A randomized phase II study comparing sequential versus simultaneous chemo-radiotherapy in patients with unresectable locally advanced squamous cell cancer of the head and neck

• Published in: Annals of oncology Vol. 5; no. 6; pp. 513 - 519
• Main Authors: Pinnarò, P., Cercato, M. C., Giannarelli, D., Carlini, P., Vecchio, M. R.Del, Impiombato, F. Ambesi, Marzetti, F., Milella, M., Cognetti, F.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.07.1994
• Subjects: Adult; Aged; Alopecia - chemically induced; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - radiotherapy; chemo-radiotherapy; Chi-Square Distribution; Cisplatin - administration & dosage; Cisplatin - adverse effects; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - radiotherapy; head and neck squamous cell cancer; Humans; Leukopenia - chemically induced; Male; Medical sciences; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neuropharmacology; Patient Compliance; Pharmacology. Drug treatments; Phlebitis - chemically induced; Psychodysleptics: hallucinogen; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Remission Induction; Antineoplastic agent; Human; Squamous cell carcinoma; Concurrent; Administration schedule; Malignant tumor; Radiotherapy; Neoadjuvant treatment; Chemotherapy; Randomization; Phase II trial; Head and neck; ENT disease; Pyrimidine derivatives; Advanced stage; Combined treatment; Fluorine Organic compounds; Platinum II Complexes
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/oxfordjournals.annonc.a058905

Background Single-modality radiotherapy is still considered standard treatment for patients with locally advanced unre-sectable cancer of the head and neck. As treatment outcome is poor, attempts to integrate chemotherapy into the overall management of these patients are ongoing. Patients and methods A randomized study was undertaken to compare a sequential with a simultaneous chemo-radiotherapy program. Between February 1986 and February 1991, 93 eligible patients with locally advanced unresect-able cancer of the head and neck were stratified by WHO PS, T and N class and primary site and then randomized to receive either three courses of neoadjuvant chemotherapy with cisplatin (100 mg/m2 i.v. d 1) and 5-fluorouracil 1000 mg/ m2days 1–5 by continuous i.v. infusion every 3 weeks prior to definitive conventional radiotherapy of 65–70 Gy (sequential treatment), or cisplatin 100 mg/m2 on days 1,22,43 given simultaneously for the duration of the same conventional radiotherapy (simultaneous treatment). Results At the end of the entire treatment 18 complete responses (47%) in the sequential-treatment arm and 18 (41%) in the simultaneous treatment arm were obtained. No statistically significant differences in the 5-yr progression-free survival, in the median time to loco-regional and distant progression and in the 5-yr overall survival were observed. Leukopenia was more frequent in the simultaneous than in the sequential arm (p = 0.03), whereas alopecia (p = 0.008) and phlebitis (p < 0.0001) were more frequent in the sequential-treatment arm. A better compliance was associated with the concomitant treatment, with 87% of the patients completing the entire radiotherapy program versus 63% of those in the sequential arm (p = 0.01). Conclusions In the present study, the two treatment arms showed similar activity (complete response, progression-free and overall survival rates). Compliance to treatment was better in the concomitant arm. These data suggest that concomitant chemo-radiation therapy might be considered an option in unresectable locally advanced cancer of the head and neck. Phase III studies are needed in order to establish the superiority of this combination of cisplatin and radiotherapy versus radiotherapy alone.