title: Combination of nedaplatin and vindesine for treatment of relapsed or refractory non-small-cell lung cancer.
abstract: OBJECTIVE
  A phase II study of nedaplatin and vindesine was conducted to evaluate their efficacy and safety for treatment of relapsed or refractory non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Between August 1996 and September 1998, 48 patients who had previously received chemotherapy, thoracic radiotherapy, and/or surgery were enrolled in the study. Patients were required to have an Eastern Cooperative Oncology Group performance status of 0 to 2 and an age between 20 and 79 years. Treatment consisted of nedaplatin (80 mg/m2, day 1) and vindesine (3 mg/m2, days 1 and 8) every 3 to 4 weeks.
  
  
  RESULTS
  Of 48 patients, 7 (14.6%) exhibited an objective response. Four (50%) of eight chemotherapy-naive patients had a partial response. However, of the 40 patients who had received prior chemotherapy, a partial response was observed in only 3 (7.5%). At a median follow-up time of 85.1 weeks, the median survival time was 43.6 weeks (95% confidence interval 34.4-52.7) for patients who had received chemotherapy, with a survival rate of 40% at 1 year. Grade 3 or 4 neutropenia occurred in 43 of 48 patients (90%), and neutropenic fever was observed in 3 of the 43 patients, one of whom died of sepsis. Pharmacokinetic and pharmacodynamic analyses of platinum were performed in 43 patients during the first cycle of chemotherapy. Percent reduction in absolute neutrophil count was correlated not only with the area under the plasma ultrafilterable platinum concentration versus time curve (r = 0.41, P = 0.007) but also with the duration of ultrafilterable platinum concentration above 1 microg/ml (r = 0.41, P = 0.007). Patients with progressive disease exhibited a shorter duration of ultrafilterable platinum concentration over 1 microg/ml (P = 0.046) than those with other responses.
  
  
  CONCLUSIONS
  A combination of nedaplatin and vindesine was unsatisfactory as second-line chemotherapy for NSCLC, although the combination was well tolerated. The duration of ultrafilterable platinum concentration above 1 microg/ml was an important pharmacokinetic parameter for predicting both chemotherapy-induced neutropenia and treatment outcome.
authors.affiliation: Department of Internal Medicine, National Shikoku Cancer Center Hospital, Matsuyama, Japan. ntakigaw@hospital.okayama-u.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Takigawa
authors.forename: Y
authors.initials: Y
authors.lastname: Segawa
authors.forename: H
authors.initials: H
authors.lastname: Ueoka
authors.forename: K
authors.initials: K
authors.lastname: Kiura
authors.forename: M
authors.initials: M
authors.lastname: Tabata
authors.forename: T
authors.initials: T
authors.lastname: Shibayama
authors.forename: I
authors.initials: I
authors.lastname: Takata
authors.forename: H
authors.initials: H
authors.lastname: Miyamoto
authors.forename: K
authors.initials: K
authors.lastname: Eguchi
authors.forename: M
authors.initials: M
authors.lastname: Harada
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D012008:Recurrence; D016019:Survival Analysis; D014751:Vindesine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D009944:Organoplatinum Compounds; C053989:nedaplatin; D014751:Vindesine