Concurrent Chemoradiation with Weekly Cisplatin for the Treatment of Head and Neck Cancers: an Institutional Study on Acute Toxicity and Response to Treatment

Background: Concurrent chemoradiation with three weekly high dose cisplatin is the non-surgical standard ofcare for the treatment of locally advanced head and neck cancers. Although this treatment regime is efficacious,it has high acute toxicity, which leads not only to increased treatment cost, but also to increased overall treatmenttime. Hence, the current study was undertaken to evaluate the acute toxicity and tumor response in head andneck cancer patients treated with concurrent chemoradiation using 40 mg/m2 weekly cisplatin, which has beenour institutional practice. Materials and Methods: This single institution retrospective study included data for287 head and neck cancer patients treated with concurrent chemoradiation from 2012 to 2014. Results: Themean age of the patients was 48.8 years. The most common site of involvement was oral cavity. Most of the studypatients presented with advanced stage disease. The mean overall treatment time was 56.9 days. Some 67.2%had overall complete response to treatment as documented till 90 days from the start of treatment. Accordingto the Radiation Therapy Oncology Group (RTOG) acute radiation morbidity scoring criteria, mucositis wasseen in 95.1% of the patients. Dermatitis and emesis were observed in 81.9% and 98.6%, respectively. Regardinghaematological toxicity, 48.8% and 29.6% suffered from anaemia and leukopenia, respectively, during treatment.Acute kidney injury was assessed using the Common Terminology Criteria for Adverse Events (CTCAE), andwas found in 18.8% of the patients. Conclusions: Concurrent chemoradiotherapy with weekly cisplatin is aneffective treatment regime for head and neck cancers with reasonable toxicity which can be used in developingcountries, where cost of treatment is so important.     

Three Weekly Versus Weekly Cisplatin as Radiosensitizer in Head and Neck Cancer: a Decision Dilemma

Cisplatin-based concurrent chemoradiation plays an undisputed key role as definitive treatment in unresectable patients with locally advanced squamous cell carcinoma head and neck or as an organ preservation strategy. Treatment with 100 mg/m2 3-weekly cisplatin is considered the standard of care but is often associated with several adverse events. The optimum drug schedule of administration remains to be defined and presently, there is insufficient data limiting conclusions about the relative tolerability of one regimen over the other. This review addresses regarding the optimal dose schedule of cisplatin focusing mainly on three-weekly and weekly dose of cisplatin based concurrent chemoradiotherapy in locally advanced head and neck cancer with an emphasis on mucositis, dermatitis, systemic toxicity, compliance, and treatment interruptions. To derive a definitive conclusion, large prospective randomized trials are needed directly comparing standard 3-weekly cisplatin (100 mg/m2) with weekly schedule (30 - 40 mg/m2) of concurrent cisplatin based chemoradiotherapy in locally advanced squamous cell carcinoma head and neck.     

Adjuvant high-dose rate brachytherapy after chemoradiation for treatment of early T-stage nasopharyngeal carcinoma

The local control of nasopharyngeal carcinoma after conventional radiotherapy has historically been suboptimal. Recently, investigators have reported improved outcomes for this patient population with the use of combined chemoradiotherapy. The purpose of this analysis of our prospective treatment protocol was to evaluate the additional value of high-dose rate intracavitary brachytherapy (HDRIB) on the disease response, local control, and survival. Between March 1999 and January 2001, 16 patients with newly diagnosed locally advanced (stage III and IV) nasopharyngeal carcinoma were treated prospectively at the Radiation Oncology Department of the National University Hospital of Singapore. All patients were staged according to the AJCC (1997) Staging System and had early T stages (T1 and T2). Treatments included concurrent external beam radiotherapy (EBRT) and chemotherapy as follows: 66 Gy to the primary tumor in conventional fractionation with cisplatin based concurrent chemotherapy followed by adjuvant cisplatin and 5-fluorouracil (5-FU) chemotherapy. Ten Gy of HDRIB in 2 weekly fractions were delivered after the completion of EBRT to all 16 patients. All patients were evaluable for treatment response, local control, survival, and toxicity analysis. The median follow-up for the whole group of patients was 18 months (range: 10-34 months). All patients obtained pathologic complete response at the primary site at 4 months after the completion of the treatment. At the time of this analysis, 15 (93.8%) patients are alive with no evidence of disease. One patient (6.2%) developed locoregional recurrence in the neck at 9 months, and distant metastasis at 11 months after the completion of treatment. Our experience has shown adjuvant HDRIB after concurrent chemoradiation offers encouraging disease response, local control, and survival. A prospective study is being planned to further evaluate the role of adjuvant HDRIB after concurrent chemoradiation on treatment outcome.     

