title: A phase II tolerability study of cisplatin plus docetaxel as adjuvant chemotherapy for resected non-small cell lung cancer.
abstract: BACKGROUND
  We undertook this phase II study to measure postoperative drug delivery and toxicity of cisplatin plus docetaxel in patients with resected stage I-III non-small cell lung cancer.
  
  
  METHODS
  The primary endpoint was amount of cisplatin delivered over a planned four cycles of adjuvant chemotherapy. Statistical design required a cohort to close if the regimen proved unlikely to improve cisplatin delivery compared with published phase III data. The first cohort was treated with docetaxel 35 mg/m2 intravenously (IV) on days 1, 8, and 15, and cisplatin 80 mg/m2 IV on day 15, every 4 weeks for four planned cycles. A second cohort was treated with docetaxel 75 mg/m2 IV plus cisplatin 80 mg/m2 IV on day 1 every 3 weeks for four planned cycles.
  
  
  RESULTS
  Sixteen patients were treated with weekly docetaxel and cisplatin every 4 weeks, with five of 16 (31%) unable to complete three cycles. Subsequently, 11 patients were treated with docetaxel and cisplatin every 3 weeks, with six of 11 (55%) unable to complete three cycles. Among the 11 patients who failed to complete three cycles, the reasons for stopping included one or more of the following: fatigue (n = 8), nausea (n = 4), febrile neutropenia (n = 1), hypotension (n = 1), and nephrotoxicity (n = 1).
  
  
  CONCLUSIONS
  The combination of cisplatin at 80 mg/m2 with docetaxel 35 mg/m2 weekly or 75 mg/m2 every 3 weeks is no better tolerated than older chemotherapy regimens. The most common reason to stop chemotherapy was intolerable fatigue. These results suggest that the most common dose-limiting toxicities are attributable to the cisplatin, given similar problems were encountered whether the docetaxel was delivered as a single dose every 3 weeks or as a lower weekly dose.
authors.affiliation: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, New York, New York 10021, USA. azzolic@mskcc.org
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Azzoli
authors.forename: Lee M
authors.initials: LM
authors.lastname: Krug
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.forename: Naiyer A
authors.initials: NA
authors.lastname: Rizvi
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Megan
authors.initials: M
authors.lastname: Dunne
authors.forename: Amy
authors.initials: A
authors.lastname: Farmer
authors.forename: Barbara
authors.initials: B
authors.lastname: Pizzo
authors.forename: Leslie
authors.initials: L
authors.lastname: Tyson
authors.forename: Teresa
authors.initials: T
authors.lastname: Seeger
authors.forename: Barbara
authors.initials: B
authors.lastname: Coleman
authors.forename: Erin
authors.initials: E
authors.lastname: Moore
authors.forename: Lauren
authors.initials: L
authors.lastname: Lastinger
authors.forename: Ennapadam
authors.initials: E
authors.lastname: Venkatraman
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rudin
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D018572:Disease-Free Survival; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D008297:Male; D008396:Maryland / Q000453:epidemiology; D008875:Middle Aged; D009518:New York / Q000453:epidemiology; D011838:Radiation-Sensitizing Agents; D012189:Retrospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D043823:Taxoids; D000077143:Docetaxel; D002945:Cisplatin