Phase II study of induction chemotherapy followed by concomitant chemoradiotherapy in advanced head and neck cancer: clinical outcome, toxicity and organ/function preservation.
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 design was a phase II non-randomized trial in hospitalized patients setting. The treatment plan consisted of 3 cycles of induction chemotherapy with cisplatin, fluorouracil (5-FU), leucovorin and interferon alpha2b (PFL-IFN) followed by 7 cycles of 5-FU, hydroxyurea and concomitant radiation for 5 days (FHX) for a total radiation dose of 70 Gy. Surgical resection was performed, when necessary, with the intent to spare organ/function. Seventeen patients were treated at one institution. Three patients had stage III and 14 patients stage IV disease. Twelve patients were analyzed for response to PFL-IFN: 2/12 (16.7%) patients achieved a CR and 10/12 (83.3%) achieved a PR for an ORR of 100%. FHX was administered on protocol to 10 patients: 4 patients (40%) had CR, 3 (30%) had PR >/=70% for an ORR of 70%, 1 patient (10%) had SD and 2 patients (20%) had PD. As for local therapy, of the 8 eligible patients who completed chemoradiotherapy, the 3 patients with CR were submitted to random biopsies, results of which were histologically negative, 3 patients with PR >/=70% underwent conservative organ-preserving surgery, and 1 patient with PR >70% refused surgery, whereas the patient with SD underwent salvage surgery, preserving voice. Thus, organ preservation was achieved in all 8 patients at the completion of all therapy: 4 patients had no surgical procedure and 4 patients only conservative surgery. Overall, after completion of all therapy, 5/8 (62.5%) patients were rendered disease-free. The median overall survival time was 23 months, the median duration of response was 6 months and the median time to progression was 9 months. Both induction chemotherapy and concomitant chemoradiotherapy resulted in significant toxicity, which consisted mainly of mucositis and thrombocytopenia. In conclusion, PFL-IFN was very active, producing high ORRs and, followed by FHX, resulted in high overall survival rates permitting an optimal organ preservation, at the cost of a severe toxicity.
Mantovani
G
G
Department of Medical Oncology and Internal Medical Sciences, University of Cagliari, I-09124 Cagliari, Italy.
Maccio
A
A
Massa
E
E
Mulas
C
C
Mudu
M C
MC
Massidda
S
S
Massa
D
D
Murgia
V
V
Ferreli
L
L
Succu
G
G
Astara
G
G
Proto
E
E
Tore
G
G
Mura
M
M
Maxia
G
G
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome