Integrating concurrent navelbine and cisplatin to hyperfractionated radiotherapy in locally advanced non-small cell lung cancer patients treated with induction and consolidation chemotherapy: feasibility and activity results

Reguart, Noemı́; Viñolas, Núria; Casas, Francesc; Gimferrer, Josep María; Agustı́, Carles; Molina, Rafael; Martı́n-Richard, Marta; Sánchez-Reyes, A.; Gascón, Pere

doi:10.1016/j.lungcan.2003.12.012

Cited by 7 publications

(4 citation statements)

References 31 publications

(39 reference statements)

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“…In patients deemed inoperable at the end of radiochemotherapy or with comorbidities excluding operation, a definitive boost of radiochemotherapy was added. This therapy was in accordance to accelerated radiotherapy reports with a final boost and concomitant chemotherapy (Reguart et al , 2004). …”

Section: Methodssupporting

confidence: 66%

βV-tubulin expression is associated with outcome following taxane-based chemotherapy in non-small cell lung cancer

et al. 2012

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Background:Tubulin-binding agents (TBAs) are effective in non-small cell lung cancer (NSCLC) treatment. Both βIII- and βV-tubulins are expressed by cancer cells and may lead to resistance against TBAs.Methods:Pre-treatment samples from 65 locally advanced or oligometastatic NSCLC patients, who underwent uniform induction chemotherapy with paclitaxel and platinum followed by radiochemotherapy with vinorelbine and platinum were retrospectively analysed by immunohistochemistry. Protein expression of βIII- and βV-tubulin was morphometrically quantified.Results:Median pre-treatment H-score for βIII-tubulin was 110 (range: 0–290), and 160 for βV-tubulin (range: 0–290). Low βIII-tubulin expression was associated with improved overall survival (OS) (P=0.0127, hazard ratio (HR): 0.328). An association between high βV-tubulin expression and prolonged progression-free survival (PFS, median 19.2 vs 9.4 months in high vs low expressors; P=0.0315, HR: 1.899) was found. Further, high βV-tubulin expression was associated with objective response (median H-score 172.5 for CR+PR vs 120 for SD+PD patients, P=0.0104) or disease control following induction chemotherapy (170 for CR+PR+SD vs 100 for PD patients, P=0.0081), but not radiochemotherapy.Conclusion:Expression of βV-tubulin was associated with treatment response and PFS following paclitaxel-based chemotherapy of locally advanced and oligometastatic NSCLC patients. Prolonged OS was associated with low levels of βIII-tubulin. Prospective evaluation of βIII/βV-tubulin expression in NSCLC is warranted.

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Section: Methodssupporting

confidence: 66%

βV-tubulin expression is associated with outcome following taxane-based chemotherapy in non-small cell lung cancer

et al. 2012

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“…For example, the Moustacchi group () found that 120 cross-links per yeast genome correspond to the DL 37 (the dose necessary to induce, on average, one lethal hit per cell). There are many examples of DNA cross-linking agents, including nitrogen mustard (), psoralens ( − ), mitomycin C (), and platinum compounds, several of which are used in cancer radiotherapy ( , ), chemotherapy ( − ) (e.g., carboplatin), or phototherapy (e.g., psoralens). The toxicity of DNA cross-links probably results from two mechanisms: they prevent strand separation, thus inhibiting both transcription and replication, and they can induce mutations and DNA rearrangements as a result of repair processes ( − ).…”

mentioning

confidence: 99%

Interstrand Cross-Links: A New Type of γ-Ray Damage in Bromodeoxyuridine-Substituted DNA

et al. 2005

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Interstrand cross-links (ICL) represent one of the most toxic types of DNA damage for dividing cells. They are induced both by natural products (e.g., psoralens + UVA) and by several chemical agents, some of which are used in chemotherapy (e.g., carboplatin and mitomycin C). Although repair mechanisms exist for interstrand cross-links, these lesions can induce mutations, chromosomal rearrangements, and cell death. Here, we report, for the first time, the formation of ICL by gamma-rays in brominated DNA. It is well established that the radiosensitization properties of bromodeoxyuridine (BrdUrd) result primarily from the electrophilic nature of the bromine, making it a good leaving group and leading to the irreversible formation of a uridinyl radical (dUrd(*)) or uridinyl anion (dUrd-) upon addition of an electron. We observe that the radiolytic loss of the bromine atom is greatly suppressed in double-stranded compared to single-stranded DNA. We have used a model DNA containing a bulge, formed by five mismatched bases, and have observed a linear dose-response for the formation of strand breaks on the single-stranded regions of both the brominated strand and the opposite nonbrominated strand. Surprisingly, we have observed the formation of interstrand cross-links exclusively in the mismatched region. Thus, we propose that the radiosensitization effects of bromodeoxyuridine in vivo will almost certainly be limited to single strand regions such as found in transcription bubbles, replication forks, mismatched DNA, and possibly the loop region of telomeres. Our results suggest that interstrand cross-links may contribute to the radiosensitization effects of BrdUrd. These findings may have profound implications for the clinical use of bromodeoxyuridine as a radiosensitizer, as well as for the development of targeted radiosensitizers.

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“…It has been shown, in an analysis of predictors for esophagitis by Werner-Wasik et al, 9 that the maximum acute esophagitis grade is associated with the use of chemotherapy and twicedaily RT. Many trials using concurrent chemotherapy with altered fractionation have shown increased grade 3 and 4 esophagitis rates Ͼ30% 6,8,16 Yet, our regimen of ART allowed us to deliver 60 Gy in 5 weeks, with essentially no severe esophagitis. At the same time, regarding survival, our median survival of 17.9 months was comparable with the median sur-vival of 17.0 months reported for the concurrent chemotherapy and once-daily RT arm in RTOG 94-10 and the median survival of 16.5 months reported for the concurrent chemotherapy and RT arm in the Japanese randomized trial.…”

Section: Discussionmentioning

confidence: 99%

“…15 We elected to use an every other week regimen of hyperfractionated, accelerated RT and chemotherapy in an attempt to reduce the acute complications-namely, esophagitis-that would occur with a continuous accelerated program, especially when combined with chemotherapy. 16 Despite the interruption, the overall RT treatment time remained relatively short, at 5 weeks.…”

mentioning

confidence: 99%

A Prospective Phase II Study of Induction Carboplatin and Vinorelbine followed by Concomitant Topotecan and Accelerated Radiotherapy (ART) in Locally Advanced Non-small Cell Lung Cancer (NSCLC)

Patel¹,

Ajlouni²,

Chapman³

et al. 2007

Journal of Thoracic Oncology

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Integrating concurrent navelbine and cisplatin to hyperfractionated radiotherapy in locally advanced non-small cell lung cancer patients treated with induction and consolidation chemotherapy: feasibility and activity results

Cited by 7 publications

References 31 publications

βV-tubulin expression is associated with outcome following taxane-based chemotherapy in non-small cell lung cancer

βV-tubulin expression is associated with outcome following taxane-based chemotherapy in non-small cell lung cancer

Interstrand Cross-Links: A New Type of γ-Ray Damage in Bromodeoxyuridine-Substituted DNA

A Prospective Phase II Study of Induction Carboplatin and Vinorelbine followed by Concomitant Topotecan and Accelerated Radiotherapy (ART) in Locally Advanced Non-small Cell Lung Cancer (NSCLC)

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