Multikinase Inhibitors for the Treatment of Asymptomatic Radioactive Iodine-Refractory Differentiated Thyroid Cancer: Global Noninterventional Study (RIFTOS MKI).

Background: Sorafenib and lenvatinib are multikinase inhibitors (MKIs) approved for patients with radioactive iodine-refractory (RAI-R) differentiated thyroid cancer (DTC). There is no consensus on when to initiate MKI treatment. The objective of this study was to evaluate time to symptomatic progression (TTSP) in patients with RAI-R DTC for whom the decision to treat with an MKI was made at study entry. Methods: International, prospective, open-label, noninterventional cohort study (NCT02303444). Eligible patients had asymptomatic progressive RAI-R DTC, with ≥1 lesion ≥1 cm in diameter and life expectancy ≥6 months. The decision to treat with an MKI was at the treating physician's discretion. Primary endpoint was TTSP from study entry. Two cohorts were evaluated: patients for whom a decision to initiate an MKI was made at study entry (Cohort 1) and patients for whom there was a decision not to initiate an MKI at study entry (Cohort 2). Cohorts were compared descriptively. Results: The full analysis set (FAS) comprised 647 patients. The median duration of observation was 35.5 months (range <1-59.4). Of 344 MKI-treated patients, 209 received sorafenib, 191 received lenvatinib, and 19 received another MKI at some point. Median TTSP was 55.4 months (interquartile range [IQR] 18.6-not estimable [NE]) overall, 55.4 months (IQR 15.2-NE) in Cohort 1 (n = 169), and 51.4 months (IQR 20.0-NE) in Cohort 2 (n = 478). TTSP ≥36 months was achieved in 64.5% of patients overall, 59.5% of patients in Cohort 1, and 66.4% of patients in Cohort 2. Median overall survival from classification as RAI-R was 167 months and median progression-free survival from start of MKI therapy was 19.2 months and from start of sorafenib therapy 16.7 months. Among sorafenib-treated patients, 70% had dose modifications, 35% had a dose reduction, 89% experienced ≥1 treatment-emergent adverse event (TEAE), and 82% experienced ≥1 drug-related TEAE. Conclusions: This real-world study provides valuable insight into outcomes in patients with asymptomatic, progressive RAI-R DTC under observation or receiving MKI treatment. TTSP in the FAS provides insight into the current prognosis for patients with RAI-R DTC in the era of MKIs. Registration: NCT02303444.

Patient-reported financial toxicity and adverse medical consequences in head and neck cancer.

OBJECTIVES: Financial toxicity (FT) is a significant barrier to high-quality cancer care, and patients with head and neck cancer (HNCA) are particularly vulnerable given their need for intensive support, daily radiotherapy (RT), and management of long-term physical, functional, and psychosocial morbidities following treatment. We aim to identify predictors of FT and adverse consequences in HNCA following RT. MATERIALS AND METHODS: We performed a prospective survey study of patients with HNCA seen in follow-up at an academic comprehensive cancer center (CCC) or Veterans Affairs hospital between 05/2016 and 06/2018. Surveys included validated patient-reported functional outcomes and the COST measure, a validated instrument for measuring FT. RESULTS: The response rate was 86% (n = 63). Younger age and lower median household income by county were associated with lower COST scores (i.e., worse FT) on multivariable analysis (p = .045 and p = .016, respectively). Patients with worse FT were more likely to skip clinic visits (RR (95% CI) 2.13 (1.23-3.67), p = .007), be noncompliant with recommended supplements or medications (1.24 (1.03-1.48), p = .02), and require supportive infusions (1.10 (1.02-1.20), p = .02). At the CCC, patients with worse FT were more likely to require feeding tubes (1.62 (1.14-2.31), p = .007). Overall, 36% reported that costs were higher than expected, 48% were worried about paying for treatment, and 33% reported at least a moderate financial burden from treatment. CONCLUSION: HNCA patients experience substantial FT from their diagnosis and/or therapy, with potential implications for medical compliance, QOL, and survivorship care.

Phase IIb, Randomized, Double-Blind Trial of GC4419 Versus Placebo to Reduce Severe Oral Mucositis Due to Concurrent Radiotherapy and Cisplatin For Head and Neck Cancer.

PURPOSE: Oral mucositis (OM) remains a common, debilitating toxicity of radiation therapy (RT) for head and neck cancer. The goal of this phase IIb, multi-institutional, randomized, double-blind trial was to compare the efficacy and safety of GC4419, a superoxide dismutase mimetic, with placebo to reduce the duration, incidence, and severity of severe OM (SOM). PATIENTS AND METHODS: A total of 223 patients (from 44 institutions) with locally advanced oral cavity or oropharynx cancer planned to be treated with definitive or postoperative intensity-modulated RT (IMRT; 60 to 72 Gy [≥ 50 Gy to two or more oral sites]) plus cisplatin (weekly or every 3 weeks) were randomly assigned to receive 30 mg (n = 73) or 90 mg (n = 76) of GC4419 or to receive placebo (n = 74) by 60-minute intravenous administration before each IMRT fraction. WHO grade of OM was assessed biweekly during IMRT and then weekly for up to 8 weeks after IMRT. The primary endpoint was duration of SOM tested for each active dose level versus placebo (intent-to-treat population, two-sided α of .05). The National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03, was used for adverse event grading. RESULTS: Baseline patient and tumor characteristics as well as treatment delivery were balanced. With 90 mg GC4419 versus placebo, SOM duration was significantly reduced (P = .024; median, 1.5 v 19 days). SOM incidence (43% v 65%; P = .009) and severity (grade 4 incidence, 16% v 30%; P = .045) also were improved. Intermediate improvements were seen with the 30-mg dose. Safety was comparable across arms, with no significant GC4419-specific toxicity nor increase of known toxicities of IMRT plus cisplatin. The 2-year follow-up for tumor outcomes is ongoing. CONCLUSION: GC4419 at a dose of 90 mg produced a significant, clinically meaningful reduction of SOM duration, incidence, and severity with acceptable safety. A phase III trial (ROMAN; ClinicalTrials.gov identifier: NCT03689712) has begun.

Real-World Treatment Patterns Among Patients Initiating Small Molecule Kinase Inhibitor Therapies for Thyroid Cancer in the United States.

INTRODUCTION: Little is known about real-world use of small molecule kinase inhibitors (SMKI) for advanced thyroid cancer in the United States. This study examined prescribing patterns of SMKI agents recommended by the National Comprehensive Cancer Center (NCCN). METHODS: This retrospective study used a national health insurance database to identify patients diagnosed with thyroid cancer during 1/1/2006-6/30/2016 and with prescription claims for NCCN-recommended SMKI during 1/1/2010-5/31/2016 whose first claim date was the index date. Inclusion also required continuous enrollment in a health plan for 3 months pre-index (baseline) and ≥ 1 month post-index (follow-up) with no claims for SMKI during baseline. Lines of therapy (LOT) were defined by the date of SMKI claims and days of drug supply. Median time to SMKI discontinuation in each LOT was estimated by Kaplan-Meier method. RESULTS: The study included 217 patients. During follow-up (mean duration 499.0 days), 35.5% of patients (n = 77) received a second or later LOT; among patients with ≥ 12 months follow-up after first LOT (LOT1) initiation, 53.1% (n = 60) received a second or later LOT. Median treatment duration was 5.0 months for LOT1 and 5.1 months for LOT2. Over the entire follow-up period (2010-2016), sorafenib was the most common regimen in LOT1 (36.9% of patients) and LOT2 (24.7%) followed by sunitinib and levantinib (13.4% each) in LOT1 and sunitinib (19.5%) in LOT2. Starting in 2015, the year lenvatinib was approved for differentiated thyroid cancer, lenvatinib was the most common first-line regimen among patients initiating LOT1 in 2015 (43.4%) and 2016 (66.7%). CONCLUSION: Sorafenib was the most common first-line agent during 2010-2014 but was supplanted by lenvatinib starting in 2015. Approximately 36-53% of patients received a second-line treatment. Median treatment duration results suggested potential benefit of SMKI in second-line therapy. SMKI treatment after first-line failure may be considered for appropriately selected patients. FUNDING: Eisai, Inc. (Woodcliff Lake, NJ).

