Neoadjuvant docetaxel and cisplatin chemotherapy followed by local irradiation is highly active on locoregionally advanced squamous cell carcinoma of the head and neck

The purpose of this study was to determine the treatment outcome of neoadjuvant docetaxel and cisplatin chemotherapy followed by local radiotherapy for chemotherapy-na?ve patients with locoregionally advanced squamous cell carcinoma of the head and neck. Thirty-seven patients with stage III or IV squamous cell carcinoma of the head and neck who received docetaxel and cisplatin regimen for a maximum of three cycles followed by radiation therapy were enrolled in this study. The overall response rate to the regimen was 91.9 per cent (34 of 37) (the complete remission rate was 48.6 per cent). The median time to treatment failure was 38 months (95 per cent confidence interval, 15-61 months). The four year estimated overall survival rates were 85.1 per cent. The most frequent moderate-to-severe toxicity was grade 3-4 neutropenia. The most common acute non-haematologic toxicities included anorexia, nausea and asthenia. Neoadjuvant docetaxel and cisplatin chemotherapy followed by radiotherapy is a feasible treatment strategy for patients with locoregionally advanced squamous cell carcinoma of the head and neck.     

Surgical complications in patients with head and neck cancer receiving chemotherapy

We evaluated postoperative complications in a randomized series of patients with head and neck cancer who received preoperative chemotherapy. Forty-two patients with advanced squamous carcinoma of the head and neck were randomized to receive either high-dose methotrexate with leucovorin calcium rescue (23 patients) or no chemotherapy (19 patients) prior to definitive conventional treatment. The two groups of patients were balanced by sex, disease site, stage, histologic grade, and prior therapy. Sixteen of the 23 patients receiving preoperative chemotherapy had postoperative complications, whereas only eight of 19 patients not receiving chemotherapy had postoperative complications. Surgical complications included wound infections, orocutaneous fistulas, and flap necrosis.     

Long-term results of a multimodal intensification regimen for previously untreated advanced resectable squamous cell cancer of the oral cavity, oropharynx, or hypopharynx

BACKGROUND: Long-term disease control of an intensified treatment regimen for previously untreated stage III and IV resectable oral cavity, oropharyngeal, or hypopharyngeal squamous cell carcinoma was analyzed. METHODS: Forty-three patients with previously untreated, advanced stage, resectable squamous carcinomas of the oral cavity, oropharynx, or hypopharynx were enrolled in a prospective phase II institutional clinical trial at a tertiary care National Cancer Institute-designated comprehensive cancer center. It includes preoperative accelerated hyperfractionated radiotherapy with concurrent cisplatin followed immediately by surgery and intraoperative radiotherapy, and completed with early postoperative weekly paclitaxel, two additional cisplatin cycles, and concurrent once-daily radiotherapy beginning on day 28 after surgery. RESULTS: Forty-three patients enrolled in the study. Protocol compliance was 53%. The range of time at risk was 10.4 to 56.23 months (median, 45 months). The locoregional (93%) and systemic (91%) disease control rates were excellent. Overall long-term survival was 79%. CONCLUSIONS: An intensive treatment regimen that improves compliance and long-term disease control is clearly feasible for this patient population.     

Is glutathione-S-transferase-pi expression a reliable predictor of chemoradiation response in cancer of the head and neck?

PURPOSE: Concurrent radiation and chemotherapy is being evaluated as an alternative treatment to surgery for patients with advanced squamous cell carcinoma of the head and neck, because organ preservation maybe possible without compromising survival. However, the response to concurrent chemoradiation treatment varies from patient to patient, and there is currently no available molecular predictor of response for this particular treatment modality. There is some evidence to indicate that glutathione S-transferase-pi (GST-pi), which is one of the drug detoxifying enzymes, may decrease the effectiveness of platinum-based chemotherapy in the treatment of a variety of tumor types. This study was performed to investigate whether GST-pi expression was correlated with response to concurrent chemotherapy and radiotherapy in patients with advanced squamous cell carcinoma of the head and neck. MATERIALS AND METHODS: Diagnostic biopsy specimens of 36 patients who underwent concurrent chemoradiotherapy for the treatment of advanced squamous cell carcinoma of the head and neck were examined for GST-pi expression by using immunohistochemistry with polyclonal antihuman GST-pi antibodies. GST-pi expression scores were compared among responders and nonresponders. RESULTS: Although the staining rate with antiGST-pi was slightly lower in the responder group in comparison with the nonresponders (82% vs 100%), the difference was not statistically significant. CONCLUSION: GST-pi expression is unlikely to be a valuable predictor of response to concurrent chemotherapy and radiation treatment in patients with advanced squamous cell carcinoma of the head and neck.     

Implications of positive surgical margins

The recently concluded Head and Neck Intergroup trial tested the addition of three courses of cis-platinum containing chemotherapy to standard treatment of surgery and postoperative radiotherapy for patients with advanced operable squamous cell carcinoma of the head and neck. Only patients with negative surgical margins were eligible for the trial. One hundred twelve patients with positive surgical margins were dropped from the trial but continued to be followed. These patients received a variety of treatments. Positive surgical margins were most often seen in nonglottic primaries and with increasing frequency as the N stage increased. Patients with positive margins who achieved a complete clinical response to subsequent treatment had a median survival of 33.8 months vs. 9.1 months for those with less than a complete clinical response. The addition of chemotherapy did not significantly alter the median survival of the positive margin patients.     

Primäre Chemotherapie bei Mundhöhlen- und Tonsillenkarzinomen Ergebnisse einer prospektiv randomisierten Studie

Although induction chemotherapy administered prior to local therapy produces encouraging initial response rates in head and neck cancer, randomized studies have failed to demonstrate an improvement in survival rates. All randomized studies included only patients with advanced stage III and IV disease. In our opinion, this is the main reason for the low rate of complete responses demonstrated in the randomized trials (maximum 18%). Frei et al. estimate that a 40%-50% complete response rate is necessary before improved survival rates are seen. To date, such complete response rates with induction chemotherapy have only been attainable in resectable T2-T3, N0-N2 disease. Therefore, we initiated a prospective randomized trial including only patients with the mentioned disease stages. Patients (pts) were randomized to receive either induction chemotherapy with three cycles of carboplatin/5-FU prior to surgery and radiotherapy (arm A, 70 pts) or standard treatment with surgery and radiotherapy (arm B, 74 pts). Patients were classified according to primary tumour site and neck disease. The observed remission rate after chemotherapy confirmed the primary estimated rate for this subgroup of patients with head and neck cancer (CR: 43%, PR: 37%, NR: 15%, PD: 5%). After a follow-up of 12-96 months overall survival was 58% in arm A and 45% in arm B (n.s.). Disease-free survival in arm A (61%) is statistically significantly better than in arm B (43%, P=0. 03). Therefore, we recommend further controlled trials to investigate the role of induction chemotherapy in patients with primary resectable carcinomas of the oral cavity and tonsils and stage T2-T3 and N0-N2 disease prior to surgery.     

Simultaneous radio- and chemotherapy for squamous cell carcinoma of the head and neck in daily clinical practice: 5 years experience in a University Hospital

Several randomized studies and meta-analyses have shown that simultaneous radio- and chemotherapy prolongs survival in patients with unresectable squamous cell carcinoma of the head and neck as compared with conventional radiotherapy. We assessed the feasibility and effectiveness of simultaneous radiotherapy (35 x 2 Gy) and chemotherapy [cisplatinum 100 mg/m(2) or carboplatin (AUC 6) on days 1, 22 and 43] in daily clinical practice in a cohort of 87 patients treated at our institute between 1998 and 2002. Eighty patients completed radiotherapy according to schedule. Eighty patients received two courses of chemotherapy and 50 patients three courses. Nephrotoxity, bone marrow suppression and ototoxicity were the most frequent side-effects. Median weight loss was 8.5%. Median survival was 15 months and 44% of the patients were alive at 2 years. Patients receiving three courses of chemotherapy had a better survival than patients receiving two or less courses. Treatment with simultaneous radio- and chemotherapy for advanced head and neck cancer is a demanding, but feasible treatment in daily clinical practice. Survival seems to be comparable with the results achieved in patients selected for clinical trials.     

A randomized trial of neoadjuvant vs concomitant chemotherapy vs radiotherapy alone in the treatment of stage IV head and neck squamous cell carcinoma

Summary Treatment results of irradiation as a single treatment for advanced stage IV unresectable head and neck cancer remains uniformly poor and apparently has not changed with the most recent improvements in oncological care. Despite several negative results of randomized studies, neoadjuvant or concomitant chemotherapy and radiotherapy seems to improve the number of complete responses and also the duration of disease-free survival. The present study was designed to determine the feasibility, potential risks and benefits of the two methods of combined treatment and radiotherapy alone on the management of advanced unresectable squamous cell carcinoma of the upper respiratory and digestive system. From 1983 to 1986, 90 patients entered the trial. Thirty patients were randomized to each study group: radiotherapy alone (70 Gy); neoadjuvant chemotherapy (vinblastine, mitomycin, cisplatin, and bleomycin) and radiotherapy; concomitant chemotherapy (cisplatin and bleomycin) and radiotherapy. An increased frequency of complete responses (33%) was seen in patients treated with the two different combinations of chemotherapy and irradiation compared to irradiation alone (10%). However, toxicity was more common in patients treated with the two modalities of combined treatment and there were no differences in overall survival rates (P = 0.706).     