Toxicity profile and clinical outcomes in locally advanced head and neck cancer patients treated with induction chemotherapy prior to concurrent chemoradiation

The use of induction chemotherapy prior to chemoradiation for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) remains controversial. We explored whether toxicity from induction chemotherapy influenced the delivery of concurrent chemoradiation. Among 171 consecutive previously unirradiated patients with HNSCC treated with combined chemotherapy and radiation, we identified 66 patients with stage III-IVB head and neck carcinoma who were treated with induction chemotherapy prior to planned chemoradiation. The most common induction regimen was docetaxel, cisplatin and 5-FU (TPF; 80%) for 2 to 3 cycles. Mean radiation dose was 72 Gy (range, 36-75 Gy). Concurrent chemotherapy regimens included cisplatin (26%), cetuximab (5%) and 5-fluorouracil/hydroxyurea (65%)-based regimens. At a median follow-up of 27 months (range, 9-56 months), the 2-year locoregional control and distant control rates were 85 and 86%, respectively. The 2-year disease-free survival and overall survival rates were 74 and 80%, respectively. Although there were no grade 5 toxicities during induction chemotherapy, 26% of patients required hospitalization for adverse events, including 5% needing intensive care. The most common high grade adverse events were grade 4 neutropenia (21%) and neutropenic fever (17%). Six percent of patients were unable to tolerate concurrent chemotherapy. The 2-year disease-free survival was significantly higher in patients able to complete induction and concurrent chemoradiation as planned (83 vs. 27%, p<0.001). Induction chemotherapy followed by concurrent chemoradiation results in promising survival rates in our cohort of advanced head and neck carcinoma patients. Due to severe toxicities in a subset of patients, this strategy is only recommended in selected high-risk patients who are carefully followed by an experienced multidisciplinary team.     

RADPLAT: an alternative to surgery?

Head and neck cancer frequently presents at a late stage, leading to a poor prognosis despite optimal treatment with surgery and/or radiotherapy. Chemotherapy for advanced disease has shown little benefit as a single-modality treatment, and the use of concurrent chemoradiation is limited by problems with severe toxicity at higher doses. RADPLAT is the acronym used to describe a new technique, combining intra-arterial delivery of cisplatin with systemic neutralization by i.v. sodium thiosulphate, and concurrent radiotherapy. This allows very high cisplatin dose intensities to be used while potentially minimizing adverse systemic effects. Initial results suggest that excellent locoregional control rates are achievable in patients with unresectable disease, with a favorable side-effect profile when compared with conventional chemoradiation protocols. In addition, RADPLAT may potentially be of benefit in selected patients with resectable disease, allowing for preservation of organ function and quality of life without compromising locoregional control or survival. While current phase II data are encouraging, phase III randomized controlled trials are required in order to directly compare RADPLAT with i.v. chemoradiation therapy, the current standard of care. This article reviews the evolution of the RADPLAT concept, from initial clinical trials to its current application in the treatment of patients with advanced head and neck cancer.     

Excellent disease control and survival in patients with advanced nasopharyngeal cancer treated with chemoradiation.