Soy Isoflavone Supplementation Increases Long Interspersed Nucleotide Element-1 (LINE-1) Methylation in Head and Neck Squamous Cell Carcinoma.

AIM: Soy isoflavones have been suggested as epigenetic modulating agents with effects that could be important in carcinogenesis. Hypomethylation of LINE-1 has been associated with head and neck squamous cell carcinoma (HNSCC) development from oral premalignant lesions and with poor prognosis. To determine if neoadjuvant soy isoflavone supplementation could modulate LINE-1 methylation in HNSCC, we undertook a clinical trial. METHODS: Thirty-nine patients received 2-3 weeks of soy isoflavone supplements (300 mg/day) orally prior to surgery. Methylation of LINE-1, and 6 other genes was measured by pyrosequencing in biopsy, resection, and whole blood (WB) specimens. Changes in methylation were tested using paired t tests and ANOVA. Median follow up was 45 months. RESULTS: LINE-1 methylation increased significantly after soy isoflavone (P < 0.005). Amount of change correlated positively with days of isoflavone taken (P = 0.04). Similar changes were not seen in corresponding WB samples. No significant changes in tumor or blood methylation levels were seen in the other candidate genes. CONCLUSION: This is the first demonstration of in vivo increases in tissue-specific global methylation associated with soy isoflavone intake in patients with HNSCC. Prior associations of LINE-1 hypomethylation with genetic instability, carcinogenesis, and prognosis suggest that soy isoflavones maybe potential chemopreventive agents in HNSCC.

Low-Cost Intervention to Increase Influenza Vaccination Rate at a Comprehensive Cancer Center.

Influenza morbidity and mortality can be severe and costly. Vaccination rates remain suboptimal in cancer patients due to provider- and patient-related factors. The objective of this study was to evaluate whether low-cost provider- and patient-focused interventions would increase influenza vaccination rates at the University of Michigan Comprehensive Cancer Center (UMCCC). This quality improvement project included all patients without documentation of influenza vaccination prior to their first outpatient appointment during the 2011-2012 and 2012-2013 influenza seasons. The multi-stepped intervention included provider and patient reminders. Influenza vaccination rates were compiled using CPT-4 codes. Same-day (with appointment) vaccination rates during the intervention seasons were compared to historical (2005-2011 seasons) controls; vaccination rates were also compared to contemporary control population at the University of Michigan Health System (UMHS). Reasons for non-adherence with vaccination were explored. The cumulative same-day vaccination rate in eligible adults was 10.1 % (2011-2012) and 9.4 % (2012-2013) compared to an average 6.9 % during influenza seasons 2005-2011. Based on logistic regression analysis, there was a 37.6 % (95 % CI 35-40.3 %) and 56.1 % (95 % CI 40.9-73 %) relative increase in the adult vaccination rate associated with the intervention, with 399 and 697 additional vaccinations, respectively, for each season. During the 2012-2013 season, the UMCCC adult vaccination rate was higher compared to the remainder of that of the UMHS. The intervention was well accepted by providers. Reasons for no vaccination were provider- and patient-related. Increasing provider and patient awareness with a simple, inexpensive intervention was associated with higher influenza vaccination rates at a large academic cancer center. The intervention is permanently implemented during influenza seasons.

