title: A phase I report of paclitaxel dose escalation combined with a fixed dose of carboplatin in the treatment of head and neck carcinoma.
abstract: BACKGROUND
  Standard therapy for advanced head and neck carcinoma is surgery and radiation, and the subsequent 5-year survival with this treatment has been less than 50%. New combined modality treatment strategies are being tested to improve survival. New chemotherapy combinations are being developed and administered simultaneously with, or sequenced with, radiation and surgery. This article reports the Phase I results of administering paclitaxel and carboplatin preoperatively. The authors' objective was to develop an outpatient chemotherapy that would downstage tumors and allow organ preservation with equal or improved survival as compared with standard therapy.
  
  
  METHODS
  Thirty-six patients with untreated Stage III/IV head and neck carcinoma were treated and were evaluable for toxicity. All patients had lesions that were measurable in perpendicular planes. A nonrandomized, Phase I design was used, according to which cohorts of patients were treated every 21 days with escalating doses of paclitaxel (150-265 mg/m2) given as a 3-hour infusion immediately preceding carboplatin. Premedication was used to avoid acute hypersensitivity reactions. Carboplatin was administered intravenously over 1 hour at a constant dose calculated with the Calvert formula (area under the curve, 7.5).
  
  
  RESULTS
  The dose-limiting toxicities were neuropathy and thrombocytopenia at a paclitaxel dose of 265 mg/m2. Neutropenic fever was observed in 30% of patients at a paclitaxel dose of 250-265 mg/m2. Other observed adverse effects included pruritus, myalgia, arthralgia, alopecia, nausea, and vomiting.
  
  
  CONCLUSIONS
  Toxicity was acceptable. The maximum tolerated dose of paclitaxel was 230 mg/m2 without hematopoietic growth factor, or 250 mg/m2 with hematopoietic growth factor, the carboplatin dose held constant, calculated at area under the curve of 7.5. Phase II studies of this combination are warranted in the treatment of these carcinomas.
authors.affiliation: Saint Louis University Health Sciences Center, Department of Internal Medicine, Missouri 63110-0250, USA.
authors.forename: F R
authors.initials: FR
authors.lastname: Dunphy
authors.forename: J H
authors.initials: JH
authors.lastname: Boyd
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.forename: C H
authors.initials: CH
authors.lastname: Dunphy
authors.forename: B R
authors.initials: BR
authors.lastname: Harrison
authors.forename: T L
authors.initials: TL
authors.lastname: Dunleavy
authors.forename: J J
authors.initials: JJ
authors.lastname: Rodriguez
authors.forename: E M
authors.initials: EM
authors.lastname: McDonough
authors.forename: J R
authors.initials: JR
authors.lastname: Minster
authors.forename: J G
authors.initials: JG
authors.lastname: Hilton
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D005334:Fever / Q000139:chemically induced; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009422:Nervous System Diseases / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D011300:Preoperative Care; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D016190:Carboplatin; D017239:Paclitaxel