PURPOSE: To determine the efficacy and safety of epirubicin, cisplatin, and infusional fluorouracil (5-FU) chemotherapy followed by radiation with concurrent cisplatin in patients with locally and/or regionally advanced nasopharyngeal cancer. PATIENTS AND METHODS: Thirty-five patients were treated with three cycles of induction chemotherapy with epirubicin 50 mg/m(2) and cisplatin 75 mg/m(2) combined with continuous-infusion 5-FU 200 mg/m(2) daily for 9 weeks, followed by concurrent chemoradiation of 60 Gy in 2-Gy fractions with cisplatin 20 mg/m(2) daily for 5 days in weeks 1 and 6. RESULTS: Median age was 43 years, 74% had World Health Organization type III histology, and 91% had stage IV disease (International Union Against Cancer, ed 4). All patients received three cycles of induction chemotherapy, and 97% completed chemoradiation. The estimated 4-year progression-free survival rate was 81% (95% CI, 59% to 93%), and the estimated 4-year overall survival rate was 90% (95% CI, 74% to 97%). Only two patients have had a locoregional relapse by the close-out date despite the use of only 60 Gy. Induction chemotherapy was well tolerated, with 11% grade 3 or 4 stomatitis, 26% grade 3 vomiting, and no episodes of febrile neutropenia. Acute toxicities of chemoradiation were as follows: 23% grade 3 or 4 vomiting, 6% febrile neutropenia, 31% grade 3 mucositis, and 23% grade 3 skin toxicity. The most prevalent grade 3 late effects were xerostomia and hearing loss. CONCLUSION: This regimen was well tolerated, can be delivered as planned, and has resulted in excellent locoregional disease control and survival in patients with locally advanced nasopharyngeal cancer.     

Longitudinal Oncology Registry of Head and Neck Carcinoma (LORHAN): analysis of chemoradiation treatment approaches in the United States

BACKGROUND:

A study was undertaken to examine the patterns of systemic therapy use in conjunction with radiation therapy for patients with locally advanced head and neck squamous cell cancer.

METHODS:

Between December 1, 2005 and May 11, 2009, 2874 patients with newly diagnosed head and neck squamous cell cancer who were scheduled to receive radiotherapy and/or drug therapy were registered in a prospective national database. The database was specifically analyzed to examine patients who received chemotherapy in conjunction with definitive radiotherapy.

RESULTS:

A total of 1144 patients received systemic therapy in conjunction with radiotherapy; 645 (56%) patients received agents concurrent with radiation therapy, 49 (4%) patients received chemotherapy before radiotherapy (induction), 224 (20%) patients received chemotherapy before and during radiotherapy (sequential), and 226 (20%) patients received chemoradiation after surgery. Single‐agent cisplatin, single‐agent cetuximab, and carboplatin plus paclitaxel were, in order, the 3 most commonly prescribed concurrent regimens. Concurrent cisplatin was more frequently used in the academic setting compared with the community setting (P = .0015). Postoperative chemoradiation, rather than radiation alone, was more commonly used in academic centers compared with community practice centers (P = <.0001).

CONCLUSIONS:

The LORHAN (Longitudinal Oncology Registry of Head and Neck Carcinoma) database is a useful barometer of current US practice patterns and can be applied to analyze future trends in the combined modality management of head and neck cancer. Sequential chemotherapy is used frequently, but cisplatin‐based concurrent chemoradiation remains the most commonly used regimen for locally advanced head and neck cancer. Cancer 2011. © 2010 American Cancer Society.     

A phase II study of concomitant boost radiation plus concurrent weekly cisplatin for locally advanced unresectable head and neck carcinomas.

