Cisplatin, Fluorouracil, and Leucovorin Induction Chemotherapy Followed by Concurrent Cisplatin Chemoradiotherapy for Organ Preservation and Cure in Patients With Advanced Head and Neck Cancer: Long-Term Follow-Up

Psyrri, Amanda; Kwong, Myron S; DiStasio, Susan A.; Lekakis, Lazaros J.; Kassar, Mohamad; Sasaki, Clarence T.; Wilson, Lynn D.; Haffty, Bruce G.; Son, Yung H.; Ross, Douglas A.; Weinberger, Paul M.; Chung, Gina G.; Zelterman, Daniel; Burtness, Barbara; Cooper, Dennis

doi:10.1200/jco.2004.01.108

Cited by 74 publications

(52 citation statements)

References 32 publications

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“…We identified only one study in the literature using a treatment regimen similar to ours (Psyrri et al, 2004). Psyrri et al (2004) reported on a phase II study with 42 patients with stages III and IV head-and-neck cancer patients. At 2 years, the authors reported a local control rate of 76.3%, DSS of 69%, overall survival of 66.7% and rate of control of distant metastases of 79%.…”

Section: Discussionmentioning

confidence: 99%

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Sequential induction chemotherapy followed by radical chemo-radiation in the treatment of locoregionally advanced head-and-neck cancer

et al. 2008

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We describe a retrospective series of patients with advanced head-and-neck cancer who were treated with induction chemotherapy followed by radical chemo-radiation. Patients treated with two cycles of induction chemotherapy followed by definitive chemoradiation for squamous cell carcinoma of the head-and-neck region, from 2001 -2006 at the Royal Marsden Hospital, formed the basis of this study. Cisplatin (75 mg m À2 ) on day 1 and 5-FU (1000 mg m À2 ) day 1 -4 was the standard regimen used for induction treatment. Cisplatin (100 mg m À2 ) on day 1 and day 29 was used for concomitant treatment. The radiation was delivered using conformal technique. Tissues containing macroscopic and microscopic disease were treated to doses of 65 Gray (Gy) in 30 fractions and 50 Gy in 25 fractions, respectively. Data on patterns of relapse and acute toxicity (NCICTCv.3.0) were collected. A total of 129 patients were included, median age was 58 (range: 27 -78). The site of tumour was: oropharynx 70 (54%), larynx 30 (23%), hypopharynx 24 (19%) and other 5 (4%). The median follow-up was 19 months (range: 4 -58). Local control, disease-specific survival and overall survival at 2 years were 71%, 68% and 63%, respectively. The distant recurrence rate at 2 years was 9%. Ten patients required dose reduction during induction chemotherapy due to toxicity. The dose of 5-FU was reduced in six patients and that of cisplatin in four patients. The incidence of grade 3/4 toxicity was: neutropenia 5%, thrombocytopenia 1%, nausea and vomiting 3%. One cycle of concurrent cisplatin was omitted in 23 patients due to toxicity. Full-dose radiotherapy was administered to 98% of patients. The incidence of grade 3/4 toxicity was: skin 20%, dysphagia 65%, mucositis 60%, neutropenia 3%, anaemia 1%, nausea and vomiting 4%, nephrotoxicity 1%. Induction chemotherapy followed by radical chemo-radiation is a safe and tolerable regimen in the treatment of advanced head-and-neck cancer. Distant recurrence rates are lower with equivalent local control and survival compared to chemo-radiation alone (historical controls).

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Section: Discussionmentioning

confidence: 99%

“…This rate is comparable to the other studies. In the phase II studies, using the sequential approach by Psyrri et al (Psyrri et al, 2004) and the SWOG study (Urba et al, 2005), the larynx preservation rates were 64.3 and 64%, respectively. Sequential treatment for advanced head-and-neck cancer SA Bhide et al…”

Section: Discussionmentioning

confidence: 99%

Sequential induction chemotherapy followed by radical chemo-radiation in the treatment of locoregionally advanced head-and-neck cancer

et al. 2008

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“…Presently, early-stage HNSCC tumors are treated with radiation or surgery (2) and in advanced cases, a multimodal approach is used often incorporating chemotherapy (3). Unfortunately, long-term survival remains relatively unchanged (4) and new therapeutic options are required to enhance overall survival (OS) of patients with HNSCC. Expression of the EGFR is associated with HNSCC pathogenesis and is upregulated in 90% of these tumors (5,6).…”

Section: Introductionmentioning

confidence: 99%

Monensin Inhibits Epidermal Growth Factor Receptor Trafficking and Activation: Synergistic Cytotoxicity in Combination with EGFR Inhibitors