Simultaneous radio‐ and chemotherapy for squamous cell carcinoma of the head and neck in daily clinical practice: 5 years experience in a University Hospital

Several randomized studies and meta‐analyses have shown that simultaneous radio‐ and chemotherapy prolongs survival in patients with unresectable squamous cell carcinoma of the head and neck as compared with conventional radiotherapy. We assessed the feasibility and effectiveness of simultaneous radiotherapy (35 × 2 Gy) and chemotherapy [cisplatinum 100 mg/m² or carboplatin (AUC 6) on days 1, 22 and 43] in daily clinical practice in a cohort of 87 patients treated at our institute between 1998 and 2002. Eighty patients completed radiotherapy according to schedule. Eighty patients received two courses of chemotherapy and 50 patients three courses. Nephrotoxity, bone marrow suppression and ototoxicity were the most frequent side‐effects. Median weight loss was 8.5%. Median survival was 15 months and 44% of the patients were alive at 2 years. Patients receiving three courses of chemotherapy had a better survival than patients receiving two or less courses. Treatment with simultaneous radio‐ and chemotherapy for advanced head and neck cancer is a demanding, but feasible treatment in daily clinical practice. Survival seems to be comparable with the results achieved in patients selected for clinical trials.     

Simultaneous chemoradiation in the treatment of advanced head and neck cancer.

Fifty-eight patients with either advanced or unresectable squamous cell carcinoma of the head and neck were randomly selected to receive either twice daily radiation alone or twice daily radiation plus concomitant chemotherapy with cisplatin and fluorouracil (5-fluorouracil). There was no advantage in survival or time to progression with the addition of chemotherapy to twice daily radiation for patients with advanced resectable cancers. In the group of patients with unresectable cancers, however, there was a statistically significant advantage to the addition of chemotherapy, both in terms of disease-free survival and date to progression.     

Total pharyngolaryngectomy for squamous cell carcinoma of the hypopharynx: a review

OBJECTIVES: To evaluate our experience with total pharyngolaryngectomy in the treatment of hypopharyngeal squamous cell carcinoma. STUDY DESIGN: Retrospective analysis of consecutively treated patients in an academic otolaryngology, head and neck department. METHODS: One hundred eighty patients who had total pharyngolaryngectomy performed for hypopharyngeal carcinoma were included in this study. Patients with a history of previous head and neck cancer were excluded. Clinicopathologic parameters were recorded and survival calculated using the Kaplan-Meier method. RESULTS: One hundred sixty-two (90%) of the patients were male, and the patients had a mean age of 62 years. The majority (91%) of patients had advanced overall clinical stage disease (stage 3,4). Thirty-one (17.8%) and 43 (24%) patients developed locoregional and metastatic disease recurrence, respectively. The 2- and 5-year disease-specific survival rates were 72% and 52%, respectively. Advanced nodal stage, perineural invasion, lymphovascular invasion, and positive margins were predictors of poor survival on univariate analysis, and lymphovascular invasion was an independent prognostic factor on multivariate analysis. CONCLUSION: Surgery and postoperative radiotherapy remains the treatment against which other modalities should be compared for advanced stage hypopharyngeal squamous cell carcinoma.     

Is routine follow-up useful after combined-modality therapy for advanced head and neck cancer?

OBJECTIVE: To evaluate the usefulness of routine follow-up in a selected group of patients with head and neck cancer. DESIGN: Retrospective cohort study with follow-up of 5 years for all patients. PATIENTS: Three hundred two patients with advanced (stage II or IV) squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx were treated with curative intent with surgery and postoperative radiation therapy between January 1, 1970, and December 31, 1990. MAIN OUTCOME MEASURE: Survival after recurrence of the index tumor or the development of a second head and neck primary tumor. RESULTS: Overall actuarial 5-year survival was 56%. Relapse occurred in 119 patients, and salvage therapy was attempted in 49 patients. Only 2 patients survived to 5 years after relapse. CONCLUSION: In patients with advanced head and neck squamous cell carcinoma, routine follow-up is more important for evaluation of treatment results and emotional support than of benefit in improving patient survival.     