Dusquetide: A novel innate defense regulator demonstrating a significant and consistent reduction in the duration of oral mucositis in preclinical data and a randomized, placebo-controlled phase 2a clinical study.

Dusquetide, a novel Innate Defense Regulator, modulates the innate immune system at a key convergence point in intracellular signaling pathways and has demonstrated activity in both reducing inflammation and increasing clearance of bacterial infection. Innate immunity has also been implicated in the pathogenesis of oral mucositis (OM), a universal toxicity of chemoradiation therapy (CRT). Testing the hypothesis that dusquetide can mitigate the development and duration of OM, preclinical studies have been completed and correlated with interim results from a Phase 2 clinical study in patients undergoing CRT for head and neck cancer. Dusquetide reduced the duration of OM in mouse and hamster models by approximately 50%, which was recapitulated by the 50% reduction of severe OM (SOM) in the Phase 2 trial. A reduction in the clinical rate of infection was also observed, consistent with previously reported preclinical studies. In aggregate, these results not only demonstrate the safety and efficacy of dusquetide in addressing this unmet medical need, but also provide proof of concept for the translation of dusquetide action between animal models and the human clinical setting, and further support the contention that innate immunity is an important driver for the initiation and continued impact of OM.

Retrospective Study of Sirolimus and Cyclophosphamide in Patients with Advanced Differentiated Thyroid Cancers.

BACKGROUND: We hypothesize that the combination of an mTOR inhibitor, sirolimus, with a well-known cytotoxic agent, cyclophosphamide, provides a well-tolerated and promising alternative treatment for advanced, differentiated thyroid cancers (DTC). METHODS: This retrospective review extracted data from patients treated for advanced DTC at the University of Michigan Comprehensive Cancer Center from 1995 through 2013. Fifteen patients treated with combination sirolimus and cyclophosphamide were identified as the sirolimus+cyp group. Seventeen patients treated with standard of care and enrolled in clinical trials were identified as the comparison group. RESULTS: The one-year progression free survival rate (PFS) was 0.45, 95% CI [0.26, 0.80] in the sirolimus+cyp population and 0.30, 95% CI [0.13, 0.67] in the comparison population. The hazard ratio for PFS from initiation of treatment was 1.47, 95% CI [0.57, and 3.78]. In patients treated as first line, one-year PFS rate was 0.57, 95% CI [0.30, 1.00] in the sirolimus+cyp group and relatively unchanged at 0.29, 95% CI [0.11, 0.74] in the comparison group. The hazard ratio for PFS for first line patients was 1.10, 95% CI[ 0.4, and 3.5]. In patients with 3 or fewer sites of metastases, the one year PFS was 0.58, 95% CI [0.33, 1.00] in the sirolimus+cyp group, and 0.37, 95% CI [0.17, 0.80] in the comparison group. The average number of toxicities was 0.87 in the sirolimus+cyp patients and 1.71 in the comparison group. CONCLUSIONS: The combination of sirolimus and cyclophosphamide was generally well tolerated with similar progression free survival, highlighting its applicability in patients with limited options.

ACR Appropriateness Criteria® thyroid carcinoma.

The ACR Head and Neck Cancer Appropriateness Criteria Committee reviewed relevant medical literature to provide guidance for those managing patients with thyroid carcinoma. The American College of Radiology Appropriateness Criteriaare evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Thyroid cancer is the most common endocrine malignancy in the United States, most often presenting as a localized palpable nodule. Surgery is the mainstay of treatment for WDTC, with most patients undergoing complete resection of their disease having good outcomes. Following surgery thyroxine supplementation should begin to suppress TSH, which unchecked can stimulate residual disease and/or metastatic progression, Adjuvant treatment with radioactive iodine (RAI) using iodine-131 ((131)I) is frequently used for diagnostic and therapeutic purposes. The use of EBRT for thyroid cancer has not been tested in well-designed, randomized, controlled trials and should, therefore, be considered on a case-by-case basis. Chemotherapy plays a minimal role in the management of WDTC. Novel biologic agents, such as systemic therapy options, are being actively investigated, and patients with metastatic thyroid cancer that is not iodine avid should be encouraged to enroll in clinical trials exploring novel systemic agents.

Outcomes evaluation of a weekly nurse practitioner-managed symptom management clinic for patients with head and neck cancer treated with chemoradiotherapy.

PURPOSE/OBJECTIVES: To determine whether improved monitoring through close follow-up with a nurse practitioner (NP) could enhance treatment compliance and decrease frequency of hospitalizations. DESIGN: Retrospective chart review. SETTING: An academic National Cancer Institute-designated comprehensive cancer center. SAMPLE: 151 patients aged 45-65 years diagnosed with stage III or IV oropharyngeal cancer. METHODS: Patients were nonrandomized to one of two groups: a prechemotherapy clinic group and a weekly NP-led clinic group. After examination of descriptive statistics, multiple linear and logistic regressions were used to compare groups across patient outcomes. MAIN RESEARCH VARIABLES: Hospitalization, chemotherapy dose deviations, and chemotherapy treatment completion. FINDINGS: The average number of visits during traditional treatment was three and, after initiation of the NP-led clinic, the number was six. The hospitalization rate was 28% in the traditional clinic group compared to 12% in the NP-led group. The rate of chemotherapy dose deviations was 48% in the traditional clinic group compared to 6% in the NP-led clinic group. Forty-six percent of patients in the traditional clinic group received the full seven scheduled doses of chemotherapy compared to 90% of patients seen in the NP-led clinic group. CONCLUSIONS: A weekly NP-led symptom management clinic reduces rates of hospitalization and chemotherapy dose deviations and increases chemotherapy completion in patients receiving intensive chemoradiotherapy for oropharyngeal cancer. IMPLICATIONS FOR NURSING: Patients receiving chemoradiotherapy benefit from close monitoring for toxicities by NPs to successfully complete their treatment and avoid hospitalization. KNOWLEDGE TRANSLATION: Early interventions to manage toxicities in patients with head and neck cancer can improve outcomes. NPs are in a key position to manage these toxicities and, when symptoms are controlled, costs are reduced.

Inactivation or loss of TTP promotes invasion in head and neck cancer via transcript stabilization and secretion of MMP9, MMP2, and IL-6.

PURPOSE: Invasion is the critical step in progression of a precancerous lesion to squamous cell carcinoma of the head and neck (HNSCC). Invasion is regulated by multiple proinflammatory mediators. Tristetraprolin (TTP) is an mRNA-degrading protein that regulates multiple proinflammatory mediators. TTP may serve as an excellent treatment target. Rap1 is a ras-like oncoprotein that induces critical signaling pathways. In this study, the role of rap1 in TTP-mediated invasion was investigated. EXPERIMENTAL DESIGN: Using complementary approaches, we modulated TTP and altered expression of interleukin (IL)-6 and matrix metalloproteinase (MMP) 2/9, which were quantified by ELISA and zymogram. Invasion was evaluated in vitro using the oral-cancer-equivalent (OCE) three-dimensional model and in vivo in the chick chorioallantoic membrane (CAM). The role of rap1 and p38 were established using knockdown strategies. RESULTS: Downregulation of TTP significantly increased invasion via secretion of MMP9/2 and IL-6. In the novel OCE and CAM invasion models of HNSCC, cells with downregulated TTP destroyed the basement membrane to invade the underlying connective tissue. Rap1 induces p38 mitogen-activated protein kinase (p38)-mediated inactivation of TTP. Inactive TTP enhances transcript stability via binding to the 3'-untranslated region (UTR). High IL-6 and MMP9 are prognostic for poor clinical outcomes in patients with HNSCC. CONCLUSIONS: Targeting the rap1-p38-TTP cascade is an attractive novel treatment strategy in HNSCC to concurrently suppress multiple mediators of invasion.

