title: Alternating gemcitabine and cisplatin with gemcitabine and radiation in stage IV squamous cell carcinoma of the head and neck.
abstract: BACKGROUND
  In order to improve our cisplatin-5-fluorouracil (5-FU)-based alternating chemo-radiotherapy regimen, in 1996 we started an investigational program to explore a modified alternating regimen including gemcitabine given both with radiosensitizing and cytotoxic intent.
  
  
  METHODS
  Based on our previous feasibility trial, we conducted a second study testing the feasibility and activity of the following schedule: gemcitabine 800 mg/m(2) on day 1 and cisplatin 20 mg/m(2) on days 2-5 (weeks 1, 4, 7 and 10) alternated with three courses of radiotherapy (RT) (weeks 2-3, 5-6 and 8-9) with conventional fractionation up to 60 Gy. Gemcitabine 300 mg/m(2) was also administered on the Monday of each week of RT.
  
  
  RESULTS
  Forty-seven patients with stage IV (41 patients) unresectable squamous cell carcinoma of the head and neck (SCC-HN) or who had relapsed after surgery (6 patients) were enrolled. None had previously received chemotherapy or radiotherapy. Eight patients (18%) did not complete the treatment. Main grade 3-4 toxicities were as follows: neutropenia (44%); neutropenia with fever (12%); thrombocytopenia (37%); anemia (30% grade 3). One patient died in therapy due to sepsis. Most patients needed hospitalization and tube-feeding or parenteral nutrition. However, 44% of patients had a weight loss >10%. Thirty-four patients had a complete response (72%). Three partial responders were rendered disease-free by surgery (final complete response rate, 79%). At a median follow-up of 38 months actuarial 3-year overall survival, progression-free survival and loco-regional control are 43%, 39% and 64%, respectively. Data of locoregional control favorably compare with those from our database of patients treated with alternating cisplatin-fluorouracil and radiation within controlled clinical trials (64% versus 40%).
  
  
  CONCLUSIONS
  The inclusion of gemcitabine into an alternating regimen seems to improve the results achievable with the original alternating program in stage IV patients. However, due to the high acute toxicity correlated, this intensive regimen should be managed by institutions well trained in multidisciplinary treatments.
authors.affiliation: Department of Medical Oncology A, National Institute for Cancer Research, Genoa, Italy. marco.benasso@istge.it
authors.forename: M
authors.initials: M
authors.lastname: Benasso
authors.forename: R
authors.initials: R
authors.lastname: Corvò
authors.forename: A
authors.initials: A
authors.lastname: Ponzanelli
authors.forename: G
authors.initials: G
authors.lastname: Sanguineti
authors.forename: I
authors.initials: I
authors.lastname: Ricci
authors.forename: E
authors.initials: E
authors.lastname: Pallestrini
authors.forename: A
authors.initials: A
authors.lastname: Santelli
authors.forename: V
authors.initials: V
authors.lastname: Vitale
authors.forename: R
authors.initials: R
authors.lastname: Rosso
mesh_terms: D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005334:Fever / Q000139:chemically induced; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018307:Neoplasms, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D009503:Neutropenia / Q000139:chemically induced; D016019:Survival Analysis; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine