Final Results of a Randomized Trial Comparing Chemotherapy Plus Radiotherapy With Chemotherapy Plus Surgery Plus Radiotherapy in Locally Advanced Resectable Hypopharyngeal Carcinomas

After neoadjuvant chemotherapy, a routine conservative approach followed by salvage surgery was evaluated in terms of local control and survival in cases of advanced potentially resectable hypopharyngeal carcinoma. Between 1985 and 1989, 92 patients with T3 or T4-N0,N3 operable squamous cell hypopharyngeal carcinomas received three courses of neoadjuvant chemotherapy every 2 weeks involving a combination of cisplatin, 100 mg/m², on day 1 and fluoruracil, 1 g/m², on days 2 to 5, followed by total laryngopharyngectomy plus postoperative radiotherapy in 47 patients (arm A) or radiotherapy alone in 45 patients (arm B). Randomization was always performed prior to chemotherapy. The response rates of tumor and node to chemotherapy were, respectively, 67% in arm A versus 79% in arm B (P > 0.05) and 54% in arm A versus 73% in arm B (P > 0.05). Grade III or IV toxicity was similar, affecting 15% of patients and 7% of cycles in arm A versus 16% of patients and 6% of cycles in arm B. After a mean follow-up of 92 months, survival was statistically better (P = 0.04) in arm A (5-year overall survival, 37%; median survival, 40 months) than in arm B (19% and 20 months) because of a better local control rate (63% versus 39%; P < 0.01). Better results were obtained for mutilant surgery in terms of local control and overall survival, regardless of response to neoadjuvant chemotherapy.     

Fluorodeoxyglucose imaging using a coincidence gamma camera to detect head and neck squamous cell carcinoma and response to chemotherapy

This prospective study was performed to evaluate the ability of a dual-head gamma camera with fluorine-18 fluorodeoxyglucose coincidence detection emission tomography (FDG-CDET) to detect primary tumor and cervical lymph nodes in head and neck squamous cell carcinoma (HNSCC), and to show the response of the carcinoma to chemotherapy. The findings were compared with those of physical examination, computed tomography (CT), and histopathology, before treatment in 61 patients, and after induction chemotherapy in 34 of them. Before treatment, the primary was detected in 93%, 79%, and 95% of cases on panendoscopy, CT, and FDG-CDET, respectively. After chemotherapy, 34 patients were evaluable for response of the primary tumor. Surgical resection was performed in 23 of them: agreement with histopathologic results for response to treatment was 74%, 69%, and 78% for panendoscopy, CT, and FDG-CDET, respectively. No surgical resection was performed in 11 of the 34 patients, but biopsies were performed before radiotherapy, and their rates of agreement with histopathologic results for response to treatment were 75%, 75%, and 67% on panendoscopy, CT, and FDG-CDET, respectively. For cervical lymph nodes, 245 sites were resected in 41 patients, and FDG-CDET appeared competitive with CT in detecting metastatic neck disease, especially after neoadjuvant chemotherapy; the accuracy was 93%. These results demonstrated the ability of FDG-CDET to detect primary tumors and cervical lymph nodes in HNSCC and to show its response to chemotherapy, as compared to the ability of CT and panendoscopy. It may be a complementary tool to evaluate residual disease after induction chemotherapy, although higher sensitivity would be required for FDG-CDET to be considered as a staging modality.     

Cisplatin and fluorouracil as neoadjuvant therapy in head and neck cancer. A preliminary report

A randomized, prospective trial utilizing cisplatin and fluorouracil as neoadjuvant chemotherapy in the treatment of advanced squamous cell carcinomas of the upper aerodigestive tract was initiated in January 1983. Sixty patients were stratified by site (oral cavity, 19; larynx, 14; hypopharynx, 14; oropharynx, 11; nasopharynx, one; and paranasal sinuses, one) and by stage (III, 19; IV, 41), and then randomized to receive either standard treatment (defined as preoperative irradiation followed by radical excision or irradiation alone) or adjuvant chemotherapy followed by standard treatment. An additional three patients were entered into the study, but withdrew. Chemotherapy consisted of three cycles for those patients in whom an objective tumor response was observed; nonresponders received standard treatment. Response to chemotherapy was complete in five and partial (greater than 50%) in 18 patients, for an overall response rate of 85%. The follow-up for surviving patients was a minimum of 24 months and a maximum of 44 months. Survival was compared for patients in both treatment groups according to the method of Lee and Desu. Despite excellent tumor response, actuarial survival was 70% in the standard treatment group as opposed to 56% in the experimental group. It was therefore evident that the high response rates reported in previous pilot studies do not necessarily result in improved survival in these cancers.     