Chemoselection as a strategy for organ preservation in patients with T4 laryngeal squamous cell carcinoma with cartilage invasion.

OBJECTIVES/HYPOTHESIS: High rates of overall survival (OS) and laryngeal preservation were achieved in two sequential phase II clinical trials in patients with stage III/IV laryngeal squamous cell carcinoma (SCC). Patients were treated with chemoradiation after a >50% primary tumor response to one cycle of neoadjuvant chemotherapy (IC). We analyzed outcomes for T4 patients with cartilage invasion from both studies. STUDY DESIGN: Retrospective. METHODS: Records from 36 patients with T4 SCC of the larynx with cartilage invasion alone (n = 16) or cartilage invasion and extralaryngeal spread (n = 20) were retrospectively reviewed. All were treated with one cycle of cisplatin (100 mg/m(2)) [or carboplatin (AUC 6)] and 5-fluorouracil (1,000 mg/m(2)/d for 5 days) (P+5FU). Those achieving >50% response at the primary tumor received chemoradiation (70 Gy; 35 fractions with concurrent cisplatin-100 mg/m(2) [carboplatin (AUC 6)] every 21 days for 3 cycles), followed by adjuvant P+5FU for complete histologic responders (CHR). Patients with <50% response after IC underwent total laryngectomy and postoperative radiation. RESULTS: Twenty-nine of 36 patients (81%) had >50% response following IC. Of these, 27 received definitive chemoradiation, 23 (85%) obtained CHR, with 58% laryngeal preservation rate. The 3-year OS was 78%, and the disease-specific survival was 80% (median follow-up 69 months). Following chemoradiation, 8/11 (73%) patients with an intact larynx had >75% understandable speech, 6/36 (17%) were g-tube dependent and 6/36 (17%) were tracheostomy dependent. CONCLUSIONS: Our results suggest that chemo-selection is a feasible organ preservation alternative to total laryngectomy for patients with T4 laryngeal SCC with cartilage invasion.

Chemoselection as a strategy for organ preservation in advanced oropharynx cancer: response and survival positively associated with HPV16 copy number.

PURPOSE: To test induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CRT) or surgery/radiotherapy (RT) for advanced oropharyngeal cancer and to assess the effect of human papilloma virus (HPV) on response and outcome. PATIENTS AND METHODS: Sixty-six patients (51 male; 15 female) with stage III to IV squamous cell carcinoma of the oropharynx (SCCOP) were treated with one cycle of cisplatin (100 mg/m(2)) or carboplatin (AUC 6) and with fluorouracil (1,000 mg/m(2)/d for 5 days) to select candidates for CRT. Those achieving a greater than 50% response at the primary tumor received CRT (70 Gy; 35 fractions with concurrent cisplatin 100 mg/m(2) or carboplatin (AUC 6) every 21 days for three cycles). Adjuvant paclitaxel was given to patients who were complete histologic responders. Patients with a response of 50% or less underwent definitive surgery and postoperative radiation. Pretreatment biopsies from 42 patients were tested for high-risk HPV. RESULTS: Fifty-four of 66 patients (81%) had a greater than 50% response after IC. Of these, 53 (98%) received CRT, and 49 (92%) obtained complete histologic response with a 73.4% (47 of 64) rate of organ preservation. The 4-year overall survival (OS) was 70.4%, and the disease-specific survival (DSS) was 75.8% (median follow-up, 64.1 months). HPV16, found in 27 of 42 (64.3%) biopsies, was associated with younger age (median, 55 v 63 years; P = .016), sex (22 of 30 males [73.3%] and five of 12 females [41.7%]; P = .08), and nonsmoking status (P = .037). HPV titer was significantly associated with IC response (P = .001), CRT response (P = .005), OS (P = .007), and DSS (P = .008). CONCLUSION: Although the numbers in this study are small, IC followed by CRT is an effective treatment for SCCOP, especially in patients with HPV-positive tumors; however, for patients who do not respond to treatment, alternative treatments must be developed.

