title: [Phase I/II clinical trial of weekly administration of docetaxel plus cisplatin for advanced non-small cell lung cancer].
abstract: OBJECTIVE
  The purpose of this phase I/II study is to investigate the safety/toxicity profile of weekly administration of docetaxel in combination with cisplatin for the chemo-naive patients with advanced non-small cell lung cancer (NSCLC), and to evaluate the efficacy of this regime.
  
  
  METHODS
  In phase I trial, 15 patients were included. IV infusion of escalating doses of docetaxel consisting of four levels from 25 to 40 mg/m2 (25, 30, 35, 40 mg/m2) on D1, 8, 15 and cisplatin of 75 mg/m2 on D1 was administered. The regime was repeated every 4 weeks. Blood samples were obtained on D1, 15 in the first cycle to measure the PK. Dose limiting toxicity (DLT) was determined in cycle 1 and defined as any grade 3 non-hematologic toxicity which could not be reverted into grade less than grade 2 within 4 days or any grade 4 hematologic toxicity. Eighty-three patients completed their phase II study with administration of docetaxel at a dose of 35 mg/m2 based on the data of phase I trial.
  
  
  RESULTS
  In the phase I trial, grade 3/4 neutropenia was mainly observed in patients who received docetaxel of 40 mg/m2 (level 4) with one patient suffering from an infection signifying dose limiting toxicity (DLT). Non-hematological toxicities including nausea/vomiting, alopecia, fluid retension and asthenia were tolerable. Based on these data, the maximum tolerence dose (MTD) did not reach the level of weekly giving docetaxel at a dose of 40 mg/m2 in combination with cisplatin 75 mg/m2 every 4 weeks. The pharmacokinetic/dynamics results There was no statistically significant difference between clearance value among the 4 dose levels of docetaxel from 25 to 40 mg/m2 when measured by Cmax and AUC. The pharmacokinetics of docetaxel was not influenced by the presence of co-administration of cisplatin when compared D1 with D15 as based on CmaxN, AUCN and CL. In the phase II trial, totally 83 patients received 216 cycles of chemotherapy. One CR (complete response) and 22 PR (partial response) were achieved with an objective response rate of 27.7% in this series and 30.7% in the evaluable patients. The 1-year survival was 48.6% with a median survival of 10.7 months (range: 3-34 months). Hematologic toxicities were the major side effects, though most were mild; grade III/IV neutropenia developed in 15%. The common non-hematologic toxicities were nausea, vomiting and asthenia.
  
  
  CONCLUSIONS
  Weekly consecutive administration of docetaxel on D1, 8, 15 for 3 weeks plus cisplatin on D1 is tolerable and effective with minimal myelosuppression in chemo-naive patients with advanced NSCLC.
authors.affiliation: Department of Medical Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences and Peaking Union Medical College; Beijing 100021, China.
authors.forename: Jun-ling
authors.initials: JL
authors.lastname: Li
authors.forename: Xiang-ru
authors.initials: XR
authors.lastname: Zhang
authors.forename: Ji-wei
authors.initials: JW
authors.lastname: Liu
authors.forename: Zhong-yuan
authors.initials: ZY
authors.lastname: Chen
authors.forename: Ying-cheng
authors.initials: YC
authors.lastname: Lin
authors.forename: Yuan-dong
authors.initials: YD
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.forename: Ke-jun
authors.initials: KJ
authors.lastname: Nan
authors.forename: Shu-ping
authors.initials: SP
authors.lastname: Song
authors.forename: Fu-cai
authors.initials: FC
authors.lastname: Han
authors.forename: Yun-zhong
authors.initials: YZ
authors.lastname: Zhu
authors.forename: Long-yun
authors.initials: LY
authors.lastname: Li
authors.forename: Yu-hong
authors.initials: YH
authors.lastname: Zheng
authors.forename: Da-Tong
authors.initials: DT
authors.lastname: Chu
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D012074:Remission Induction; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D014839:Vomiting / Q000139:chemically induced
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D002945:Cisplatin