A comparison of radiotherapy or radiochemotherapy with symptomatic treatment alone in patients with advanced head and neck carcinomas

The choice of palliative treatment and the prognostic factors in unresectable head and neck cancer cases continue to be controversial. In the present study we compared the survival rates of untreated stage IV head and neck cancer patients with cases managed prospectively at A.C. Camargo Hospital for Cancer with neoadjuvant chemotherapy, concomitant chemotherapy or radiotherapy alone. Previous results had shown that while the type of treatment did not influence survival rates (P = 0.706), tumor response to treatment (whether complete, partial or none) significantly influenced survival (P = 0.00002). In the present study we compared the survival rates in the groups with untreated patients (who remained untreated until death) with the same demographic and clinical characteristics of patients receiving treatment. We found that there was a significant difference between the survival rates of the untreated group and those of the treated groups that was independent of the type of treatment performed (P < 0.00001) or the tumor response to treatment (P < 0.0001). Received: 19 October 1998 / Accepted: 15 April 1999     

Sequential external beam radiotherapy and high-dose-rate intracavitary brachytherapy in T1 and T2 nasopharyngeal carcinoma: an evaluation of long-term outcome

OBJECTIVES/HYPOTHESIS: The standard treatment for nonmetastatic nasopharyngeal carcinoma (NPC) is external beam radiotherapy (EBRT), with or without chemotherapy. Because local control in NPC is an independent prognostic factor for distant metastases and survival, various dose-escalation strategies have been used to reduce recurrences at the primary site. The objective of this report was to evaluate the outcome of adjuvant high-dose-rate intracavitary brachytherapy (HDRIB) in patients with T1 and T2 NPC. STUDY DESIGN AND METHODS: Thirty-three consecutive patients with T1 and T2 NPC were treated prospectively according to a standardized institutional protocol between March 1999 and July 2001. Seventeen patients with stage I/II disease were treated with EBRT to 66 Gy followed by HDRIB (10 Gy in 2 weekly 5 Gy fractions). The remaining 16 patients with Stage III to IVb disease received chemotherapy in addition to radiation. All patients were assessed for treatment response, local control, survival, and toxicity. RESULTS: Median follow-up for all surviving patients was 67 (range 52-76) months. Local failure occurred in two patients; both subsequently underwent successful salvage treatments. Three patients died of metastatic disease, whereas two died of unrelated causes. Five year local control, overall survival, and disease-free survival rates were 93.8%, 83.9% and 78.4%, respectively. All patients experienced acute or late radiotherapy-related sequelae. However, no grade 4/5 toxicities were reported. Specifically, toxicities that could be attributed to brachytherapy were not seen, except for in one patient who developed severe choanal stenosis. CONCLUSIONS: EBRT supplemented by HDRIB produced superior local control rates for T1 and T2 NPC at 5 years of follow-up, with acceptable rates of acute and late toxicities.     

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).     

Prospective phase II trial of concomitant boost radiotherapy for stage II nasopharyngeal carcinoma: an evaluation of response and toxicity

INTRODUCTION: Stage II nasopharyngeal carcinoma (NPC) treated with conventionally fractionated radiotherapy results in loco-regional control of around 80%. This report aims to document the outcome of Stage II NPC patients treated with external beam radiotherapy delivered using an accelerated concomitant boost (C-Boost) schedule. METHODS AND MATERIALS: Twenty-five 1997 AJCC Stage II NPC patients were enrolled and analyzed in this preliminary report. The primary tumor and clinically involved nodes received a total dose of 72 Gy in 42 fractions. C-Boost for gross disease consisted of 18 Gy in 12 fractions commencing on day 19 and was delivered at least 6 hours after the first dose. Patients were assessed for response, survival, and toxicity. RESULTS: With a median follow-up of 24 months, only one patient had pathologically confirmed local recurrence, necessitating IMRT. Two developed distant metastases for which they received chemotherapy. One died from systemic disease after refusing treatment for persistent neck lymphadenopathy. Two-year loco-regional control rates, overall survival and disease-free survival rates were 96%, 96%, and 88%, respectively. All patients experienced some degree of acute and/or late toxicity. However, the toxicity profile was comparable to that seen following standard fractionation. Acute or late toxicities directly attributable to C-Boost were not observed. CONCLUSION: This C-Boost radiotherapy regimen administers a substantially higher biologically effective dose compared with conventional radiation schedules. Preliminary locoregional control and survival rates are promising with no significant acute and/or late toxicities.     

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.     

