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.
机构:
Ist Neurotraumatol Italiano INI, Clin Oncol Unit, Rome, ItalyIst Neurotraumatol Italiano INI, Clin Oncol Unit, Rome, Italy
Lanzetta, G.
Rozzi, A.
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Ist Neurotraumatol Italiano INI, Clin Oncol Unit, Rome, Italy
Az Osped S Camillo Forlanini, Dept Thorac Surg, Rome, ItalyIst Neurotraumatol Italiano INI, Clin Oncol Unit, Rome, Italy
Rozzi, A.
Di Martino, M.
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Az Osped S Camillo Forlanini, Dept Thorac Surg, Rome, ItalyIst Neurotraumatol Italiano INI, Clin Oncol Unit, Rome, Italy
Di Martino, M.
Martelli, M.
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机构:Ist Neurotraumatol Italiano INI, Clin Oncol Unit, Rome, Italy
Martelli, M.
Capalbo, C.
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Ist Neurotraumatol Italiano INI, Clin Oncol Unit, Rome, ItalyIst Neurotraumatol Italiano INI, Clin Oncol Unit, Rome, Italy
Capalbo, C.
Portarena, I.
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Ist Neurotraumatol Italiano INI, Clin Oncol Unit, Rome, ItalyIst Neurotraumatol Italiano INI, Clin Oncol Unit, Rome, Italy
Portarena, I.
Frati, L.
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Univ Roma La Sapienza, Expt Med & Pathol Dept, Rome, ItalyIst Neurotraumatol Italiano INI, Clin Oncol Unit, Rome, Italy
机构:
Natl Yang Ming Univ, Sch Med, Chest Dept, Taipei Vet Gen Hosp, Taipei 112, TaiwanNatl Yang Ming Univ, Sch Med, Chest Dept, Taipei Vet Gen Hosp, Taipei 112, Taiwan