title: Quality versus quantity of life in the treatment of patients with advanced small-cell lung cancer? A randomized phase III comparison of weekly carboplatin and teniposide versus cisplatin, adriamycin, etoposide alternating with cyclophosphamide, methotrexate, vincristine and lomustine. Swiss Group for Clinical Cancer Research (SAKK).
abstract: BACKGROUND
  Based on a promising pilot study with weekly carboplatin and teniposide (CBDCA/VM) the Swiss Group for Clinical Cancer Research (SAKK) performed a randomised phase III trial in patients with extensive-disease small-cell lung cancer aimed at the development of an effective palliative treatment with low subjective toxicity.
  
  
  METHODS
  From September 1989 to September 1991 patients were randomised to a weekly regimen of CBDCA/VM or to our 'standard chemotherapy' of cisplatin, adriamycin and etoposide alternating with cyclophosphamide, methotrexate, vincristine and lomustine (PAV-CyMOC).
  
  
  RESULTS
  The trial was closed before the planned accrual of 140 evaluable patients due to a significant survival difference shown by an interim analysis. Of the 61 patients 59 were eligible and included in the final analysis. The results achieved with the PAV-CyMOC regimen were significantly better than those observed in patients treated with weekly CBDCA/VM (remission rate of 65% vs. 29%; p = 0.006). The median survival of patients treated with the PAV-CyMOC combination was significantly longer than that of patients receiving weekly CBDCA/VM (260 days vs. 147 days; p = 0.0035). The 1-year survival rate was 30% in the PAV-CyMOC arm compared to 4% in the CBDCA/VM-treated patients. As expected, side effects including myelosuppression, alopecia and mucositis were significantly more pronounced in patients treated with the PAV-CyMOC regimen. No significant difference was found in patient-rated tumor symptoms and general quality-of-life categories.
  
  
  CONCLUSIONS
  Contrary to our initial expectation that we would achieve similar therapeutic results with less subjective toxicity, in this randomised prospective trial the results achieved by weekly carboplatin and teniposide were significantly inferior in terms of remission rate and survival to those of our 'standard regimen' of cisplatin, adriamycin and etoposide alternating with cyclophosphamide, methotrexate, vincristine and lomustine. The weekly regimen was less toxic than the standard chemotherapy. Whether patients are willing to accept a significant trade-off between quantity and quality of life remains to be evaluated.
authors.affiliation: Department of Medicine, Kantonsspital, Luzern, Switzerland.
authors.forename: R A
authors.initials: RA
authors.lastname: Joss
authors.forename: P
authors.initials: P
authors.lastname: Alberto
authors.forename: C
authors.initials: C
authors.lastname: Hürny
authors.forename: M
authors.initials: M
authors.lastname: Bacchi
authors.forename: S
authors.initials: S
authors.lastname: Leyvraz
authors.forename: B
authors.initials: B
authors.lastname: Thürlimann
authors.forename: T
authors.initials: T
authors.lastname: Cerny
authors.forename: G
authors.initials: G
authors.lastname: Martinelli
authors.forename: R
authors.initials: R
authors.lastname: Stahel
authors.forename: C
authors.initials: C
authors.lastname: Ludwig
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000009:adverse effects; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage / Q000009:adverse effects; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D010166:Palliative Care; D011446:Prospective Studies; D011788:Quality of Life; D011795:Surveys and Questionnaires; D015996:Survival Rate; D013713:Teniposide / Q000009:adverse effects; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D014750:Vincristine; D005047:Etoposide; D008130:Lomustine; D004317:Doxorubicin; D003520:Cyclophosphamide; D013713:Teniposide; D016190:Carboplatin; D002945:Cisplatin; D008727:Methotrexate