Functional Organ Preservation in Locally Advanced Laryngeal Squamous Cell Carcinoma: Is there a Role for Induction Chemotherapy?

Concurrent chemoradiation (CRT) is currently the most effective strategy for organ preservation in locally advanced laryngeal squamous cell carcinoma (SCC) unsuitable for function-preserving surgery. The larynx preservation approach of induction chemotherapy followed by radiotherapy in responders is based on the hypothesis that tumours that show a satisfactory response to induction chemotherapy are more likely to respond to radiation-based treatment. This enables the use of chemotherapy response to identify patients who are more likely to achieve long-term disease control with organ-preserving therapies. An induction chemotherapy response allows prognostication, outcome prediction and treatment selection in patients with locally advanced laryngeal SCC. Excellent survival outcomes have been achieved with induction chemotherapy followed by CRT as definitive therapy in responders. The addition of docetaxel to cisplatin and 5-fluorouracil induction chemotherapy has also resulted in higher larynx preservation rates. Future organ preservation studies should assess whether induction chemotherapy with docetaxel, cisplatin and 5-fluorouracil followed by CRT in responders improves survival compared with an unselected approach of primary CRT in all eligible patients with T2 or T3 laryngeal SCC. The primary end point of such studies should be laryngo-oesophageal dysfunction-free survival, which focuses on the treatment goals of survival, disease control and laryngeal–oesophageal function after therapy. In addition, the inclusion of patients with N2 or N3 disease will help to determine whether the addition of docetaxel, cisplatin and 5-fluorouracil to CRT reduces the incidence of distant relapse in advanced laryngeal SCC. Other areas of interest include the use of concurrent cetuximab in place of platinum-based chemotherapy with radiotherapy in larynx preservation and the search for better predictive markers of successful larynx preservation than induction chemotherapy response.     

Candidates for larynx preservation: the next step?

Nonsurgical treatment approaches to enable larynx preservation in patients who would otherwise undergo laryngectomy have evolved over recent years. Randomized trials have demonstrated that concurrent chemotherapy and radiotherapy is more effective than doublet cisplatin and 5-fluorouracil (5-FU) (PF)-based induction chemotherapy and radiotherapy in enabling larynx preservation. However, concurrent chemotherapy and radiotherapy is also associated with more toxicities than induction PF followed by radiotherapy. The triplet induction regimen of docetaxel, cisplatin, and 5-FU (TPF) is more effective than PF and is now considered to be the standard induction chemotherapy regimen for future larynx preservation trials. Manipulating the postinduction treatment regimen may help to improve larynx preservation rates, and possibly survival, and the use of concurrent chemoradiotherapy and radiotherapy plus the epidermal growth factor receptor inhibitor cetuximab has been investigated in this setting. Determining the most effective treatment approach for larynx preservation will involve conducting a trial comparing concurrent chemotherapy and radiotherapy with sequential TPF induction chemotherapy followed by either radiotherapy or cetuximab plus radiotherapy. Collaboration among international groups is required to assess which approach would be most beneficial in terms of larynx function preservation, disease control, and survival.     

Role of multimodal treatment in oropharynx, larynx, and hypopharynx cancer

Due to recent advances in radiation fractionation, radiochemotherapy, and conservative surgical techniques, the concept of multimodal therapy in head and neck cancer is currently changing. The recently published RTOG Phase III trial 9003, with 1,113 patients accrued, showed that hyperfractionation and accelerated fractionation with concomitant boost are more efficacious than standard fractionation for locally-advanced head and neck cancer. Acute, but not late, toxicity was also increased. Three meta-analyses have suggested that the impact of chemotherapy in head and neck cancer is small but is highly associated with the timing of therapy. Concomitant administration of radiation therapy and chemotherapy led to an absolute benefit in 5-year survival of about 10%. This finding has been further supported by recently published randomized prospective trials comparing concomitant radiochemotherapy with radiotherapy alone in advanced head and neck cancer. There is now clear evidence that radiochemotherapy provides a substantial and statistically significant improvement in survival and local-regional control, as compared to radiotherapy alone. Radiochemotherapy should be considered an accepted standard of care in cancers of the oropharynx, particularly for patients with locally-advanced disease who have a good performance status. Two randomized studies conducted by the Department of Veterans' Affairs and the EORTC, with a total of 534 patients accrued, showed that induction chemotherapy followed by radiotherapy of responders yields survival rates equal to those of total laryngectomy with postoperative radiotherapy. After 4 years, one-half to two-thirds of survivors of the chemotherapy arm retained a functional larynx. Larynx preservation using induction chemotherapy can now be regarded as feasible but still investigational. Current phase II studies show excellent larynx preservation rates using a primary concomitant radiochemotherapy with an altered fractionation regimen. More clinical and laboratory research is required to further evaluate the different treatment options of the multimodality concept, and to develop prognostic models that will allow individualization of the therapy.     

