title: Quality of life in phase II trials: a study of methodology and predictive value in patients with advanced breast cancer treated with paclitaxel plus granulocyte colony-stimulating factor.
abstract: BACKGROUND
  Despite the clinical benefit that may be associated with reduction of tumor volume, chemotherapy may produce physical or psychological distress that could compromise a patient's quality of life. Although palliation may be as relevant as tumor response in patients with metastatic breast cancer, quality of life is not commonly evaluated in phase II clinical trials of new therapeutic agents.
  
  
  OBJECTIVE
  We evaluated the utility of quality-of-life assessment in two phase II clinical trials of patients receiving paclitaxel (Taxol) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) as salvage therapy for metastatic breast cancer.
  
  
  METHODS
  A battery of instruments (i.e., Memorial Symptom Assessment Scale [MSAS], Functional Living Index-Cancer [FLIC], Rand Mental Health Inventory [MHI], Brief Pain Inventory [BPI], and Memorial Pain Assessment Card [MPAC]) designed to capture information about social, psychological, and functional aspects of quality of life, as well as symptom prevalence and distress, was completed prior to treatment; serial assessments were obtained at regular intervals during the treatment period. Univariate and multivariate analyses were performed evaluating base-line quality-of-life parameters and standard prognostic factors in relation to outcome measures of survival, tumor response, and toxicity. For 30 consecutive patients with extensive prior chemotherapy for metastatic disease, longitudinal data were analyzed associating tumor response to changes in quality-of-life scores throughout the course of treatment with paclitaxel.
  
  
  RESULTS
  Base-line scores of two validated quality-of-life instruments, the MSAS and the FLIC, independently predicted the overall survival (P < .01 for each). In this model, however, neither standard prognostic factors nor quality of life instruments predicted the likelihood of tumor response or the probability of encountering grade 3 or grade 4 nonhematologic toxicity. With serial assessments of quality of life, the majority of patients who achieved partial tumor response or stable disease reported improved or unchanged quality-of-life scores, while those patients with progressive disease experienced rapid deterioration in quality of life.
  
  
  CONCLUSIONS
  Base-line quality-of-life assessment may provide prognostic information distinct from that obtained through standard prognostic indicators alone. The combination of two factors--extent of disease and a base-line quality-of-life assessment--predicted survival more accurately than either used separately. Evaluation of quality-of-life outcomes in relation to tumor response may illuminate previously unmeasured palliative effects of chemotherapy, such as pain relief, as well as the burdens it imposes.
  
  
  CONCLUSIONS
  Information obtained from quality-of-life assessment in conjunction with phase II testing of new chemotherapeutic agents for metastatic breast cancer can guide quality-of-life evaluation planned in large, randomized future studies.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Seidman
authors.forename: R
authors.initials: R
authors.lastname: Portenoy
authors.forename: T J
authors.initials: TJ
authors.lastname: Yao
authors.forename: J
authors.initials: J
authors.lastname: Lepore
authors.forename: E K
authors.initials: EK
authors.lastname: Mont
authors.forename: J
authors.initials: J
authors.lastname: Kortmansky
authors.forename: N
authors.initials: N
authors.lastname: Onetto
authors.forename: L
authors.initials: L
authors.lastname: Ren
authors.forename: J
authors.initials: J
authors.lastname: Grechko
authors.forename: M
authors.initials: M
authors.lastname: Beltangady
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy / Q000523:psychology*; D017322:Clinical Trials, Phase II as Topic; D005240:Feasibility Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000009:adverse effects*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011788:Quality of Life; D011795:Surveys and Questionnaires; D016019:Survival Analysis
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D017239:Paclitaxel