taxane and Head-and-Neck-Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Combined Modality Therapy; Head and Neck Neoplasms; Humans; Induction Chemotherapy; Neoplasm Metastasis; Organ Sparing Treatments; Radiotherapy, Intensity-Modulated; Taxoids; Treatment Outcome

To systematically review the efficacy and safety of taxane, cisplatin, and fluorouracil (Tax-PF) as induction chemotherapy for advanced head and neck cancer.. Literature about the efficacy and safety of Taxane-cisplatin-fluorouracil as induction chemotherapy for advanced head and neck cancer was retrieved from digital databases of PubMed, Embase, SpringerLink, MEDLINE and the Cochrane Library before February 2015. Data extraction and quality assessment of included studies were conducted by two reviewers independently. Stata 13.0 was then used to perform Meta-analysis.. A total 7 randomized controlled trials involving 2,702 were included. The 3-year OS rate [HR = 1.14, 95% CI (1.03, 1.25), P < 0.01], 3-year PFS rate [HR = 1.24, 95% CI (1.08, 1.43), P < 0.01], 5-year OS rate [HR = 1.30, 95% CI (1.09, 1. 55), P < 0. 01], 5-year PFS rate [HR = 1.39, 95% CI (1.14, 1.70), P < 0.01] and ORR to chemotherapy [OR = 1.66, 95% CI (1.35, 2.05), P < 0.01] of the patients in the Tax-PF group were statistically superior to those in the PF group. In terms of toxicities, the incidence of febrile neutropenia [OR = 2.36, 95% CI (1.62, 3.46), P < 0.01], alopecia [OR = 8.22, 95% CI (3.99, 16.92), P < 0.01], diarrhea [OR = 1.57, 95% CI (1.05, 2.36), P< 0.05] and leucopenia [OR = 2.79, 95% CI (1.86, 4.21), P < 0.01] was higher in the Tax-PF group than that in the PF group.. The Tax-PF induction chemotherapy improved PFS and OS, and the ORR was better as compared to PF-based therapy regimens at the cost of a higher incidence of adverse events.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Cisplatin; Fluorouracil; Head and Neck Neoplasms; Humans; Induction Chemotherapy; Randomized Controlled Trials as Topic; Taxoids

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.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Cisplatin; Disease-Free Survival; Fluorouracil; Head and Neck Neoplasms; Humans; Induction Chemotherapy; Middle Aged; Randomized Controlled Trials as Topic; Taxoids; Treatment Outcome

The strategy of induction chemotherapy prior to planned definitive local therapy for head and neck squamous cell carcinoma has been studied for over 30 years, and appears to have a role in select clinical situations. Here we review landmark studies regarding induction chemotherapy, both in the pre-taxane era and in the current taxane era, and we address some of the unresolved questions regarding the role of induction chemotherapy in head and neck cancer.

Topics: Antineoplastic Agents; Bridged-Ring Compounds; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Head and Neck Neoplasms; Humans; Neoadjuvant Therapy; Patient Selection; Taxoids

As therapy for locoregionally advanced head and neck cancer (HNC) has evolved, treatment has become increasingly aggressive and cure rates have risen. However, survival still remains poor. The evolving standard of care has focused on the concurrent use of chemotherapy with more aggressive radiotherapy; however, patients continue to recur locally and/or regionally, albeit at a diminished rate, and distant metastases have become a major site of fatal recurrence, while long-term local and acute systemic toxicities have increased. As a result of these changes in outcomes and a re-evaluation of earlier historical data by meta-analyses, interest in cisplatin and 5-fluorouracil (PF) induction chemotherapy has re-emerged and evolved. Most recently randomized studies comparing PF with PF plus a taxane, in particular docetaxel (TPF regimen), have demonstrated markedly superior survival with the three-drug regimens. TPF is now considered the standard of care for induction chemotherapy. Induction chemotherapy followed by chemoradiotherapy, known as sequential therapy, has been shown to be safe and effective. This approach is promising and may have a survival advantage over chemoradiotherapy alone. Both TPF induction and sequential therapy are considered appropriate platforms upon which the new molecularly targeted agents can be tested.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Chemotherapy, Adjuvant; Cisplatin; Clinical Trials as Topic; Combined Modality Therapy; Fluorouracil; Head and Neck Neoplasms; Humans; Meta-Analysis as Topic; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Remission Induction; Survival Analysis; Taxoids

Proof of principle that molecularly targeted therapy is a valid therapeutic approach for squamous cell carcinoma of the head and neck (SCCHN) has emerged with epidermal growth factor receptor targeting agents. Other interesting targets, such as Src, insulin-like growth factor 1 receptor, and the proteasome, have been shown in vitro to play key roles in SCCHN, and their inhibition is currently being studied in phase II trials. Identification of predictive biomarkers of resistance or sensitivity to these therapies remains one of the main challenges in the optimal selection of patients most likely to benefit from them. However, clinical trials with these novel agents need to be designed rationally to improve the overall outcome of patients. Given the emerging evidence that human papilloma virus-related SCCHN is a distinct disease, it should be studied in specific trials.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carboplatin; Carcinoma, Squamous Cell; Cetuximab; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Drug Delivery Systems; Fluorouracil; Head and Neck Neoplasms; Humans; Multicenter Studies as Topic; Neoplasm Metastasis; Neoplasm Recurrence, Local; Survival Rate; Taxoids; Time Factors

This review presents new data on the role of taxanes and targeted therapies in the management of squamous cell carcinoma of the head and neck.. Taxane-containing triplets are clearly superior as an induction regimen in locally advanced squamous cell carcinoma of the head and neck when compared with cisplatin/5 fluorouracil which has been the standard for two decades. Preliminary data suggest that the addition of a taxane to cisplatin/5 fluorouracil as induction regimen followed by chemoradiation may be superior to chemoradiation alone. The addition of cetuximab to radiation prolongs locoregional control and survival without increasing mucositis. Areas of active investigation are the search for epidermal growth factor receptor mutations and the optimal way of integrating epidermal growth factor receptor-directed therapies into standard management. Meanwhile new targets are explored.. Taxane/cisplatin/5 fluorouracil induction chemotherapy is clearly superior to cisplatin/5 fluorouracil. Epidermal growth factor receptor directed therapies can safely be combined with radiation and the combination shows encouraging results.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carcinoma, Squamous Cell; Cisplatin; ErbB Receptors; Fluorouracil; Head and Neck Neoplasms; Humans; Neoadjuvant Therapy; Taxoids

Cases with head and neck squamous cell carcinoma (HNSCC) have clinically advanced tumors. The curative treatments for advanced HNSCC are radiotherapy and/or surgical resection. However, standard treatment alone is less successful for advanced HNSCC. Accordingly, two modalities using chemotherapy are applied as preoperative treatment for HNSCC. First, multi-drug chemotherapy has been administered as neoadjuvant chemotherapy (NAC). As a result during the past 20 years, NAC without a high complete response (CR) rate has never improved the long-term outcome of advanced cases. Therefore, the development of intensive chemotherapy regimen with a high CR rate including taxanes is ongoing. On the other hand, organ preservation modality has been under investigation using combined radiotherapy with NAC regimen with a dose reduction of administered chemotherapeutic drugs or a new chemotherapy regimen including taxanes (concomitant or concurrent chemoradiotherapy). In this strategy, impact chemotherapy with almost the same anti-tumor effect as NAC and with a potential of radiation sensitizer is necessary.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carcinoma, Squamous Cell; Cisplatin; Fluorouracil; Head and Neck Neoplasms; Humans; Neoadjuvant Therapy; Pharyngeal Neoplasms; Preoperative Care; Radiotherapy Dosage; Remission Induction; Taxoids

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. The five-year survival rate of HNSCC has not improved even with major technological advancements in surgery and chemotherapy. Currently, docetaxel, cisplatin, and 5-fluoruracil (TPF) treatment has been the most popular chemotherapy method for HNSCC; but only a small percentage of HNSCC patients exhibit a good response to TPF treatment. Unfortunately, at present, no reasonably effective prediction model exists to assist clinicians with patient treatment. For this reason, patients have no other alternative but to risk neoadjuvant chemotherapy in order to determine their response to TPF. In this study, we analyzed the gene expression profile in TPF-sensitive and non-sensitive patient samples. We identified a gene expression signature between these two groups. We further chose 10 genes and trained a support vector machine (SVM) model. This model has 88.3% sensitivity and 88.9% specificity to predict the response to TPF treatment in our patients. In addition, four more TPF responsive and four more TPF non-sensitive patient samples were used for further validation. This SVM model has been proven to achieve approximately 75.0% sensitivity and 100% specificity to predict TPF response in new patients. This suggests that our 10-genes SVM prediction model has the potential to assist clinicians to personalize treatment for HNSCC patients.

Topics: Adult; Aged; Antineoplastic Agents; Bridged-Ring Compounds; Cisplatin; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Hypopharyngeal Neoplasms; In Vitro Techniques; Male; Middle Aged; Support Vector Machine; Taxoids

To assess the use of radiotherapy (RT) or concurrent chemoradiotherapy (CRT) following taxane-based induction chemotherapy (T-ICT) in locally advanced head and neck squamous cell carcinoma (LAHNSCC) and to evaluate the tolerability of CRT after T-ICT. From 01/2006 to 08/2012, 173 LAHNSCC patients treated as a curative intent by T-ICT, followed by definitive RT/CRT were included in this analysis. There was an 86% objective response (OR) after ICT among 154 evaluable patients. Forty-four patients received less than three cycles (25%) and 20 received only one cycle of T-ICT. The 3-year actuarial overall survival (OS) was 49% and there was no OS difference according to the type of ICT (regimen or number of cycle) or the addition of concurrent CT (cisplatin, carboplatin, or cetuximab) to RT. In multivariate analysis (MVA), clinically involved lymph node (cN+), age more than 60 years, the absence of OR after ICT, and performance status of at least 1 predicted for a decreased OS, with hazard ratios (HR) of 2.8, 2.2, 2.1, and 2, respectively. The 3-year actuarial locoregional control (LRC) and distant control (DC) rates were 52 and 73%, respectively. In MVA, the absence of OR after ICT (HR: 3.2), cN+ (HR: 3), and age more than 60 years (HR: 1.7) were prognostic for a lower LRC whereas cN+ (HR: 4.2) and carboplatin-based T-ICT (HR: 2.9) were prognostic for a lower DC. The number of cycles (≤ 2) received during ICT was borderline significant for DC in the MVA (P=0.08). Among patients receiving less than or equal to three cycles of ICT, higher outcomes were observed in patients who received cisplatin-based T-ICT (vs. carboplatin-based T-ICT) or subsequent CRT (vs. RT). T-ICT in our experience, followed by RT or CRT, raises several questions on the role and type of induction, and the efficacy of CRT over RT. The role of RT or CRT following induction, although feasible in these advanced patients, awaits answers from randomized trials.

Topics: Adult; Aged; Antineoplastic Agents; Bridged-Ring Compounds; Carboplatin; Carcinoma, Squamous Cell; Cetuximab; Chemoradiotherapy; Cisplatin; Disease-Free Survival; Feasibility Studies; Female; Head and Neck Neoplasms; Humans; Induction Chemotherapy; Male; Middle Aged; Neoplasm Recurrence, Local; Squamous Cell Carcinoma of Head and Neck; Taxoids; Young Adult

