Carboplatin and Paclitaxel Plus ASA404 as First-Line Chemotherapy for Extensive-Stage Small-Cell Lung Cancer: A Multicenter Single Arm Phase II Trial (SAKK 15/08)

被引：18

作者：

Frueh, Martin ^{[1
]}

Cathomas, Richard ^{[2
]}

Siano, Marco ^{[1
]}

Tscherry, Gregor ^{[3
]}

Zippelius, Alfred ^{[4
]}

Mamot, Christoph ^{[5
]}

Erdmann, Andreas ^{[6
]}

Krasniqi, Fatima ^{[4
]}

Rauch, Daniel

Simcock, Mathew

Kuettel, Erika

Fustier, Pierre ^{[7
]}

Pless, Miklos ^{[8
]}

机构：

[1] Cantonal Hosp St Gallen, Dept Oncol & Hematol, St Gallen, Switzerland

[2] Cantonal Hosp Graubunden, Dept Med Oncol, Chur, Switzerland

[3] Hosp Uster, Dept Med, Uster, Switzerland

[4] Univ Basel Hosp, Dept Med Oncol, CH-4031 Basel, Switzerland

[5] Cantonal Hosp Aarau, Dept Med Oncol, Aaru, Switzerland

[6] Cantonal Hosp Baden, Dept Med, Baden, Switzerland

[7] Swiss Grp Clin Canc Res, Coordinating Ctr, SAKK, Bern, Switzerland

[8] Kantonsspital Winterthur, Dept Med Oncol, Winterthur, Switzerland

来源：

CLINICAL LUNG CANCER | 2013年 / 14卷 / 01期

关键词：

Extensive stage small cell lung cancer; Phase II trial; Serotonin; Small cell; Vascular disrupting; Vascular disruptive agent; 5,6-DIMETHYLXANTHENONE-4-ACETIC ACID DMXAA; CROSS-RESISTANT CHEMOTHERAPY; PLATINUM-BASED CHEMOTHERAPY; TUMOR-NECROSIS-FACTOR; FLAVONE-8-ACETIC ACID; ANTIVASCULAR AGENT; RANDOMIZED-TRIAL; CISPLATIN; DOXORUBICIN; ETOPOSIDE;

D O I：

10.1016/j.cllc.2012.04.001

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We explored the tumor-vascular disrupting agent ASA404 plus carboplatin and paclitaxel in extensive-stage small-cell lung cancer. The trial was prematurely closed after 17 patients. Progression-free survival (PFS) at 24 weeks, median PFS, overall response rate, and 1-year survival were 41%, 7 months, 94%, and 57%, respectively. No unexpected toxicities occurred. Although the overall response rate was high, PFS was not prolonged. Introduction: Small-cell lung cancer (SCLC) is a highly vascularized tumor. ASA404 is a tumor vascular disrupting agent. This is the first trial to report the effects of combining chemotherapy with ASA404 in SCLC. Methods: Patients with untreated metastatic SCLC were treated with carboplatin (area under curve, 6) plus paclitaxel (175 mg/m(2)) plus ASA404 (1800 mg/m(2)) on day 1 every 21 days for up to 6 cycles. The primary endpoint was the progression-free survival (PFS) rate at 24 weeks. Results: Median age was 61 years; 53% were women, 41% had weight loss; and 96% had a performance status of 0-1. Twelve patients completed all 6 cycles, and most adverse events were related to chemotherapy. Median PFS and time to progression were 7.0 months (95% CI, 5.7-9.4 months) and 7.5 months (95% CI, 5.7-9.4 months), respectively. The progression-free survival (PFS) rate at 24 weeks was 41% (95% CI, 18%-65%). The overall response rate was 94%. The median overall survival time was 14.2 months (95% CI, 8.2-16.0 months) and 1-year survival was 57%. The median follow-up time was 17.7 months. Due to negative results with ASA404 in non-small-cell lung cancer trials, the trial was stopped prematurely after 17 of 56 planned patients were being accrued. Conclusions: This is the first report of a clinical trial with a vascular disrupting agent in SCLC. No unexpected toxicity was observed. PFS was not prolonged with carboplatin and paclitaxel plus ASA404. Clinical Lung Cancer, Vol. 14, No. 1, 34-9 (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：34 / 39

页数：6

共 44 条

[31] Cisplatin, Irinotecan, and Bevacizumab for Untreated Extensive-Stage Small-Cell Lung Cancer: CALGB 30306, a Phase II Study [J].

Ready, Neal E. ;

Dudek, Arkadiusz Z. ;

Pang, Herbert H. ;

Hodgson, Lydia D. ;

Graziano, Stephen L. ;

Green, Mark R. ;

Vokes, Everett E. .

JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (33) :4436-4441

[32] RANDOMIZED STUDY OF CYCLOPHOSPHAMIDE, DOXORUBICIN, AND VINCRISTINE VERSUS ETOPOSIDE AND CISPLATIN VERSUS ALTERNATION OF THESE 2 REGIMENS IN EXTENSIVE SMALL-CELL LUNG-CANCER - A PHASE-III TRIAL OF THE SOUTHEASTERN CANCER STUDY-GROUP [J].

