Chemotherapy In Head Research Articles

Efficacy of second-line erlotinib in patients postprogression of first-line chemotherapy in head and neck cancers.

Oral tyrosine kinase inhibitor (gefitinib and erlotinib) have been used in the palliative treatment of head and neck cancers with limited success. In this report, we aim to quantify the symptomatic benefit, progression-free survival (PFS) and overall survival (OS) when erlotinib is given as second-line treatment in Head and neck cancers. This was a post-hoc retrospective analysis of a randomized study comparing metronomic chemotherapy with cisplatin. A patient who progressed on chemotherapy and had a PS0-2 were offered second-line chemotherapy. Patients who had received erlotinib (150 mg PO OD) as second line treatment were selected for this analysis. Erlotinib was discontinued in case of either progression of disease or if the patient had intolerable side effects. Patient were monitored 1-week after the start of erlotinib and subsequently at monthly intervals. The toxicity was recorded in accordance with CTCAE version 4.02 (NCI,USA) and the response were graded in accordance with RECIST version 1.1. All of these patients were followed-up till death. Twenty-three patients were identified. The median age of these patients at the start of the second line was 47 years (interquartile range 40.5-51.75 years). The primary site of distribution was oral cavity primary in 17 patients (77.3%) and nonoral cavity primary in 05 (22.7%) patients. The immediate last chemotherapy regimen received was cisplatin in 9 patients (40.9%) and metronomic chemotherapy in 13 patients (59.1%). Symptomatic benefits post second-line erlotinib was seen in 18 patients (81.8%). The most common adverse events (any grade) seen were anemia in 20 patients (90.9%), rash in 10 patients (45.5%) and diarrhea in 7 patients (31.8%).The best radiological response documented were a partial response in 04 patients (19.2%). The median estimated PFS and OS were 110 days (95% confidence interval [CI]: 61-175 days) and 156 days (95% CI: 126-185 days) respectively. Erlotinib single agent has promising activity in the second line and needs to be explored in future studies.

Hypericum perforatum and neem oil for the management of acute skin toxicity in head and neck cancer patients undergoing radiation or chemo-radiation: a single-arm prospective observational study.

BackgroundRadiation dermatitis is common in patients treated with combined radiotherapy and chemotherapy for head and neck malignancies. Its timely and adequate management is of uttermost importance for both oncological outcomes and global quality of life. We prospectively evaluated the role of hypericum perforatum and neem oil (Holoil®; RIMOS srl, Mirandola, Italy) in the treatment of acute skin toxicity for patients undergoing radiotherapy or chemo-radiotherapy for head and neck cancer.MethodsA consecutive series of 28 head and neck cancer patients submitted to radiotherapy (RT) was enrolled onto this mono-institutional single-arm prospective observational study. Patients undergoing both definitive or post-operative radiotherapy were allowed, either as exclusive modality or combined with (concomitant or induction) chemotherapy. We started Holoil treatment whenever bright erythema, moderate oedema or patchy moist desquamation were observed. Holoil® was used during all RT course and during follow up time, until acute skin toxicity recovery.ResultsThe maximum detected acute skin toxicity was Grade 1 in 7% of patients, Grade 2 in 68%, Grade 3 in 25%, while at the end of RT was Grade 0 in 3.5%, Grade 1 in 32%, Grade 2 in 61%, Grade 3 in 3.5%. For patients having G2 acute skin toxicity, it mainly started at weeks 4-5; for those having G3, it began during weeks 5-6. Median times spent with G2 or G3 toxicity were 17.5 and 11 days. Patients having G2 acute skin toxicity had a dermatitis worsening in 27% of case (median occurrence time: 7 days). G3 events were reconverted to a G2 profile in all patients (median time: 7 days). Those experiencing a G2 skin event were converted to a G1 score in 23% of cases (median time: 14 days). Time between maximum acute skin toxicity and complete skin recovery after RT was 27 days.ConclusionsHoloil® proved to be a safe and active option in the management of acute skin toxicity in head and neck cancer patients submitted to RT or chemo-radiotherapy. A prophylactic effect in the prevention of moist desquamation may be hypothesized for hypericum and neem oil and need to be tested within a prospective controlled study.