Therapie der Rezidiv- und Fernmetastasen bei Plattenepithelkarzinomen des Kopf- und Halsbereichs

In many cases squamous cell carcinoma of the head and neck is already in an advanced stage when initially diagnosed. Despite definitive treatment, loco-regional recurrences and metastases are common and patients ultimately require systemic treatment. Epidermal growth factor receptor (EGFR) inhibitors have proven to significantly prolong survival and have therefore become the first line treatment in recurrent and metastatic squamous cell carcinoma of the head and neck in addition to platinum and 5-FU treatment. Good results have also been reported for EGFR inhibitors in cases where platinum-based treatment has failed. Further strategies, such as salvage surgery, platinum-based chemotherapy, targeted therapy, chemoradiation and reirradiation are currently under investigation to reduce toxicity and improve survival and health-related quality of life.     

Intra-arterial chemotherapy less intensive than RADPLAT with concurrent radiotherapy for resectable advanced head and neck squamous cell carcinoma: a prospective study

OBJECTIVES: This study was designed to evaluate the efficacy and feasibility of our intra-arterial chemotherapy protocol with a lower amount and frequency of cisplatin delivery than in RADPLAT for the treatment of resectable advanced head and neck cancer. METHODS: Fifty-one patients with advanced squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx were included in this prospective study. The patients were treated with 3 courses of cisplatin (100 mg at 1 treatment, intra-arterial) and sodium thiosulfate (28 g at 1 treatment, intravenous) once every 2 weeks during concurrent radiotherapy (66 to 70 Gy, 2 Gy per fraction, daily for 5 days over 7 weeks). Nodal metastases larger than 3 cm in diameter were treated with an additional 50 mg of cisplatin. The patients with less than 50% tumor reduction after 40 Gy and 2 courses of chemotherapy were treated with surgery. RESULTS: The protocol was completed for 49 patients. All living patients had a minimum follow-up period of 2 years. Including the 3 patients with salvage surgery, local disease-free control was achieved in 39 patients (80%). For 36 patients (73.5%), disease-free primary organs were preserved at 2 years after treatment. Locoregional disease-free control for 2 years was obtained for 38 patients (77.6%), in 30 of them without salvage surgery. The patients treated with surgery had an overall survival rate similar to that of the patients with a complete response (80% and 84.6%, respectively). The patients with a partial response had a worse prognosis (40%; p = .0069). CONCLUSIONS: This treatment regimen is feasible and effective for advanced resectable head and neck cancer.     

Induction VBM plus radiotherapy, versus radiotherapy alone for advanced head and neck cancer: long-term results

Between 1978 and 1981, 85 patients with advanced squamous cell carcinoma of the head and neck were randomized to receive induction VBM followed by radiotherapy, or radiotherapy alone. The shortest follow-up is thus 6 years. The median survival of patients receiving induction chemotherapy was 46 weeks, that of the radiotherapy group alone was 75 weeks. As the two groups were not balanced despite randomization, multivariate methods (GLIM) were used to identify significant prognostic factors. These were: response to radiotherapy (P less than 0.001), nodal status (P less than 0.001), age (P less than 0.01), and histological grade (P less than 0.01). Neither treatment with, nor response to, chemotherapy had a significant effect on survival.     

Functional organ preservation after chemoradiotherapy in elderly patients with loco-regionally advanced head and neck squamous cell carcinoma

The aim of the present investigation is to evaluate the outcome after induction chemotherapy and concurrent multi-drug chemoradiotherapy (IC/CCRT) with or without post-chemoradiation neck dissection in medically fit elderly patients with loco-regionally advanced head and neck squamous cell carcinoma (HNSCC). Retrospective study including 44 elderly patients (median age 71 years; range 66–77 years) with previously untreated, inoperable, histologically proven non-metastatic stage III or IV HNSCC. Following one cycle of IC, two cycles of cis-platinum and 5-fluorouracil CCRT with conventional fractionated radiotherapy up to a dose of 66–70 Gy were administrated. A neck dissection was recommended for patients with node metastasis larger than 3 cm regardless of the response to therapy and for patients who had suspected persistent neck disease 8–12 weeks after completing treatment. Salvage surgery was considered for histologically proven persistent or recurrent tumor in the primary site. Time-to-event data were described using Kaplan–Meier actuarial curves. Overall, 37 patients (84.1%) completed the planned treatment. There were no cases of treatment-related deaths. Twenty-nine patients (65.9%) developed severe toxicities with grade 4 toxicity accounting for 22.7%. The median follow-up time in survivors was 41 months. Three-year overall survival, progression-free survival, and functional progression-free survival estimates were 70.9, 67.0, and 57.3%, respectively. In selected medically fit elderly patients with loco-regionally advanced HNSCC, cis-platinum-based chemoradiotherapy can be successfully applied, with moderate adverse events, in attempt to preserve a functional upper aerodigestive tract.     