Induction chemotherapy followed by definitive chemoradiotherapy is an intensified treatment approach for locally advanced squamous cell carcinoma of the head and neck (HNSCC) that might be associated with high rates of toxicity.. The data of 40 consecutive patients who underwent induction chemotherapy with docetaxel-containing regimens followed by intensity-modulated radiotherapy (IMRT) and concomitant systemic therapy for unresectable locally advanced HNSCC were retrospectively analyzed. Primary objectives were RT-related acute and late toxicity. Secondary objectives were response to induction chemotherapy, locoregional recurrence-free survival (LRRFS), overall survival (OS), and influencing factors for LRRFS and OS.. The median follow-up for surviving patients was 21 months (range, 2-53 months). Patients received a median of three cycles of induction chemotherapy followed by IMRT to 72 Gy. Three patients died during induction chemotherapy and one during chemoradiotherapy. Acute RT-related toxicity was of grade 3 and 4 in 72 and 3 % of patients, respectively, mainly dysphagia and dermatitis. Late RT-related toxicity was mainly xerostomia and bone/cartilage necrosis and was of grade 3 and 4 in 15 % of patients. One- and 2-year LRRFS and OS were 72 and 49 % and 77 and 71 %, respectively.. Induction chemotherapy followed by chemoradiotherapy using IMRT was associated with a high rate of severe acute and late RT-related toxicities in this selected patient cohort. Four patients were lost because of fatal complications. Induction chemotherapy did not compromise the delivery of full-dose RT; however, the use of three cycles of concomitant cisplatin was impaired.

Topics: Adult; Aged; Antineoplastic Agents; Bridged-Ring Compounds; Chemoradiotherapy, Adjuvant; Female; Head and Neck Neoplasms; Humans; Induction Chemotherapy; Male; Middle Aged; Radiation Injuries; Radiotherapy, Conformal; Taxoids; Treatment Outcome

To determine the potential activity and tolerability of sequential treatment in head and neck cancer, we conducted a phase II trial based on induction chemotherapy of two cycles of taxotere, cisplatin and 5-fluorouracil followed by radiotherapy plus weekly cetuximab.. Thirty-six patients with stage III or IV squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx were treated and evaluated for response and acute toxicity.. Eighty-one percent of patients had stage IV disease and 42% had hypopharyngeal and oral cavity primaries. The overall response rate was 81.8%, with 60.6% complete response and 33.3% partial response. Severe toxicities were febrile neutropenia (6%) during induction chemotherapy and dermatitis (48%), mucositis (33%) and dysphagia (12%) during the concurrent phase.. Our protocol proved to be feasible, effective and well tolerated. This sequential strategy should be further investigated.

Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carcinoma, Squamous Cell; Cetuximab; Chemoradiotherapy; Cisplatin; Feasibility Studies; Female; Fluorouracil; Follow-Up Studies; Head and Neck Neoplasms; Humans; Induction Chemotherapy; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Remission Induction; Survival Rate; Taxoids; Treatment Outcome

Pre-RT ND in patients with HNSCC undergoing organ preservation treatment is safe, advantageous, poses no additional morbidity owing to the elective neck dissection, and may possibly improve survival outcomes.. Establish the role of pre-radiation neck dissection (pre-RT ND) in patients with head & neck squamous cell carcinoma (HNSCC) undergoing organ preservation treatment.. Fourteen patients with histologically confirmed HNSCC in stages III approximately IV with proven regional metastasis were enrolled in the organ preservation approach incorporating pre-RT ND at a tertiary referral center between May 1998 and August 2004. Site matched patients treated with organ preservation intent in the conventional fashion were used as controls. Data were collected for their diagnosis, management, treatment outcome, and follow up.. Disease free survival was significantly better for the pre-RT ND group. There was no significant difference in overall survival, pattern of recurrence, and primary organ preservation rate between the two groups. No significant morbidity owing to neck dissection was noted in patients who underwent neck dissection. Although the delivery of radiation to the primary site was delayed for patients in the pre-RT ND group, it did not influence the major outcomes.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neck Dissection; Neoplasm Metastasis; Neoplasm Recurrence, Local; Radiotherapy Dosage; Radiotherapy, Adjuvant; Taxoids

