p53 mutations do not predict response to paclitaxel/radiation for nonsmall cell lung carcinoma

Safran, Howard; King, Thomas C.; Choy, Hak; Gollerkeri, Ashwin; Kwakwa, Helena; Lopez, Francisco F.; Cole, Bernard F.; Myers, James R.; Tarpey, Joseph; Rosmarin, Alan G.

doi:10.1002/(sici)1097-0142(19960915)78:6<1203::aid-cncr6>3.0.co;2-a

Cited by 65 publications

(26 citation statements)

References 36 publications

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“…This notion that perhaps p53 pathways may not be crucial to the action of antitubulin agents is supported by the apparent lack of in vivo association between the p53 status of cancer cells and the paclitaxel response. 25 In H23 cells with 246 IIe mt-p53, which was reported to behave in a dominant-negative fashion according to a yeast-based assay, 22 Ad-p53 did not confer increased chemosensitivity to DNA-damaging agents. The lack of synergistic enhancement of chemosensitivity may be explained by the dominant-negative effect of endogenous mt-p53.…”

Section: Discussionmentioning

confidence: 95%

Synergistic effects of adenovirus expressing wild-type p53 on chemosensitivity of non-small cell lung cancer cells

et al. 2000

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The infection of recombinant adenovirus expressing wild-type p53 (Ad-p53) to lung cancer cells that harbor mutant p53 genes improves their response to cis-diamminedichloroplatinum(II). In this study, we tested whether this improvement in response is also seen in wild-type p53 (wt-p53)-containing cancer cells and whether this phenomenon is universal with other commonly used chemotherapeutic agents, including etoposide, 7-ethyl-10-hydrocycamptothecin, paclitaxel, and docetaxel. Using a panel of 7 non-small cell lung cancer cell lines with wild-type (2) or abnormal (2 null, 3 point-mutated) p53, we examined in vitro cytotoxicity using a tetrazolium-based colorimetric assay (3-(4,5-diethylthiazoyl-2-yl)-2,5-diphenyltetrazolium bromide assay) and analyzed the combined effects of Ad-p53 and chemotherapeutic agents using the isobologram method. Ad-p53 and DNA-damaging agents (cis-diamminedichloroplatinum(II), etoposide, and 7-ethyl-10-hydrocycamptothecin) showed synergistic effects in six of seven cell lines but additive effects against a p53-mutated cell line. In contrast, Ad-p53 showed additive effects with the antitubulin agents (paclitaxel and docetaxel) in all four of the cell lines tested. Furthermore, we examined this synergistic interaction between Ad-p53 and DNA-damaging agents by flow cytometric analysis and DNA fragmentation analysis. Both analyses revealed that a sublethal dose of Ad-p53 augmented the apoptotic response induced by DNA-damaging agents in six of seven cell lines. Our results suggest that Ad-p53 may synergistically enhance the chemosensitivity of the majority of non-small cell lung cancers to DNA-damaging agents due to augmentation of apoptosis. Cancer Gene Therapy (2000) 7, 537-544

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Section: Discussionmentioning

confidence: 95%

Synergistic effects of adenovirus expressing wild-type p53 on chemosensitivity of non-small cell lung cancer cells

et al. 2000

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“…(15). In preclinical models and clinical experience, taxanes do not require the presence of an intact p53 pathway for apoptosis induction in contrast to DNA-damaging agents, including cisplatin (16,17). As loss of functional p53 commonly occurs in lung cancer, sequential use of a taxane after a platinum (or other p53-dependent drug/regimen) and before the emergence of clinical drug resistance is theoretically attractive.…”

Section: Discussionmentioning

confidence: 99%

Randomized Phase II Trial of Sequential Chemotherapy in Advanced Non-Small Cell Lung Cancer (SWOG 9806)

Edelman¹,

Clark²,

Chansky³

et al. 2004

Clinical Cancer Research

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Purpose: Improving chemotherapeutic efficacy in nonsmall cell lung cancer (NSCLC) will require the development of new drugs or new strategies to better use currently available agents. Sequential administration offers an opportunity to increase drug diversity while maintaining dose intensity. On the basis of the data indicating the activity of taxanes as second-line therapy and the lack of efficacy for more than three cycles of platinum-based therapy, this randomized Phase II study tested the concept of planned sequential chemotherapy in advanced NSCLC.Experimental Design: Patients with selected stage IIIb (pleural effusion)/stage IV NSCLC, performance status of 0 -1 and normal organ function were eligible. Therapy: arm 1, carboplatin (area under the curve ‫؍‬ 5.5 mg/ml ؋ min day 1) and gemcitabine (1000 mg/m 2 days 1 and 8 every 21 days ؋ 3) followed by paclitaxel (225 mg/m 2 every 21 days ؋ 3) or arm 2, cisplatin (100 mg/m 2 day 1), vinorelbine (25 mg/m 2 days 1 and 8 every 21 d ؋ 3) followed by docetaxel (75-100 mg/m 2 every 21 days ؋ 3). Results: Two-hundred four patients were accrued, of whom, 178 were eligible and evaluable. Eighty percent of patients were stage IV on arm 1 and 85% on arm 2. Response rates were 21 and 28% on arms 1 and 2, respectively. Median, 1-year and 2-year survivals were 9 months, 34 and 13%, and 9 months, 36 and 8%, on arms 1 and 2, respectively.Conclusions: Sequential therapy, as used in this study, resulted in comparable efficacy to previous Southwest Oncology Group trials of two drug combinations in this population; however, it failed to meet criteria for further study.

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“…P53 immunohistochemistry, which is performed easily on paraffin embedded material at the time of diagnosis, coupled with confirmatory mutation analysis, could define a subset of patients with a markedly poorer prognosis who may benefit from more intense chemotherapy, possibly including agents that are less susceptible to P53-related chemoresistance. 40,45,46 These issues may be addressed definitively by a larger study with comprehensive P53 mutation analysis and longer followup.…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of P53 status in Ewing sarcoma

Álava¹,

Antonescu²,

Panizo³

et al. 2000

Cancer

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p53 mutations do not predict response to paclitaxel/radiation for nonsmall cell lung carcinoma

Cited by 65 publications

References 36 publications

Synergistic effects of adenovirus expressing wild-type p53 on chemosensitivity of non-small cell lung cancer cells

Synergistic effects of adenovirus expressing wild-type p53 on chemosensitivity of non-small cell lung cancer cells

Randomized Phase II Trial of Sequential Chemotherapy in Advanced Non-Small Cell Lung Cancer (SWOG 9806)

Prognostic impact of P53 status in Ewing sarcoma

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