ROTH, BJ ;

JOHNSON, DH ;

EINHORN, LH ;

SCHACTER, LP ;

CHERNG, NC ;

COHEN, HJ ;

CRAWFORD, J ;

RANDOLPH, JA ;

GOODLOW, JL ;

BROUN, GO ;

OMURA, GA ;

GRECO, FA .

JOURNAL OF CLINICAL ONCOLOGY, 1992, 10 (02) :282-291

[33] 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a novel antivascular agent: phase I clinical and pharmacokinetic study [J].

Rustin, GJS ;

Bradley, C ;

Galbraith, S ;

Stratford, M ;

Loadman, P ;

Waller, S ;

Bellenger, K ;

Gumbrell, L ;

Folkes, L ;

Halbert, G .

BRITISH JOURNAL OF CANCER, 2003, 88 (08) :1160-1167

[34] Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer [J].

Scagliotti, Giorgio Vittorio ;

Parikh, Purvish ;

von Pawel, Joachim ;

Biesma, Bonne ;

Vansteenkiste, Johan ;

Manegold, Christian ;

Serwatowski, Piotr ;

Gatzemeier, Ulrich ;

Digumarti, Raghunadharao ;

Zukin, Mauro ;

Lee, Jin S. ;

Mellemgaard, Anders ;

Park, Keunchil ;

Patil, Shehkar ;

Rolski, Janusz ;

Goksel, Tuncay ;

de Marinis, Filippo ;

Simms, Lorinda ;

Sugarman, Katherine P. ;

Gandara, David .

JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (21) :3543-3551

[35] Phase II Trial of Sunitinib Maintenance Therapy After Platinum-Based Chemotherapy in Patients with Extensive-Stage Small Cell Lung Cancer [J].

Schneider, Bryan J. ;

Gadgeel, Shirish M. ;

Ramnath, Nithya ;

Wozniak, Antoinette J. ;

Dy, Grace K. ;

Daignault, Stephanie ;

Kalemkerian, Gregory P. .

JOURNAL OF THORACIC ONCOLOGY, 2011, 6 (06) :1117-1120

[36] Vascular targeting agents enhance chemotherapeutic agent activities in solid tumor therapy [J].

Siemann, DW ;

Mercer, E ;

Lepler, S ;

Rojiani, AM .

INTERNATIONAL JOURNAL OF CANCER, 2002, 99 (01) :1-6

[37] Marked potentiation of the antitumour activity of chemotherapeutic drugs by the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) [J].

Siim, BG ;

Lee, AE ;

Shalah-Zwain, S ;

Pruijn, FB ;

McKeage, MJ ;

Wilson, WR .

CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2003, 51 (01) :43-52

[38] RANDOMIZED COMPARISON OF ETOPOSIDE-CISPLATIN VS ETOPOSIDE-CARBOPLATIN AND IRRADIATION IN SMALL-CELL LUNG-CANCER - A HELLENIC COOPERATIVE ONCOLOGY GROUP-STUDY [J].

SKARLOS, DV ;

SAMANTAS, E ;

KOSMIDIS, P ;

FOUNTZILAS, G ;

ANGELIDOU, M ;

PALAMIDAS, P ;

MYLONAKIS, N ;

PROVATA, A ;

PAPADAKIS, E ;

KLOUVAS, G ;

THEOCHARIS, D ;

PANOUSAKI, E ;

BOLETI, E ;

SPHAKIANOUDIS, G ;

PAVLIDIS, N .

ANNALS OF ONCOLOGY, 1994, 5 (07) :601-607

[39] Phase III Study of Pemetrexed Plus Carboplatin Compared With Etoposide Plus Carboplatin in Chemotherapy-Naive Patients With Extensive-Stage Small-Cell Lung Cancer [J].

Socinski, Mark A. ;

Smit, Egbert F. ;

Lorigan, Paul ;

Konduri, Kartik ;

Reck, Martin ;

Szczesna, Aleksandra ;

Blakely, Johnetta ;

Serwatowski, Piotr ;

Karaseva, Nina A. ;

Ciuleanu, Tudor ;

Jassem, Jacek ;

Dediu, Mircea ;

Hong, Shengyan ;

Visseren-Grul, Carla ;

Hanauske, Axel-Rainer ;

Obasaju, Coleman K. ;

Guba, Susan C. ;

Thatcher, Nick .

JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (28) :4787-4792

[40] Randomized Phase II Study of Bevacizumab in Combination With Chemotherapy in Previously Untreated Extensive-Stage Small-Cell Lung Cancer: Results From the SALUTE Trial [J].

Spigel, David R. ;

Townley, Peter M. ;

Waterhouse, David M. ;

Fang, Liang ;

Adiguzel, Ibrahim ;

Huang, Jane E. ;

Karlin, David A. ;

Faoro, Leonardo ;

Scappaticci, Frank A. ;

Socinski, Mark A. .

JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (16) :2215-2222

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