Given a lack of universally-accepted standard-of-care treatment for patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), study objectives were to assess treatment utilization and survival outcomes for R/M HNSCC in the real-world setting.. A multi-site retrospective chart review was conducted in Europe (Germany, United Kingdom, Italy, Spain), Asia Pacific (Australia, South Korea, Taiwan), and Latin/North America (Brazil and Canada) to identify patients who initiated first-line systemic therapy for R/M HNSCC between January 2011 and December 2013. Patients were followed through December 2015 to collect clinical characteristics, treatment and survival data.. Among 733 R/M HNSCC patients across 71 sites, median age was 60 years (inter-quartile range 54-67), 84% male, and 70% Eastern Cooperative Oncology Group performance status 0-1; 32% had oral cavity and 30% oropharyngeal cancers. The most common first-line regimen across all countries consisted of platinum-based combinations (73%), including platinum + 5-fluorouracil (5-FU) (26%), cetuximab + platinum ± 5-FU (22%), or taxane + platinum ± 5-FU (16%). However, use of different platinum-based combinations varied substantially; administration of cetuximab + platinum ± 5-FU was frequent in Italy (81%), Germany (46%) and Spain (38%), whereas use in other countries was limited. Median follow-up was 22.6 months (95% confidence interval [CI]: 21.5-24.6 months). Median real-world overall survival was only 8.0 months (95% CI: 7.0-8.0), with one-year survival reaching only 30.9% (95% CI: 27.5-34.3).. Systemic therapies used in clinical practice for patients with R/M HNSCC vary substantially across countries. Prognosis remains poor in this patient population, highlighting the need for newer, more efficacious treatments.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Australia; Brazil; Bridged-Ring Compounds; Canada; Cetuximab; Confidence Intervals; Europe; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Kaplan-Meier Estimate; Male; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Platinum Compounds; Republic of Korea; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Taiwan; Taxoids; Treatment Outcome

There are few data regarding the role of human papilloma virus (HPV) in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).. A retrospective chart review was carried out using our electronic medical record (EPIC) for all patients diagnosed with HPV-positive R/M HNSCC between 2010 and 2014 with minimum of 6 months of follow-up in order to assess progression-free survival (PFS) and overall survival (OS).. We assessed 11 patients who underwent a variety of treatments. PFS and OS were 7 and 34+ months, respectively. Four patients (36%) were still alive and disease-free (median OS of 39+ months). Three disease-free patients had been treated with taxane, platinum and 5-fluorouracil as aggressive curative systemic therapy. Another patient treated with TPF was disease-free for 25 months and died of disease at 42 months.. Our study demonstrates favorable prognosis for patients with HPV-positive R/M HNSCC and that aggressive systemic treatment can lead to a prolonged disease-free period or possibly cure, even after metastasis.

Topics: Bridged-Ring Compounds; Carcinoma, Squamous Cell; Disease-Free Survival; Fluorouracil; Follow-Up Studies; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Organoplatinum Compounds; Papillomavirus Infections; Prognosis; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Taxoids

Microtubules (MTs) are components of the cytoskeleton made up of polymerized alpha and beta tubulin dimers. MT structure and function must be maintained throughout the cell cycle to ensure proper execution of mitosis and cellular homeostasis. The protein tyrosine phosphatase, PTPN13, localizes to distinct compartments during mitosis and cytokinesis. We have previously demonstrated that the HPV16 E6 oncoprotein binds PTPN13 and leads to its degradation. Thus, we speculated that HPV infection may affect cellular proliferation by altering the localization of a PTPN13 phosphatase substrate, EphrinB1, during mitosis. Here we report that EphrinB1 co-localizes with MTs during all phases of the cell cycle. Specifically, a cleaved, unphosphorylated EphrinB1 fragment directly binds tubulin, while its phosphorylated form lacks MT binding capacity. These findings suggest that EphrinB1 is a novel microtubule associated protein (MAP). Importantly, we show that in the context of HPV16 E6 expression, EphrinB1 affects taxane response in vitro. We speculate that this reflects PTPN13's modulation of EphrinB1 phosphorylation and suggest that EphrinB1 is an important contributor to taxane sensitivity/resistance phenotypes in epithelial cancers. Thus, HPV infection or functional mutations of PTPN13 in non-viral cancers may predict taxane sensitivity.