Antiemetic therapy of fosaprepitant, palonosetron, and dexamethasone combined with cisplatin-based chemotherapy for head and neck carcinomas

Conclusion: Concomitant antiemetic therapy comprising fosaprepitant, palonosetron, and dexamethasone is effective for head and neck carcinoma. Objective: A patient diary was constructed to determine the effectiveness of concomitant antiemetic therapy with a neurokinin-1 receptor antagonist (fosaprepitant), 5-hydroxytryptamine receptor antagonist (palonosetron), and dexamethasone in accordance with guidelines. Methods: Subjects comprised 41 patients who received 71 courses of chemotherapy, along with fosaprepitant, palonosetron, and dexamethasone. A patient diary was compiled concerning the presence/absence of vomiting, vomiting episodes, presence/absence of rescue therapy, food intake, presence/absence of nausea, and general condition. Results: The frequency of the primary end point of complete response in the overall phase was 69.0%. The proportion of patients with no vomiting in the overall phase was 90.1%. In the acute phase, the proportion of no nausea and slight nausea together was 91.5%, no change in and slightly reduced food intake together was 87.3%, and the proportion of good general condition and relatively good general condition was 85.9%. In the delayed phase, the proportion of no nausea and slight nausea together was 56.3%, no change in and slightly reduced food intake together was 43.7%, and the proportion of good general condition and relatively good general condition together was 53.5%.

18F]-FDG PET-CT prediction of response to induction chemotherapy in head and neck squamous cell carcinoma: Preliminary findings

ObjectivesThe present study assessed the predictive value of [18F]-FDG PET-CT (positron emission tomography with 18-fluoro-eoxyglucose radiotracer, coupled to computerized tomography) for response to induction chemotherapy in head and neck squamous cell carcinoma (HNSCC). Material and methods[18F]-FDG PET-CT was systematically performed before treatment initiation and after the first cycle of chemotherapy. Results were compared with those of endoscopy and pathologic analysis of biopsy and surgical specimens. ResultsThis preliminary study included 21 previously untreated HNSCC patients. A decrease of more than 30% in SUVmax (maximum standard uptake value) during induction was predictive of tumor response to chemotherapy (P=0.04). PET-CT measurement of hypermetabolic volume based on a predetermined SUV threshold (SUV=2.5), on the other hand, proved non-predictive. ConclusionThese preliminary findings are promising. A larger sample, however, would be required in order to determine a more precise SUVmax reduction cut-off threshold during induction. Other methods for determining metabolic volume thresholds will be investigated. If functional imaging proves contributive, it could enable early screening of non-responders, avoiding unnecessary intoxication.

A phase II study comparing metronomic chemotherapy with chemotherapy (single-agent cisplatin), in patients with metastatic, relapsed, or inoperable squamous cell carcinoma of head and neck.

6017 Background: Cetuximab based regimen is the recommended palliative chemotherapy for head and neck squamous cell cancers. However, due to financial constraints, toxic intravenous chemotherapy wi...

Current status of medical oncology in Japan--reality gleaned from a questionnaire sent to designated cancer care hospitals.

Medical oncology in Japan has a relatively short history, with specialist certification starting in 2006, resulting in 867 certified medical oncologists as of 2014. Although the national government has appointed 397 Designated Cancer Care Hospitals, little is known about the actual situations of medical oncology services at these institutions. Questionnaires regarding the presence of a medical oncology department, the number of physicians in the department, the presence of certified medical oncologists and the degree of the medical oncologists' responsibilities for drug therapies in adults with solid cancers were sent to all 397 institutions between 21 January and 1 May 2013. The response rate was 68.0%. Among the responses, 39.4% of the institutions had medical oncology departments with a median of three physicians. Most of the medical oncology departments were primarily responsible, as evaluated according to patient number, for the treatment of limited disease categories. The medical oncologists were significantly more responsible for molecular-targeted therapy than for chemotherapy in head and neck cancer or for cytokine therapy in renal cell carcinoma. The wide variety of adverse events associated with molecular-targeted therapy might have enhanced the roles of medical oncologists. As the proportion of hospitals with a medical oncology department increased according to the number of certified medical oncologists working at the institution, cultivating medical oncologists seems to be an urgent task for advancing medical oncology in Japan. The present study provides fundamental data for the future development of medical oncology in Japan. The present study is to uncover the current situation of medical oncology in Japan.

The effect of cilengitide in combination with irradiation and chemotherapy in head and neck squamous cell carcinoma cell lines

Integrins are highly attractive targets in oncology due to their involvement in angiogenesis in a wide spectrum of cancer entities. Among several integrin inhibitors under clinical evaluation, cilengitide is the most promising compound. However, little is known about the cellular processes induced during cilengitide therapy in combination with irradiation and cisplatin in head and neck squamous cell carcinoma (HNSCC). The cytostatic effect of cilengitide was assessed by proliferation assay in the three HNSCC cell lines SCC25, FaDu and CAL27. Combination experiments with cisplatin and irradiation were performed. Possible synergistic effects were calculated in combination index (CI) analyses. Colony forming inhibition was investigated in clonogenic assays. Real-time PCR arrays were used to evaluate target protein gene expression patterns. Flow cytometry was used to detect apoptosis. Used alone, cilengitide has only minor cytotoxic effects in HNSCC cell lines. However, combination with cisplatin resulted in synergistic growth inhibition in all three cell lines. Irradiation showed synergism in short-term experiments and in colony forming assays, an additive effect was detected. Real-time PCR assay detected downregulation of the antiapoptotic protein Bcl-2 after exposure of cells to cilengitide. Cilengitide in combination with cisplatin and irradiation may be a feasible option for the treatment of patients with head and neck cancer. However, further investigations are required to understand the exact mechanism that leads to synergistic cytotoxicity.

When is chemotherapy in head and neck squamous cell carcinoma not indicated?

associated with treatment. The goals of HNSCC therapy can be categorized as either curative, employing either surgery and/or radiotherapy as a therapeutic backbone, or palliative, where symptom management and maintenance or improvement of quantity and quality of life are the primary focus. Systemic therapies (chemotherapy and targeted molecular therapeutics) have been an important addition to the therapeutic armamentarium against HNSCC. Although generally palliative when employed as a single treatment modality, systemic therapy concurrent with radiation has become an important curative option for patients with advanced locoregional disease as initial therapy or in the high-risk postoperative setting. Randomized clinical trials have demonstrated that systemic therapy concurrent with Introduction

Cetuximab plus platinum-based chemotherapy in head and neck squamous cell carcinoma: a retrospective study in a single comprehensive European cancer institution.

BackgroundThe use of cetuximab in combination with platinum (P) plus 5-fluorouracil (F) has previously been demonstrated to be effective in the treatment of metastatic squamous cell cancer of head and neck (SCCHN). We investigated the efficacy and outcome of this protocol as a first-line treatment for patients with recurrent or metastatic disease. We evaluated overall-survival (OS), progression-free-survival (PFS), overall response rate (ORR) and the treatment toxicity profile in a retrospective cohort.Patients and MethodsThis study enrolled 121 patients with untreated recurrent or metastatic SCCHN. The patients received PF+ cetuximab every 3 weeks for a maximum of 6 cycles. Patients with stable disease who received PF+ cetuximab continued to receive cetuximab until disease progressed or unacceptable toxic effects were experienced, whichever occurred first.ResultsThe median patient age was 53 (37–78) years. The patient cohort was 86.8% male. The addition of cetuximab to PF in the recurrent or metastatic setting provided an OS of 11 months (Confidential Interval, CI, 95%, 8.684–13.316) and PFS of 8 months (CI 95%, 6.051–9.949). The disease control rate was 48.9%, and the ORR was 23.91%. The most common grade 3 or 4 adverse events in the PF+ cetuximab regimen were febrile neutropenia (5.7%), skin rash (3.8%) and mucosistis (3.8%).ConclusionsThe results of this study suggest that cetuximab plus platinum–fluorouracil chemotherapy is a good option for systemic treatment in advanced SSCHN patients. This regimen has a well-tolerated toxicity profile.