A phase II evaluation of a 3-hour infusion of paclitaxel, cisplatin, and 5-fluorouracil in patients with advanced or recurrent squamous cell carcinoma of the head and neck: Southwest Oncology Group study 0007.

BACKGROUND: Previous data from an institutional pilot study in patients with advanced or recurrent squamous cell carcinoma of the head and neck (SCCHN) who received treated a combined chemotherapy regimen of paclitaxel, cisplatin, and 5-fluorouracil indicated an overall response rate of 60% and a median survival of 6 months. To validate these results and to determine the feasibility of this combination, a Phase II study was conducted by the Southwest Oncology Group (SWOG S0007). METHODS: Patients with advanced or recurrent SCCHN were eligible if they had received 1 previous regimen of induction/adjuvant chemotherapy or no prior systemic therapy. Patients received treatment with paclitaxel (135 mg/m(2) on Day 1), followed by cisplatin (75 mg/m(2) on Day 1), and 5-fluorouracil (1000 mg/m(2)per day as a 96-hour continuous infusion on Days 1-4) every 21 days. RESULTS: Seventy-six patients received a combined total of 286 cycles of chemotherapy. Sixty-nine patients were evaluable for response. There were 5 complete responses (7%) and 23 partial responses (33%) partial responses, for an overall response rate of 41%. The median progression-free survival was 4 months, and the median overall survival was 10 months. Six treatment-related deaths were documented, including deaths in 2 patients who had a Zubrod PS of 2. Grade 3 or 4 neutropenia (according to National Cancer Institute Common Toxicity Criteria [version 2.0]) was observed in 47% of patients. Other Grade 3 or 4 adverse events included mucositis (34% of patients), nausea (20% of patients), anemia (9% of patients), and neuropathy (8% of patients). CONCLUSIONS: The combination of paclitaxel, cisplatin, and 5-fluorouracil had efficacy similar to that of standard treatment regimens in patients with advanced or recurrent SCCHN but with increased toxicity.

Single-cycle induction chemotherapy selects patients with advanced laryngeal cancer for combined chemoradiation: a new treatment paradigm.

PURPOSE: Primary chemoradiotherapy in patients with advanced laryngeal cancer can achieve high rates of organ preservation without sacrificing survival compared with radiation alone or conventional laryngectomy. Appropriate selection of patients for organ preservation approaches could enhance overall treatment outcome and quality of life. We conducted a phase II organ preservation trial for patients with stage III and IV larynx cancer to determine whether late salvage surgery rates could be decreased and survival improved by selecting patients for organ preservation based on response to a single cycle of induction chemotherapy. PATIENTS AND METHODS: The chemotherapy was cisplatin 100 mg/m2 on day 1 and fluorouracil 1,000 mg/m(2)/d for 5 days. Patients who achieved less than 50% response had immediate laryngectomy. Patients who achieved more than 50% response went on to concurrent chemoradiotherapy. Histologic complete responders after chemoradiotherapy received two more cycles of chemotherapy. Patients with residual disease after chemoradiotherapy had planned salvage surgery. RESULTS: Of 97 eligible patients, 73 (75%) achieved more than 50% response and received chemoradiotherapy. A total of 29 patients (30%) had salvage surgery; 19 patients (20%) had early salvage surgery after the single cycle of induction chemotherapy, three patients (3%) had late salvage surgery after chemoradiotherapy, six patients (6%) eventually had salvage surgery for recurrence, and one patient had laryngectomy for chondroradionecrosis. The median follow-up time was 41.9 months. The overall survival rate at 3 years is 85%. The cause-specific survival rate was 87%. Larynx preservation was achieved in 69 patients (70%). CONCLUSION: These results confirm excellent larynx preservation and improved overall survival rates compared with historical results.