title: Caffeine-potentiated chemotherapy for patients with high-grade soft tissue sarcoma: long-term clinical outcome.
abstract: BACKGROUND
  Caffeine, which has a DNA-repair inhibiting effect, enhances the cytocidal effects of anticancer drugs and radiation. The present study was performed to assess the efficacy of caffeine-potentiated chemotherapy for high-grade soft tissue sarcoma (STS).
  
  
  METHODS
  A non-randomised prospective clinical trial was initiated for 90 patients with non-metastatic (stages II and III) or metastatic (stage IV) STS. Following doxorubicin or ifosfamide combined with caffeine, with or without radiotherapy, 88 patients were treated surgically. A radiographic and histological response to chemotherapy was assessed. Local-recurrence free, distant-metastasis free and overall survival were analyzed by multivariate analysis.
  
  
  RESULTS
  Radiographic and histological response rates were 57.8% and 42%, respectively. The local recurrence rate was 23.7% in stages II and III and 13.6% in stage IV. Lung metastases newly developed in 21 (35.6%) patients at stages II and III. With a median follow-up period of 52 months, the overall 5-year cumulative survival rate at stages II and III was 80.7%. Local recurrence-free survival for the histological responders and distant metastasis-free survival for the radiographic responders at stages II and III were significantly improved compared to the non-responders (p=0.004 and p=0.034). Overall survival for the radiographic responders at all stages was significant longer than for the non-responders (p=0.009).
  
  
  CONCLUSIONS
  Caffeine-potentiated chemotherapy resulted in a favourable radiographic response and prolonged overall survival of the patients at all stages.
authors.affiliation: Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Kensuke
authors.initials: K
authors.lastname: Yamauchi
authors.forename: Masami
authors.initials: M
authors.lastname: Kawahara
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Katsuro
authors.initials: K
authors.lastname: Tomita
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002110:Caffeine / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D018572:Disease-Free Survival; D004357:Drug Synergism; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011300:Preoperative Care; D012509:Sarcoma / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D002110:Caffeine