title: Six-week induction chemotherapy followed by concomitant chemoradiation therapy in stage IV head and neck cancer: a phase II study with organ-sparing purposes.
abstract: The purpose of the study was to assess response rate, clinical outcome, organ/function preservation and toxicity in head and neck cancer patients treated with induction chemotherapy followed by concomitant chemoradiotherapy and, when necessary, limited surgery. The study was a phase II non-randomized trial. Induction chemotherapy consisted of 6 weekly doses of carboplatin at AUC of 2 and docetaxel 30 mg/m(2) (1 h) followed by 5 cycles of docetaxel 25 mg/m(2)/day 1, 5-FU 600 mg/m(2) c.i. days 1-5, hydroxyurea 500 mg orally every 12 h for 11 and concomitant twice daily radiation therapy at 150 cGy/fraction given every other week per 5 cycles (TFHX), for a total radiation dose of 75 Gy. 13 cis-retinoic acid was administered for chemoprevention and systematic prophylaxis of mucositis with systemic amifostine and local GM-CSF was administered to all patients during TFHX. Conservative surgical resection was reserved to patients with no optimal response (PR > or =70%), whereas radical surgery was performed as salvage treatment. Thirteen patients (mean age 54.9 years, range 44-62; 12/13 site oropharynx, all stage IV) were enrolled: 31% of patients had ECOG performance status (PS) 0 and 69% had PS 1. Response to induction chemotherapy was analyzed in 12 patients: 2/12 (16.7%) achieved a partial response (PR) for an overall response (ORR) of 16.7%, 10/12 (83.3%) achieved stable disease (SD). TFHX was administered to 7 patients: 2 patients (28.6%) had complete remission (CR), 1 patient (14.3%) had PR for an ORR of 42.9%, 3 patients (42.8%) had SD and 1 patient (14.3%) had PD. At the completion of TFHX, 1 patient underwent local therapy. The toxicity was mild and consisted in: grade 3/4 neutropenia (7.7%), anemia (23.1%), diarrhea (15.4%), mucositis (7.7%), neurotoxicity (7.7%) during induction chemotherapy. During TFHX only 42.8% of grade 3/4 mucositis was observed. All patients spared organ/function. In conclusion, this regimen has been found feasible for its acceptable toxicity, particularly mucositis. However, the overall response rate and the data on survival were not satisfactory.
authors.affiliation: Cattedra e Divisione di Oncologia Medica, Policlinico Universitario di Cagliari, Presidio di Monserrato, Strada Statale 554, bivio Sestu, 09042 Monserrato, Cagliari, Italy. mantovan@pacs.unica.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Mantovani
authors.forename: Elena
authors.initials: E
authors.lastname: Massa
authors.forename: Giorgio
authors.initials: G
authors.lastname: Astara
authors.forename: Viviana
authors.initials: V
authors.lastname: Murgia
authors.forename: Giulia
authors.initials: G
authors.lastname: Gramignano
authors.forename: Luca
authors.initials: L
authors.lastname: Ferreli
authors.forename: Paolo
authors.initials: P
authors.lastname: Camboni
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Lusso
authors.forename: Miria
authors.initials: M
authors.lastname: Mocci
authors.forename: Clelia
authors.initials: C
authors.lastname: Madeddu
authors.forename: Loredana
authors.initials: L
authors.lastname: Mura
authors.forename: Maria Caterina
authors.initials: MC
authors.lastname: Mudu
authors.forename: Ernesto
authors.initials: E
authors.lastname: Proto
authors.forename: Giorgio
authors.initials: G
authors.lastname: Tore
authors.forename: Manfredi
authors.initials: M
authors.lastname: Mura
authors.forename: Antonio
authors.initials: A
authors.lastname: Macciò
authors.forename: Antonello
authors.initials: A
authors.lastname: Ferreli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Amichetti
mesh_terms: D000328:Adult; D004999:Amifostine / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D003131:Combined Modality Therapy; D016207:Cytokines / Q000097:blood; D000077143:Docetaxel; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016879:Salvage Therapy; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage
chemical_list: D016207:Cytokines; D020738:Leptin; D043823:Taxoids; D000077143:Docetaxel; D014212:Tretinoin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016190:Carboplatin; D004999:Amifostine; D006918:Hydroxyurea