Neck dissection in the management of regional metastases in patients with undifferentiated nasopharyngeal carcinomas

Residual regional disease after the primary treatment of nasopharyngeal carcinoma is still considered to be a therapeutic problem. The limitations of prophylactic radical radiation, further doses of irradiation as a useful salvage procedure, and the effects on vital structures were the reasons that we employed a therapeutic protocol consisting of radical neck dissection after 40 Gy of radiotherapy and a full tumor dose after surgery. The initial treatment consisted of chemotherapy. Between 1977 and 1991 surgical removal of residual neck metastases was performed in 44 patients with undifferentiated nasopharyngeal carcinomas who had regional metastases at the time of diagnosis. Fourteen patients (group A) had radical neck dissections after initial chemotherapy (using doxorubicin, etoposide, bleomycin and/or 5-fluouracil) and between two courses of locoregional radiotherapy. The remaining 30 patients (group B) were operated on after finishing chemotherapy and locoregional radiotherapy (group B 1) or receiving only full-dose locoregional radiotherapy (group B 2). All patients had histopathologically proven complete remission of primary tumors before neck surgery. The five-year survival rates for group A were 78%, 40% for group B 1 and 27% for group B 2. There were statistically significant differences between groups A and B (P < 0.01), but not between groups B 1 and B 2. In group A one patient died from subsequent distant metastases and two from local tumor recurrences. Twenty patients died in group B, regional relapses occurred in 40% of the patients in group B 1 and 33% in group B 2, while distant metastases developed in 40% of group B 2. These findings again showed that radical neck dissection was an effective approach for controlling neck disease. When performed after initial chemotherapy and between two courses of radiotherapy, surgery significantly improves the prognosis of patients with positive regional lymph nodes at the time of diagnosis. Received: 2 June 1998 / Accepted: 21 October 1998     

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.     

扁桃体癌治疗及预后因素分析

目的 回顾性分析扁桃体癌的治疗疗效,并探讨影响扁桃体癌的预后因素.方法 1997年4月至2008年4月中山大学肿瘤防治中心共收治经病理证实、无远处转移的扁桃体癌61例,其中末分化癌2例,低分化鳞癌26例,中高分化鳞癌33例.根据AJCC2002年第6版分期标准,Ⅰ期9例,Ⅱ期7例,Ⅲ期23例,Ⅳ期22例.27例患者行单纯放疗,23例行放疗联合化疗,6例行手术联合术后放疗,诱导化疗加手术联合术后放疗3例,放疗后外科挽救加化疗2例.结果 随访率为96.7%.Kaplan-Metier方法 计算全组5年总生存率为50.2%.16例Ⅰ-Ⅱ期患者中,8例行单纯放疗,5年生存率为50.0%,6例行手术联合术后放疗,5年生存率为83.3%,二者差异无统计学意义(P=0.318).45例Ⅲ-Ⅳ期患者,单纯放疗19例,5年生存率为51.5%,放疗联合化疗21例,5年生存率为36.4%,手术联合放疗为主的治疗5例,5年生存率为75.0%,三者差异无统计学意义(P=0.239).T1-T4期5年生存率分别为91.8%、46.8%、29.1%、0%(χ~2=30.168,P<0.001).Cox多因素分析显示T分期、治疗结束时原发灶和颈部转移淋巴结疗效为影响预后的独立危险因素(P<0.05).结论 局部早期(Ⅰ-Ⅱ期)扁桃体癌的治疗,基于器官功能保全原则,倾向于选择单纯放疗,局部晚期(Ⅲ-Ⅳ期)扁桃体癌的治疗模式与疗效的关系仍需进一步研究.T分期、治疗结束时原发灶和颈部转移淋巴结疗效为影响预后的独立危险因素.     

The chemotherapy of head and neck cancer

Chemotherapy in head and neck cancer can be given in metastatic disease at presentation, in locally far advanced disease not amendable for curative treatment with surgery and/or radiotherapy, in the neo-adjuvant setting, in recurrent disease after previous surgery and radiotherapy and either concurrent or alternating with radiotherapy. Most data are gathered in the recurrent and locally far advanced disease setting. Combination therapy (with agents such as cisplatinum, 5-FU and methotrexate) have shown some improvements in response rate, however no obvious survival advantage over monotherapy in the treatment of patients with metastatic or advanced locoregional cancer of the head and neck has been observed. In the neo-adjuvant setting, chemotherapy is helpful in preserving the larynx and hypopharynx but has no proven impact (positive or negative) on survival. New compounds and approaches are needed to improve survival in head and neck cancer. Among the new options for chemotherapy in metastatic/recurrent disease are the taxanes. With monotherapy docetaxel, response rates of 23%-42% are seen, and, when used in combination with cisplatinum and 5-FU, response rates of 52-100% have been reported in phase I/II trials. A phase III trial of the addition of docetaxel to standard neo-adjuvant therapy with cisplatinum and 5-FU is now underway.     

