Phase II Organ Preservation Trial Using Cisplatin Concomitant With Radiation Therapy in Advanced Laryngeal Cancer Patients Who Have Responded to Induction Chemotherapy With Taxotere, Cisplatin, and 5-Fluorouracil (TPF)
试验速览
- 阶段
- 2 期
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Improvement in larynx preservation free survival
研究概览
简要总结
Treatment of patients with one cycle of induction chemotherapy to select for organ preservation of the larynx has been proven as a standard approach. When compared to historical controls. The investigators propose to study patients with a similar treatment strategy (i.e. one cycle of induction chemotherapy followed by two more chemotherapy cycles, in advanced nodal disease, followed by chemoradiation for those responding to the initial chemotherapy. Those who fail to respond or fail in radiation will directly undergo surgery. The novelty of the proposed study is that non responders and failures will be given the opportunity of larynx preserving supracricoid laryngectomy. The investigators will attempt to reduce toxicity from induction chemotherapy and improve potency with the use of docetaxel/cisplatin/5-fluorouracil (TPF) in place of the standard regimen of cisplatin and 5-fluorouracil (PF). Emerging data demonstrates that induction regimens containing triplets with platinum, 5-fluorouracil, and taxanes produce higher response rates and less overall toxicity when compared to induction strategies utilizing PF
详细描述
The optimal treatment of patients with laryngeal cancer remains controversial. Standard treatment options have included laryngectomy with or without radiation (RT) and radiation alone with surgical salvage (RTSS).
Because of the significant functional morbidity associated with laryngectomy, the Department of Veterans Affair Cooperative Studies Program completed a randomized, prospective study of 332 patients that compared a new organ preservation treatment strategy to conventional laryngectomy and radiation. The experimental treatment arm involved three cycles of neoadjuvant chemotherapy followed by definitive radiation among patients who had a partial (>50%) clinical tumor response. Final results of this study demonstrated comparable 2, 3, 4, and 10 year survival rates between treatment groups, with successful laryngeal preservation in 66% of the surviving patients randomized to receive neoadjuvant chemotherapy.
This study led to a dramatic re-assessment of the treatment approach for advanced laryngeal and hypopharyngeal cancer patients, who face total laryngectomy. Based on these results, Second approach was designed and tested in a Phase II study at the University of Michigan .In this study, 97 patients were treated with one cycle of induction chemotherapy. Seventy-five percent had a >50% reduction of tumor and were treated with chemo-RT (cisplatin 100 mg/m2 x 3 cycles), and 25% were non-responders who underwent total laryngectomy followed by RT. The overall 3-year survival rate was 85%,and the larynx preservation rate was 70%. This study included over 30 percentage of patients with advanced stage 4 disease, however did not specifically evaluate there outcome and therefore did not directly address the role of organ preservation in advanced disease which is considered a controversial issue in head and neck literature.
In this study all patients (25 %) who did not respond to the initial chemotherapy were referred to total laryngectomy and therefore there were 30 %of patients who eventually underwent total laryngectomy.Lately several series suggest the option of partial laryngectomy as an alternative to total laryngectomy as initial treatment for advanced larynx cancer ,in cases in which the cricoids cartilage and arytenoids are not involved.Supracricoid subtotal laryngectomy spares at least one arytenoid and offers organ preservation and can also be performed according to many articles as salvage surgery in cases of radiation failure,and therefore if performed in the right indications can improve the percentage of total laryngectomy free patients without compromising survival. This will reflect of course on quality of life It has been suggested lately that the use of aggressive induction chemotherapy may improve outcome. The combination of Taxotere with Cisplatin and 5-fluorouracil has been shown to be more effective than the standard cisplatin and 5-fluorouracil without an elevation in side effects .It has been suggested that the three cycles of induction chemotherapy may lower the rate of distant metastases which is high in advanced disease
Objectives
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have pathologically confirmed previously untreated, resectable, squamous cell carcinoma of the larynx.
- •Disease must be Stage III or IV.
- •Tumor must be potentially surgically resectable and curable with conventional surgery and radiation therapy.
- •Patients must undergo pre-treatment endoscopic tumor staging and CT scanning of chest and neck.(pet scan optional)
- •Eastern Cooperative Oncology Group (ECOG) Performance status 0-
- •Pre-treatment laboratory criteria:
- •WBC > 3500/ul, granulocyte > 1500/ul.
- •Platelet count > 100,000/ul.
- •Calculated or measured creatinine clearance > 60 cc/min.
- •AST and ALT < 2.5 X ULN
- •Patients must give documented informed consent to participate in this study.
排除标准
- •Prior head and neck malignancy or active non-head and neck malignancy. Except for cured non-melanoma skin cancer,
- •Prior head and neck radiation.
- •Documented evidence of distant metastases.
- •Active infection.
- •Pregnancy or lactation. Patients must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry, for the duration of study participation and for 3 months after discontinuing therapy.
- •Any medical or psychiatric illness which in the opinion of the principal investigator would compromise the patient's ability to tolerate this treatment.
- •Age < 18 years.
- •Patients with psychiatric/social situations that would limit compliance with study requirements are not eligible.
- •Patients with Grade > 2 peripheral neuropathy.
- •Any history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate
- •Criteria for supracricoid resection for chemo selection non responders
- •Inclusion Criteria :
- •At least one functional arytenoids (physical and radiological examinations)
- •Involvement of thyroid cartilage including extrathyroid cartilage extension.
- •Exclusion criteria:
- •Subglottic extension anteriorly.
- •Pre epiglottic extension.
- •Subglottic extension laterally.
- •Interarytenoid involvement.
- •Two Arytenoids involved.
- •Criteria for supracricoid resection for Chemoradiation failure:
- •Inclusion Criteria:
- •At least one functional arytenoid (physical and radiological examinations)
- •Involvement of thyroid cartilage (with no radiological evidence for extra thyroid Extension).
- •Exclusion Criteria:
- •Extrathyroid cartilage extension.
- •Involvement preepiglottic space.
- •Subglottic extension.
- •Interarytenoid involvement.
研究组 & 干预措施
larynx preservation
Decision between surgery and Chemo-rt according to response to initial induction chemotherapy
干预措施: laryngoscopy (Procedure)
larynx preservation
Decision between surgery and Chemo-rt according to response to initial induction chemotherapy
干预措施: Taxotere (Docetaxel), Cisplatin, 5FU (Drug)
结局指标
主要结局
Improvement in larynx preservation free survival
时间窗: 5 years
次要结局
- Improvement in overall survival in patients treated under this regimen in comparison to historical control(5 years)