Advanced carcinoma of the larynx: Results of surgery and radiotherapy without induction chemotherapy (1980–1985): A multivariate analysis

Induction chemotherapy has been proposed in the case of advanced laryngeal cancer in order to preserve laryngeal function in those patietns who are complete responders. To clarify the treatment policies, a restrospective multicentric analysis of 116 patients with advanced carcinoma of the larynx treated by radical surgery and postoperative radiotherapy was carried out in order to evaluate prognostic factors for local control and survival.

Between 1980 and 1985, 116 patients with Stage III squamous cell carcinoma of the larynx underwent radical surgery and postoperative radiotherapy with a curative intent. Treatments were very homogenous, and doses delivered were in the range of 50–65 Gy according to nodal involvement and surgical margins status.

The local recurrence rate and the local disease-free survival rate at 5 years were 22.5% and 76.3%, respectively. Actuarial survival at 5 years was 68.3% with 44 patients stil alive who no evidence of disease (NED) with more than 5 years follow-up. For both overall survival and relapse-free survival, cervical node involvement with capsular rupture was found to be the only significant adverse pronostic factor in univariate and multivariate analysis. No other parameter was predictive either for local recurrence or for survival.

Local prognosis and survival depend largely on nodal involvement and capsular rupture while increasing doses of radiation strategy is likely to reduce the risk of local and nodal recurrence. Preservation of functional larynx is certainly an important goal to achieve when treating advanced carcinoma of the larynx, provided that local failure rate and survival be similar. In the unique randomized study previously published in the literature comparing radical surgery and postoperative radiotherapy to induction chemotherapy and radiotherapy, the local-regional failure rate was drastically increased in the chemotherapy arm. Other results from well-designed controlled studies are awaited before recommending systemic induction chemotherapy and larynx preservation in complete responders. On the other hand, testing synchronous or alternated chemotherapy vs. induction chemotherapy may address the pending questions about the optimal treatment of advanced laryngeal carcinoma.     

TPF: a rational choice for larynx preservation?

For many years, the standard approach for the treatment of resectable squamous cell carcinoma of the head and neck was surgery, with or without subsequent radiotherapy. However, the morbidity associated with this approach, particularly for patients requiring total laryngectomy, can severely impair a patient's quality of life. The finding that patients whose tumors responded to chemotherapy showed a good response to subsequent radiotherapy opened up the possibility of a new organ-preserving management strategy for patients with resectable disease. Randomized studies demonstrated that induction chemotherapy with a cisplatin-5-fluorouracil (5-FU) doublet (PF) prior to radiotherapy enabled larynx preservation in a substantial proportion of patients, compared with surgery plus radiotherapy, without compromising survival. The benefit in terms of larynx preservation when using platinum-based doublet induction chemotherapy followed by radiotherapy, compared with concurrent chemotherapy and radiotherapy, is less clear, although the sequential approach appears to be better tolerated. Adding the taxane docetaxel to PF, to create the TPF triplet regimen, led to significantly higher larynx preservation and laryngectomy-free survival rates than with the PF doublet. TPF is now the accepted standard induction chemotherapy regimen for future clinical trials in resectable disease. Methods for improving postinduction treatment strategies are being explored.     

Larynx preservation with combined chemotherapy and radiation therapy in advanced but resectable head and neck cancer

Forty patients with advanced, resectable squamous cell carcinoma of the larynx, oropharynx, or hypopharynx whose surgery would have required total laryngectomy (TL), were treated with one to three cycles of cisplatin-based chemotherapy before local therapy with the goal of larynx preservation. Clinical complete responses (CRs) or partial responses (PRs) to chemotherapy were seen in 26 of 40 patients (65%). Three patients with primary-site disease unresponsive to chemotherapy underwent resection of the primary lesion and neck dissection followed by radiation therapy (RT). Thirty-seven patients were referred after chemotherapy for RT +/- neck dissection. Thirty-one of 40 patient (78%) were rendered disease-free (no evidence of disease [NED]). With a median follow-up of 49 months (range, 31 to 76), the overall actuarial survival rate for the group was 58% at 2 years and 33% at 5 years. The failure-free survival rate was 42% and 33% at 2 and 5 years, respectively. Seven patients refused recommended TL throughout their course. This may have adversely affected survival results. A greater proportion of patients who achieved a CR or PR to chemotherapy remained disease-free compared with those who achieved less than a PR (P less than .001). Sixteen patients relapsed, 10 with locoregional disease. Six patients underwent TL, either for initial induction failure or at relapse, for an actual larynx-preservation rate of 34 of 40 patients (85%). If the seven patients who refused TL are included, the anticipated preservation rate is 27 of 40 patients (68%). Larynx preservation with combined chemotherapy and radiation is feasible and effective in patients with advanced, resectable squamous cell carcinoma of the head and neck (SCHN). This treatment approach requires a motivated patient, careful patient monitoring, and close interdisciplinary cooperation among oncologists.     

Individual patient data meta-analyses in head and neck carcinoma: what have we learnt?]

Carcinoma of the upper aerodigestive tract (oral cavity, oropharynx, hypopharynx, nasopharynx, larynx) are frequent tumors for which surgery and/or radiotherapy are the main therapeutic agents. The main results of meta-analyses based on the collection of individual patients data are reported: 1) The meta-analysis on chemotherapy, regrouping data of nearly 11,000 patients issued from 63 randomized trials showed an absolute benefit of 4% at five years in overall survival, in favor of chemotherapy (P<0.0001). Most of the benefit was seen with concomitant radiochemotherapy, however with a relatively large heterogeneity in this subgroup of trials. An update of this meta-analysis was performed including 24 additional trials, which confirmed the magnitude of the benefit due to concomitant chemotherapy (8% at 5 years). 2) The meta-analysis on larynx preservation, using induction chemotherapy in larynx and hypopharynx carcinomas. No significant difference was seen between the control arm with total laryngectomy and the larynx preservation approach. 3) The meta-analysis on chemotherapy in nasopharynx carcinomas, from the data of 11 randomized trials including 2722 patients, and comparing the radiotherapy to radio-chemotherapy (1979-2001). The results showed an absolute benefit of 6% at five years in overall survival, in favor of chemotherapy (P<0.0001). Most of the benefit was seen with concomitant radiochemotherapy. 4) Finally, a meta-analysis on altered fractionated RT, compared to conventional RT in 15 randomized trials regrouping 6515 patients. The results showed a small but significant improvement in favor of altered fractionated RT for overall survival and local control with an absolute benefit at five years of 3 and 6%, respectively.     

Docetaxel and squamous cell carcinoma of the head and neck

Chemotherapy in head and neck carcinoma is used as palliative treatment but also as induction treatment or combined treatment with concurrent radiation therapy. Platinum and 5-fluorouracil are the most commonly used cytotoxic agents. Docetaxel is an active drug for treating head and neck carcinoma. For patients with recurrent or metastatic disease, docetaxel could be used either as a second line chemotherapy or a first line for patients who received previously platinum or 5FU. In combination with platinum and 5FU, used as induction chemotherapy the TPF regimen is a very active treatment with an overall response rate of 85 to 90% with a manageable acute toxicity rate. This approach is under investigation in terms of ability to obtain more larynx preservation compared to the standard approach with platinum and 5FU. Docetaxel is a radiosensitizer. Concurrent radiochemotherapy using docetaxel alone is feasible, Trials are needed to define the optimal regimen for combining radiation, platinum and docetaxel.     

The role of chemotherapy in locally advanced head and neck squamous cell carcinoma

The role of chemotherapy in multimodality treatment for locally advanced head and neck squamous cell carcinoma, although firmly established, presents several unresolved issues. Concomitant platinum-based chemoradiation (CRT) is a standard treatment for unresectable, resectable but nonsurgically treated, and postoperative high-risk patients with locally advanced head and neck squamous cell carcinoma. However, no clear conclusion can be drawn regarding the optimal platinum compound or combinations to use, the type of schedule, and number of cycles (ie, platinum total dose) to be delivered. Cetuximab administered concomitantly with radiotherapy has not been directly compared with CRT but offers a potential different approach using a noncytotoxic systemic agent. In the organ preservation setting, CRT, although yielding a superior 5-year larynx preservation rate, showed similar outcomes to induction chemotherapy (IC) followed by radiation in terms of 5-year laryngectomy-free survival and overall survival, with a higher incidence of grade 3-4 mucositis. The role of IC in nonorgan preservation programs has not yet been established. Phase III trials comparing concomitant CRT versus IC followed by CRT are ongoing with results anticipated in the near future.     

Attempts to improve organ preservation in patients with squamous cell carcinoma of the head and neck

When surgical resections are performed for patients with locally advanced head and neck cancer, a critical consideration is which organs and functions of patients are sacrificed. In attempts to improve the organ preservation rate in patients with advanced squamous cell carcinoma of the head and neck (SCCHN), chemotherapy has been used either before(neoadjuvant or induction), with (concurrent or concomitant), after (adjuvant) radiotherapy, or as alternating treatment with radiotherapy. A recent systematic review using meta-analysis has revealed that concurrent chemotherapy with radiotherapy shows a significant benefit for the survival rate of patients with SCCHN when compared with radiotherapy alone, and is superior to neoadjuvant chemotherapy. However, no standard concurrent chemoradiotherapy regimen has been defined,although concurrent chemotherapy together with regimens including cisplatin has been considered to be most effective for SCCHN. We combined radiotherapy concurrently with chemotherapy including cisplatin, 5-fluorouracil, methotrexate, and leucovorin in patients with advanced resectable SCC of the hypopharynx to minimize the necessity of radical surgery and preserve the functional larynx. In conclusion, previous reports and our data show that an organ preservation treatment approach using concurrent chemoradiotherapy is feasible.     

Induction chemotherapy for head and neck cancer: recent data

The addition of chemotherapy to radiotherapy in the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN) patients improves survival. Meta-analyses of randomized trials have indicated that the benefit of this approach is associated with the timing of chemotherapy administration. It has been demonstrated that the greatest survival benefit over locoregional treatment alone is seen with the concurrent administration of chemotherapy and radiotherapy. However, sequential chemotherapy administration, in the form of induction chemotherapy followed by radiotherapy or concurrent chemoradiotherapy, has been successful as a strategy for organ function preservation in patients with potentially resectable SCCHN. In addition, a meta-analysis of trials using platinum and 5-fluorouracil (PF)-containing induction regimens demonstrated a significant survival benefit for this approach over locoregional treatment alone in locally advanced disease. In recent years, the introduction of the taxanes into induction chemotherapy has provided physicians with more active regimens. The triplet combination induction regimen of docetaxel, cisplatin, and 5-fluorouracil has been shown to be more effective in prolonging survival than the doublet PF. Current trials are testing whether the addition of induction chemotherapy to standard concomitant chemoradiotherapy is superior to concomitant chemoradiotherapy alone.     

Expanding role of the medical oncologist in the management of head and neck cancer

The multidisciplinary approach to treating squamous cell carcinoma of the head and neck is complex and evolving. This article aims to review some recent developments in squamous cell carcinoma of the head and neck, in particular the expanding role of chemotherapy in its management. Surgery and radiotherapy have remained the mainstay of therapy. Chemotherapy is increasingly being incorporated into the treatment of squamous cell carcinoma of the head and neck. Previously, radiotherapy following surgery was the standard approach to the treatment of locoregionally advanced resectable disease. Data from randomized trials have confirmed the benefits of concurrent chemoradiotherapy in the adjuvant setting. Chemoradiotherapy is also the recommended approach for unresectable disease. Induction chemotherapy has been useful in resectable disease where organ preservation is desirable, but this approach was inferior for the goal of larynx preservation, while leading to similar survival when compared with concomitant chemoradiotherapy. There is recent evidence that taxanes added to induction chemotherapy with cisplatin and fluorouracil result in improved survival outcomes. Novel targeted agents, such as epidermal growth factor receptor antagonists, are showing promise in the treatment of patients with both locoregionally advanced and recurrent/metastatic squamous cell carcinoma of the head and neck.     

Cetuximab in the management of locoregionally advanced head and neck cancer: Expanding the treatment options?

The treatment of locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) has evolved in recent years as a consequence of a better understanding of the potential benefits associated with altered radiation fractionation regimens, concurrently administered chemotherapy and radiotherapy (chemoradiotherapy) and induction chemotherapy. Concurrent chemoradiotherapy is a treatment option for technically resectable disease, where functional morbidity precludes the use of surgery. Induction chemotherapy followed by radiotherapy may also be used in this setting, and has been validated for larynx preservation. Concurrent chemoradiotherapy is a standard treatment approach for medically fit patients with locoregionally advanced unresectable disease. However, the toxicity burden of additional chemotherapy in both the concurrent chemoradiotherapy and induction chemotherapy settings can have implications for treatment compliance and may impede the administration of chemotherapy and/or radiotherapy to schedule. The epidermal growth factor receptor (EGFR)-targeted IgG1 monoclonal antibody, cetuximab (Erbitux®), has shown significant clinical benefits in the treatment of both locoregionally advanced and recurrent and/or metastatic SCCHN. A phase III study in locoregionally advanced disease demonstrated significant improvements in locoregional control and progression-free and overall survival with cetuximab plus radiotherapy compared with radiotherapy alone, and overall survival benefits were maintained at 5 years. The addition of cetuximab to concurrent chemoradiotherapy has been shown to be feasible in phase II trials and is being investigated in phase III trials. Preliminary evidence suggests that cetuximab could be incorporated into induction management strategies. Taken together, these data support an important role for cetuximab in the treatment paradigm for locoregionally advanced SCCHN.     

