title: Lonidamine plus cyclophosphamide in the treatment of adanced non-small cell lung cancer in the elderly: a phase II study.
abstract: OBJECTIVE
  The aim of this Phase II trial was to verify the therapeutic activity and tolerability of chemotherapy with lonidamine (LND) plus cyclophosphamide (CTX) in advanced non-small cell lung cancer (NSCLC) in the elderly. The rationale of the combination is reported. CTX showed mild toxicity, with a 12% objective response (OR) in monochemotherapy; LND potentiated the in vitro antiproliferative activity of alkylating agents, mainly CTX, without increasing myelotoxicity, particularly important in the elderly.
  
  
  METHODS
  The schedule consisted of CTX, 600 mg/m2/i.v. on day 1 every 21 days for 6 cycles; LND, 450 mg/die/p.o. from day 1 to progression.
  
  
  RESULTS
  Between November 1990 and April 1991, 41 patients with stage III-IV NSCLC were enrolled; 35 were assessable for response. Median age was 73 years (range, 71-79 years); 13 patients (32%) presented stage III A, 20 (49%) stage III b, and 8 (19%) stage IV disease. Cardiovascular conditions and/or chronic respiratory failure contraindicated surgical treatment in stage III A patients. Of enrolled patients, 14.6% experienced PR, 48.8% SD and 14.6% dropped out of the study. Median time to progression was 4 months (range, 2-9 months) and median survival 9 months (range 3-45 months). No patient showed WHO grade IV LND-related toxicity. In 1 patient (2.5%), LND was discontinued after 5 therapy cycles due to WHO grade III myalgia; in 80% of patients, LND oral dosage was reduced to 300 mg/day due to WHO grade II myalgia, and 20% of patients completed treatment with the full dose.
  
  
  CONCLUSIONS
  CTX plus LND can be considered a well tolerated therapeutic approach in the elderly with NSCLC with good PS and good liver, renal and cardiac conditions, but 14.6% PR is a slightly better result as compared with 12% PR obtainable with CTX alone as reported in the literature, even though most patients presented with advanced disease and no specific toxic effect was observed. Therefore, a confirmatory randomized trial (CTX vs CTS plus LND) would hardly be useful.
authors.affiliation: Divisione di Pneumologia VIII, Unità Operativa CNR-ACRO, Ospedale, C. Forlanini, Roma, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Salvati
authors.forename: A
authors.initials: A
authors.lastname: Antilli
authors.forename: A R
authors.initials: AR
authors.lastname: Cruciani
authors.forename: A
authors.initials: A
authors.lastname: Lombardi
authors.forename: L
authors.initials: L
authors.lastname: Mugnaini
authors.forename: F
authors.initials: F
authors.lastname: Nunziati
authors.forename: N
authors.initials: N
authors.lastname: Perrone
authors.forename: L
authors.initials: L
authors.lastname: Portalone
authors.forename: M
authors.initials: M
authors.lastname: Signora
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007191:Indazoles / Q000008:administration & dosage / Q000009:adverse effects; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male
chemical_list: D000970:Antineoplastic Agents; D007191:Indazoles; D003520:Cyclophosphamide; C016371:lonidamine