Induction Chemotherapy in Head and Neck Cancer: Are we Too Ambitious?

Induction Chemotherapy in Head and Neck Cancer: Are we Too Ambitious?

Candidal carriage, isolation and species variation in patients undergoing radiotherapy and chemotherapy for head and neck tumours

Background: Opportunistic fungal infections, mainly candidiasis, is common in immunocompromised patients such as those undergoing chemo or radiatiotherapy and pose a great threat. Hence this study was done, attempting to find out the candidal carrier state and species variation, in such patients. Aims and Objectives: To determine the prevalence and speciation of Candida colonizing in the oral cavity of individuals attending to the cancer clinics in south India. Materials and Methods: Study groups comprised of 50 healthy, asymptomatic individuals as controls (Group I); 50 patients on : chemotherapy (Group - II) and 50 patients undergoing radiotherapy for head and neck cancers (Group - III). Mycological tests for the candidal isolation and speciation were done. Results: A total of 49 cases showed candidal culture positivity (32.67%). Candidal carriage was highest in Group II and Group III (38%). C. albicans was the most prevalent species (30%). The culture positivity and the colony forming unit/ml from the subjects of control group and the study group were highly significant, in pair-wise comparisons. Conclusion: Patients undergoing chemotherapy and radiotherapy for head and neck cancers are at a risk of developing oral candidiasis due to immunosuppression. C. albicans is the predominant isolate, but non-albicans species are also emerging as opportunistic pathogens. All may cause a similar spectrum of disease but differences in disease severity and antifungal susceptibility are noted. Hence, speciation can help to target the treatment of the disease in a much better way.

Oral mucositis prevention and management by therapeutic laser in head and neck cancers.

Oral mucositis is considered a severe complication in cancer patients receiving radiotherapy or chemotherapy for head and neck cancer. The aim of this review study was to assess the effect of low level laser therapy for prevention and management of oral mucositis in cancer patients. The electronic databases searched included Pubmed, ISI Web of Knowledge and Google scholar with keywords as "oral mucositis", "low level laser therapy" from 2000 to 2013. The results of most studies showed that photobiomodulation (PBM) reduced the severity of mucositis. Also, it can delay the appearance of severe mucositis. Low level laser therapy is a safe approach for management and prevention of oral mucositis.

Chemotherapy of Head and Neck Cancer

Head and neck cancers comprise a heterogenous group of cancers that require a multidisciplinary approach. Surgery, radiation therapy, chemotherapy and, more recently, target therapy are often employed in various combinations in an attempt to eradicate both clinically apparent and occult disease. The role of chemotherapy in multimodality treatment for locally advanced head and neck squamous cell carcinoma, although firmly established, presents several unresolved issues. Concomitant platinum-based chemoradiation (CRT) is a standard treatment for unresectable, resectable but nonsurgically treated, and postoperative high-risk patients with locally advanced head and neck squamous cell carcinoma. Cetuximab administered concomitantly with radiotherapy has not been directly compared with CRT but offers a potential different approach using a noncytotoxic systemic agent. In recent years taxanes have been shown activity in head and neck cancers and are being incorporated into neo-adjuvant and concomitant chemotherapy regimens. � Korean J Otorhinolaryngol-Head Neck Surg 2014;57(5):291-6

頭頸部扁平上皮癌におけるTPF療法の安全性に関する検討

ドセタキセル，シスプラチン，5-FUの3剤併用療法（以下，TPF療法）による導入化学療法は広く行われ，また再発・遠隔転移例に対する使用報告例も少なくない。以前に化学療法などで治療された経験のある前治療群と，これまでに化学療法を行ってない初回治療群に分けて，当院で頭頸部扁平上皮癌に対してTPF療法を行った94例について，1コース施行後の安全性を検討した。白血球減少と好中球減少で群間に差はなかったが，発熱性好中球減少症を初回治療群は54例中16例（29%），前治療群では39例中20例（51%）に認め治療を要した。また，前治療群の2例で治療関連死が生じた。前治療が行われた症例にTPF療法を行う場合は厳重な管理が必要であることが示された。

EP-1099: Favourable outcomes with systemic anti cancer chemotherapy in Head and Neck cancer at a UK tertiary cancer centre