Topics: Animals; Antineoplastic Agents; Bridged-Ring Compounds; Carcinoma, Squamous Cell; Cell Line; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Ephrin-B1; Head and Neck Neoplasms; HEK293 Cells; Human papillomavirus 6; Humans; Immunoblotting; MCF-7 Cells; Mice, Inbred C57BL; Microscopy, Confocal; Microtubule-Associated Proteins; Microtubules; Oncogene Proteins, Viral; Paclitaxel; Protein Binding; Repressor Proteins; RNA Interference; Taxoids

Phase III trials have shown that the addition of a taxane to cisplatin/5FU-based induction chemotherapy (TPF) improves response rates and overall survival in unresectable stage III/IV head and neck cancer. We sought to assess the tolerability, compliance and clinical outcomes of this treatment regime.. A retrospective study of patients treated within a single centre between September 2007 and November 2010. Toxicities were graded according to CTCAE version 3.0. Survival, distant metastasis and local control rates are expressed as percentages at two years using the Kaplan-Meier method.. A total of 100 patients were identified (11% stage III, 86% stage IV) and 32% of patients were admitted as an emergency after TPF. The rate of neutropenic fever was 31%, this number fell to 9% when prophylactic G-CSF was used. In addition, 89% of patients underwent radical chemoradiation. Of these, 96% completed the full radiotherapy course. However, only 64% of patients received a minimum of two cycles of concurrent platinum chemotherapy. The two-year overall survival, metastasis free survival and local control rates were 62.6%, 88.5% and 73.3%, respectively.. TPF chemotherapy can be delivered safely in a non-trial cohort of patients. There is, however, a significant reduction in concurrent chemotherapy dose intensity. The long-term impact of this remains unclear.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Chemoradiotherapy; Cisplatin; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Kaplan-Meier Estimate; Male; Neoplasm Metastasis; Retrospective Studies; Taxoids

The prognosis of cutaneous angiosarcoma (CAS), especially for patients with tumours > 5 cm has been reported to be dismal, even after conventional surgery and radiotherapy (S + RT).. To demonstrate the efficacy of chemoradiotherapy with taxane (T + RT) and maintenance chemotherapy.. We retrospectively reviewed 16 patients with CAS treated with T + RT and 12 patients treated with S + RT. None had distant metastasis. Tumour sites included the scalp (n = 25) and limbs (n = 3). The chemotherapy regimens used in T + RT were monthly docetaxel (n = 10), biweekly docetaxel (n = 1), weekly docetaxel (n = 5) and weekly paclitaxel (n = 1). The median radiation dose was 70 Gy. Nine patients receiving T + RT continued chemotherapy as maintenance therapy (monthly docetaxel in nine patients and monthly paclitaxel in two patients) and four patients receiving S + RT received adjuvant chemotherapy (weekly docetaxel).. The response ratio of T + RT was 94% (14 complete remission and one partial remission). The 5-year overall survival (OS) rate of patients receiving T + RT was statistically higher than those receiving conventional S + RT (56% and 8%, respectively; P < 0·01). Moreover, patients who received T + RT with maintenance chemotherapy showed a significant improvement in OS than those receiving T + RT alone (P < 0·01). There was a strong trend for relapse-free survival, but it was not significant (P = 0·07). These data indicate that maintenance chemotherapy is crucial for long-term survival after T + RT.. From these results, we suggest that T + RT followed by maintenance chemotherapy is a plausible method for managing CAS, especially large tumours that are difficult to manage with S + RT alone.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Chemoradiotherapy; Combined Modality Therapy; Docetaxel; Drug Administration Schedule; Female; Head and Neck Neoplasms; Hemangiosarcoma; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Paclitaxel; Retrospective Studies; Scalp; Skin Neoplasms; Taxoids; Treatment Outcome