BACKGROUND AND PURPOSE: This phase II study evaluated the efficacy and toxicity of weekly cisplatin along with concomitant boost accelerated radiation regimen in patients with locally advanced unresectable head and neck carcinoma. MATERIAL AND METHODS: A total of 94 patients (median age, 58 years) with UICC stage III (n = 19) and IV (n = 75) cancer of the oropharynx, larynx, hypopharynx and oral cavity were included. Patients received radiotherapy with a concomitant boost scheme (1.8 Gy on days 1-40 and 1.5 Gy boost on days 25-40 with a total dose of 72 Gy) and concurrent cisplatin, 40 mg/m(2) weekly, for the first 4 weeks. RESULTS: Most patients (95%) received both radiation and chemotherapy according to protocol. Toxicity was manageable with grade III mucositis and pharyngeal-oesophageal toxicity in 85 and 50% of patients, respectively. Haematological toxicity was mild. Four patients (4%) died due to complications. With a median follow of 41 months, median overall survival and time to progression were 27 and 25 months, respectively. The estimated overall survival at 4 years was 41%. CONCLUSIONS: Concomitant boost accelerated radiation plus concurrent weekly cisplatin is a feasible schedule in patients with locally advanced unresectable head and neck carcinoma, with acceptable toxicity and survival data.     

Comparison of concurrent chemoradiation therapy with weekly cisplatin versus monthly fluorouracil plus cisplatin in FIGO stage IIB-IVA cervical cancer

Objective

Concurrent chemoradiation therapy (CCRT) is the standard treatment for locally advanced cervical cancer. Although the optimal chemotherapeutic regimen is not yet defined, previous randomized trials have demonstrated that 5-fluorouracil (5-FU) plus cisplatin every 3 weeks and weekly cisplatin are the most popular regimens. The purpose of this study was to compare the outcomes of weekly CCRT with cisplatin and monthly CCRT with 5-FU plus cisplatin for locally advanced cervical cancer.

Methods

We retrospectively reviewed data from 255 patients with FIGO stage IIB-IVA cervical cancer. Patients were classified into two CCRT groups according to the concurrent chemotherapy: weekly CCRT group, consisted of CCRT with weekly cisplatin for six cycles; and monthly CCRT group, consisted of CCRT with cisplatin and 5-FU every 4 weeks for two cycles followed by additional consolidation chemotherapy for two cycles with the same regimen.

Results

Of 255 patients, 152 (59.6%) patients received weekly CCRT and 103 (40.4%) received monthly CCRT. The mean follow-up period was 39 months (range, 1 to 186 months). Planned CCRT was given to 130 (85.5%) patients in weekly CCRT group and 84 (81.6%) patients in monthly CCRT group, respectively. Severe adverse effects were more common in the monthly CCRT group than in the weekly CCRT group. There were no statistically significant differences in progression-free survival and overall survival between the two groups (p=0.715 and p=0.237).

Conclusion

Both weekly CCRT and monthly CCRT seem to have similar efficacy for patients with locally advanced cervical cancer, but the weekly cisplatin is better tolerated.     

Safety and effectiveness of prophylactic gastrostomy tubes for head and neck cancer patients undergoing chemoradiation

BACKGROUND: We would like to assess the safety and effectiveness of prophylactic percutaneous endoscopic gastrostomy (PEG) tube feedings during concurrent chemoradiation for head and neck cancer. METHODS: Patients who underwent chemotherapy and radiation for head and neck malignancies were evaluated for their ability to resume oral feeding following treatment. All patients underwent PEG tube placement prior to the treatment because of the expected mucositis. Gastrostomy tubes were removed following treatment when the patients were able to resume oral feedings without aspiration. RESULTS: Between March 1999 and 2006, 104 patients with locally advanced head and neck cancer underwent concurrent chemotherapy and radiation. One patient declined placement of gastrostomy tube. Ninety patients (86%) developed grade 3-4 mucositis during chemoradiation. Five patients died during treatment from aspiration pneumonia and sepsis. One hundred two patients lost weight during treatment. The mean and median weight loss during concurrent therapy was, respectively, 8.5 and 8 kg (1-23.5 kg). Following treatment, tube feedings were continued 1-41 months (mean: 8 months; median: 5 months) because of continued weight loss, chronic dysphagia, or aspiration. At a median follow-up of 19 months (1-62 months), no patient developed serious complications from tube feedings. CONCLUSION: Dysphagia resulting from the severe mucositis produced severe weight loss, despite tube feedings. Gastrostomy tube feedings are safe. Gastrostomy tubes should be placed prophylactically for patients undergoing chemoradiation for head and neck cancer.     