Patterns of cancer recurrence in the postoperatively irradiated neck

Data from 92 patients with stage III or IV squamous cell carcinoma of the head and neck treated with surgery and planned postoperative radiotherapy were analyzed to determine the incidence and patterns of tumor recurrence. Overall, recurrent tumor in the cervical region developed in 19 patients (21%). Of these, eight were in the neck alone and 11 in both the neck and the primary site. All recurrences were in the ipsilateral cervical region and none in the contralateral neck. The presence of two or more metastatic nodes at the time of surgery correlated with tumor recurrence and decreased survival. Extracapsular tumor spread increased the recurrence rate. Our data suggest that postoperative radiotherapy decreases ipsilateral cervical tumor recurrence in only those patients with more than two metastatic lymph nodes, and contralateral neck recurrence in all patients.     

Association of Head and Neck Oncologists of Great Britain

Anti-Thrombin 111 as an Indicator of Advanced Head and Neck Malignancy Whether to use laser surgery or radiotherapy in the primary treatment of stage 0 and 1 glottic carcinomas. An evaluation based on long-term results after radiotherapy of 151 cases Phase Ill randomized trial of chemotherapy in end stage head and neck cancer Cisplatin Concentration in Tumours of the Head and Neck Repair of Oral-Oropharyngeal Defects with Masseter Crossover Flap The efficiency of voice production after successful irradiation of laryngeal carcinoma Thyroid disease and recurrent nerve paralysis The effect of tracheostomy on survival and peristomal recurrence after primary laryngectomy. Tumour clearance at resection margins in total laryngectomy-A clinicopathological study Patterns of spread of squamous cell carcinoma within the mandible     

Combined therapy for resectable head and neck cancer. A phase 3 intergroup study

This Head and Neck Intergroup (Radiation Therapy Oncology Group, Southwest Oncology Group, Eastern Cooperative Oncology Group, Cancer and Leukemia Group B, Northern California Oncology Group, and Southeastern Cancer Study Group) phase 3 randomized prospective trial was opened for registration January 1985. It is an evaluation of the role of chemotherapy for previously untreated advanced stage resectable squamous cell carcinoma of the head and neck. As of March 1, 1988, there has been a total of 535 patients registered. There are 266 patients analyzable with 133 in each treatment group. The surgical, chemotherapy, and radiation therapy toxic reactions are in the tolerable range with the worst toxic reactions reported in those patients receiving both surgery and radiation therapy. Compliance continues to be a major challenge to patient accrual. The most common cause for cases not being randomized involves positive margins of surgical resection. Patient refusal or surgical complications are other common reasons.     

Prospektive Phase-II-Studie zur neoadjuvanten Radiochemotherapie fortgeschrittener, operabler Mundh?hlenkarzinome

PURPOSE: The purpose of simultaneous chemoradiotherapy is to increase local-regional control and to decrease the incidence of distant metastases. Regimens containing cisplatin/5-FU chemotherapy are widely accepted as standard treatment in advanced head and neck cancer. Most studies reported promising response and survival data, but also severe mucosal toxicity. In recent years the newly developed drug Taxol demonstrated interesting activity in head and neck cancer as a single agent as well as in combination drug regimens. In the present outpatient phase II trial, we investigated the combination of Taxol/carboplatin with 40 Gy radiotherapy in a neoadjuvant setting of operable stage III/IV squamous cell carcinoma of the oral cavity and oropharynx. PATIENTS AND METHODS: Fifty-three patients were enrolled in this trial during the period from May 1998 to October 2000 and received five cycles weekly of Taxol (40 mg/m2) and carboplatin (AUC 1.5) with conventional radiotherapy (40 Gy). Within 3-4 weeks after chemoradiotherapy resection of the primary tumor and the regional neck nodes was performed. RESULTS: Fifty-two patients were evaluable for toxicity and response. Complete response was observed in 31 of 52 patients (CR 60%), and partial remission was seen in 21 of 52 patients (PR 40%). In 30 of 52 patients complete pathologic response (pCR 58%) was documented in the resection specimens. The 1-, 2-, and 3-year overall survival rate was calculated as 84%. CONCLUSION: Our present results demonstrated impressive clinical and pathological response rates of concurrent Taxol/carboplatin and radiotherapy as a preoperative treatment modality in advanced oral and oropharyngeal cancer.