The role of neck dissection after chemoradiotherapy for oropharyngeal cancer with advanced nodal disease

OBJECTIVE: To analyze and compare the effectiveness of sequential platinum-based chemotherapy and radiotherapy with and without selective neck dissection in patients with N2a and greater stage node-positive squamous cell carcinoma of the oropharynx. DESIGN: Nonrandomized controlled trial. SETTING: Tertiary referral center. PATIENTS: Sixty-six patients with squamous cell carcinoma of the oropharynx staged N2a or greater. INTERVENTIONS: Platinum-based induction chemotherapy followed by definitive radiation therapy; and selective neck dissections 6 to 10 weeks following the completion of radiation therapy in patients with radiographic evidence suggesting residual neck disease. MAIN OUTCOME MEASURES: Locoregional recurrence and disease-free survival. RESULTS: Of 66 patients, 24 (36%) had complete responses in the primary local tumor (oropharynx) and regional disease (neck nodes), as assessed clinically and radiographically. These patients had lower rates of locoregional recurrence than did patients showing no or partial responses, but the differences were not significant (P>.05). Of 18 patients undergoing neck dissection, 10 (56%) had pathological evidence of residual tumor. Patients showing a complete response of regional and neck disease had significantly improved disease-specific and overall survival (P = .01 for both) compared with patients showing no or partial responses of their neck disease. Patients with no or partial responses who underwent neck dissections had significantly improved overall survival compared with similar patients who did not undergo neck dissections (P = .002). CONCLUSIONS: Even in patients with bulky nodal disease, a complete response in the neck to sequential chemotherapy and radiotherapy may indicate that neck surgery is not necessary for good locoregional control and improved disease-free survival. Neck dissection is recommended for patients with no or partial radiographic responses.     

Importance of neoadjuvant chemotherapy in olfactory neuroblastoma treatment: Series report and literature review

Introduction and objectives

Olfactory neuroblastoma (ONB) is a rare entity that constitutes less than 5% of nasosinusal malignancies. Mainstream treatment consists in surgical resection +/? adjuvant radiotherapy. By exposing results observed with apparition of new therapeutic options as neoadjuvant chemotherapy, the objective is to evaluate a series and a review of the current literature.

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.     

Immune Reactivity Does Not Predict Chemotherapy Response,Organ Preservation,or Survival in Advanced Laryngeal Cancer

Objective To determine whether pretreatment lymphocyte subpopulations correlate with tumor response to induction chemotherapy as part of an organ preservation treatment approach in patients with advanced laryngeal cancer. Study Design A prospective clinical trial in patients with advanced laryngeal cancer was undertaken to determine whether the frequency of late salvage laryngectomy and overall survival could be improved using one cycle of neoadjuvant chemotherapy to select patients for organ preservation. Pretreatment peripheral blood lymphocyte subpopulations for CD3, CD4, CD8, NK, and B cells were correlated with tumor response to induction chemotherapy, larynx preservation, and survival, to determine whether immune parameters could be useful in patient selection. Methods The study setting was a tertiary referral academic health center. Studied were 53 patients with stage III (42%) or IV (57%) larynx cancer. Most patients had supraglottic cancers (73%) and positive clinical nodes (51%). Sixty‐eight percent had greater than 50% tumor response after one cycle of induction chemotherapy and then received concurrent chemoradiation and two cycles of adjuvant chemotherapy. Lymphocyte subpopulations were measured in 39 patients. Mean follow‐up was 23.3 months (range, 5–61 mo). Results A total of 18 (34%) patients underwent laryngectomy. Only 4 cases were late salvage resections (13–35 mo after treatment). Fourteen cases were planned surgery after initial chemotherapy. Of the lymphocyte subpopulations measured, CD8 levels were significantly lower in stage IV patients and tended to be lower in patients with successful organ preservation. However, no significant differences in lymphocyte subpopulations were found among responders and nonresponders to chemotherapy. Overall survival was 88%. Conclusions One cycle of neoadjuvant chemotherapy was effective in selecting patients for organ preservation. The regimen of definitive concurrent and adjuvant chemotherapy was associated with an unexpectedly high 2‐year survival rate. Lymphocyte subsets were not significant predictors of responding patients or survival. Further study of other biological markers useful in selecting patients for organ preservation are needed.     

A comparison of combined modalities and single modality in the management of advanced head and neck tumors

Advanced head and neck cancer patients can be managed by single modality or combined modalities, Between 1976 and 1979, three treatment groups were retrospectively identified. One group received induction chemotherapy, surgery, and postoperative radiation therapy. The second group received chemotherapy followed by radiotherapy. The third group was treated during the same time period with radiation alone. These groups were matched with respect to age, site of primary tumor, nodal status, absence of metastatic disease, and no prior cancer treatment. The combined modality groups were initially treated with two doses of cis-platinum and a bleomycin infusion. Evaluation of tumor response was done 2 weeks following chemotherapy; 24 patients had surgery and postoperative radiation, 23 had radiotherapy without surgery and 24 patients were treated with radiotherapy alone. Median survival was 22 and 13 months respectively for the 2 combined modality groups and 4.7 months for the radiotherapy group. Disease-free survival was a projected value of 40 and 35 months for the combined modality groups and an actual 3 months for the radiotherapy group. Combined modality treatment with chemotherapy and surgery and/or radiotherapy offers a higher response rate and prolonged survival than radiotherapy alone.     

Survival analysis of laryngeal carcinoma without laryngectomy, radiotherapy, or chemotherapy

This study aimed at investigating the survival rate and prognostic factors of laryngeal carcinoma patients in the absence of the use of laryngectomy, radiotherapy, and chemotherapy. A total of 167 cases of laryngeal carcinoma without the use of laryngectomy, radiotherapy, or chemotherapy were analyzed retrospectively. Surveyed items included age, smoking history, tumor family history, tuberculosis history, primary site, pathological grade, T-stage, N-stage, clinical stage, and whether tracheotomy had been performed. Survival rates were calculated using the Kaplan–Meier method. For univariate analysis, comparison among/between groups was performed using the log-rank test. Multivariate analysis was carried out using the Cox proportional hazard model. Overall median survival time was 16?±?1.44?months, and overall 1- and 2-year survival rates were 56.4 and 26.5%, respectively. No patient survived over 5?years in cases diagnosed for more than 5?years (except for cases that were lost). The median survival time of clinical stage 0/I/II was 28?±?3.81?months, and 1- and 2-year survival rates were 79.3 and 59.3%, respectively; the median survival time of III/IV clinical stages was 11?±?1.32?months, and 1- and 2-year survival rates were 45.5 and 10.6%, respectively. Univariate analysis showed that primary site, pathological grade, T-stage, N-stage, and clinical stage were significant prognostic factors for the survival of the patients (P?<?0.05). Whether tracheotomy had been performed was not significant for affecting survival rates. Multivariate analysis showed survival rates were statistically correlated with T-stage and N-stage (P?<?0.05). The development of laryngeal carcinoma course was faster, without treatment to the tumor itself, even if palliative surgery such as tracheostomy would not improve the survival rate. In laryngeal carcinoma patients with no surgery, radiotherapy or chemotherapy, the factors affecting the survival rates include primary site, pathological grade, T-stage, N-stage, and clinical stage, and of them, T-stage and N-stage are the independent prognostic factors.     

Induction chemotherapy with cisplatinum, 5-fluorouracil, bleomycin, mitomycin C and hydroxyurea for previously untreated locally advanced squamous cell carcinomas of the head and neck

Fifty-three patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) were treated with a combined modality treatment consisting of three cycles of induction chemotherapy before definitive surgery and/or radiotherapy. Two additional cycles of the same chemotherapy were given after local-regional therapy. The chemotherapeutic regimen included cisplatinum 100 mg/m2 on day 1, 5-fluorouracil 1000 mg/m2 as a continuous infusion on days 2-6, bleomycin 15 units i.m. on days 15 and 29, mitomycin C 4 mg/m2 i.v. on day 22 and hydroxyurea 1000 mg/m2 p.o. on days 23-27. Each cycle was repeated every 42 days. Forty-nine patients are evaluable for response. There were 37 men and 12 women, with a median age of 58 years (range 18-75 years) and performance status of 80 (range 40-90). Sixteen patients (33%) demonstrated a complete response, 20 (41%) a partial response, yielding a 74% response rate to induction chemotherapy; 12 (24%) patients had stable disease and 1 (2%) progressive disease. The actuarial survival of those patients who completed the whole treatment program was 65% at 2 years and 47% at 3 years. Toxicities included nausea and vomiting (66%). anemia (34%), leukocytopenia (54%), thrombocytopenia (22%), stomatitis (36%), diarrhea (10%), alopecia (78%), hear impairment (4%) and transient creatinine elevation (2%). The results of the present study showed that induction chemotherapy with the above regimen produced a high rate of complete responses and can be safely combined with local-regional therapy to improve local tumor control and increase disease-free survival in patients with locally advanced SCCHN.