Concomitant adjuvant chemoradiotherapy with weekly low-dose cisplatin for high-risk squamous cell carcinoma of the head and neck: a phase II prospective trial

Aims

Several randomised trials have tested adjuvant regimens using concomitant high-dose cisplatin and radiotherapy to improve outcome in high-risk locally advanced squamous cell head and neck cancer (HNSCC), showing a substantial increase in locoregional control and disease-free survival, despite a higher and eventually detrimental toxicity profile. The aim of the present phase II single-stage prospective study was to investigate whether a weekly cisplatin-based chemoradiotherapy regimen might be able to improve patients’ compliance compared with standard-dose cisplatin with similar outcome results.

Materials and methods

Between January 2004 and November 2008, 54 patients with high-risk locally advanced HNSCC were enrolled on to this phase II trial. Patient characteristics were: median age 59.7 years, Eastern Cooperative Oncology Group performance status 1 in 72% of patients and stage IV disease in 82%, extracapsular nodal spread in 67% and positive/close surgical margins in 37%. Patients received cisplatin (30 mg/m²) once a week for 7-8 weeks concurrent with external beam radiotherapy delivered with a median dose of 66.6 Gy (1.8 Gy each day; five fractions/week) on the primary site and 50 Gy (2 Gy each day) for the lower neck.

Results

Major acute toxicity of the combined treatment, defined as grade 3-4 mucositis, was observed in 35.2% of patients. No fatal complications occurred, with 81.5% of patients completing the planned regimen. Late reactions were mild (total 16% with a grade 3 dysphagia rate of 12%). The locoregional control rate was 82%; 5 year overall and disease-free survival were 63 and 62%, respectively.

Conclusions

Concomitant adjuvant chemoradiotherapy with weekly cisplatin seems to be a feasible and well-tolerated therapeutic approach in ‘unfit’ patients. Clinical results seem to be at least comparable with those previously reported. However, to draw any definitive conclusion, large confirmatory phase III randomised trials are demanded.     

Concurrent chemoradiotherapy versus induction chemotherapy followed by chemoradiotherapy (sequential approach) in the management of head and neck cancer

Concurrent chemoradiation is considered the standard-of-care for locally advanced head and neck cancer of the hypopharynx, oropharynx and larynx, as well as unresectable disease. This paradigm was challenged by the introduction of induction chemotherapy (IC), which demonstrated non-inferiority in regards of overall survival (OS), along with increased organ preservation, when compared to the surgery and radiotherapy. More recently, IC followed by concurrent chemoradiation, the so-called sequential approach was developed in an attempt to decrease metastatic spread and improve locoregional control (LRC) rates, with much controversy amongst experts. A careful evaluation by a multidisciplinary team is necessary to recognize which patients should be offered this therapeutic approach due to a significantly greater rate of toxicity. Herein, we analyze the most current available evidence regarding the use of sequential therapy versus concurrent chemoradiation. Different factors including toxicity profile, adherence and patient characteristics play a major role in choosing the most appropriate treatment regimen.     

Neoadjuvant chemotherapy/gefitinib followed by concurrent chemotherapy/radiation therapy/gefitinib for patients with locally advanced squamous carcinoma of the head and neck

BACKGROUND:

The authors evaluated the feasibility, toxicity, and efficacy of gefitinib added to first‐line combined‐modality therapy for patients with locally advanced squamous carcinoma of the head and neck.

METHODS:

Patients with biopsy‐proven locally advanced squamous carcinoma of the head and neck who had low expected cure rates with local treatment modalities alone were eligible for this treatment. All patients received a 6‐week induction course of docetaxel, carboplatin, infusional 5‐fluorouracil, and gefitinib (250 mg daily). Gefitinib was continued while patients received concurrent weekly docetaxel and radiation therapy. After the completion of radiation therapy, gefitinib was continued until patients developed disease progression or for a maximum of 24 months.

