Long-term outcomes with concurrent carboplatin, paclitaxel and radiation therapy for locally advanced, inoperable head and neck cancer

Agarwala, Sanjiv S.; Cano, Elmer R.; Heron, Dwight E.; Johnson, James H.; Myers, Eugene N.; Sandulache, Vlad C.; Bahri, Sanjeev; Ferris, Robert L.; Wang, Y.; Argiris, Athanassios

doi:10.1093/annonc/mdm088

Cited by 47 publications

(36 citation statements)

References 18 publications

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“…Examination of CTAB-treated wild-type [p53(ϩ/ϩ)] and mutant [p53(Ϫ/Ϫ)] colon cancer HCT116 cells (Bunz et al, 1998) demonstrated very similar sensitivity (data not shown), suggesting that CTAB-mediated toxicity is independent of p53 status, thereby increasing the potential applicability of CTAB to many different human cancers. Moreover, its favorable toxicity profile, ability to induce apoptosis in cancer cells at much lower concentrations than its antimicrobial application (Pang and Willis, 1997), and capacity to delay tumor growth in FaDu xenograft models comparable with paclitaxel (Davis et al, 2002), a commonly used chemotherapeutic agent in the clinical management of HNC patients (Agarwala et al, 2007), all suggest that optimizing the bioavailability and pharmacokinetics of CTAB could provide an exciting opportunity for the development of a highly effective drug candidate, capable of exploiting the metabolic aberrations of human head and neck cancers.…”

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confidence: 99%

Potential Use of Cetrimonium Bromide as an Apoptosis-Promoting Anticancer Agent for Head and Neck Cancer

Ito

Yip²,

Katz³

et al. 2009

Mol Pharmacol

119

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A potential therapeutic agent for human head and neck cancer (HNC), cetrimonium bromide (CTAB), was identified through a cell-based phenotype-driven high-throughput screen (HTS) of 2000 biologically active or clinically used compounds, followed by in vitro and in vivo characterization of its antitumor efficacy. The preliminary and secondary screens were performed on FaDu (hypopharyngeal squamous cancer) and GM05757 (primary normal fibroblasts), respectively. Potential hit compounds were further evaluated for their anticancer specificity and efficacy in combination with standard therapeutics on a panel of normal and cancer cell lines. Mechanism of action, in vivo antitumor efficacy, and potential lead compound optimizations were also investigated. In vitro, CTAB interacted additively with ␥ radiation and cisplatin, two standard HNC therapeutic agents.CTAB exhibited anticancer cytotoxicity against several HNC cell lines, with minimal effects on normal fibroblasts; a selectivity that exploits cancer-specific metabolic aberrations. The central mode of cytotoxicity was mitochondria-mediated apoptosis via inhibition of H ϩ -ATP synthase activity and mitochondrial membrane potential depolarization, which in turn was associated with reduced intracellular ATP levels, caspase activation, elevated sub-G 1 cell population, and chromatin condensation. In vivo, CTAB ablated tumor-forming capacity of FaDu cells and delayed growth of established tumors. Thus, using an HTS approach, CTAB was identified as a potential apoptogenic quaternary ammonium compound possessing in vitro and in vivo efficacy against HNC models.

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Section: Downloaded Frommentioning

confidence: 99%

Potential Use of Cetrimonium Bromide as an Apoptosis-Promoting Anticancer Agent for Head and Neck Cancer

Ito

Yip²,

Katz³

et al. 2009

Mol Pharmacol

119

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“…Paclitaxel -representative of the second generation chemotherapy -has been used in SCCHN single-agent [7,14] or platinum-based radiochemotherapy protocols [2,6,8,15,22,25]. Current treatment strategies often use hyperfractionated or hyperfractionated-accelerated radiotherapy protocols to enhance efficacy.…”

Section: Introductionmentioning

confidence: 99%

Definitive radiochemotherapy of advanced head and neck cancer with carboplatin and paclitaxel

et al. 2011

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“…We and others have previously reported that 8% to 20% of long-term survivors may become G-tube dependent. 11,12,[17][18][19] Higher doses of radiation therapy have been associated with higher rates of long-term enteral feeding. 17,20 Our group previously reported that there was no association between mean total radiation dose and G-tube dependence 6 months post-CRT.…”

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confidence: 99%

Management of patients treated with chemoradiotherapy for head and neck cancer without prophylactic feeding tubes: The University of Pittsburgh experience

et al. 2009

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Objectives/Hypothesis:Mucositis and dysphagia are common complications of chemoradiotherapy (CRT) for head and neck cancer that may necessitate nutritional support with a gastrostomy tube (G‐tube).Methods:We reviewed records of patients who underwent and completed CRT, which included at least one traditional chemotherapeutic, for previously untreated head and neck cancer. G‐tubes were placed as needed. The timing and duration of G‐tube placement and treatment‐related complications and risk factors for long‐term G‐tube use were analyzed.Results:A total of 91 consecutive patients who received CRT, 68 as primary and 23 as postoperative treatment, were studied. Radiation doses ranged from 59.4 to 74 Gy (median, 70 Gy). Seventy‐nine percent of patients received platinum‐based therapy during CRT. Severe mucositis occurred in 40% of patients. Forty percent of patients required G‐tube placement (15 prior to CRT and 21 during CRT). Median duration of G‐tube use was 5.8 months. Two patients who had a G‐tube placed during CRT developed a G‐tube‐related complication. At 6 and 12 months, 15 (18%) and four (6%) patients who were disease free were using G‐tubes, respectively. Patients with G‐tubes placed prior to CRT or advanced T stage had longer G‐tube dependence.Conclusions:With aggressive supportive care it is feasible to avoid G‐tubes in the majority of patients undergoing CRT for head and neck cancer. G‐tube placement prior to CRT due to pre‐existing dysphagia and advanced T stage are associated with prolonged G‐tube dependence. Laryngoscope, 2010

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Long-term outcomes with concurrent carboplatin, paclitaxel and radiation therapy for locally advanced, inoperable head and neck cancer

Abstract: Treatment with concurrent carboplatin, paclitaxel and radiation is safe and offers curative potential for poor prognosis patients with locally advanced SCCHN.

Cited by 47 publications

References 18 publications

Potential Use of Cetrimonium Bromide as an Apoptosis-Promoting Anticancer Agent for Head and Neck Cancer

Potential Use of Cetrimonium Bromide as an Apoptosis-Promoting Anticancer Agent for Head and Neck Cancer

Definitive radiochemotherapy of advanced head and neck cancer with carboplatin and paclitaxel

Management of patients treated with chemoradiotherapy for head and neck cancer without prophylactic feeding tubes: The University of Pittsburgh experience

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