title: Extended survival observed in adoptive activated T lymphocyte immunotherapy for advanced lung cancer: results of a multicenter historical cohort study.
abstract: OBJECTIVE
  To clarify the long-term effect of immunotherapy, the effect of adoptive activated T lymphocyte immunotherapy on advanced lung cancer was evaluated in terms of survival time. In addition, the performance status of cancer patients under immunotherapy was examined.
  
  
  METHODS
  Over 5 × 10(9) alpha-beta T lymphocytes cultured ex vivo with an immobilized anti-CD3 antibody and interleukin-2 were injected intravenously into patients, once every 2 weeks for 3 months or longer. Follow-up of these patients was carried out using clinical records and by telephone interview questionnaire. Patients undergoing immunotherapy in immunotherapy clinics and those undergoing other anticancer therapies without immunotherapy in seven hospitals in Tokyo were enrolled in this study. Data were analyzed by a third-party statistician. Performance status was studied on another series of various cancer patients who underwent immunotherapy.
  
  
  RESULTS
  The overall median survival time of the patients with the best supportive care, which was obtained using Kaplan-Meier's model, was 5.6 months, and those with immunotherapy alone, chemotherapy alone, and immuno-chemotherapy were 12.5, 15.7, and 20.8 months, respectively. Using Cox' proportional hazard model, we examined the possible factors on survival time by univariate analysis. Then, the patients were stratified by gender and histological type for multivariate analysis. Significantly low hazard ratios were observed for immunotherapy and radiotherapy in males with squamous cancer; for chemotherapy and radiotherapy in male with adenocarcinoma; and for immunotherapy in females with adenocarcinoma. Addition of immunotherapy to chemotherapy resulted in a statistically significant decrease in hazard ratio in females with adenocarcinoma. Studies on the performance status (PS), determined according to the European Cooperative Oncology Group criteria, revealed a continuous high level of PS under immunotherapy until around 2 months before death, in contrast to the gradual increase of tumor marker level.
  
  
  CONCLUSIONS
  The effectiveness of immunotherapy on advanced lung cancer is limited but may extend life span under certain conditions. Immunotherapy itself provided no clinical benefit by itself as compared with chemotherapy, but a significant additive effect of immunotherapy on chemotherapy was observed in females with adenocarcinoma. Moreover, immunotherapy can maintain good quality of life of the patients until near the time of death.
authors.affiliation: Lung Cancer Immunotherapy Evaluation Group, Tokyo, Japan. iwai@j-immunother.com
authors.forename: Kazuro
authors.initials: K
authors.lastname: Iwai
authors.forename: Kenzo
authors.initials: K
authors.lastname: Soejima
authors.forename: Shoji
authors.initials: S
authors.lastname: Kudoh
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Umezato
authors.forename: Toru
authors.initials: T
authors.lastname: Kaneko
authors.forename: Kouji
authors.initials: K
authors.lastname: Yoshimori
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tokuda
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Akira
authors.initials: A
authors.lastname: Mizoo
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Setoguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kamigaki
authors.forename: Katsunada
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Shigenori
authors.initials: S
authors.lastname: Goto
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000276:immunology / Q000401:mortality* / Q000628:therapy*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000401:mortality* / Q000628:therapy*; D002478:Cells, Cultured; D015331:Cohort Studies; D003131:Combined Modality Therapy / Q000379:methods / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods* / Q000706:statistics & numerical data; D007376:Interleukin-2 / Q000494:pharmacology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000401:mortality* / Q000628:therapy*; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000187:drug effects / Q000637:transplantation*; D016896:Treatment Outcome
chemical_list: D057134:Antibodies, Neutralizing; D017252:CD3 Complex; C508594:IL2 protein, human; D007376:Interleukin-2