RESULTS:

Sixty‐two patients (53% with stage IV disease) received protocol treatment, and 50 patients (81%) were able to complete the regimen. The addition of gefitinib increased the incidence of grade 3/4 mucositis (27%) and diarrhea (16%) during induction therapy but did not appear to add substantially to toxicity during concurrent chemoradiation. The estimated 3‐year progression‐free and overall survival rates for the entire group were 41% and 54%, respectively.

CONCLUSIONS:

The addition of gefitinib was associated with a moderate increase in toxicity with this combined modality regimen, particularly during induction therapy. Although this regimen was efficacious, the survival results overlap with results reported with chemoradiation alone. The role of epidermal growth factor receptor inhibitors in first‐line, combined‐modality therapy for patients with head and neck cancer remains undefined. Cancer 2009. © 2009 American Cancer Society.     

Necessity for adjuvant neck dissection in setting of concurrent chemoradiation for advanced head-and-neck cancer

PURPOSE: Neck dissection has traditionally played an important role in the treatment of patients with squamous cell carcinoma of the head and neck who present with regionally advanced neck disease (N2-N3). Radiotherapy and concurrent chemotherapy improves overall survival in advanced head-and-neck cancer compared with radiotherapy alone. The necessity for postchemoradiation neck dissection is controversial. The intent of this report was to define the value of neck dissection in this patient population better. METHODS AND MATERIALS: Patients with locally advanced squamous carcinoma of the head and neck who also presented with nodal disease and underwent hyperfractionated radiotherapy and concurrent cisplatin/5-fluorouracil chemotherapy constituted the study population. Adjuvant modified neck dissection (MND) was planned 6 to 8 weeks after completion of chemoradiation in those patients who had a biopsy-proven pathologically complete response at the primary tumor site, irrespective of the clinical/radiographic neck response. A cohort of patients underwent electrode assessment of tumor oxygenation. Pathologic findings from the MND were used to compute the negative and positive predictive values and overall accuracy of the clinical/radiographic response (cCR). Regional control, failure-free survival, and survival were compared according to whether patients actually underwent MND. RESULTS: A total of 154 patients received concurrent chemoradiation. Of these, 108 presented with nodal disease: N1, n = 30; and N2-N3, n = 78. MND was performed in 65 (60%) of 108 patients, including 13 (43%) of 30 with Stage N1 and 52 (66%) of 78 with Stage N2-N3. For N1 patients, the negative predictive value of a cCR, positive predictive value of less than a cCR, and the overall accuracy for clinical response was 92%, 100%, and 92%, respectively. For N2-N3 patients, the corresponding values were 74%, 44%, and 60%. Patients with poorly oxygenated tumors were more likely to have residual disease at MND. The median follow-up was 4 years. The 4-year disease-free survival rate was 70% for N1 patients, irrespective of the clinical response or whether MND was performed. The 4-year disease-free survival rate was 75% for N2-N3 patients who had a cCR and underwent MND vs. 53% for patients who had a cCR but did not undergo MND (p = 0.08). The 4-year overall survival rate was 77% vs. 50% for these two groups of patients (p = 0.04). CONCLUSION: The clinical and pathologic responses in the neck correlated poorly with one another for patients with N2-N3 neck disease undergoing concurrent chemoradiation for advanced head-and-neck cancer. MND still appears to confer a disease-free survival and overall survival advantage with acceptably low morbidity. Tumor oxygenation assessment may be useful in selecting patients who are especially prone to have residual disease. Better tools need to be developed to determine prospectively whether this procedure is required for individual patients.     

