De Pas Tommaso, Putzu Carlo, Curigliano Giuseppe, Noberasco Cristina, Boselli Sabrina, Catania Chiara, Orlando Laura, Milani Alessandra, Spaggiari Lorenzo, de Braud Filippo
New Drugs Development Unit, Italy.
Lung Cancer. 2006 Dec;54(3):359-64. doi: 10.1016/j.lungcan.2006.08.016. Epub 2006 Oct 6.
In a previous phase I dose-escalation study, we showed a weekly administration of paclitaxel (TAX) and gemcitabine (GEM) to be active and very well tolerated in non-small-cell lung cancer (NSCLC) patients, with the lack of interaction between drugs. The dose of GEM 1500 mg/m(2) and TAX 100 mg/m(2) was selected for phase II studies due to its predictable kinetic behaviour and less severe thrombocytopenia.
Fifty-four chemo-naïve patients with advanced NSCLC (53 patients: stage IV) received TAX (100mg/m(2) i.v. infusion over 1h) followed by GEM 1500 mg/m(2) over 30 min) on days 1, 8, 15 and 21 of a 28-day cycle.
The objective response rate was 46% (95% CI 32-61), median OS of 10.4 ms (95% CI 6.5-4.3), and a 1-year survival rate of 53%. Grades 3 and 4 haematological toxicity consisted of non-febrile neutropenia and thrombocytopenia in 13 and 4% of the cycles, respectively. Grade 3 non-haematological toxicities were observed in three patients (asthenia, diarrhoea and neuropathy), and were always reversible.
This weekly schedule of TAX and GEM is highly active in chemo-naïve NSCLC patients and confirms the low toxicity profile already observed in a previous phase I study.
在先前的一项I期剂量递增研究中，我们发现每周给予非小细胞肺癌（NSCLC）患者紫杉醇（TAX）和吉西他滨（GEM）具有活性且耐受性良好，两种药物之间不存在相互作用。由于其可预测的动力学行为和较轻的血小板减少症，选择吉西他滨1500mg/m²和紫杉醇100mg/m²的剂量进行II期研究。
54例初治晚期NSCLC患者（53例为IV期）在28天周期的第1、8、15和21天接受TAX（100mg/m²静脉输注1小时），随后接受GEM 1500mg/m²（30分钟）。
客观缓解率为46%（95%CI 32-61），中位总生存期为10.4个月（95%CI 6.5-14.3），1年生存率为53%。3级和4级血液学毒性分别在13%和4%的周期中表现为非发热性中性粒细胞减少和血小板减少。3例患者出现3级非血液学毒性（乏力、腹泻和神经病变），且均为可逆性。
这种TAX和GEM的每周给药方案在初治NSCLC患者中具有高活性，并证实了先前I期研究中已观察到的低毒性特征。
