Gemcitabine, paclitaxel, and cisplatin as induction chemotherapy for patients with biopsy‐proven Stage IIIA(N2) nonsmall cell lung carcinoma

Abstract

We examined how ionizing radiation (IR) delivered under either severe hypoxia (< 0.1% O2) or normoxia affects the expression of hypoxia inducible factor 1α (HIF‐1α) and the angiogenic factors vascular endothelial growth factor (VEGF) and angiopoietins 1, 2 and 4 in U87 human glioblastoma cells. IR was delivered as single doses of 0, 2, 5, 10 and 20 Gy after 6‐hr hypoxic incubation and in normoxic controls. Irradiation at any dose did not affect the cellular protein levels of any of the angiopoietins, whereas hypoxia led to increasing levels of both angiopoietin‐4 and angiopoietin‐2. Levels of angiopoietin‐1 protein were unaltered throughout the observation period. A dose‐dependent increase in levels of secreted VEGF in the medium occurred after IR at doses from 5–20 Gy. In hypoxic cells, 20 Gy IR induced an additional significant increase in VEGF relative to nonirradiated hypoxic control cells with elevated baseline VEGF levels induced by hypoxia. HIF‐1α and glucose transporter‐1 (Glut‐1) were not correspondingly upregulated by IR. Blocking HIF‐1α by antisense treatment induced a reduced baseline VEGF at normoxia, while the relative upregulation of VEGF by IR was unaffected. These data provide evidence that VEGF is upregulated by IR by mechanisms independent of HIF‐1 transactivation. © 2003 Wiley‐Liss, Inc.

Long Term Follow-Up of Neoadjuvant-Adjuvant Combination Treatment of Iiia Stage Non-Small-Cell-Lung Cancer: Results of Neoadjuvant Carboplatin/Vinorelbine and Carboplatin/Paclitaxel Regimens Combined With Selective Adjuvant Chemotherapy According to in-Vitro Chemoresistance Test

“…In two studies with comparable . Cisplatin with the third generation cytotoxic agents in phase II studies show overall response rates (ORRs) from 54 % to 74 %, but only a small number of these studies have calculated the 3-year survival 18,27,28 , which was 33 % with a docetaxel/ cisplatin neoadjuvant protocol 13 and 20 % in a gemcitabine/cisplatin study 27 . Vinorelbine in neoadjuvant treatment has been used in combination only with cisplatin 29 , or with cisplatin and gemcitabine 30 and ORRs were 53.6 % and 58.5 %, respectively.…”

Management of Locally Advanced Non Small Cell Lung Cancer from a Surgical Perspective

“…It is important to note that all five of these trials used older chemotherapeutic agents. There are a series of more recent phase II trials evaluating induction therapy for stage III NSCLC using third-generation, platinum-based chemotherapy [18][19][20][21][22][23] ( Table 3). Response rates with these agents were 40-74%, much higher than with the older regimens.…”

Induction cisplatin-gemcitabine-paclitaxel plus concurrent radiotherapy and gemcitabine in the multimodality treatment of unresectable stage IIIB non-small cell lung cancer

“…Based on these premises and on our personal experience [5][6][7], we have explored the hypothesis that first line induction chemotherapy could reduce the loco-regional impact of a subsequent radio-chemotherapy approach (decrease in tumor volume, decrease in irradiated volume) with a potentially more acceptable toxicity profile.…”