Dayekh

Johnson‐Obaseki

Corsten

et al. 2014

Molecular Cancer Therapeutics

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Targeting the EGFR, with inhibitors such as erlotinib, represents a promising therapeutic option in advanced head and neck squamous cell carcinomas (HNSCC). However, they lack significant efficacy as single agents. Recently, we identified the ability of statins to induce synergistic cytotoxicity in HNSCC cells through targeting the activation and trafficking of the EGFR. However, in a phase I trial of rosuvastatin and erlotinib, statininduced muscle pathology limited the usefulness of this approach. To overcome these toxicity limitations, we sought to uncover other potential combinations using a 1,200 compound screen of FDA-approved drugs. We identified monensin, a coccidial antibiotic, as synergistically enhancing the cytotoxicity of erlotinib in two cell line models of HNSCC, SCC9 and SCC25. Monensin treatment mimicked the inhibitory effects of statins on EGFR activation and downstream signaling. RNA-seq analysis of monensin-treated SCC25 cells demonstrated a wide array of cholesterol and lipid synthesis genes upregulated by this treatment similar to statin treatment. However, this pattern was not recapitulated in SCC9 cells as monensin specifically induced the expression of activation of transcription factor (ATF) 3, a key regulator of statin-induced apoptosis. This differential response was also demonstrated in monensin-treated ex vivo surgical tissues in which HMG-CoA reductase expression and ATF3 were either not induced, induced singly, or both induced together in a cohort of 10 patient samples, including four HNSCC. These results suggest the potential clinical utility of combining monensin with erlotinib in patients with HNSCC. Mol Cancer Ther; 13(11); 2559-71. Ó2014 AACR.

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“…However, such treatment regimens are also frequently associated with significant short-term and long-term undesirable effects. [9][10][11][12] Novel approaches using cell-based immunotherapy have also been examined in human subjects with promising preliminary results. [13][14][15] Nevertheless, these modalities are still experimental.…”

mentioning

confidence: 99%

Gold(III) porphyrin complex is more potent than cisplatin in inhibiting growth of nasopharyngeal carcinoma in vitro and in vivo

Sun

Chen

et al. 2009

Intl Journal of Cancer

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Nasopharyngeal carcinoma (NPC) is a common neoplasm in Southeastern Asia, and cisplatin-containing regimens for combinational chemotherapy are widely used for treating locally recurrent or metastatic diseases. However, resistance to cisplatin is not infrequently seen and its associated side effects may be life-threatening. In this report, another metallo-pharmaceutical agent gold(III) porphyrin complex [Au(TPP)]Cl was investigated in comparison to cisplatin for its in vitro and in vivo anticancer effects. Through induction of the intrinsic apoptosis pathway, [Au(TPP)]Cl exhibited 100-fold higher potency than cisplatin in killing NPC cells, including cisplatin-sensitive and cisplatin-resistant variants, and also an variant harboring the Epstein-Barr virus. In addition, a safety concentration window was demonstrated, allowing [Au(TPP)]Cl to kill tumors with minimal cytotoxicity to noncancerous cells. More importantly, weekly intraperitoneal injection of 3 mg/kg [Au(TPP)]Cl was more effective than the same dose of cisplatin in inducing tumor apoptosis in vivo and remarkably inhibited tumor growth in animals without any noticeable side effect. [Au(TPP)]Cl therefore is a promising chemotherapeutic agent that deserves further development as a novel drug for the treatment of advanced NPC, in particular, for cases with cisplatin-resistance.

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Cisplatin, Fluorouracil, and Leucovorin Induction Chemotherapy Followed by Concurrent Cisplatin Chemoradiotherapy for Organ Preservation and Cure in Patients With Advanced Head and Neck Cancer: Long-Term Follow-Up

Abstract: Induction chemotherapy with PFL followed by concurrent cisplatin chemoradiotherapy is well tolerated and results in a good likelihood of organ preservation and excellent PFS and OS.

Cited by 74 publications

References 32 publications

Sequential induction chemotherapy followed by radical chemo-radiation in the treatment of locoregionally advanced head-and-neck cancer

Sequential induction chemotherapy followed by radical chemo-radiation in the treatment of locoregionally advanced head-and-neck cancer

Monensin Inhibits Epidermal Growth Factor Receptor Trafficking and Activation: Synergistic Cytotoxicity in Combination with EGFR Inhibitors

Gold(III) porphyrin complex is more potent than cisplatin in inhibiting growth of nasopharyngeal carcinoma in vitro and in vivo

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