EP-1099: Favourable outcomes with systemic anti cancer chemotherapy in Head and Neck cancer at a UK tertiary cancer centre

P27 and BCL2 expression predicts response to chemotherapy in head and neck squamous cell carcinomas

Head and neck squamous cell carcinomas (HNSCCs) are characterized by marked heterogeneity in their biological behavior and response to treatment. Our goal was the identification of biomarkers that can be used to predict response to chemotherapy in these patients. The expression of EGFR, p53, Cyclin D1, p16, p21, p27, p-AKT, HIF-1α, Caspase 3 and BCL2 was analyzed by immunohistochemistry in 41 primary laryngeal/hypopharyngeal squamous cell carcinomas of patients that received induction chemotherapy (cisplatin and 5-fluorouracil) as part of their treatment. Positive expression of p27 and BCL2 had a significant predictive value for chemotherapy response in univariate analysis. The combination of both proteins was not superior in predicting the response to chemotherapy. Furthermore, p27 expression was the only significant predictor of chemotherapy response in multivariate analysis (P=0.015). p27 Expression may serve as predictive biomarker of response to induction chemotherapy in HNSCC patients.

Vascular priming enhances chemotherapeutic efficacy against head and neck cancer

The need to improve chemotherapeutic efficacy against head and neck squamous cell carcinomas (HNSCC) is well recognized. In this study, we investigated the potential of targeting the established tumor vasculature in combination with chemotherapy in head and neck cancer. Experimental studies were carried out in multiple human HNSCC xenograft models to examine the activity of the vascular disrupting agent (VDA) 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in combination with chemotherapy. Multimodality imaging (magnetic resonance imaging, bioluminescence) in conjunction with drug delivery assessment (fluorescence microscopy), histopathology and microarray analysis was performed to characterize tumor response to therapy. Long-term treatment outcome was assessed using clinically-relevant end points of efficacy. Pretreatment of tumors with VDA prior to administration of chemotherapy increased intratumoral drug delivery and treatment efficacy. Enhancement of therapeutic efficacy was dependent on the dose and duration of VDA treatment but was independent of the chemotherapeutic agent evaluated. Combination treatment resulted in increased tumor cell kill and improvement in progression-free survival and overall survival in both ectopic and orthotopic HNSCC models. Our results show that preconditioning of the tumor microenvironment with an antivascular agent primes the tumor vasculature and results in enhancement of chemotherapeutic delivery and efficacy in vivo. Further investigation into the activity of antivascular agents in combination with chemotherapy against HNSCC is warranted.

Taxane-Cisplatin-Fluorouracil As Induction Chemotherapy in Locally Advanced Head and Neck Cancers: An Individual Patient Data Meta-Analysis of the Meta-Analysis of Chemotherapy in Head and Neck Cancer Group

PURPOSE Cisplatin plus fluorouracil (PF) induction chemotherapy has been compared with taxane (docetaxel or paclitaxel), cisplatin, and fluorouracil (Tax-PF) in randomized trials in locoregionally advanced head and neck cancers (LAHNCs). The aim of this meta-analysis was to study the efficacy and toxicity of Tax-PF and PF and identify differences in outcomes in subsets of patients. METHODS Five randomized trials representing 1,772 patients were identified. Updated individual patient data (IPD) were retrieved for all trials. The log-rank test, stratified by trial, was used for comparison. Interaction or trend tests were used to study the interaction between covariates and treatment. Results Median follow-up was 4.9 years. The hazard ratio (HR) of death was 0.79 (95% CI, 0.70 to 0.89; P < .001; absolute benefit at 5 years: 7.4%) in favor of Tax-PF. Heterogeneity was significant (P = .08, I(2) = 51%) and related to one trial. There was no more heterogeneity after exclusion of this trial (P = .99, I(2) = 0%), and HR of death was 0.72 (95% CI, 0.63 to 0.83) in favor of Tax-PF. There was no interaction between treatment effect and the following patient covariates: age, sex, performance status, tumor stage, or site. Tax-PF was associated with significant reductions of progression, locoregional failure, and distant failure compared with PF, with HRs of 0.78 (95% CI, 0.69 to 0.87; P < .001), 0.79 (95% CI, 0.66 to 0.94; P = .007), and 0.63 (95% CI, 0.45 to 0.89; P = .009) respectively. CONCLUSION This IPD meta-analysis shows the superiority of Tax-PF over PF as induction chemotherapy. Its precise role in the management of LAHNC remains to be determined.

