Cisplatin Plus Gemcitabine or Vinorelbine for Elderly Patients With Advanced Non–Small-Cell Lung Cancer: The MILES-2P Studies

2007 ◽  
Vol 25 (29) ◽  
pp. 4663-4669 ◽  
Author(s):  
Cesare Gridelli ◽  
Paolo Maione ◽  
Alfonso Illiano ◽  
Franco Vito Piantedosi ◽  
Adolfo Favaretto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Elderly Patients ◽  
Phase I ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Unacceptable Toxicity

PurposeTwo phase I/II trials were done to evaluate the feasibility of cisplatin combined with gemcitabine or vinorelbine in elderly patients with advanced non–small-cell lung cancer (NSCLC).Patients and MethodsPatients with advanced NSCLC who were older than 70 years of age and who had a performance status of 0 to 1 were eligible. Cisplatin was given on day 1 (a starting dose of 50 mg/m2with increasing increments of 10 mg/m2at each level) and gemcitabine (1,000 mg/m2) or vinorelbine (25 mg/m2) on days 1 and 8. Cycles were repeated every 21 days. A two-stage flexible optimal design was applied in the phase II study, and unacceptable toxicity was the primary end point.ResultsOverall, 159 patients were enrolled: 38 in phase I and 121 in phase II studies. Cisplatin was feasible at 60 mg/m2with gemcitabine and at 40 mg/m2with vinorelbine. With the former combination, 50 of 60 (83.3%) patients were treated without unacceptable toxicity; objective responses were reported in 26 of 60 patients (43.5%; 95% CI, 30.6 to 56.8); median progression-free and overall survivals were 25.3 and 43.6 weeks, respectively. With the latter combination, 50 (82.0%) of 61 patients were treated without unacceptable toxicity; objective responses were reported in 22 of 61 patients (36.1%; 95% CI, 24.2 to 49.4); median progression-free and overall survivals were 21.1 and 33.1 weeks, respectively.ConclusionBoth cisplatin (60 mg/m2) plus gemcitabine and cisplatin (40 mg/m2) plus vinorelbine are feasible and active in the treatment of elderly patients with advanced NSCLC. The former combination, which provides a higher dose of cisplatin, deserves comparison versus single-agent chemotherapy in this setting of patients.

A phase I trial of S-1 plus vinorelbine in patients with unresectable advanced or metastatic non-small cell lung cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19098-e19098
Author(s):  
H. Suyama ◽  
Y. Shigeoka ◽  
T. Igishi ◽  
S. Matsumoto ◽  
M. Kodani ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase I ◽  
Small Cell Lung Cancer ◽  
Dose Level ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Phase I Trial ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung

e19098 Background: We reported the efficacy of the combination treatment of tegafur-uracil (UFT) and vinorelbine (VNR) for the elderly patients (pts) (>70) with advanced non-small cell lung cancer (NSCLC) in ASCO 2007 (Abstract - No. 18075). Although the cisplatin-based doublets are still milestone for the pts with advanced NSCLC, non-platinum based doublet regimens remain as a matter of development judging from recent meta-analysis. Tegafur-5-chloro-2,4-dihydroxypyridine-potassium oxonate (S-1), a new oral fluoropyrimidine, has been studied extensively, and appears promising for various kinds of cancers including NSCLC. Thus, we conducted this phase I trial using VNR and new oral fluoropyrimidine, S-1. Methods: Pts with advanced NSCLC, who had received at least one prior platinum-containing regimen, were eligible. In this phase I study, VNR was infused on days 1 and 8, and S-1 was administered from day 2 to day 6 and from day 9 to day 13 of a 3-week cycle. The starting dose of S-1 was 80 mg/m2/day and, if necessary, the dose was decreased to 65 mg/m2/day; VNR was increased from 20 to 25 mg/m2 in this trial. Results: From August 14, 2007 to April 1, 2008, 8 pts enrolled in this study. Median age was 61 (range 49–75). Dose limiting toxicity (DLT) was evaluated during the first 6 weeks of the treatment. No DLT was observed at dose level I (80 mg/m2/day S-1, 20 mg/m2 VNR). At dose level II (80 mg/m2/day S-1, 25 mg/m2 VNR), DLT in the form of neutropenia, hyperglycemia and hyponatremia was observed in 3 of 5 pts. The maximum tolerated dose (MTD) for the present treatment was 80 mg/m2/day S-1 and 25 mg/m2 VNR; the recommended tolerable dose for future phase II trials is therefore 80 mg/m2/day S-1 and 20 mg/m2 VNR. Conclusions: Three-week cycle of VNR (20 mg/m2), infused on days 1 and 8; S-1 (80 mg/m2/day), administered from day 2 to day 6 and from day 9 to day 13, is being examined in our phase II trial for first-or second-line treatment of NSCLC. No significant financial relationships to disclose.

Phase I trial of docetaxel and cisplatin in previously untreated patients with advanced non-small-cell lung cancer.

1997 ◽  
Vol 15 (2) ◽  
pp. 750-758 ◽  
Author(s):  
M J Millward ◽  
J Zalcberg ◽  
J F Bishop ◽  
L K Webster ◽  
A Zimet ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase I ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Prior Chemotherapy ◽  
Phase Ii Studies

PURPOSE To determine the maximum-tolerated doses (MTDs), principal toxicities, and pharmacokinetics of the combination of docetaxel and cisplatin administered every 3 weeks to patients with advanced non-small-cell lung cancer (NSCLC) who have not received prior chemotherapy and to recommend a dose for phase II studies. PATIENTS AND METHODS Patients with advanced NSCLC and performance status 0 to 2 who had not received prior chemotherapy received docetaxel over 1 hour followed by cisplatin over 1 hour with hydration. Dose levels studied were (docetaxel/cisplatin) 50/75, 75/75, 75/100, and 100/75 mg/m2 repeated every 3 weeks. Colony-stimulating factor (CSF) support was not used. Pharmacokinetics of docetaxel and cisplatin were studied in the first cycle of therapy. Most patients (79%) had metastatic disease or intrathoracic recurrence after prior radiation and/or surgery. RESULTS Of 24 patients entered, all were assessable for toxicity and 18 for response. The MTD schedules were docetaxel 75 mg/m2 with cisplatin 100 mg/m2 (dose-limiting toxicities [DLTs] in five of six patients), and docetaxel 100 mg/m2 with cisplatin 75 mg/m2 (DLTs in two of two patients, including one fatal toxicity). Limiting toxicities were febrile neutropenia and nonhematologic, principally diarrhea and renal. Two patients had neutropenic enterocolitis. Pharmacokinetics of both drugs were consistent with results from single-agent studies, which suggests no major pharmacokinetic interaction. Neutropenia was related to docetaxel area under the plasma concentration-versus-time curve (AUC). An alternative schedule was investigated, with cisplatin being administered over 3 hours commencing 3 hours after docetaxel, but toxicity did not appear to be less. Independently reviewed responses occurred in eight of 18 patients (44%; 95% confidence interval, 22% to 69%), most following 75 mg/m2 of both drugs. CONCLUSION Docetaxel 75 mg/m2 over 1 hour followed by cisplatin 75 mg/m2 over 1 hour is recommended for phase II studies. The responses seen in this phase I study suggest a high degree of activity of this combination in previously untreated advanced NSCLC.

A phase I/II, pharmacokinetic (PK) and pharmacogenomic (PG) study of weekly irinotecan (CPT-11) therapy for elderly patients with advanced non-small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2539-2539
Author(s):  
H. Isobe ◽  
N. Yamamoto ◽  
H. Kunikane ◽  
N. Masuda ◽  
K. Eguchi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Elderly Patients ◽  
Phase I ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Phase I Study ◽  
Small Cell ◽  
Small Cell Lung ◽  
Level 1

