Dose-finding Study of Docetaxel Added to Ifosfamide and Cisplatin Followed by Concomitant Capecitabine and Radiotherapy in the Treatment of Locally Advanced Squamous Cell Carcinoma of the Head and Neck

• Published in: Anticancer research Vol. 26; no. 3B; pp. 2317 - 2324
• Main Authors: RECCHIA, Francesco, SAGGIO, Gaetano, CESTA, Alisia, AMICONI, Giovanna, DI BLASIO, Anna, CANDELORO, Giampiero, VALERIANI, Maurizio, TOMBOLINI, Vincenzo, REA, Silvio
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01-05-2006
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Capecitabine; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - radiotherapy; Cisplatin - administration & dosage; Combined Modality Therapy - adverse effects; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Dose-Response Relationship, Drug; Feasibility Studies; Female; Fluorouracil - analogs & derivatives; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - radiotherapy; Humans; Ifosfamide - administration & dosage; Male; Medical sciences; Middle Aged; Neoplasm Staging; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Radiotherapy - adverse effects; Survival Rate; Taxoids - administration & dosage; Tumors; Antineoplastic agent; Capecitabine; Cancerology; Taxane derivatives; ENT disease; Advanced stage; Head and neck carcinoma; Antimitotic; Pyrimidine nucleoside; Dose; Advanced head and neck cancer; Platinum II Complexes; Squamous cell carcinoma; Ifosfamide; Fluoropyrimidine derivatives; Docetaxel; Malignant tumor; Radiotherapy; Cisplatin; Alkylating agent; Oxazaphosphinane derivatives; Treatment; Nitrogen mustard; radiation therapy; Head and neck cancer
• ISSN: 0250-7005; 1791-7530

Background: Docetaxel (DOC) is a promising new drug in the management of squamous cell carcinoma of the head and neck. The
aim of this phase I study was to determine the toxicity and maximum tolerated dose (MTD) as well as to obtain preliminary
data on the activity of DOC combined with fixed doses of ifosfamide (IFO) and cisplatin (CDDP), followed by concomitant capecitabine
(C) and radiation therapy in the organ-sparing treatment of patients with locally advanced, inoperable squamous cell carcinoma
of the head and neck (A-SCCHN). Patients and Methods: Chemotherapy and radiotherapy-naïve patients with A-SCCHN were treated
in cohorts of three with escalating doses of DOC administered on day 1. The doses of DOC ranged from 40 mg/m 2 up to the dose-limiting toxicity (DTL). Fixed doses of IFO (1200 mg/m 2 ) with mesna and CDDP (20 mg/m 2 ) were administered on days 1 to 4, every 4 weeks. Patients who had achieved a response received definitive radiation therapy
(6000 cGy) concomitantly with C (1000 mg/m 2 /day). Results: Twenty-four patients were entered into the study. The MTD of DOC was 70 mg/m 2 . A total of 99 courses of chemotherapy were given. Grade 3 and 4 hematological toxicities were observed in twelve and nine
patients, respectively, while grade 3 gastrointestinal toxicity occurred in four patients. Concomitant C and radiation therapy
demonstrated a tolerable toxicity profile. An overall response rate of 83.3% (95% CI: 65.6% to 95.2%) was obtained, with a
median time to progression and overall survival of 15.6 and 22.3 months, respectively. Conclusion: Out-patient administration
of DOC, IFO and CDDP for A-SCCHN was safe and did not affect the ability to administer chemo-radiotherapy on schedule. Myelosuppression
was the DLT.