Standard treatment for unresectable advanced head and neck squamous cell carcinoma is chemoradiotherapy, which can be toxic, particularly among patients with coexisting medical conditions. We report our experience with the hypofractionated radiotherapy regimen Irradiation HypoFractionnée 2 Séances Quotidiennes (IHF2SQ).. We retrospectively reviewed 78 patients treated with the IHF2SQ regimen. Radiotherapy was administrated as 2 fractions of 3 Gy per day (days 1 and 3), during the first, third, fifth, and seventh week of treatment with concurrent platinum-based chemotherapy.. Tolerance was excellent. Forty-one patients had complete or partial response. Median overall survival (OS) was 12.9 months and median progression-free survival (PFS) was 10.3 months. One-year OS, specific survival (SS), and PFS were 58%, 71%, 51.5%, respectively. Independent predictive factors increasing the PFS were response to chemoradiotherapy, male sex, and laryngeal tumor location.. This regimen is an alternative to conventional chemoradiotherapy with good response rates and acceptable toxicity for selected patients.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carboplatin; Carcinoma, Squamous Cell; Cetuximab; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Docetaxel; Dose Fractionation, Radiation; Female; Fluorouracil; Follow-Up Studies; Head and Neck Neoplasms; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Palliative Care; Radiotherapy; Retrospective Studies; Sex Factors; Taxoids

To conduct a retrospective review of 168 consecutively treated locally advanced head-and-neck cancer (LAHNC) patients treated with intensity-modulated radiotherapy (IMRT)/chemotherapy, to determine the rate and risk factors for developing hypothyroidism.. Intensity-modulated radiotherapy was delivered in 33 daily fractions to 69.3 Gy to gross disease and 56.1 Gy to clinically normal cervical nodes. Dose-volume histograms (DVHs) of IMRT plans were used to determine radiation dose to thyroid and were compared with DVHs using conventional three-dimensional radiotherapy (3D-RT) in 10 of these same patients randomly selected for replanning and with DVHs of 16 patients in whom the thyroid was intentionally avoided during IMRT. Weekly paclitaxel (30 mg/m(2)) and carboplatin area under the curve-1 were given concurrently with IMRT.. Sixty-one of 128 evaluable patients (47.7%) developed hypothyroidism after a median of 1.08 years after IMRT (range, 2.4 months to 3.9 years). Age and volume of irradiated thyroid were associated with hypothyroidism development after IMRT. Compared with 3D-RT, IMRT with no thyroid dose constraints resulted in significantly higher minimum, maximum, and median dose (p < 0.0001) and percentage thyroid volume receiving 10, 20, and 60 Gy (p < 0.05). Compared with 3D-RT, IMRT with thyroid dose constraints resulted in lower median dose and percentage thyroid volume receiving 30, 40, and 50 Gy (p < 0.005) but higher minimum and maximum dose (p < 0.005).. If not protected, IMRT for LAHNC can result in higher radiation to the thyroid than with conventional 3D-RT. Techniques to reduce dose and volume of radiation to thyroid tissue with IMRT are achievable and recommended.

Topics: Age Factors; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carboplatin; Combined Modality Therapy; Dose Fractionation, Radiation; Female; Head and Neck Neoplasms; Humans; Hypothyroidism; Male; Middle Aged; Paclitaxel; Radiation Injuries; Radiography; Radiotherapy, Intensity-Modulated; Retrospective Studies; Risk Factors; Taxoids; Thyroid Gland

Squamous cell carcinomas of the head and neck are highly responsive to induction chemotherapy. However, randomized trials have failed to demonstrate a survival advantage with the addition of induction chemotherapy to locoregional therapy consisting of surgery and/or radiation therapy. Currently, concomitant radiation and chemotherapy has emerged as a standard and has optimized locoregional control in head and neck cancer. In this setting, the addition of induction chemotherapy may further improve outcome by enhancing both locoregional and distant control. As interest in induction regimens is renewed, we elected to conduct a systematic review of trials of induction chemotherapy for locoregionally advanced head and neck cancer. The most studied combination-cisplatin plus fluorouracil (5-FU)--achieves objective response rates of about 80%. In a meta-analysis, induction with platinum/5-FU resulted in a small survival advantage over locoregional therapy alone. The introduction of a taxane into induction chemotherapy regimens has produced promising results. Induction chemotherapy should be the subject of further clinical research in head and neck cancer. Randomized clinical trials in which the control arm is concurrent chemoradiotherapy and the experimental arm is induction chemotherapy followed by concurrent chemoradiotherapy are planned. Platinum/taxane combinations are the preferred regimens for further study in the induction setting and a suitable platform with which to investigate the addition of novel targeted agents.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carcinoma, Squamous Cell; Cisplatin; Clinical Trials as Topic; Fluorouracil; Head and Neck Neoplasms; Humans; Taxoids

