title: Phase I study of pemetrexed, cisplatin, and concurrent radiotherapy in patients with locally advanced non-small cell lung cancer.
abstract: OBJECTIVE
  Concurrent chemoradiotherapy in well-selected locally advanced non-small cell lung cancer (LANSCLC) is considered as standard therapy. However, the choice of anticancer agents is still unresolved. Our objectives were to determine the maximum tolerated dose and recommended dose of pemetrexed in combination with cisplatin, with concurrent late course accelerated hyperfractionated (LCAF) intensity modulated radiotherapy (IMRT) in patients with LANSCLC and to investigate the safety and efficacy.
  
  
  METHODS
  The chemotherapy was cisplatin (25 mg/m(2) × 3 days) plus pemetrexed with doses escalating from 400 to 500 mg/m(2). The dose level was increased every 3 patients. The gross tumor volumes of concurrent LCAF IMRT were delineated according to [(18)F] fluorodeoxyglucose positron emission tomography computed tomography imaging. To spare functional lung, single photon emission photography lung perfusion imaging was used to optimize the plans. The total radiation dose was limited such that the V20 of bilateral lung is no more than 35%.
  
  
  RESULTS
  Nine patients with LANSCLC were enrolled in this study. The median radiation dose was 70.8 Gy. The response rate was 66.7% with a complete remission rate of 33.3%. Toxicity was mild with only 1 patient experiencing dose limiting toxicity in 500 mg/m(2) level. Obviously, the maximum tolerated dose was not reached as per the definition. As the systemically active chemotherapy dose was reached, further dose escalation was discontinued, and the recommended dose of pemetrexed for a phase II study was 500 mg/m(2).
  
  
  CONCLUSIONS
  The combination of pemetrexed and cisplatin with concurrent LCAF IMRT optimized based on single photon emission photography lung perfusion imaging is well tolerated in patients with LANSCLC. Full therapeutic doses of the chemotherapy can be safely administered. The initial results showed signs of efficacy.
authors.affiliation: Sixth Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, PR China.
authors.forename: Bao-Sheng
authors.initials: BS
authors.lastname: Li
authors.forename: He-Yi
authors.initials: HY
authors.lastname: Gong
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Yi
authors.forename: Jin-Mimg
authors.initials: JM
authors.lastname: Yu
authors.forename: Zhong-Tang
authors.initials: ZT
authors.lastname: Wang
authors.forename: Zi-Cheng
authors.initials: ZC
authors.lastname: Zhang
authors.forename: Hong-Fu
authors.initials: HF
authors.lastname: Sun
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Li
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D009367:Neoplasm Staging; D000068437:Pemetrexed; D049268:Positron-Emission Tomography; D050397:Radiotherapy, Intensity-Modulated; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D002945:Cisplatin