The Efficacy of Induction Chemotherapy with Docetaxel,Cisplatin and 5-fluorouracil Combined with Cisplatin Concurrent Chemoradiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma: A Matched Pair Analysis

AimsThe role of induction chemotherapy (ICT) for head and neck squamous cell carcinoma (HNSCC) is controversial. The aim of the study was to assess the benefit of ICT with docetaxel, cisplatin and 5-fluorouracil (5-FU) (TPF) when combined with concurrent cisplatin chemoradiotherapy (CRT) for HNSCC.Materials and methodsPatients with HNSCC treated between January 2005 and December 2010 with radical intent with either TPF or cisplatin and 5-FU (PF) ICT and documented intention to proceed with concurrent cisplatin CRT were identified retrospectively. The use and choice of ICT regimen was at the clinician's discretion. In total, 68 patients treated with TPF were identified and were matched for T and N stage and tumour site to 68 patients treated with PF. A survival analysis was carried out using Kaplan–Meier and the Cox proportional hazards model.ResultsThe median follow-up was 29.9 versus 36.3 months for the TPF and PF groups, respectively. Three year locoregional relapse-free survival (RFS), distant RFS, RFS, cancer-specific survival and overall survival rates for the TPF and PF groups were 84.2, 91.6, 82.6, 81.3 and 74.9% versus 73.7, 84.9, 71.9, 72.1 and 62.9%, respectively. On multivariate analysis, treatment with TPF predicted for improved locoregional RFS (P = 0.03) and overall survival (P = 0.05).ConclusionThe addition of docetaxel to a cisplatin doublet ICT regimen before concurrent CRT may improve disease control for locally advanced HNSCC.     

Concurrent radiochemotherapy in locally-regionally advanced oropharyngeal squamous cell carcinoma: analysis of treatment results and prognostic factors

Background

Concurrent radiochemotherapy is a recommended treatment option for patients with locally advanced squamous cell head and neck carcinomas with recent data showing the most significant absolute overall and event-free survival benefit achieved in patients with oropharyngeal tumours. The aim of this study was to analyse the results of three-dimensional conformal radiotherapy given with concomitant weekly cisplatin in patients with advanced oropharyngeal carcinoma and to identify prognostic factors influencing outcomes of this patients category.

Methods

Sixty-five patients with stage III or IV squamous cell carcinoma of the oropharynx who underwent concurrent radiochemotherapy between January 2005 and December 2010 were retrospectively analyzed. All patients received radiotherapy to 70 Gy/35 fractions/2 Gy per fraction/5 fractions per week. Concurrent chemotherapy consisted of weekly cisplatin (30 mg/m²) started at the first day of radiotherapy.

Results

Median age was 57 years (range, 36 to 69 years) and 59 (90.8%) patients were male. Complete composite response was achieved in 47 patients (72.3%). Local and/or regional recurrence was the most frequent treatment failure present in 19 out of 25 patients (76.0%). At a median follow-up of 14 months (range, 5 to 72 months), 2-year local relapse-free, regional relapse-free, locoregional relapse-free, disease-free, and overall survival rates were 48.8%, 57.8%, 41.7%, 33.2% and 49.7%, respectively. On multivariate analysis the only significant factor for inferior regional relapse-free survival was the advanced N stage (p?=?0.048). Higher overall stage was independent prognostic factor for poorer local relapse-free survival, locoregional relapse-free survival and disease-free survival (p?=?0.022, p?=?0.003 and p?=?0.003, respectively). Pre-treatment haemoglobin concentration was an independent prognostic factor for local relapse-free survival, regional relapse-free survival, locoregional relapse-free survival, disease-free survival, and overall survival (p?=?0.002, p?=?0.021, p?=?0.001, p?=?0.002 and p?=?0.002, respectively).

Conclusions

Poor treatments results of this study suggested that introduction of intensity-modulated radiotherapy, use of induction chemotherapy followed by concurrent radiochemotherapy, accelerated radiotherapy regimens, and molecular targeted therapies could positively influence treatment outcomes. The incorporation of reversal of anaemia should be also expected to provide further improvement in locoregional control and survival in patients with advanced squamous cell carcinoma of the oropharynx.     

Radiotherapy and concurrent low-dose paclitaxel in locally advanced head and neck cancer.

In our prospective study we examined the use of low-dose paclitaxel concurrently with radiation for patients with locally advanced head and neck cancer, who were not eligible for concurrent chemoradiation due to their poor general condition. Twenty-six patients were treated with external beam radiotherapy and received concomitantly 2 mg/m(2) paclitaxel three times a week. Beside an acceptable efficacy (RR: 65%, 2-year overall survival 46%) the treatment was well tolerated and resulted in a favorable toxicity profile. This regimen is resource effective and allowed successive therapy if it was necessary and therefore may serve as an alternative for patients in poor condition with locally advanced head and neck cancer.     

Hyperthermia classic commentary: ‘Arrhenius relationships from the molecule and cell to the clinic’ by William Dewey,Int. J. Hyperthermia, 10:457–483, 1994

Purpose: The management of head and neck cancer requires skilled integration of multiple modalities such as surgery, radiation, chemotherapy and hyperthermia. Chemoradiation can benefit from the addition of a proven modality such as hyperthermia in increasing survival, disease-free survival and quality of life without increasing the risk of complication.

The purpose of this retrospective study was to evaluate the feasibility and efficacy of hyperthermia with chemoradiation in advanced head and neck cancers.

Materials and methods: Between January 2004 and May 2008 40 patients with advanced head and neck cancers were allocated for hyperthermia with chemoradiotherapy. All patients underwent radiation on a telecobalt machine. A total dose of 70 Gy in 7 weeks with conventional fractionation was given with weekly chemotherapy of cisplatin 50 mg or paclitaxel 60 mg. Patients underwent hyperthermia on a radiofrequency machine at 8.2 MHz for 30 min at 41°–43°C with 10 min pre-cooling to 5°C.

Results: No patient had life-threatening complications. Only 38 out of 40 patients were eligible for assessment of immediate response as one patient died during treatment and the other did not complete treatment. Complete response was 76.23% (29 pts), and 23.68% (9 pts) had partial response. Overall survival by the Kaplan?Meir method was 75.69% at 1 year and 63.08% at 2 years.

No enhanced mucosal or thermal toxicities were documented as compared to our earlier experience with chemoradiation.

Conclusion: This retrospective analysis demonstrates the feasibility and efficacy of chemoradiation with hyperthermia in advanced head and neck cancer. The study is encouraging enough to start a randomised trial to compare chemoradiation with triple modality of treatment.     

Efficacy and Safety of Concomitant Chemoradiotherapy with Cisplatin and Docetaxel in Patients with Locally Advanced Squamous Cell Head and Neck Cancers

Background: Chemoradiation (CRT) using cisplatin-based regimens has become the standard of care in thetreatment of squamous cell head and neck cancers (SCHNC). The impact of taxanes as radiosensitizing agentswith concurrent CRT regimens is unknown. We therefore retrospectively evaluated the efficacy and tolerabilityof a weekly cisplatin+docetaxel combination with CRT in locally advanced SCHNC. Methods: Sixty-six patientswith locally advanced SCHNC (39.4% stage IV, 53% stage III, and 7.6% stage II) were assessed retrospectively.Total radiation dose to the PTV of gross disease (primary and/or node) was 70 Gy/ 35 fractions, 5 fractions perweek. Minimum doses of 60 Gy and 50 Gy were administered to PTVs of elective high risk and low risk disease,respectively. Chemotherapy (CT) consisted of weekly cisplatin (20 mg/m2)+docetaxel (20 mg/m2) concurrentlywith RT. Results: The median age of the patients was 58 years (range, 32-77). Objective response rate was 83.3%.The 2-year progression-free survival (PFS) and overall survival (OS) were 75.7% and 78.3%, respectively.The most common grade 3 and 4 toxicities were mucositis (36.4%), nausea and vomiting (12.1%), neutropenia(4.5%). Conclusion: Weekly cisplatin and docetaxel concurrent with RT for locally advanced SCHNC was foundtolerable with high efficacy.     

The role of taxanes and targeted therapies in locally advanced head and neck cancer

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.