The objective of this project was to determine the mechanisms in which docetaxel enhances Ad-p53 tumor suppressive effects in head and neck cancer.. In advanced head and neck squamous cell carcinoma (HNSCC), the 5-year survival rate is less than 40%. Because patients with advanced HNSCC have a high rate of local-regional failure (40-60%) with existing treatment modalities, aggressive local therapy approaches need to be developed. Previous data show that docetaxel or Ad-p53 alone have significant anti-tumor activity in HNSCC. Before testing whether a combination approach (Ad-p53 and docetaxel) could be developed in clinical trials, preclinical experiments were performed.. The p53 gene was overexpressed in 2 head and neck squamous carcinoma (HNSCC) cell lines, HN30 and HN12, and a murine Balb/c mucoepidermoid carcinoma (BMEC) cell line. Docetaxel's enhancement of adenoviral transduction (bGAL expression), coxsakie-adenovirus receptor (CAR) expression, and Ad-p53 induction of apoptosis (Annexin V expression) were measured. The modulation of regulators in the cell cycle, apoptosis and signal transduction pathways were measured using Western blot.. Docetaxel increased adenoviral transduction, which was dependent on the dose of docetaxel and levels of Ad-bGAL. The enhanced viral transduction was due in part to the upregulation of the CAR protein. Pretreatment with docetaxel enhanced Ad-p53-induced apoptosis through increased expression of exogenous p53. Together, the combination of docetaxel and Ad-p53 altered expression of key regulators in the cell cycle, apoptosis and signal transduction pathways with an increase in the expression of p53, bax, cleaved PARP, cleaved caspase-3 and phosphorylation of c-Jun at position at Ser. Cyclin A and B1 expression were down regulated by docetaxel and Ad-p53. When comparing the docetaxel-resistant to sensitive cell lines, the altered expression of p27 and skp1 by docetaxel and Ad-p53 were dissimilar between these cell lines.. Docetaxel enhanced Ad-p53 transduction and increased expression of exogenous p53 gene transfer, apoptosis, and antitumor mechanisms. These results support a clinical combination of docetaxel with p53 gene therapy in patients with head and neck cancer.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Bridged-Ring Compounds; Carcinoma, Squamous Cell; Cell Line, Tumor; Combined Modality Therapy; Docetaxel; Enterovirus; Genetic Therapy; Head and Neck Neoplasms; Humans; Mice; Mice, Inbred BALB C; Protein Biosynthesis; Taxoids; Transduction, Genetic; Tumor Suppressor Protein p53

In most new cases of head and neck squamous cell carcinoma, especially in the pharynx and oral cavity, the tumors are advanced. Multidisciplinary treatments including chemotherapy in addition to definitive treatments, e.g., surgery and/or radiotherapy, have been applied. However, these treatments have not improved the poor prognosis for advanced head and neck carcinomas. A new curative treatment modality including chemotherapy and having a high complete response rate, e.g., a regimen consisting of taxanes, CDDP and 5-FU, is desirable. In addition, new therapeutic drugs against malignant solid tumors have been developed. The literature on thymidylate synthase inhibitor, dihydropyrimidine dehydrogenase inactivator, p-glycoprotein inhibitor, anti-epidermal growth factor receptor antibody, antiangiogenic drugs, COX-2 inhibitor and retinoids that may be applied in cases of head and neck carcinoma in the future, are reviewed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Bacterial Proteins; Bridged-Ring Compounds; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Cyclooxygenase 2; Endothelial Growth Factors; ErbB Receptors; Fibroblast Growth Factor 2; Fluorouracil; Head and Neck Neoplasms; Humans; Isoenzymes; Lymphokines; Membrane Proteins; Prostaglandin-Endoperoxide Synthases; Retinoids; Taxoids; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors