Long-term results of full-dose gemcitabine with radiation therapy compared to 5-fluorouracil with radiation therapy for locally advanced pancreas cancer

Purpose

To retrospectively compare the efficacy and toxicity of full-dose gemcitabine based chemoradiotherapy (GemRT) versus 5-fluorouracil (5-FU) based chemoradiotherapy (5FURT) for locally advanced pancreas cancer (LAPC).

Methods

From January 1998 to December 2008, 93 patients with LAPC were treated either with 5FURT (n = 38) or GemRT (n = 55). 5FURT consisted of standard-field radiotherapy given concurrently with infusional 5-FU or capecitabine. GemRT consisted of involved-field radiotherapy given concurrently with full-dose gemcitabine (1000 mg/m² weekly) with or without erlotinib. The follow-up time was calculated from the time of diagnosis to the date of death or last contact.

Results

Patient characteristics were not significantly different between treatment groups. The overall survival (OS) was significantly better for GemRT compared to 5FURT (median 12.5 months versus 10.2 months; 51% versus 34% at 1 year; 12% versus 0% at 3 years; 7% versus 0% at 5 years, respectively; all P = 0.04). The OS benefit of GemRT was maintained on subset analysis without concurrent erlotinib or with sequential gemcitabine (all P < 0.05). The rates of distant metastasis, subsequent hospitalization, acute and late grade 3-5 gastrointestinal toxicities were not significantly different between the GemRT and 5FURT groups.

Conclusions

GemRT was associated with an improved OS compared to standard 5FURT. This approach yielded long-term survivors and was not associated with increased hospitalization or severe gastrointestinal toxicity.     

Targeted agents in non-small cell lung cancer (NSCLC): clinical developments and rationale for the combination with thoracic radiotherapy

In recent years there has been undoubted progress in the evaluation and development of targeted agents for non-small cell lung cancer (NSCLC). A major contributor has been the discovery of molecular subtypes harbouring a critical oncogenic driver mutation, specifically sensitizing mutations in the epidermal growth factor receptor (EGFR) gene and the EML4-ALK gene translocation. Radiotherapy is a cornerstone of therapy for the curative intent treatment of early stage, localized disease; and for the palliation of symptoms in advanced, metastatic disease. In this molecular targeted era there is limited understanding of how best to combine targeted agents with radiotherapy and in general clinical studies with radiotherapy have lagged behind studies of targeted agents with chemotherapy. Here we summarise the progress made to date and highlight future directions.     

Radiotherapy technical considerations in the management of locally advanced pancreatic cancer: American-French consensus recommendations

Pancreatic carcinoma is a leading cause of cancer-related mortality. Approximately 30% of pancreatic cancer patients present with locally advanced, unresectable nonmetastatic disease. For these patients, two therapeutic options exist: systemic chemotherapy or chemoradiotherapy. Within this context, the optimal technique for pancreatic irradiation is not clearly defined. A search to identify relevant studies was undertaken using the Medline database. All Phase III randomized trials evaluating the modalities of radiotherapy in locally advanced pancreatic cancer were included, as were some noncontrolled Phase II and retrospective studies. An expert panel convened with members of the Radiation Therapy Oncology Group and GERCOR cooperative groups to review identified studies and prepare the guidelines. Each member of the working group independently evaluated five endpoints: total dose, target volume definition, radiotherapy planning technique, dose constraints to organs at risk, and quality assurance. Based on this analysis of the literature, we recommend either three-dimensional conformal radiation therapy or intensity-modulated radiation therapy to a total dose of 50 to 54 Gy at 1.8 to 2 Gy per fraction. We propose gross tumor volume identification to be followed by an expansion of 1.5 to 2 cm anteriorly, posteriorly, and laterally, and 2 to 3 cm craniocaudally to generate the planning target volume. The craniocaudal margins can be reduced with the use of respiratory gating. Organs at risk are liver, kidneys, spinal cord, stomach, and small bowel. Stereotactic body radiation therapy should not be used for pancreatic cancer outside of clinical trials. Radiotherapy quality assurance is mandatory in clinical trials. These consensus recommendations are proposed for use in the development of future trials testing new chemotherapy combinations with radiotherapy. Not all of these recommendations will be appropriate for trials testing radiotherapy dose or dose intensity concepts.     

奈达铂联合紫杉醇与顺铂联合紫杉醇同步放化疗对Ⅲ期非小细胞肺癌的疗效对照研究

目的探讨奈达铂替代顺铂与紫杉醇联合同步放化疗,对不能手术的ⅢA期和ⅢB期非小细胞肺癌患者的疗效及耐受性。方法实验组(TN组)30例:采用紫杉醇50 mg/m2(ivgtt,d1)+奈达铂30 mg/m2(ivgtt,d1)化疗,每周1次,同期行胸部放疗(63 Gy/7周/34次)。对照组(TP组)30例:顺铂(30 mg/m2,ivttt,d1)代替奈达铂,余治疗同实验组。结果同步化放疗后评价疗效:实验组和对照组有效率分别为85.7%和80.0%[χ2=0.02(校正),P>0.05],两组比较差异无统计学意义。实验组和对照组白细胞减少发生率分别为57.1%(16/28)和55.0%(11/20)(P>0.05),两组比较差异无统计学意义;贫血发生率分别为28.6%(8/28)和30.0%(6/20)(P>0.05),两组比较差异无统计学意义;血小板下降发生率分别为39.3%(11/28)和20.0%(4/20)(P>0.05),两组比较差异无统计学意义;肝功能损害,放射性肺炎和放射性食管炎发生率实验组和对照组比较差异均无统计学意义;肾功能损害发生率及恶心、呕吐发生率实验组明显低于对照组,差异有统计学意义;体重下降(>10%)发生率实验组明显低于对照组,差异有统计学意义。结论奈达铂联合紫杉醇同步放疗对III期非小细胞肺癌的疗效确切,且患者耐受性良好。