases, stage II 6 cases, stage III 28 cases and stage IV was 44 cases. For the treatment, 29 cases were done extrapleurectomy, 58 cases were chemotherapy and other 39 cases were best supportive care. Median survival term of 132 cases were 9.5 months with 9.8 months of pleural origin and 5.6 months of peritoneal origin. By the clinical staging, stage I and II were 17.2 months, stage III 10.4 months and stage IV 5.4 months. By the treatment, extrapleurectomy was 18.1 months, chemotherapy 8.0 months and palliative care was 5.7 months. Seventy six percent cases were induced by occupational asbestos exposure and the mean exposuring time was 27.6 years and the mean latency was 43 years. Occupational histories were mainly shipbuilders, carpenters, electricians and piping workers. Summary: Seventy-six percent of Japanese malignant mesothelioma appeared by the occupational exposure to asbestos. Seventy-eight percent of final diagnosis were done by histological examination of tumor tissue. Extrapleurectomy was effective for the prognosis. [Table: see text] No significant financial relationships to disclose.