title: Long-term results of induction chemotherapy followed by concurrent chemotherapy and thoracic irradiation in limited small cell lung cancer.
abstract: BACKGROUND
  Small cell lung cancer (SCLC) is a chemoresponsive tumor but overall survival remains poor even in limited disease (LD). With the aim of eradicating chemoresistant tumor cells and reducing toxicity, we investigated in this phase II trial the feasibility and outcome of a sequential approach of induction chemotherapy (CT) followed, in responding patients with LD-SCLC, by intensified platinum-based CT and concurrent thoracic irradiation (TI).
  
  
  METHODS
  We treated 55 consecutive LD-SCLC patients with three 21-day cycles of cyclophosphamide, epiadriamycin and vincristine (CEV) as induction CT. In 44 (80%) patients there was an objective response and they received treatment intensification consisting of TI and concomitant CT with carboplatin and etoposide plus recombinant granulocite colony stimulating factor. Twenty-five (57%) patients were submitted to twice-daily thoracic irradiation (TDTI; 1.5 Gy per fraction, to a total dose of 45 Gy) and 19 (43%) to once-daily thoracic irradiation (ODTI; 2 Gy per fraction, to a total dose of 50 Gy).
  
  
  RESULTS
  Median follow up was 75 months (range, 42-102). Of 44 patients submitted to intensification with TI plus CT, 32 (73%) had a complete and 12 (27%) a partial response. Median overall survival of all 55 patients was 17 months with actuarial survival probabilities of 2 and 5 years, 32 and 25%, respectively. Analysis of patient sub-groups showed a 5-month median survival in non-responders, 19 in TDTI and 17 in ODTI patients, respectively. Two and 5 year survival probabilities were 0% in non-responders, 40 and 35% in TDTI and 39 and 21% in ODTI patients, respectively. At present, 13 of 44 responders are still alive, of which nine (20%) have been progression-free from 45 to 93 months (median 60). Treatment failure was registered in 31 (70%) of 44 patients who received both induction and intensification treatment. One-half of patients had intrathoracic recurrence, eight of which only local and the remaining seven local and distant. Fourteen (32%) patients had brain metastases. Grade 3-4 neutropenia occurred in 24 (55%) patients with no differences between treatment groups. Grade 3 esophagitis was registered in four (9%) patients: in 3/25 (12%) and 1/19 (5%) of those who received TDTI and ODTI, respectively (P=not significant). Acute radiation pneumonitis occurred in three (12%) patients submitted to TDTI. No clinically debilitating pulmonary fibrosis, permanent esophageal stricture or toxic death was observed.
  
  
  CONCLUSIONS
  In LD-SCLC patients late concurrent CT plus TI is feasible and effective. Our long-term results are similar to the best reported in the literature. Despite the high incidence of complete response obtained, however, one-half of the patients had intrathoracic relapse and one-third brain metastases.
authors.affiliation: Radiation Oncology Center, Policlinico-Hospital, Via S. Sonnino, No. 47, Loc. S. ta Lucia, 06125, Perugia, Italy. ernesto.maranzano@libero.it
authors.forename: Ernesto
authors.initials: E
authors.lastname: Maranzano
authors.forename: Lucio
authors.initials: L
authors.lastname: Crinò
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Piro
authors.forename: Luisa
authors.initials: L
authors.lastname: Meacci
authors.forename: Sergio
authors.initials: S
authors.lastname: Bracarda
authors.forename: Verena
authors.initials: V
authors.lastname: de Angelis
authors.forename: Samir
authors.initials: S
authors.lastname: Darwish
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Minotti
authors.forename: Bianca Moira
authors.initials: BM
authors.lastname: Panizza
authors.forename: Filippo
authors.initials: F
authors.lastname: de Marinis
authors.forename: Paolo
authors.initials: P
authors.lastname: Latini
authors.forename: Maurizio
authors.initials: M
authors.lastname: Tonato
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D004941:Esophagitis / Q000139:chemically induced; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D013534:Survival; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D015251:Epirubicin; D014750:Vincristine; D003520:Cyclophosphamide