Radiosensitization with chemotherapeutic agents

Caffo, Orazio

doi:10.1016/s0169-5002(01)00382-8

Cited by 34 publications

(27 citation statements)

References 65 publications

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“…First, in an attempt to treat distant micrometastases, we used a two-drug combination of cisplatin plus docetaxel -one of the most active regimens for advanced NSCLC (Schiller et al, 2002). Cisplatin, the key drug in the treatment of NSCLC (Le Chevalier et al, 1999), has potent radiosensitising effects (DeWit, 1987), and docetaxel, a new active drug for NSCLC (Creane et al, 1999), also is a radiosensitising agent (Caffo, 2001). We thus considered that cisplatin plus docetaxel would be an excellent regimen to incorporate in concurrent chemoradiotherapy for LA-NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Preoperative concurrent chemoradiotherapy with cisplatin and docetaxel in patients with locally advanced non-small-cell lung cancer

et al. 2004

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The objective of this study was to assess the feasibility and effectiveness of an induction chemoradiotherapy regimen followed by surgery in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). A total of 22 patients with LA-NSCLC were treated with induction chemoradiotherapy consisting of cisplatin (40 mg m À2 ) and docetaxel (40 mg m À2 ) given on days 1, 8, 29 and 36 plus concurrent thoracic irradiation at a dose of 40 -60 Gy (2 Gy fraction À1 day À1 ). Surgical resection was performed within 6 weeks after completion of induction therapy. Objective response to the induction therapy was obtained in 16 patients (73%). In all, 20 patients (91%) underwent surgery and complete resection was achieved in 19 patients (86%). Pathological downstaging and pathological complete response were obtained in 14 (64%) and five (23%) patients, respectively. With a median follow-up period of 32 months, the calculated 3-year overall and progression-free survival rates were 66 and 61%, respectively. It is noteworthy that the 3-year overall survival rate in 14 patients achieving pathological downstaging was extremely high (93%). Toxicity was manageable with standard approaches. No treatment-related deaths occurred. This combined modality treatment is feasible and highly effective in patients with LA-NSCLC. The results warrant further large-scale study to confirm the effectiveness of this regimen.

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Section: Discussionmentioning

confidence: 99%

Preoperative concurrent chemoradiotherapy with cisplatin and docetaxel in patients with locally advanced non-small-cell lung cancer

et al. 2004

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“…1 Docetaxel is used in the clinic, either alone or in combination with other chemotherapeutic agents, for the treatment of breast, gastric, prostate, head and neck, ovarian as well as lung cancer. 3 Chemotherapeutic drugs such as docetaxel administered at subtoxic doses may act by means of a radio-sensitisation mechanism 4 and the combination of low-dose chemotherapy and thoracic radiotherapy has been shown to improve the prognosis of locally advanced non-small cell lung cancer (NSCLC). 5 The clearance of docetaxel is a result of its metabolism, a complex process involving among other different isoforms of the CYP3A enzyme and excretion, docetaxel is a substrate for the efflux membrane-localised transporter P-gp, encoded by the gene ABCB1.…”

Section: Introductionmentioning

confidence: 99%

SNPs in genes coding for ROS metabolism and signalling in association with docetaxel clearance

et al. 2010

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The dose of docetaxel is currently calculated based on body surface area and does not reflect the pharmacokinetic, metabolic potential or genetic background of the patients. The influence of genetic variation on the clearance of docetaxel was analysed in a two-stage analysis. In step one, 583 single-nucleotide polymorphisms (SNPs) in 203 genes were genotyped on samples from 24 patients with locally advanced non-small cell lung cancer. We found that many of the genes harbour several SNPs associated with clearance of docetaxel. Most notably these were four SNPs in EGF, three SNPs in PRDX4 and XPC, and two SNPs in GSTA4, TGFBR2, TNFAIP2, BCL2, DPYD and EGFR. The multiple SNPs per gene suggested the existence of common haplotypes associated with clearance. These were confirmed with detailed haplotype analysis. On the basis of analysis of variance (ANOVA), quantitative mutual information score (QMIS) and Kruskal-Wallis (KW) analysis SNPs significantly associated with clearance of docetaxel were confirmed for GSTA4, PRDX4, TGFBR2 and XPC and additional putative markers were found in CYP2C8, EPHX1, IGF2, IL1R2, MAPK7, NDUFB4, TGFBR3, TPMT (2 SNPs), (Po0.05 or borderline significant for all three methods, 14 SNPs in total). In step two, these 14 SNPs were genotyped in additional 9 samples and the results combined with the genotyping results from the first step. For 7 of the 14 SNPs, the results are still significant/borderline significant by all three methods: ANOVA, QMIS and KW analysis strengthening our hypothesis that they are associated with the clearance of docetaxel.

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“…In addition to its radio-sensitizing properties [8], full-dose induction chemotherapy prior to concurrent CT-RT could reduce the risk of metastatic relapses, reduce the tumor volume to be irradiated, and thereby reduce the severity of radio-induced esophagitis. The CALGB [9] showed the feasibility of this approach and yielded encouraging survival rates, despite highest oesophagitis rates.…”

Section: Introductionmentioning

confidence: 99%

“…Recent cytotoxic agents have proved more effective than older drugs in metastatic NSCLC [8,10]. Docetaxel monotherapy is active in both first-and second-line treatment [11] of advancedstage NSCLC.…”

Section: Introductionmentioning

confidence: 99%

Docetaxel and concurrent radiotherapy after two cycles of induction chemotherapy with cisplatin and vinorelbine in patients with locally advanced non-small-cell lung cancer

Vergnenègre¹,

Daniel²,

Léna³

et al. 2005

Lung Cancer

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Radiosensitization with chemotherapeutic agents

Cited by 34 publications

References 65 publications

Preoperative concurrent chemoradiotherapy with cisplatin and docetaxel in patients with locally advanced non-small-cell lung cancer

Preoperative concurrent chemoradiotherapy with cisplatin and docetaxel in patients with locally advanced non-small-cell lung cancer

SNPs in genes coding for ROS metabolism and signalling in association with docetaxel clearance

Docetaxel and concurrent radiotherapy after two cycles of induction chemotherapy with cisplatin and vinorelbine in patients with locally advanced non-small-cell lung cancer

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