title: Induction chemotherapy with docetaxel, cisplatin, fluorouracil, and leucovorin for squamous cell carcinoma of the head and neck: a phase I/II trial.
abstract: OBJECTIVE
  A phase I/II trial of docetaxel, cisplatin, fluorouracil (5-FU), and leucovorin (TPFL5) induction chemotherapy for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).
  
  
  METHODS
  Twenty-three previously untreated patients with stage III or IV SCCHN and Eastern Cooperative Oncology Group functional status less than or equal to 2 were treated with TPFL5. Postchemotherapy home support included intravenous fluids, prophylactic antibiotics, and granulocyte colony-stimulating factor (G-CSF). Docetaxel dose was escalated to determine the maximum-tolerated dose (MTD). Fifteen patients were treated with three cycles of TPFL5 at MTD. Patients who achieved either a partial response (PR) or complete response (CR) to three cycles of TPFL5 then received definitive twice-daily radiation therapy. Toxicity and clinical and pathologic response to TPFL5 were assessed.
  
  
  RESULTS
  Twenty-three patients received a total of 69 cycles of TPFL5. The MTD was determined to be docetaxel 60 mg/m2. Dose-limiting toxicity (DLT) was neutropenia. Additional significant toxicities at MTD were nausea, mucositis, diarrhea, peripheral neuropathy, and sodium-wasting nephropathy. The overall response rate to TPFL5 was 100%, which included 14 of 23 (61%) clinical CRs and nine of 23 (39%) clinical PRs. Primary-site clinical and pathologic CR rates were 19 of 22 (86%) CRs and 20 of 22 (91%) CRs, respectively. Eight patients had less than a CR in the neck to chemotherapy and, therefore, had postradiation neck dissections, four of which were positive for residual tumor.
  
  
  CONCLUSIONS
  TPFL5 is a tolerable induction regimen in patients with good performance status. The DLT is neutropenia with significant mucositis, diarrhea, peripheral neuropathy, and sodium-wasting nephropathy. The high response rates to TPFL5 justify further evaluation of this combination of agents in the context of formal clinical trials.
authors.affiliation: Division of Biostatistics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. alexandervcolevas@dfci.harvard.edu
authors.forename: A D
authors.initials: AD
authors.lastname: Colevas
authors.forename: P M
authors.initials: PM
authors.lastname: Busse
authors.forename: C M
authors.initials: CM
authors.lastname: Norris
authors.forename: M
authors.initials: M
authors.lastname: Fried
authors.forename: R B
authors.initials: RB
authors.lastname: Tishler
authors.forename: M
authors.initials: M
authors.lastname: Poulin
authors.forename: R L
authors.initials: RL
authors.lastname: Fabian
authors.forename: T J
authors.initials: TJ
authors.lastname: Fitzgerald
authors.forename: A
authors.initials: A
authors.lastname: Dreyfuss
authors.forename: E S
authors.initials: ES
authors.lastname: Peters
authors.forename: S
authors.initials: S
authors.lastname: Adak
authors.forename: R
authors.initials: R
authors.lastname: Costello
authors.forename: J J
authors.initials: JJ
authors.lastname: Barton
authors.forename: M R
authors.initials: MR
authors.lastname: Posner
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D000077143:Docetaxel; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D043823:Taxoids
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil