Phase I/II Study of Escalating Doses of Vinorelbine in Combination With Oxaliplatin in Patients With Advanced Non–Small-Cell Lung Cancer

2001 ◽  
Vol 19 (2) ◽  
pp. 458-463 ◽  
Author(s):  
Isabelle Monnet ◽  
Patrick Soulié ◽  
Hubert de Cremoux ◽  
Sabine Saltiel-Voisin ◽  
Mohammed Bekradda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase I ◽  
Small Cell Lung Cancer ◽  
Dose Level ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Fixed Dose ◽  
Platinum Compound ◽  
Small Cell Lung ◽  
Dose Levels

PURPOSE: Oxaliplatin is a platinum compound active in non–small-cell lung cancer (NSCLC) patients, and vinorelbine (VNB) is an active reference agent. This phase I/II study was performed to determine the dose-limiting toxicity (DLT), the maximum-tolerated dose (MTD), and the recommended dose (RD) of a VNB/oxaliplatin combination given to previously untreated patients with advanced NSCLC. PATIENTS AND METHODS: Oxaliplatin was given at the fixed dose of 130 mg/m2 (2-hour intravenous [IV] infusion) on day 1. VNB was administered on days 1 and 8 (10-minute IV infusion), with doses starting at 22 mg/m2/d and escalated by 2 mg/m2 increments until MTD. Treatment was repeated every 3 weeks. No special hydration measures or prophylactic granulocyte colony-stimulating factors were used. RESULTS: Twenty-seven patients (20 men, 7 women) received 110 cycles total at six different VNB dose levels. Neutropenia was the DLT. Although no patient experienced DLT at the highest dose level (32 mg/m2/d), multiple treatment delays (54% of cycles) and dose reductions (34% of cycles) were required at this dose level. Others toxicities were mainly limited to grade 1 peripheral neuropathy and grade 1/2 nausea/vomiting. The relative dose-intensity of administered VNB from dose levels 3 to 6 (26 to 32 mg/m2) remained stable, whereas grade 3/4 neutropenia increased. All patients were assessable for activity; there were 10 objective responses, including one complete response (37% response rate). CONCLUSION: The present combination can be safely administered in an outpatient setting. The RD is VNB 26 mg/m2 days 1 and 8 with oxaliplatin 130 mg/m2 day 1 every 3 weeks.

A phase I study of weekly topotecan and vinorelbine in recurrent lung cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17140-17140
Author(s):  
M. A. Beldner
Keyword(s):  
Lung Cancer ◽  
Phase I ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Phase I Study ◽  
Single Agent ◽  
Small Cell ◽  
Fixed Dose ◽  
Small Cell Lung ◽  
Cytotoxic Effects

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.

A phase I and pharmacologic study of belotecan in combination with cisplatin in patients with previously untreated extensive-stage disease small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18053-18053
Author(s):  
J. Lee ◽  
D. Lee ◽  
K. Bae ◽  
S. Kim ◽  
C. Suh ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Antitumor Activity ◽  
Phase I ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Fixed Dose ◽  
Small Cell Lung ◽  
Stage Disease ◽  
Extensive Stage

18053 Background: Belotecan (CKD602) is a novel camptothecin derivative antitumor agent. This phase I study was designed to determine the maximum-tolerated dose (MTD), toxicity profile, and dose-limiting toxicity (DLT) of belotecan in combination with cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer (ED SCLC). Furthermore, pharmacokinetics (PK) and preliminary antitumor activity of belotecan against SCLC were evaluated. Methods: Patients with ED SCLC, age 18–70, ECOG PS 0–2, no prior chemotherapy and adequate organ function were eligible. Cisplatin with fixed dose of 60 mg/m2 was administered intravenously (i.v.) over 2 hours on day 1. Belotecan was administered iv as intermittent 30-minute infusions on days 1 to 4, starting dose of 0.40 mg/m2/day with increment of 0.05 mg/m2/day. Modified Fibonacci escalation was used (3 to 6 patients per cohort) and intra-patient dose escalation was not allowed. PK of belotecan was determined during the first treatment using non-compartmental pharmacokinetic analysis. Results: Seventeen patients were treated at 4 dose levels (0.40 to 0.55 mg/m2/day). At 0.55 mg/m2/day of belotecan, the DLT of grade 4 neutropenia with fever occurred in 2 of 5 patients, and therefore the MTD was 0.50 mg/m2/day. Interestingly, out of 17 patients, there were 14 partial responses (82.4%; 95% CI, 63.4% to 100.0%). PK analysis revealed that at 0.50 mg/m2/day, plasma clearance of belotecan was 5.78 ± 1.32 L/hr and terminal half-life was 8.55 ± 2.12 hr. Fraction of excreted amount in urine was 37.36 ± 5.55 %. PK of belotecan were not altered by administration of cisplatin, as compared with historical control. Conclusions: The MTD of belotecan was 0.50 mg/m2/day for intermittent 30-min i.v. infusion for 4 days in combination with cisplatin 60 mg/m2 on day 1 every 3 weeks. Furthermore, very promising antitumor activity against SCLC was observed. The phase II study is being conducted now. No significant financial relationships to disclose.

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/II study of amrubicin and nedaplatin in patients with untreated, advanced non-small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7569-7569
Author(s):  
Hiroaki Senju ◽  
Daiki Ogawara ◽  
Yoichi Nakamura ◽  
Minoru Fukuda ◽  
Katsumi Nakatomi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase I ◽  
Small Cell Lung Cancer ◽  
Dose Level ◽  
Cell Lung Cancer ◽  
Phase I Study ◽  
Maximum Tolerated Dose ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

7569 Background: We conducted a phase I/II study of combination chemotherapy with nedaplatin (CDGP) and amrubicin (Amr) for patients with untreated, advanced non small-cell lung cancer (NSCLC). Methods: Eligible patients were having adequate organ function and PS of 0-1. CDGP was given on day 1 and amrubicin on days 1, 2 and 3. The treatment was repeated every 3 weeks. We fixed the dose of CDGP as 100 mg/m2, and escalated the dose of amrubicin from a starting dose of 25 mg/m2 by 5mg/m2 per each levels until the maximum tolerated dose (MTD). The MTD was defined as the dose level at which at least two of three or two of six patients experienced a dose-limiting toxicity (DLT). Results: Between June 2009 and May 2011, 36 patients were enrolled. In the phase I study, two DLTs occurred in six patients at level 2; dose level 1 was therefore recommended (25 mg/m2 Amr, 100mg/m2 CDGP). DLTs included cerebral infarction and grade 4 thrombocytopenia. In the phase II study, including phase I study, a total of 36 patients were enrolled and 132 cycles of chemotherapy were conducted. Grade 3 or 4 neutropenia, grade 3 anemia and grade 3 or 4 thrombocytopenia occurred in 75%, 16.6% and 19.4% in all cycles, respectively. Febrile neutropenia occurred in 4cycles (3%) but all of them were controllable. Eighteen patients achieved a partial response and the overall response rate was 51.4%. Conclusions: Combination of CDGP and Amr was highly effective and well tolerable in patients with untreated, advanced NSCLC.

Phase I-II study of high-dose epirubicin in advanced non-small-cell lung cancer.

1992 ◽  
Vol 10 (2) ◽  
pp. 297-303 ◽  
Author(s):  
R Feld ◽  
R Wierzbicki ◽  
P L Walde ◽  
F A Shepherd ◽  
W K Evans ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase I ◽  
Small Cell Lung Cancer ◽  
Dose Level ◽  
Cell Lung Cancer ◽  
Response Rate ◽  
Small Cell ◽  
High Dose ◽  
Small Cell Lung ◽  
Febrile Episodes

PURPOSE A phase I multicenter trial was performed to determine the maximum-tolerated dose (MTD) of epirubicin, given on 3 consecutive days every 3 weeks to previously untreated patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS After appropriate staging and a baseline multiple-gated angiogram (MUGA) scan, at least four patients were entered at each dose level, starting at 35 mg/m2 of epirubicin given intravenously (IV) daily for 3 days (105 mg/m2) and escalating by 5 mg/m2 per injection in each dose level (15 mg/m2 per course). Epirubicin was administered up to a maximum dose of 60 mg/m2/d for 3 days (180 mg/m2). The MTD was determined to be 55 mg/m2/d for 3 days (165 mg/m2) after treating a total of 35 (33 assessable) patients. Nadir granulocyte counts and associated febrile episodes comprised the dose-limiting toxicity, but there were no treatment-related deaths. A phase II trial was performed using a dose of 50 mg/m2/d for 3 days (150 mg/m2) every 3 weeks with no dose escalation, but with dose reduction for toxicity as required. A total of 30 patients were entered onto this phase of the study. RESULTS The major toxicity, as in the phase I trial, was neutropenia with five febrile episodes, again with no treatment-related deaths. An overall response rate of 12 of 63 (19%) was noted in the combined patient population of the phase I-II trial, with 95% confidence intervals of 10% to 31%. When the response rate was analyzed by histology, only one of 17 (6%) patients with squamous histology, as compared with 11 of 46 (24%) with non-squamous histology, responded, but this did not reach statistical significance (P = .15). CONCLUSIONS High-dose epirubicin is tolerable and is an active single agent in NSCLC. It should be combined with relatively nonmyelosuppressive agents such as cisplatin to try to obtain higher response rates and extend the survival in this disease.

A dose finding and PK/PD study of weekly amrubicin in patients with refractory or relapsed lung cancer: Central Japan Lung Study Group (CJLSG) 0601 trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13517-e13517
Author(s):  
C. Kitagawa ◽  
H. Saka ◽  
T. Adachi ◽  
S. Kajikawa ◽  
K. Mori ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Dose Level ◽  
Cell Lung Cancer ◽  
Maximum Tolerated Dose ◽  
Small Cell ◽  
Dose Finding ◽  
Weekly Dose ◽  
Small Cell Lung ◽  
Dose Levels

e13517 Background: Amrubicin (AMR) is a potent topoisomerase II inhibitor, and a promising agent for both small cell and non-small cell lung cancer. AMR is usually administered on days 1–3 intravenously. However, it causes severe, occasionally fatal, toxicity of leucopenia and neutropenia. The purpose of this study was to evaluate the safety and tolerability of AMR, to determine the recommended weekly dose, and to conduct a PK/PD study in patients with chemotherapy-refractory or recurrent lung cancer. Methods: Refractory or relapsed non-small cell and small cell lung cancer patients after 1 or 2 regimens, younger than 80 and with adequate main organ functions were eligible. AMR was initiated 45 mg/m2 given weekly (on day 1 and 8 q3wks). The dose level was increased by 5 mg/m2 by modified Fibonacci dose escalation scheme. Dose limiting toxicity (DLT) was assessed on the 1st cycle. Results: 16 patients were enrolled. Patients were 7 small cell lung cancer and 9 non-small cell lung cancer. 54 cycles (median: 3, range: 1–6) were administered in 5 dose levels. In 65 mg/m2 level, 3 patients had DLTs. The maximum tolerated dose was 65 mg/m2. The recommended weekly AMR dose was determined to be 60 mg/m2. Leucocytopenia, neutropenia, thrombocytopenia, and the dose level were correlated (p<0.001, p=0.0012, p=0.043) respectively. Leucocytopenia, neutropenia, and amrubicinol (AMR-OH) Cmax were correlated (p=0.042, p=0.047) respectively. AUC (AUC extrapolated to concentration-zero) of AMR and AMR-OH did not depend on the dose levels. The pharmacokinetic results are shown in the Table. [Table: see text] [Table: see text]

scholarly journals P1.01-91 A Phase I Study of Fixed Dose Vinorelbine and Escalating Doses of Ifosfamide in First-Line Advanced Non-Small Cell Lung Cancer

2018 ◽  
Vol 13 (10) ◽  
pp. S498
Author(s):  
J. Surujballi ◽  
D. Breadner ◽  
D. Morris ◽  
A. O'Connor ◽  
F. Whiston ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase I ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Phase I Study ◽  
Small Cell ◽  
Fixed Dose ◽  
Small Cell Lung ◽  
First Line

Phase I/II Study of Gemcitabine Plus Vinorelbine as First-Line Chemotherapy of Non–Small-Cell Lung Cancer

2000 ◽  
Vol 18 (2) ◽  
pp. 405-405 ◽  
Author(s):  
Vito Lorusso ◽  
Francesco Carpagnano ◽  
Giuseppe Frasci ◽  
Nicola Panza ◽  
Gaetano Di Rienzo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase I ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Stage Iv ◽  
Small Cell ◽  
Stage Iiib ◽  
Fixed Dose ◽  
Small Cell Lung

PURPOSE: To determine the maximum-tolerated dose of gemcitabine when combined with a fixed dose of vinorelbine in the treatment of non–small-cell lung cancer (NSCLC) and to evaluate in a phase II trial the activity of this combination. PATIENTS AND METHODS: Sixty-eight patients with stage IIIB/IV NSCLC were treated with vinorelbine at fixed dose of 30 mg/m2 intravenously and gemcitabine at increasing dose levels from 800 to 1,500 mg/m2 intravenously on days 1 and 8 every 3 weeks. RESULTS: In phase I, dose-limiting toxicity occurred at the dosage of 1,500 mg/m2 gemcitabine, with three of five patients developing grade 4 thrombocytopenia. In phase II, with gemcitabine at 1,200 mg/m2, 19 (36%) of 52 assessable patients responded. Objective response was observed in 11 (39%) of 28 patients with stage IIIB disease and in eight (33%) of 24 patients with stage IV. The median time to progression was 29 weeks (range, 2 to 41 weeks; 35 weeks and 16 weeks for stages IIIB and IV, respectively), and median survival was 54 weeks (range, 2 to 84+ weeks; 63 weeks and 42 weeks for stages IIIB and IV, respectively). One-year survival was 64% for patients with stage IIIB disease and 29% for those with stage IV. Clinical benefit response was observed in 29 (59%) of 49 assessable patients. Grade 4 leukopenia and thrombocytopenia were uncommon (6% and 8% of cases, respectively); however, grade 3/4 leukothrombocytopenia occurred more frequently in patients aged more than 70 years (52% and 24%, respectively). CONCLUSION: The combination of vinorelbine and gemcitabine is effective and tolerable in the treatment of NSCLC, thus deserving randomized trials with cisplatin combination regimens.

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