2539 Background: CPT-11 is commonly used to treat lung cancer, but there is little evidence about its efficacy in elderly patients. The aim of this study was to determine the recommended dose (RD) of CPT-11 for weekly administration to elderly patients, and to assess its efficacy and safety. In addition, a PK and PG study was performed to investigate the influence on the clinical outcome. Methods: CPT-11 was infused intravenously on Days 1 and 8 (every 21 days). In the phase I study, the dosage of CPT-11 was escalated from 60 (Level 1) to 80 (Level 2) and 100 mg/m2 (Level 3). PK of CPT-11 and SN-38, and UGT1A1 polymorphism were analyzed during the first treatment cycle in the phase II study. Results: In the phase I study, 12 patients were enrolled (level 1/2/3=6/3/3) and the RD was determined to be 100 mg/m2. The 37 patients in phase II had the following characteristics: male/female=25/12, median age=77 (71–88), IIIB/IV=10/27, PS 0/1=12/25. The overall response rate and the disease control rate (PR+SD) was 8% and 73%, respectively. The median survival time was 441 days and the 1-year survival rate was 54.0%. Grade 3/4 neutropenia and diarrhea occurred in 27% and 8%, respectively. The AUCs for both CPT-11 and SN-38 were significantly correlated with neutropenia (P=0.0095, P=0.0004). Both the UGT1A1*6 and UGT1A1*28 genotypes were significantly correlated with the AUC ratio, leukopenia, and neutropenia ( Table ). Conclusion: CPT-11 monotherapy is considered to be effective for non-small cell lung cancer in elderly patients because good survival with tolerable adverse events were achieved. The UGT1A1*6 and UGT1A1*28 genotypes might both influence the toxicity of irinotecan in Asians. [Table: see text] [Table: see text]

Phase I and pharmacokinetic (PK) study of Nedaplatin (254-S) in elderly patients with advanced non-small cell lung cancer (NSCLC)

Lung Cancer ◽  
2000 ◽  
Vol 29 (1) ◽  
pp. 69 ◽  
Author(s):  
T Kurata ◽  
T Tamura ◽  
N Yamamoto ◽  
I Sekine ◽  
H Kunitoh ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Elderly Patients ◽  
Phase I ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

Phase II, Multicenter, Uncontrolled Trial of Single-Agent Sorafenib in Patients With Relapsed or Refractory, Advanced Non–Small-Cell Lung Cancer

2009 ◽  
Vol 27 (26) ◽  
pp. 4274-4280 ◽  
Author(s):  
George R. Blumenschein ◽  
Ulrich Gatzemeier ◽  
Frank Fossella ◽  
David J. Stewart ◽  
Lisa Cupit ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Continuous Treatment ◽  
Small Cell Lung

PurposeSorafenib is an oral multikinase inhibitor that targets the Ras/Raf/MEK/ERK mitogenic signaling pathway and the angiogenic receptor tyrosine kinases, vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor β. We evaluated the antitumor response and tolerability of sorafenib in patients with relapsed or refractory, advanced non–small-cell lung cancer (NSCLC), most of whom had received prior platinum-based chemotherapy.Patients and MethodsThis was a phase II, single-arm, multicenter study. Patients with relapsed or refractory advanced NSCLC received sorafenib 400 mg orally twice daily until tumor progression or an unacceptable drug-related toxicity occurred. The primary objective was to measure response rate.ResultsOf 54 patients enrolled, 52 received sorafenib. The predominant histologies were adenocarcinoma (54%) and squamous cell carcinoma (31%). No complete or partial responses were observed. Stable disease (SD) was achieved in 30 (59%) of the 51 patients who were evaluable for efficacy. Four patients with SD developed tumor cavitation. Median progression-free survival (PFS) was 2.7 months, and median overall survival was 6.7 months. Patients with SD had a median PFS of 5.5 months. Major grades 3 to 4, treatment-related toxicities included hand-foot skin reaction (10%), hypertension (4%), fatigue (2%), and diarrhea (2%). Nine patients died within a 30-day period after discontinuing sorafenib, and one patient experienced pulmonary hemorrhage that was considered drug related.ConclusionContinuous treatment with sorafenib 400 mg twice daily was associated with disease stabilization in patients with advanced NSCLC. The broad activity of sorafenib and its acceptable toxicity profile suggest that additional investigation of sorafenib as therapy for patients with NSCLC is warranted.

Sign in / Sign up

Export Citation Format

Share Document