Laryngeal preservation in head and neck cancer: multidisciplinary approach

Since the first total laryngectomy was undertaken, efforts have been made to avoid removing the entire larynx. For a long time, partial surgery and radiotherapy were the only options that could preserve the larynx. Development of active chemotherapy regimens has prompted an era of intensive clinical research. Induction chemotherapy followed by radiotherapy in patients with objective responses has been shown to allow conservation of the larynx in nearly two-thirds of individuals, without any effect on survival; concurrent chemoradiotherapy also provides high rates of laryngeal preservation, again without affecting survival; and induction chemotherapy followed by concurrent chemoradiotherapy is under investigation. In the meantime, partial open surgery and endoscopic carbon dioxide laser procedures are feasible in selected moderately advanced laryngopharyngeal cancers as an alternative to destructive surgery. Altered fractionation radiotherapy can also be used in management of these tumours, and targeted treatments have opened a new area of clinical research. Findings of basic research and modern imaging should provide useful approaches for selection of patients for various strategies.     

Place de la chimiothérapie d’induction dans les carcinomes épidermoïdes de la tête et du cou localement avancés inopérables (hors préservation laryngée)

Head and neck carcinomas are serious diseases for which surgery is the main treatment. In roughly two thirds of cases, diagnosis is made at an advanced stage, which prevents optimal surgical resection. In this frequently occurring situation, the treatment usually recommended was a combination of radiotherapy and platinum-based chemotherapy. Several phase III trials have recently assessed an induction chemotherapy with platinum, docetaxel and 5 fluorouracil (TPF) followed by either radiotherapy or radiochemotherapy. These trials show an overall survival rate after induction chemotherapy equal or superior to conventional radiochemotherapy. The meaning of these studies is limited by several factors: a non-optimal comparison arm, patient selection depending on a good PS and the real TPF toxicity in non-selected patients. The use of induction chemotherapy must be conditional on cautious thorough evaluation after multidisciplinary discussion based on pros and cons. The latter will be discussed herein.     

诱导化疗联合同期放化疗对局部晚期鼻咽癌的远期疗效

背景与目的:诱导加同期放化疗有提高鼻咽癌患者无瘤生存率和总生存率的趋势,本研究对比鼻咽癌接受单纯放疗或诱导加同期放化疗的生存率差异,探讨增加诱导及同期化疗对鼻咽癌生存率的影响.方法:将1997年1月至1998年12月在中山大学肿瘤防治中心接受诱导加同期顺铂联合氟尿嘧啶方案化疗3～5疗程联合放疗75例鼻咽癌与同时期接受单纯根治性放疗的局部晚期住院患者460例的生存期进行比较.生存相关分析用Cox回归分析,组间生存率比较采用Kaplan-Meier法.结果:两组间生存率和无瘤生存率差异有统计学意义,放疗加化疗组优于单纯放疗组(P＜0.05).Ⅲ期患者组单纯放射治疗者中位生存期和中位无瘤生存期分别为85.1个月和82.9个月,而化疗加放疗组为94.5个月和89.5个月,两组差异有统计学意义(P＜0.05).Ⅳa期患者组单纯放射治疗者中位生存期和中位无瘤生存期分别为44.4个月和40.3个月,化疗加放疗组为82.4个月和69.6个月,两组差异同样有统计学意义(P＜0.05).Cox回归分析显示,临床分期和化疗与否是独立预后因素.结论:诱导化疗加同期放化疗治疗鼻咽癌可提高Ⅲ、Ⅳa期患者的生存率.     

Quimioterapia de inducción seguida de radioquimioterapia como alternativa a la laringuectomía en el tratamiento del cáncer de cabeza y cuello localmente avanzado

Objective

To evaluate survival in patients with loco-regional advanced head and neck cancer treated with induction chemotherapy and to assess possible larynx preservation in good responders.

Materials and methods

Between December 1997 and June 2000, patients (n=46) diagnosed as having advanced head and neck carcinoma were treated with induction chemotherapy (CT). This was followed by radiotherapy (RT) + CT if there had been complete response (CR) or partial response (RP) >80%; or followed by total laryngectomy and adjuvant RT if CR or PR was <80%.

Results

Of the 46 patients studied, 57 (80%) had CR, 10% had PR and 10% had no response or disease progression (DP). Median survival was 33%, followup was of 50 months during which the overall survival was 36%, disease-free survival (DFS) was 60% and loco-regional control was 51%.

Conclusion

RT-CT resulted in high rates of disease resolution and speech preservation in patients who, traditionally, had poor clinical and functional outcomes.     

Larynx preservation, state of the art]

Larynx preservation in advanced pharyngolaryngeal cancers has been a major challenge in clinical research over the past two decades. Subtotal surgery (endoscopic laser surgery, supracricoid partial laryngectomies and hemilaryngopharyngectomies) has allowed reducing the indications of the so-called "mutilating" surgery. On the other hand, the modification of fractionation has notably improved the results of definitive irradiation (but most probably for supraglottic tumors). The main clinical research has been carried out with either sequential or concurrent chemo-irradiation. Induction chemotherapy followed by irradiation in good responders or by surgery in poor responders allowed to preserve the larynx in around half the cases without deleterious impact on overall survival. Concurrent chemo-irradiation trials suggested that the larynx preservation rates could be increased but overall survival remained unchanged and mucositis was a notable side effect. The next step could be the combination of induction chemotherapy followed by concurrent chemo-irradiation in good responders. Finally, the place of new drugs (taxanes, targeted therapies) is to be explored in this context.     

放化疗顺序对鼻咽癌治疗效果的差异研究

目的 探究放化疗顺序对鼻咽癌治疗效果的差异.方法 收集经临床影像学检查及病理检查确诊的鼻咽癌患者129例,根据治疗方案不同将患者分为诱导组(n=65)和同期组(n=64),其中诱导组采用顺铂+5-氟尿嘧啶(5-Fu)诱导化疗加调强放疗治疗,同期组采用顺铂同期放化疗治疗.对两组患者的疗效、不良反应发生情况及生存情况进行比较.结果 诱导组与同期组患者治疗的总有效率比较,差异无统计学意义(P﹥0.05);同期组患者的胃肠道反应及白细胞下降发生率均明显高于诱导组.两组患者的随访时间为6～97个月,中位随访时间40个月,诱导组患者的中位生存时间为45个月(95％CI:39.228～50.772),同期组患者的中位生存时间为43个月(95％CI:35.159～50.841),两组患者的生存情况比较,差异无统计学意义(χ2=0.796,P﹥0.05).结论 诱导化疗加调强放疗治疗局部晚期鼻咽癌的疗效与同期放化疗相近,但同期放化疗不良反应较重.     

Induction chemotherapy with paclitaxel and cisplatin and CT-based 3D radiotherapy in patients with advanced laryngeal and hypopharyngeal carcinomas--a possibility for organ preservation.

BACKGROUND: To evaluate the effect of paclitaxel/cisplatin induction chemotherapy (ICHT) and CT-based radiotherapy (RT) on larynx preservation, tumor control, and survival in patients with larynx/hypopharynx carcinoma eligible for total laryngectomy (TL) or TL plus partial pharyngectomy (TLPP). PATIENTS AND METHODS: Fifty patients eligible for TL or TLPP were enrolled onto a prospective study and treated with ICHT (200 mg/m(2) paclitaxel, 100 mg/m(2) cisplatin; day 1, 22). In patients with complete or partial tumor response RT (69.9 Gy in 5.5 weeks at the gross tumor, 50.4 Gy in the lymphatic drainage; single dose: 1.8 Gy, concomitant boost: 1.5 Gy) was applied. Non-responders had TL/TLPP and RT with total doses adapted to the radicality of tumor resection (56-70 Gy). RESULTS: The response rate to ICHT was 88% (10% complete, 78% partial response). At a median follow-up period of 25 months the larynx preservation rate was 84%. The 2-year local-regional control rate was 91% and the 2-year overall survival rate was 72.3%. The 3-year estimate to survive with functional larynx is 60%. CONCLUSION: In a large portion of patients eligible for TL or TLPP the larynx was preserved by paclitaxel/cisplatin ICHT and 3D RT.