title: Randomised phase II trial of 4 dose levels of single agent docetaxel in performance status (PS) 2 patients with advanced non-small cell lung cancer (NSCLC): DOC PS2 trial. Manchester lung cancer group.
abstract: BACKGROUND
  The role of chemotherapy for advanced NSCLC patients and ECOG PS2 remains controversial. We evaluated 4 doses of 3-weekly docetaxel to identify a less toxic, clinically effective dose.
  
  
  METHODS
  Seventy-three patients with stage III (22%) (unsuitable for radical surgery/radiotherapy) and IV (78%) NSCLC were randomized to receive 4 doses of 3-weekly docetaxel, for 4 cycles: arm (A) 40 mg/m(2) (n=17), arm (B) 50 mg/m(2) (n=17), arm (C) 60 mg/m(2) (n=19), arm (D) 50 mg/m(2) escalated by 10 mg/m(2) to a maximum of 70 mg/m(2) (n=19). Primary endpoints: maximum tolerated dose, RR, duration of response, symptom improvement, toxicity and QoL. Secondary endpoint: overall survival (OS). Patients and disease characteristics were well balanced. Median age was 67 (range 45-81), there were 32 male and 41 female, histology subtype: squamous/adenocarcinoma/mixed/NOS=42%/49%/4%/5%.
  
  
  RESULTS
  Seven patients did not receive any treatment because of deterioration in PS or death. 50% of patients in arm D, who received more than one cycle, received dose escalation. There was no statistical difference in the number of cycles administered (arms A, B and D: median 2 cycles and arm C: median 3 cycles) and no difference in RR: arm A=6%, arm B=6%, arm C=10%, and arm D=0%. There was no statistically significant difference in grade 3/4 neutropenia and thrombocytopenia between the four arms. No difference was observed in hospitalization rate, blood transfusions, antibiotics administration and non-haematological toxicity. QoL: no difference in total scores between baseline and cycles 1-4. There was a significant decrease in pain scores from baseline to post cycles 2 and 3 (p=0.025 and p=0.002, respectively). There was no difference in OS (p=0.992). Median survival and 6-month survival were 61, 86, 88 and 97 days and 29%, 33%, 21% and 26% for arms A, B, C, and D, respectively.
  
  
  CONCLUSIONS
  Clinical efficacy of docetaxel was observed at all dose levels. Higher dose levels were not associated with increased toxicities, use of IV antibiotics or hospitalization rates. However, the median survival observed is shorter than historical data and do not support further evaluation of these doses of single agent docetaxel in this population.
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom. raffaele.califano@christie.nhs.uk
authors.forename: Raffaele
authors.initials: R
authors.lastname: Califano
authors.forename: Richard
authors.initials: R
authors.lastname: Griffiths
authors.forename: Paul
authors.initials: P
authors.lastname: Lorigan
authors.forename: Linda
authors.initials: L
authors.lastname: Ashcroft
authors.forename: Paul
authors.initials: P
authors.lastname: Taylor
authors.forename: Paul
authors.initials: P
authors.lastname: Burt
authors.forename: Lip
authors.initials: L
authors.lastname: Lee
authors.forename: Abbas
authors.initials: A
authors.lastname: Chittalia
authors.forename: Margaret
authors.initials: M
authors.lastname: Harris
authors.forename: Corinne
authors.initials: C
authors.lastname: Faivre-Finn
authors.forename: Nick
authors.initials: N
authors.lastname: Thatcher
authors.forename: Fiona
authors.initials: F
authors.lastname: Blackhall
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D024221:Antineoplastic Protocols; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D000077143:Docetaxel; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia; D011788:Quality of Life; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D013921:Thrombocytopenia; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel