title: Lonidamine significantly increases the activity of epirubicin in patients with advanced breast cancer: results from a multicenter prospective randomized trial.
abstract: OBJECTIVE
  Some evidence in vitro and in vivo shows that lonidamine (LND) can positively modulate the activity of doxorubicin and epirubicin (EPI). On this basis, a multicenter prospective randomized trial was performed in patients with advanced breast cancer (BC) to determine if the addition of LND to EPI could increase the response rate of EPI alone.
  
  
  METHODS
  From May 1991 to May 1993, 207 patients were enrolled onto this study and randomized to receive intravenous (IV) EPI (60 mg/m2 on days 1 and 2) alone or with LND (600 mg orally daily). EPI administration was repeated every 21 days until tumor progression or for a maximum of eight cycles. LND was administered continuously until chemotherapy withdrawal.
  
  
  RESULTS
  Response rate was significantly superior for the EPI plus LND scheme compared with the single-agent EPI either considering assessable patients (60.0% v 39.8%; P < .01) or including all registered patients according to an intention-to-treat analysis (55.3% v 37.5%; P < .02). The distribution of the response rate according to the site of disease did not show any significant difference between the treatment arms, except for the patient subgroup with liver metastases in which the combination EPI plus LND resulted in a significant improvement of responses than EPI alone. Toxicity was moderate, and except for myalgia, no adjunctive side effects were observed in the EPI plus LND arm. Overall survival and time to progression were similar in both groups.
  
  
  CONCLUSIONS
  This study confirms in vivo that the administration of EPI is enhanced by the concomitant LND administration.
authors.affiliation: Oncologia Medica e Ginecologia Oncologica, Universita di Torino, Turin, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Dogliotti
authors.forename: A
authors.initials: A
authors.lastname: Berruti
authors.forename: T
authors.initials: T
authors.lastname: Buniva
authors.forename: P
authors.initials: P
authors.lastname: Zola
authors.forename: M G
authors.initials: MG
authors.lastname: Baù
authors.forename: A
authors.initials: A
authors.lastname: Farris
authors.forename: M G
authors.initials: MG
authors.lastname: Sarobba
authors.forename: A
authors.initials: A
authors.lastname: Bottini
authors.forename: P
authors.initials: P
authors.lastname: Alquati
authors.forename: F
authors.initials: F
authors.lastname: Deltetto
authors.forename: P
authors.initials: P
authors.lastname: Gosso
authors.forename: C
authors.initials: C
authors.lastname: Monzeglio
authors.forename: G
authors.initials: G
authors.lastname: Moro
authors.forename: M
authors.initials: M
authors.lastname: Sussio
authors.forename: D
authors.initials: D
authors.lastname: Perroni
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004357:Drug Synergism; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007191:Indazoles / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D007191:Indazoles; D015251:Epirubicin; C016371:lonidamine