Phase II trial of dose-dense paclitaxel, cisplatin, 5-fluorouracil, and leucovorin with filgrastim support in patients with squamous cell carcinoma of the head and neck.
BACKGROUND
The current study evaluated the feasibility and clinical activity of a combination of paclitaxel, cisplatin, 5-fluorouracil (5-FU), and leucovorin administered on a biweekly schedule to patients with recurrent or unresectable squamous cell carcinoma of the head and neck (HNSCC).


METHODS
Patients with recurrent or unresectable HNSCC were eligible if they had received a previous regimen of neoadjuvant chemotherapy, concurrent chemoradiotherapy, or no previous systemic therapy. Patients received paclitaxel (175 mg/m2 on Day 1), cisplatin (35 mg/m2 on Days 1 and 2), leucovorin (200 mg/m2 on Day 1), and 5-FU (1000 mg/m2 per day as a 48-hour continuous intravenous infusion on Days 1 and 2) every 2 weeks. Patients received subcutaneous filgrastim (300 microg per day) on Days 3-9 of each cycle. Treatment was administered on an outpatient basis for a maximum of six cycles.


RESULTS
Thirty-five patients received a combined total of 194 treatment cycles. Eighteen complete responses (51%) and 12 partial responses (34%) were documented, for an overall response rate of 86% (30 of 35 patients). The median progression-free survival duration was 14 months, and the median overall survival duration was 18 months. Two toxicity-related deaths were documented (one due to neutropenic sepsis and the other due to catheter-related pulmonary embolism). Grade 4 neutropenia was observed in one patient. Other severe (Grade 3 or 4) toxic effects included mucositis (14%), anemia (6%), thrombosis (6%), thrombocytopenia (3%), and neuropathy (3%).


CONCLUSIONS
The current dose-dense, four-agent, taxane-containing biweekly schedule was feasible and effective in patients with recurrent or unresectable HNSCC. However, given the single-center nature of the current study and the highly selected study population, further validation of these findings is recommended.
Hitt
Ricardo
R
Department of Medical Oncology, University Hospital 12 de Octubre, Madrid, Spain.
Jimeno
Antonio
A
Millán
Jose María
JM
Castellano
Daniel
D
Cortés-Funes
Hernán
H
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D000069585:Filgrastim; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011994:Recombinant Proteins; D018805:Sepsis / Q000139:chemically induced; D016019:Survival Analysis; D016896:Treatment Outcome
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D017239:Paclitaxel; D000069585:Filgrastim; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil