Preclinical and clinical evaluation of four gemcitabine plus carboplatin schedules as front-line treatment for stage IV non-small-cell lung cancer

被引:15
|
作者
Bajetta, E
Stani, SC
De Candis, D
Zaffaroni, N
Zilembo, N
Cortinovis, D
Aglione, S
Mariani, L
Formisano, B
Bidoli, P
机构
[1] Ist Nazl Studio & Cura Tumori, Med Oncol Unit B, I-20133 Milan, Italy
[2] Ist Nazl Studio & Cura Tumori, Unit Expt Oncol C, I-20133 Milan, Italy
[3] Ist Nazl Studio & Cura Tumori, Unit Med Stat & Biometry, I-20133 Milan, Italy
关键词
carboplatin; gemcitabine; non-small-cell lung cancer;
D O I
10.1093/annonc/mdg060
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: To explore the activity and tolerability of gemcitabine (GEM) and carboplatin (CBDCA) in non-small-cell lung cancer (NSCLC) we tested four administration sequences on H460 NSCLC cells, and at the same time performed a randomized phase II trial using analogous schedules. Patients and methods: GEM was given first in two in vitro sequences, and CBDCA first in the other two; interaction was quantified calculating a combination index. Eighty-eight chemotherapy-naive, stage IV NSCLC patients were randomly assigned to receive either: GEM (1000 mg/m(2)) on days 1 and 8 and CBDCA (AUC 5 mg.min/ml) on day 1, 4 h before GEM (arm A); same as arm A except CBDCA given 4 h after GEM (arm 13); GEM on days 1 and 8 and CBDCA on day 2 (arm Q; GEM on days 2 and 9 and CBDCA on day I (arm D). Courses were repeated every 21 days. Results: In the preclinical study, CBDCA given before GEM produced a synergistic cytotoxic effect. Two complete and 29 partial responses occurred in 86 of 88 treated patients (intention-to-treat analysis 35%; 95% confidence interval 25.5% to 46.8%). One- and 2-year survivals were 44% and 11%, respectively. Grade 3/4 thrombocytopenia occurred in 11%; grade 3/4 neutropenia in 17% and non-hematological toxicity was insignificant. Median survival was 11 months (range 7-18+), but better in patients receiving CBDCA first (arms A and D) (13 versus 9 months) than in patients receiving GEM first (arms B and Q. The response was greater (50% versus 31%) in arm A than in the other arms. Conclusions: The CBDCA/GEM combination is safe and active against stage IV NSCLC. Our preclinical and clinical findings suggest that administration of CBDCA before GEM gives the better outcome.
引用
收藏
页码:242 / 247
页数:6
相关论文
共 50 条
  • [31] Front-line weekly chemotherapy with gemcitabine for unfit patients with non-small cell lung cancer (NSCLC)
    Ferrigno, D
    Buccheri, G
    LUNG CANCER, 2004, 45 (03) : 373 - 380
  • [32] Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stage IIIB or IV non-small-cell lung cancer: A phase III randomized study of the London Lung Cancer Group
    Rudd, RM
    Gower, NH
    Spiro, SG
    Eisen, TG
    Harper, PG
    Littler, JAH
    Hatton, M
    Johnson, PWM
    Martin, WMC
    Rankin, EM
    James, LE
    Gregory, WM
    Qian, W
    Lee, SM
    JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (01) : 142 - 153
  • [33] Second line chemotherapy with carboplatin and gemcitabine in non small cell lung cancer
    Tassinari, D
    Arcangeli, V
    Panzini, M
    Oliverio, G
    Gianni, L
    Fochessati, F
    Passini, G
    Sartori, S
    Ravaioli, A
    ANNALS OF ONCOLOGY, 2000, 11 : 11 - 11
  • [34] WEEKLY PACLITAXEL-CARBOPLATIN AS FRONT-LINE CHEMOTHERAPY IN ELDERLY PATIENTS WITH LOCALLY ADVANCED/METASTATIC (STAGE IIIB-IV) NON-SMALL-CELL LUNG CANCER. A PHASE II STUDY
    Lanzetta, G.
    Rozzi, A.
    Di Martino, M.
    Martelli, M.
    Capalbo, C.
    Portarena, I.
    Frati, L.
    ANNALS OF ONCOLOGY, 2004, 15 : 33 - 33
  • [35] Results of a phase I/II trial of carboplatin/gemcitabine plus celecoxib for first-line treatment of stage IIIB/IV non-small cell lung cancer (NSCLC).
    Burton, JD
    El-Sayah, D
    Cherry, M
    Bhargava, M
    Terjanian, T
    Odaimi, M
    Vesoniaraki, M
    Lowry, J
    Forte, F
    Friscia, P
    JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (16) : 682S - 682S
  • [36] Chemoimmunotherapy for stage IV non-small-cell lung cancer
    Uprety, Dipesh
    LANCET ONCOLOGY, 2019, 20 (09): : E466 - E466
  • [37] Phase III Study by the Norwegian Lung Cancer Study Group: Pemetrexed Plus Carboplatin Compared With Gemcitabine Plus Carboplatin As First-Line Chemotherapy in Advanced Non-Small-Cell Lung Cancer
    Gronberg, Bjorn H.
    Bremnes, Roy M.
    Flotten, Oystein
    Amundsen, Tore
    Brunsvig, Paal Fr.
    Hjelde, Harald H.
    Kaasa, Stein
    von Plessen, Christian
    Stornes, Froydis
    Tollali, Terje
    Wammer, Finn
    Aasebo, Ulf
    Sundstrom, Stein
    JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (19) : 3217 - 3224
  • [38] A randomized phase II trial using two different treatment schedules of gemcitabine and carboplatin in patients with advanced non-small-cell lung cancer
    Masters, Gregory A.
    Argiris, Athanassios E.
    Hahn, Elizabeth A.
    Beck, J. Thaddeus
    Rausch, P. Gregory
    Ye, Zhishen
    Monberg, Matthew J.
    Bloss, Leslie P.
    Curiel, Rafael E.
    Obasaju, Coleman K.
    JOURNAL OF THORACIC ONCOLOGY, 2006, 1 (01) : 19 - 24
  • [39] Paclitaxel plus gemcitabine may be as active and well tolerated as paclitaxel plus carboplatin for advanced non-small-cell lung cancer
    Chen, YM
    CANCER TREATMENT REVIEWS, 2003, 29 (01) : 69 - 71
  • [40] A multicenter phase II study of docetaxel and carboplatin combination as front-line treatment in advanced non-small cell lung cancer
    Giannakakis, T
    Kakolyris, S
    Theodoropoulos, E
    Kouroussis, C
    Michailakis, E
    Papadouris, S
    Tsitoura, M
    Kalbakis, K
    Souglakos, J
    Agelaki, S
    Vardakis, N
    Georgoulias, V
    ANTICANCER RESEARCH, 2002, 22 (6B) : 3743 - 3748