Abstract 2064: SF3B1 inhibitors sensitize head and neck squamous cell carcinoma to Bcl-xL inhibition by regulating Mcl-1 alternative splicing.

Abstract This study explored the application of the alternative splicing of Bcl-2 family protein Mcl-1 in combination chemotherapy for head and neck squamous cell carcinoma (HNSCC) cell lines: meayamycin B (SF3b inhibitor) switched the pre-mRNA alternative splicing of Mcl-1 from anti-apoptotic to pro-apoptotic; the combination of meayamycin B with ABT-737 (Bcl-xL inhibitor) rapidly stimulated apoptosis in a panel of HNSCC cells, overcoming the HPV-16-mediated Mcl-1 over-expression. Western blotting and semi-quantitative RT-PCR as well as qPCR afforded evaluation of the expression of Mcl-1 splicing variants at mRNA and protein levels. Apoptosis status was monitored by using caspase 3/7 activity assays and Annexin V/7-AAD staining. siRNA was used to specifically knock down HPV-16 E6 gene. Meayamycin B exhibited 0.1-10 nM ED50 values in HNSCC cell lines that are mostly resistant to ABT-737. In HPV-16 positive HNSCC, E6 oncogene affords moderate resistance to meayamycin B. The combination of meayamycin B and ABT-737 synergistically induced apoptosis in HNSCC cell lines regardless of HPV status. These data demonstrate the potential of meayamycin B, both as a single agent and in combination with Bcl-xL inhibitors, for both research and targeted molecular therapeutic purposes for HNSCC. Citation Format: Yang Gao. SF3B1 inhibitors sensitize head and neck squamous cell carcinoma to Bcl-xL inhibition by regulating Mcl-1 alternative splicing. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2064. doi:10.1158/1538-7445.AM2013-2064

Palliative chemotherapy in head and neck squamous cell cancer - What is best in Indian population? A time without symptoms, treatment toxicity score based study

Background:Patients with recurrent and metastatic head and neck Squamous Cell Cancer (HNSCC) have poor prognosis with limited treatment options. In view of decimal prognosis, the treatment decision should include quality of life (QOL) issues, cost-effectiveness besides the response rates and survival.Aim:Present retrospective analysis was conducted to evaluate efficacy (disease-free survival), pharmacoeconomics, and toxicity profile of four (4) different regimens, viz. gefitinib alone, gefitinib with methotrexate, methotrexate alone, or 5-FU with cisplatin.Materials and Methods:Case records between 2007 September and 2008 September were analyzed, 68 patients were found suitable for analysis. Patients received gefitinib (250 mg/day), methotrexate as 50 mg intramuscular weekly or a combination of the same or 5-FU 750 mg/m2/day for 4 days along with cisplatin 75 mg/m2/day on day 1 in 21-day cycle.Results:A total of 68 patients received therapy. Fifty-one patients have clinically meaningful response (stable disease + complete + partial responses) (75%) and had symptomatic improvement. The median progression-free survival was significantly superior in responders (those who achieved partial or complete response) (8.4 months vs. 3.1 months, P=0.001). Methotrexate with gefitinib had maximum median survival and better overall QOL compared to the other treatment regimens. Weekly methotrexate is relatively cost-effective followed by methotrexate with gefitinib and gefitinib alone. 5-FU with cisplatin in our experience does not appear so attractive in view of high complication rates (when given in full doses) and prolonged hospital stay.Conclusion:Based on the results of this retrospective analysis, methotrexate weekly as single agent or in combination with gefitinib appears as an attractive alternative regimen for patients with metastatic HNSCC including those having poor performance status. A prospective study was planned and submitted to the local ethics committee based on above results to validate these results and compare methotrexate and gefitinib arm with 5-FU + cisplatin.